Process mapping strategies to prevent subcutaneous implantable cardioverter-defibrillator infections.

BACKGROUND: Infection remains a major complication of cardiac implantable electronic devices and can lead to significant morbidity and mortality. Implantable devices that avoid transvenous leads, such as the subcutaneous implantable cardioverter-defibrillator (S-ICD), can reduce the risk of serious infection-related complications, such as bloodstream infection and infective endocarditis. While the 2017 AHA/ACC/HRS guidelines include recommendations for S-ICD use for patients at high risk of infection, currently, there are no clinical trial data that address best practices for the prevention of S-ICD infections. Therefore, an expert panel was convened to develop a consensus on these topics. METHODS: An expert process mapping methodology was used to achieve consensus on the appropriate steps to minimize or prevent S-ICD infections. Two face-to-face meetings of high-volume S-ICD implanters and an infectious diseases specialist, with expertise in cardiovascular implantable electronic device infections, were conducted to develop consensus on useful strategies pre-, peri-, and postimplant to reduce S-ICD infection risk. RESULTS: Expert panel consensus on recommended steps for patient preparation, S-ICD implantation, and postoperative management was developed to provide guidance in individual patient management. CONCLUSION: Achieving expert panel consensus by process mapping methodology for S-ICD infection prevention was attainable, and the results should be helpful to clinicians in adopting interventions to minimize risks of S-ICD infection.

Diagnosis and management of subcutaneous implantable cardioverter-defibrillator infections based on process mapping.

BACKGROUND: Infection is a well-recognized complication of cardiovascular implantable electronic device (CIED) implantation, including the more recently available subcutaneous implantable cardioverter-defibrillator (S-ICD). Although the AHA/ACC/HRS guidelines include recommendations for S-ICD use, currently there are no clinical trial data that address the diagnosis and management of S-ICD infections. Therefore, an expert panel was convened to develop consensus on these topics. METHODS: A process mapping methodology was used to achieve a primary goal - the development of consensus on the diagnosis and management of S-ICD infections. Two face-to-face meetings of panel experts were conducted to recommend useful information to clinicians in individual patient management of S-ICD infections. RESULTS: Panel consensus of a stepwise approach in the diagnosis and management was developed to provide guidance in individual patient management. CONCLUSION: Achieving expert panel consensus by process mapping methodology in S-ICD infection diagnosis and management was attainable, and the results should be helpful in individual patient management.

The development of a training course for clubfoot treatment in Africa: learning points for course development.

BACKGROUND: Clubfoot is a common congenital musculoskeletal disorder that causes mobility impairment. There is a lack of trained mid-level personnel to provide clubfoot treatment in Africa and there is no standard training course. This prospective study describes the collaborative and participatory approach to the development of a training course for the treatment of clubfoot in children in resource constrained settings. METHODS: We used a systems approach to evaluate the development of the training course. Inputs: The research strategy included a review of context and available training materials, and the collection of data on current training practices. Semi-structured interviews were conducted with seven expert clubfoot trainers. A survey of 32 international and regional trainers was undertaken to inform practical issues. The data were used to develop a framework for training with advice from two technical groups, consisting of regional and international stakeholders and experts. PROCESS: A consensus approach was undertaken during workshops, meetings and the sharing of documents. The design process for the training materials took twenty-four months and was iterative. The training materials were piloted nine times between September 2015 and February 2017. Processes and materials were reviewed and adapted according to feedback after each pilot. RESULTS: Fifty-one regional trainers from Africa (18 countries), 21 international experts (11 countries), 113 local providers of clubfoot treatment (Ethiopia, Rwanda and Kenya) and local organising teams were involved in developing the curriculum and pilot testing. The diversity of the two technical advisory groups allowed a wide range of contributions to the collaboration. Output: The resulting curriculum and content comprised a two day basic training and a two day advanced course. The basic course utilised adult learning techniques for training novice providers in the treatment of idiopathic clubfoot in children under two years old. The advanced course builds on these principles. CONCLUSION: Formative research that included mixed methods (both qualitative and quantitative) was important in the development of an appropriate training course. The process documentation from this study provides useful information to assist planning of medical training programmes and may serve as a model for the development of other courses.

An Update on Pediatric Environmental Health Specialty Units: Activities and Impacts, 2015-19.

OBJECTIVE: Pediatric Environmental Health Specialty Units (PEHSUs) address health concerns impacting children and their families related to environmental hazards by providing consultation and education to families, communities, and health care professionals. This analysis evaluated the productivity of the national PEHSU program. METHODS: PEHSUs reported data on services provided to US communities between October 1, 2014 and September 30, 2019. Descriptive statistics and qualitative analysis are presented. RESULTS: During this period, 6102 consultations and 4644 educational outreach activities were recorded. PEHSU faculty and staff published 462 articles, reviews, book chapters, fact sheets, commentaries, short informational pieces, and other materials between 2014 and 2019. These included 190 articles in scientific peer-reviewed journals and 29 textbook chapters to increase professional capacity in pediatric and reproductive environmental health. Lead, other metals, substances of abuse, pesticides, mold, and air pollution were frequently reported as agents of concern and educational topics. Requests for an overview of pediatric environmental health and outdoor pollutants were other frequently reported topics. CONCLUSIONS: PEHSUs work to decrease harmful exposures and improve children's health. They serve as expert resources for families, health care professionals, and communities on health effects related to environmental exposures. Data show the breadth and depth of concerns addressed and demonstrate the productivity and impact of this national program.

Structural complexity in ramp-compressed sodium to 480 GPa.

The properties of all materials at one atmosphere of pressure are controlled by the configurations of their valence electrons. At extreme pressures, neighboring atoms approach so close that core-electron orbitals overlap, and theory predicts the emergence of unusual quantum behavior. We ramp-compress monovalent elemental sodium, a prototypical metal at ambient conditions, to nearly 500 GPa (5 million atmospheres). The 7-fold increase of density brings the interatomic distance to 1.74 Å well within the initial 2.03 Å of the Na+ ionic diameter, and squeezes the valence electrons into the interstitial voids suggesting the formation of an electride phase. The laser-driven compression results in pressure-driven melting and recrystallization in a billionth of a second. In situ x-ray diffraction reveals a series of unexpected phase transitions upon recrystallization, and optical reflectivity measurements show a precipitous decrease throughout the liquid and solid phases, where the liquid is predicted to have electronic localization. These data reveal the presence of a rich, temperature-driven polymorphism where core electron overlap is thought to stabilize the formation of peculiar electride states.

Upper- vs. Lower-Body Exercise Performance in Female and Male Cross-Country Skiers.

Purpose: To investigate the interaction between exercise modality (i.e., upper- and lower-body exercise) and sex in physiological responses and power output (PO) across the entire intensity spectrum (i.e., from low to maximal intensity). Methods: Ten male and 10 female cross-country (XC) skiers performed a stepwise incremental test to exhaustion consisting of 5 min stages with increasing workload employing upper-body poling (UP) and running (RUN) on two separate days. Mixed measures ANOVA were performed to investigate the interactions between exercise modalities (i.e., UP and RUN) and sex in physiological responses and PO across the entire exercise intensity spectrum. Results: The difference between UP and RUN (ΔUP-RUN), was not different in the female compared with the male XC skiers for peak oxygen uptake (18 ± 6 vs. 18 ± 6 mL·kg-1·min-1, p = 0.843) and peak PO (84 ± 18 vs. 91 ± 22 W, p = 0.207). At most given blood lactate and rating of perceived exertion values, ΔUP-RUN was larger in the male compared with the female skiers for oxygen uptake and PO, but these differences disappeared when the responses were expressed as % of the modality-specific peak. Conclusion: Modality-differences (i.e., ΔUP-RUN) in peak physiological responses and PO did not differ between the female and male XC skiers. This indicates that increased focus on upper-body strength and endurance training in female skiers in recent years may have closed the gap between upper- and lower-body endurance capacity compared with male XC skiers. In addition, no sex-related considerations need to be made when using relative physiological responses for intensity regulation within a specific exercise modality.

Device-related infection in de novo transvenous implantable cardioverter-defibrillator Medicare patients.

BACKGROUND: Cardiac device infection is a serious complication of implantable cardioverter-defibrillator (ICD) placement and requires complete device removal with accompanying antimicrobial therapy for durable cure. Recent guidelines have highlighted the need to better identify patients at high risk of infection to assist in device selection. OBJECTIVE: To estimate the prevalence of infection in de novo transvenous (TV) ICD implants and assess factors associated with infection risk in a Medicare population. METHODS: A retrospective cohort study was conducted using 100% Medicare administrative and claims data to identify patients who underwent de novo TV-ICD implantation (July 2016-December 2017). Infection within 720 days of implantation was identified using ICD-10 codes. Baseline factors associated with infection were identified by univariable logistic regression analysis of all variables of interest, including conditions in Charlson and Elixhauser comorbidity indices, followed by stepwise selection criteria with a P ≤ .25 for inclusion in a multivariable model and a backwards, stepwise elimination process with P ≤ .1 to remain in the model. A time-to-event analysis was also conducted. RESULTS: Among 26,742 patients with de novo TV-ICD, 519 (1.9%) developed an infection within 720 days post implant. While more than half (54%) of infections occurred during the first 90 days, 16% of infections occurred after 365 days. Multivariable analysis revealed several significant predictors of infection: age <70 years, renal disease with dialysis, and complicated diabetes mellitus. CONCLUSION: The rate of de novo TV-ICD infection was 1.9%, and identified risk factors associated with infection may be useful in device selection.

Unmet Needs of People With Parkinson's Disease and Their Caregivers During COVID-19-Related Confinement: An Explorative Secondary Data Analysis.

Self-perceived unmet needs in people with typical and atypical parkinsonism (PwP) and their caregivers, support network, personalized ways to address self-perceived unmet needs during confinement, as well as the prevalence of self-reported COVID-19 related symptoms, confirmed SARS-CoV-2 infection, and self-reported COVID-19 related hospitalization in Luxembourg and the Greater Region were assessed. From 18th March to 10th April 2020, 679 PwP were contacted by phone. Data was collected in the form of a semi-structured interview. The thematic synthesis identified 25 themes where PwP need to be supported in order to cope with consequences of the pandemic, and to adapt their daily and health-related activities. The present work highlights that in the context of personalized medicine, depending on the individual needs of support of the patient the identified self-perceived unmet needs were addressed in various ways ranging from one-directed information over interaction up to proactive counseling and monitoring. Family and health professionals, but also other support systems were taking care of the unmet needs of PwP (e.g., shopping, picking-up medication, etc.) during the pandemic. 7/606 PwP (1.15%) reported COVID-19 related symptoms, 4/606 (0.66%) underwent a rRT-PCR-based diagnostic test and 2/606 (0.33%) were confirmed as SARS-CoV-2 positive. None of these PwP reported being hospitalized due to COVID-19. Our results will allow health professionals to expand their services in a meaningful way i.e., personalize their support in the identified themes and thus improve the healthcare of PwP in times of crisis.

In vivo model of human pathogen infection and demonstration of efficacy by an antimicrobial pouch for pacing devices.

BACKGROUND: Device-related infections represent a significant clinical challenge. Once established, these infections prove difficult to treat with existing antibiotic regimens, compromising the health of device recipients, and usually requiring surgical intervention to resolve. OBJECTIVE: The purpose of this study was to determine the efficacy of the AIGIS(RX) antibacterial envelope (TyRx Pharma, Inc., Monmouth Junction, NJ, USA) designed to reduce device-related infections by incorporating minocycline and rifampin in a controlled release polymer. METHODS: An infection was established in a rabbit model by creating bilateral subcutaneous implant pockets, into which a pacing device with or without AIGIS(RX) was placed. The incisions were closed, and a defined dose of bacteria was infused into each implant pocket. After 7 days, devices were explanted and sampled for viable bacteria by swabbing and sonication. RESULTS: Initial studies evaluated the ability of the AIGIS(RX) pouch to reduce Staphylococcus epidermidis (S. epi) infection in this model using clinical and quantitative microbial endpoints. Results demonstrate S. epi infection in all control samples, while no pathogens were recovered from samples with the AIGIS(RX) pouch. Systemic antibiotic levels were undetectable. Additional studies tested the efficacy of the AIGIS(RX) pouch with additional bacterial strains, Staphylococcus capitis, Escherichia coli, and Acinetobacter Baumannii. In each case, the device and implant pocket with the AIGIS(RX) pouch was free of any signs of infection. An assessment of biofilm produced by Acinetobacter demonstrated the elimination of biofilm formation on the implanted device. CONCLUSION: These results demonstrate that in this animal model, the AIGIS(RX) device reduces the risk for infection of viable pathogens within implant pockets.

Type I collagen structure regulates cell morphology and EGF signaling in primary rat hepatocytes through cAMP-dependent protein kinase A.

Adhesion to type 1 collagen elicits different responses dependent on whether the collagen is in fibrillar (gel) or monomeric form (film). Hepatocytes adherent to collagen film spread and proliferate, whereas those adherent to collagen gel remain rounded and growth arrested. To explore the role of potential intracellular inhibitory signals responsible for collagen gel-mediated growth arrest, cAMP-dependent protein kinase A (PKA) was examined in hepatocytes adherent to collagen film or gel. PKA activity was higher in hepatocytes on collagen gel than on film during G1 of the hepatocyte cell cycle. Inhibition of PKA using H89 increased cell spreading on collagen gel in an EGF-dependent manner, whereas activation of PKA using 8-Br-cAMP decreased cell spreading on collagen film. PKA inhibition also restored ERK activation, cyclin D1 expression and G1-S progression on collagen gel, but had no effect on cells adherent to collagen film. Analysis of EGF receptor phosphorylation revealed that adhesion to collagen gel alters tyrosine phosphorylation of the EGF receptor, leading to reduced phosphorylation of tyrosine residue 845, which was increased by inhibition of PKA. These results demonstrate that fibrillar type 1 collagen can actively disrupt cell cycle progression by inhibiting specific signals from the EGF receptor through a PKA-dependent pathway.

Patient, family and nurse experiences with patient presence during handovers in acute care hospital settings: a systematic review of qualitative evidence.

OBJECTIVE: The objective of this systematic review was to synthesize the best available evidence on patients', family members' and nurses' experiences with bedside handovers in acute care settings. INTRODUCTION: The transfer of patient information between nurses represents a critical component of safety within health care. Conducting handover at the bedside allows patients and families to participate in information exchanges. Studies that address bedside handover highlight benefits and concerns with their implementation. Insight into patients', families' and nurses' experiences with bedside handovers can help to identify the most appropriate and safest approach to handovers. INCLUSION CRITERIA: The current review considered patients, family members and nurses in the acute care hospital setting. Nurses included licensed nurses, registered nurses, practical nurses, nursing assistants, nurse researchers, and advanced practice nurses. METHODS: A three-step search strategy was used to identify English language qualitative primary research studies. Two reviewers independently appraised the included studies using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Qualitative Research. Qualitative studies that considered attitudes, beliefs and experiences of patients, families and nurses on patient presence during bedside handover were considered for this review. Papers included in the review were from 1998 to 2017. RESULTS: The review included 12 qualitative publications. Key findings were extracted and classified as unequivocal (U) or credible (C). A total of 96 findings were extracted and aggregated into 14 categories. From the 14 categories, five synthesized findings were developed: i) becoming more informed; ii) upholding confidentiality and privacy; iii) varying desire and ability to participate; iv) individualizing patient care; and v) challenges in conducting bedside handovers can be overcome with adaptive practices. CONCLUSIONS: This review captured the experiences of patients, families and nurses with patient presence during bedside handovers in a hospital setting. For the most part, patients and families describe bedside handover positively, reporting feeling more informed and engaged in care. This review highlights areas where patients' and nurses' views on bedside reporting may differ, particularly in the areas of desire to participate and the need for confidentiality. Although hospital environments can create challenges in sharing personal patient information at the bedside, these may be overcome through education and by the adoption of a flexible and individualized approach.

A Patient Decision Aid App for Patients With Chronic Kidney Disease: Questionnaire Study.

BACKGROUND: The Dialysis Guide (DG) is a patient decision aid (PDA) available as an app and developed for mobile phones for patients with chronic kidney disease facing the decision about dialysis modality. OBJECTIVE: The aim of this study was to uncover the applicability of the DG as a PDA. METHODS: The respondents completed a questionnaire before and after using the DG. The respondents' decisional conflicts were examined using the Decisional Conflict Scale, and the usability of the app was examined using the System Usability Scale (SUS). The change in decisional conflict was determined with a paired t test. RESULTS: A total of 22 respondents participated and their mean age was 65.05 years; 20 out of 22 (90%) had attended a patient school for kidney disease, and 13 out of 22 (59%) had participated in a conversation about dialysis choice with a health professional. After using the DG, the respondents' decisional conflicts were reduced, though the reduction was not statistically significant (P=.49). The mean SUS score was 66.82 (SD 14.54), corresponding to low usability. CONCLUSIONS: The DG did not significantly reduce decisional conflict, though the results indicate that it helped the respondents decide on dialysis modality. Attending a patient school and having a conversation about dialysis modality choice with a health professional is assumed to have had an impact on the decisional conflict before using the DG. The usability of the DG was not found to be sufficient, which might be caused by the respondents' average age. Thus, the applicability of the DG cannot be definitively determined.

The feasibility of a training course for clubfoot treatment in Africa: A mixed methods study.

BACKGROUND: There is no available training programme with standard elements for health workers treating clubfoot in Africa. Standardised training with continued mentorship has the potential to improve management of clubfoot. We aimed to evaluate the feasibility of such a training programme among clubfoot providers in Africa, and assess implications for training effectiveness and scale up. METHOD: We used participatory research with trainers from 18 countries in Africa over two years to devise, pilot and refine a 2-day basic and a 2-day advanced clubfoot treatment course. (The Africa Clubfoot Training or 'ACT' Course.) The pilots involved training 113 participants. Mixed methods (both qualitative and quantitative) were used for evaluation. We describe and synthesise the results using the eight elements proposed by Bowen et al (2010) to assess feasibility. All participants completed feedback questionnaires, and interviews were conducted with a subset of participants. We undertook a narrative description of themes raised in the participant questionnaires and interviews. Descriptive statistics were used to compare pre- and post-course scores for confidence and knowledge. RESULTS: 113 participants completed pre and post-course measures (response rate = 100%). Mean participant confidence increased from 64% (95%CI: 59-69%) to 88% (95%CI: 86-91%) post course. Mean participant knowledge increased from 55% (95%CI: 51-60%) to 78% (95%CI: 76-81%) post course. No difference was found in mean for either subscale of cadre or sex. The qualitative analysis generated themes under four domains: 'practical learning in groups', 'interactive learning', 'relationship with the trainer' and 'ongoing supervision and mentorship'. CONCLUSION: The Africa Clubfoot Training package to teach health care workers to manage clubfoot is likely to be feasible in Africa. Future work should evaluate its impact on short and long term treatment outcomes and a process evaluation of implementation is required.

Nursing students' experiences with clinical placement in residential aged care facilities: a systematic review protocol of qualitative evidence.

REVIEW QUESTION/OBJECTIVE: The objective of this review is to analyze and synthesize the best available evidence on nursing students' experiences with clinical placement in residential aged care facilities.The specific review questions are.

The Use of Smartphones in Norwegian Social Care Services.

This study aims to understand how smartphone technology was perceived by social workers responsible for piloting social services software and the experiences of involving end-users as co-developers. The pilot resulted in an improved match between the smartphone software and workflow as well as mutual learning experiences among the social workers, clients, and the vendor. The pilot study revealed several graphical user interface (GUI) and functionality challenges. Implementing an ICT social service smartphone application may further improve efficiencies for social workers serving citizens, however; this study validates the importance to study end-users' experiences with communication and the real-time use of the system in order reap the anticipated benefits of ICT capabilities for smart phone social service applications.

Skin-to-Skin Care After Birth for Moderately Preterm Infants.

OBJECTIVE: To investigate the feasibility and safety of skin-to-skin care after birth for moderately preterm infants. DESIGN: Prospective cohort study. SETTING: The study was conducted at the maternity wards and NICUs of three study sites in Norway. PARTICIPANTS: Ninety preterm infants born vaginally with gestational ages of 32 weeks/0 days to 34 weeks/6 days. METHODS: Comparison of groups of preterm infants who received skin-to-skin care or conventional treatment in incubators after birth. RESULTS: Median gestational age and birth weight were similar in the two groups: 33 weeks/5 days versus 34 weeks/3 days (p = .464) and 2,100 versus 2,010 g (p = .519). There were no differences in the first body temperature (p = .841) and blood glucose level (p = .539) between the groups. CONCLUSION: Early skin-to-skin contact in the delivery room for moderately preterm infants may be feasible and safe.

Cost-effectiveness of club-foot treatment in low-income and middle-income countries by the Ponseti method.

BACKGROUND: Club foot is a common congenital deformity affecting 150 000-200 000 children every year. Untreated patients end up walking on the side or back of the affected foot, with severe social and economic consequences. Club foot is highly treatable by the Ponseti method, a non-invasive technique that has been described as highly suitable for use in resource-limited settings. To date, there has been no evaluation of its cost-effectiveness ratio, defined as the cost of averting one disability-adjusted life year (DALY), a composite measure of the impact of premature death and disability. In this study, we aimed to calculate the average cost-effectiveness ratio of the Ponseti method for correcting club foot in sub-Saharan Africa. METHODS: Using data from 12 sub-Saharan African countries provided by the international non-profit organisation CURE Clubfoot, which implements several Ponseti treatment programmes around the world, we estimated the average cost of the point-of-care treatment for club foot in these countries. We divided the cost of treatment with the average number of DALYs that can be averted by the Ponseti treatment, assuming treatment is successful in 90% of patients. RESULTS: We found the average cost of the Ponseti treatment to be US$167 per patient. The average number of DALYs averted was 7.42, yielding a cost-effectiveness ratio of US$22.46 per DALY averted. To test the robustness of our calculation different variables were used and these yielded a cost range of US$5.28-29.75. This is less than a tenth of the cost of many other treatment modalities used in resource-poor settings today. CONCLUSIONS: The Ponseti method for the treatment of club foot is cost-effective and practical in a low-income country setting. These findings could be used to raise the priority for implementing Ponseti treatment in areas where patients are still lacking access to the life-changing intervention.

Dexamethasone effects on rat hepatocyte spheroid formation and function.

Hepatocytes cultured on moderately adhesive surfaces or in spinner flasks spontaneously self-assemble into spherical tissue-like aggregates (spheroids). These spheroids have smooth surfaces and tissue-like polarized cell morphology, including bile canalicular-like channels, and maintain high viability and liver-specific functions for extended culture periods. Dexamethasone (DEX), a synthetic glucocorticoid, is known to elicit various responses in gene expression, and is often added to hepatocyte culture medium. The morphology and liver-specific protein production of hepatocyte spheroids were assessed under DEX concentrations ranging from 50 nM to 10 microM. DEX altered the kinetics of spheroid formation in a concentration-dependent fashion, with increasing concentrations inhibiting aggregation and promoting aggregate disassembly on culture dishes. DEX addition to spinner cultures resulted in smaller, more irregularly shaped spheroids and a higher incidence of aggregate clumping. Albumin and urea production were also higher in DEX cultures, but this effect was not as sensitive to concentration and occurred irrespective of the state of aggregation. RTPCR was utilized to assess the mRNA levels of extracellular matrix proteins, E-cadherin, and cytochrome P-450 enzymes. Results indicated a slight increase in fibronectin and collagen III mRNA early in the cultures, possibly contributing to the changes in morphology observed.

OA28†At the clinical shores - palliative care volunteers and population health in new south wales (NSW).

BACKGROUND: In October 2014 a detailed mapping study of volunteers in palliative care services in NSW was undertaken for the first time. This presentation will provide a thematic analysis of the initial findings. AIMS: The aim of this study was to provide a thematic analysis of the occupational terrain of palliative care volunteers across NSW as part of a project to develop the capacity of palliative care volunteer services and to raise public awareness of their work. METHOD: A total of 44 Volunteer Coordinators, clinicians and other health service staff were surveyed across 38 services mostly by telephone and face-to-face meetings using a 21 question survey which measured quantitative and qualitative data. RESULTS: The survey clarified the number and distribution of the 38 palliative care services, 1,242 volunteers and 22 full-time-equivalent volunteer coordinators in NSW. Data included comments made by participants in the survey, and thematic analysis reveals that the palliative care volunteers are constructed as neither exclusively clinical nor non-clinical in nature. CONCLUSION: Palliative care volunteers metaphorically stand at the shores of the clinical domains, interacting collegially with the clinician but identifying with the public and acting to guide people ashore and through the expert landscape. The report concludes that given the emergent nature of palliative care practice there are precedents for the inclusion of palliative care volunteers more extensively within communities of practice at strategic, policy and operational contexts, but this might actually do a disservice to the unique function of volunteers as coast watchers.

Ovarian carcinoma spheroids disaggregate on type I collagen and invade live human mesothelial cell monolayers.

Ovarian carcinoma patients frequently develop malignant ascites containing single and aggregated tumor cells, or spheroids. Spheroids have been shown to be resistant to many therapies, but their contribution to ovarian cancer dissemination remains undetermined. We have previously shown that ascites spheroids adhere to extracellular matrix (ECM) proteins and live human mesothelial cells via beta1 integrin subunits. Here, we assessed the ability of spheroids that were generated from the human ovarian carcinoma cell line NIH:OVCAR5 to disseminate and invade in vitro. Spheroids were seeded on ECM proteins for 24 h. While laminin and type IV collagen stimulated some cell migration, spheroids completely disaggregated on type I collagen substrates. A monoclonal antibody against the beta1 integrin subunit significantly inhibited disaggregation on all proteins tested. To test their invasive ability, spheroids were added to monolayers of live human LP9 mesothelial cells. Within 24 h, the spheroids adhered and disaggregated on top of the monolayers, and within a week had established foci of invasion encompassing a 200-fold larger surface area. Addition of a monoclonal antibody against the beta1 integrin subunit drastically reduced spheroid invasion into the mesothelial cell monolayers. GM 6001, a broad-scale matrix metalloproteinase inhibitor, also significantly blocked spheroid invasion into the mesothelial cell monolayers. Epsilon-amino-N-caproic acid, a serine protease inhibitor, partially inhibited spheroid invasion. Based on their ability to attach to, disaggregate on, and invade into live human mesothelial cell monolayers, spheroids should thus be regarded as potential contributors to the dissemination of ovarian cancer.