Positive Patient Outcomes Research Articles

Safety and Efficacy of Achilles Repair Using the Mini-Open Approach in Supine Versus Prone Position: A Retrospective Study.

PurposeSurgical repair of the Achilles tendon is a common procedure in cases of acute rupture. Open Achilles tendon surgery with a traditional extensile approach is most often performed in the prone position, but this can lead to numerous complications. The mini-open approach for repair in the supine position may avoid the risks of the prone position. The purpose of this study is to compare perioperative outcomes and differences in cost between patients undergoing acute Achilles rupture repair with mini-open approach, incision of approximately 3 cm, in the supine position versus traditional approach in the prone position.MethodsPatients who underwent surgical repair of acute Achilles rupture at a single institution were retrospectively identified using Current Procedural Terminology (CPT) code 27650. Complication rates and the total cost charged to the insurance companies of both the supine and prone groups were calculated.ResultsA total of 80 patients were included for analysis, 26 supine and 54 prone. The difference in average total time in the operating room was statistically significant. The prone position took approximately 15% more time (118.7 minutes) compared to the supine position (100 minutes) (p = 0.001). While not statistically significant, the total cost for the supine group ($19,889) was less than the for the prone group ($21,722) (p = 0.153) Average postoperative pain score, infection rate, dehiscence rate, sepsis rate, and deep vein thrombosis (DVT) rate were also similar between the two groups. No patient in either group experienced re-rupture of the Achilles tendon within the first year of primary repair.ConclusionThe mini-open approach in the supine position may be advantageous in the repair of acute Achilles rupture in that it reduces total time in the operating room and total cost while maintaining positive patient outcomes. Prospective clinical studies are warranted to validate these assessments.

Telehealth Interventions and Outcomes Across Rural Communities in the United States: Narrative Review.

BackgroundIn rural communities, there are gaps in describing the design and effectiveness of technology interventions for treating diseases and addressing determinants of health.ObjectiveThe aim of this study is to evaluate literature on current applications, therapeutic areas, and outcomes of telehealth interventions in rural communities in the United States.MethodsA narrative review of studies published on PubMed from January 2017 to December 2020 was conducted. Key search terms included telehealth, telemedicine, rural, and outcomes.ResultsAmong 15 included studies, 9 studies analyzed telehealth interventions in patients, 3 in health care professionals, and 3 in both patients and health care professionals. The included studies reported positive outcomes and experiences of telehealth use in rural populations including acceptability and increased satisfaction; they also noted that technology is convenient and efficient. Other notable benefits included decreased direct and indirect costs to the patient (travel cost and time) and health care service provider (staffing), lower onsite health care resource utilization, improved physician recruitment and retention, improved access to care, and increased education and training of patients and health care professionals.ConclusionsTelehealth models were associated with positive outcomes for patients and health care professionals, suggesting these models are feasible and can be effective. Future telehealth interventions and studies examining these programs are warranted, especially in rural communities, and future research should evaluate the impact of increased telehealth use as a result of the COVID-19 pandemic.

Rural influences on the social network dynamics of district nursing services: A qualitative meta-synthesis.

Background and AimsAs demands on healthcare services grow, fiscal restrictions place increased emphasis on services outside of traditional healthcare settings. Previous research into long‐term‐conditions suggests that social network members (including weaker ties such as acquaintances, community groups, and healthcare professionals) play a key role in illness management. There is limited knowledge about the engagement of social networks in supporting people who are receiving medical interventions at home. This qualitative metasynthesis explores the work and the interactions between district nurses (DN) and informal network members supporting people who are receiving medical interventions at home and living in rural areas.MethodsA search was undertaken on CINAHL, Medline, and PsychINFO for qualitative research articles from 2009 to 2019. Studies that examined DN in rural locations and/or social network support in rural locations were eligible. Fourteen articles were selected.ResultsThematic analysis of results and discussion data from the studies resulted in four themes being developed: the development of both transactional and friend‐like nurse‐patient ties in rural localities, engagement of the wider network in the delivery of good care, blurring of professional boundaries in close community relationships, and issues accessing and navigating formal and informal support in the context of diminishing resources in rural areas.These findings suggest that DNs in rural localities work beyond professional specialties and experience to provide emotional support, help with daily tasks, and build links to communities. There was also evidence that nurses embedded within rural localities developed friend‐like relationships with patients, and negotiated with existing support networks and communities to find support for the patient.ConclusionsFindings indicated that developing strong links with patients and members of their networks does not automatically translate into positive outcomes for patients, and can be unsustainable, burdensome, and disruptive. DNs developing weak ties with patients and building awareness of the structure of individual networks and local sources of support offers avenues for sustainable and tailored community‐based nursing support.

Safety attitudes build safety culture: Nurse/midwife leaders improving health care using quantitative data.

We aim to determine safety attitudes of nurses and midwives across a Local Health District in Australia and compare results 1 year later following facilitated feedback of results. Positive safety cultures are imperative for positive patient and staff outcomes. Staff member's attitude contribute to an organisations safety culture but can differ between health professional groups and across different subcultures. The Safety Attitudes Questionnaire (SAQ-Short version) was administered to all nurses and midwives within a Local Health District in NSW, Australia in 2019 and 2020. Results were facilitated back to nursing/midwifery leadership teams with an expectation of developing and enacting an action plan, based on results. Of the six domains in the SAQ-Short version, five domains scores increased significantly (p < .001) over the time period. Measures over time are important to establish differences in perceptions and feedback on impact of actions. Facilitated feedback of results shows meaning when nursing/midwifery leadership staff have data explained and an opportunity to discuss and plan. This study shows that facilitated feedback of quantitative survey results brings improved results when a survey is replicated. Nurse managers should enact a contextualized action plan with teams based on survey results to influence improvement in safety attitudes of staff.

Blood-Based Multi-Cancer Detection Using a Novel Variant Calling Assay (DEEPGENTM): Early Clinical Results.

Simple SummaryCancer remains a worldwide concern with significant burdens on the population and healthcare systems. Studies have shown that early detection is paramount in positive patient outcomes, although the standard of care screening is limited to a few cancers. When a tumor cell dies, it releases DNA into the bloodstream. This cell-free DNA can be extracted, and specific mutations identified. Technologies based on this principle are gaining popularity amongst physicians for cancer patients to inform personalized treatment. Additionally, if platforms are sensitive enough, blood-based multi-cancer screening can be performed. DEEPGENTM is a next-generation sequencing platform that has been optimized for early cancer detection. This study is a preliminary analysis of cancer detection rates across seven cancers using the DEEPGENTM platform.This is an early clinical analysis of the DEEPGENTM platform for cancer detection. Newly diagnosed cancer patients and individuals with no known malignancy were included in a prospective open-label case-controlled study (NCT03517332). Plasma cfDNA that was extracted from peripheral blood was sequenced and data were processed using machine-learning algorithms to derive cancer prediction scores. A total of 260 cancer patients and 415 controls were included in the study. Overall, sensitivity for all cancers was 57% (95% CI: 52, 64) at 95% specificity, and 43% (95% CI: 37, 49) at 99% specificity. With 51% sensitivity and 95% specificity for all stage 1 cancers, the stage-specific sensitivities trended to improve with higher stages. Early results from this preliminary clinical, prospective evaluation of the DEEPGENTM liquid biopsy platform suggests the platform offers a clinically relevant ability to differentiate individuals with and without known cancer, even at early stages of cancer.

Effects of preoperative oral carbohydrate administration combined with postoperative early oral intake in elderly patients undergoing hepatectomy with acute-phase inflammation and subjective symptom burden: A prospective randomized controlled study

BackgroundEnhanced recovery after surgery (ERAS) has received increasing attention. Preoperative oral carbohydrate and postoperative early oral feeding (POC-PEOF) as the basic nutrition administration in the ERAS program suffers from low adherence. The role and benefits of administering POC-PEOF in elderly patients with hepatocellular carcinoma (HCC) are unclear. Therefore, the randomized controlled trial evaluated the effects of POC-PEOF in elderly patients with HCC undergoing hepatectomy with inflammation and patient self-reported symptom burden compared with the corresponding outcomes of traditional fasting protocols. MethodsElderly patients with HCC (n = 126) were randomly assigned to two groups using the sealed envelope technique. Sixty-three patients were included in the intervention (POC-PEOF) group and received POC-PEOF administration, whereas the 63 patients in the control (FAST) group underwent conventional fasting. Acute-phase inflammation markers, patient self-reported symptom burdens, and postoperative outcomes were compared between the two groups. ResultsThe average age was 69.60 ± 5.00 years in the POC-PEOF group and 70.44 ± 6.15 years in the FAST group. Compared to prolonged fasting, POC-PEOF achieved significant positive results, including lower overall levels of inflammatory response mediators (CRP, IL-6) on postoperative day (POD) 1, POD 3, and POD 5 (P < 0.05), lower patient self-reported symptom burdens of thirst, hunger, anxiety and nausea (P < 0.05), faster gastrointestinal function return with shortened times to first flatus and first defecation (48.31 ± 13.24 h vs. 96.26 ± 23.12 h and 72.87 ± 21.12 h vs. 144.34 ± 23.31 h, and P = 0.034 and P = 0.013, respectively). Furthermore, the average postoperative hospitalization duration in the POC-PEOF group was shorter than that in the FAST group (6.93 ± 0.98 d vs. 8.12 ± 1.15 d, P = 0.042). There was no significant difference of total complications between the groups (25.39 % vs 36.51 %, RR 0.696, 95 % CI 0.408–0.187, P = 0.177). ConclusionPOC-PEOF helps lessen acute-phase inflammation and relieves the subjective symptom burden, which can ensure better positive postoperative outcomes in elderly HCC patients undergoing hepatectomy.

Early vagus nerve stimulator implantation as a main predictor of positive outcome in pediatric patients with epileptic encephalopathy.

We describe a multicenter experience with VNS implantation in pediatric patients with epileptic encephalopathy. Our goal was to assess VNS efficacy and identify potential predictors of favorable outcome. This was a retrospective study. Inclusion criteria were: ≤18 years at the time of VNS implantation and at least one year of follow-up. All patients were non-candidates for excisional procedures. Favorable clinical outcome and effective VNS therapy were defined as seizure reduction >50%. Outcome data were reviewed at one, two, three and five years after VNS implantation. Fisher's exact test, Kaplan-Meier and multiple logistic regression analysis were employed. Twenty-seven patients met inclusion criteria. Responder rate (seizure frequency reduction ≥ 50%) at one-year follow-up was 25.9%, and 15.3% at last follow-up visit. The only variable significantly predicting favorable outcome was time to VNS implantation, with the best outcome achieved when VNS implantation was performed within five years of seizure onset (overall response rate of 83.3% at one year of follow-up and 100% at five years). In total, 63% of patients evidenced improved QOL at last follow-up visit. Only one patient exited the study due to an adverse event at two years from implantation. Early VNS implantation within five years of seizure onset was the only predictor of favorable clinical outcome in pediatric patients with epileptic encephalopathy. Improved QOL and a very low incidence of adverse events were observed.

Standardizing Care for Patients with Insulin Pumps

<h3>Introduction</h3> An increase in the number of patient with subcutaneous insulin pumps was noted in the surgical population. Multiple types of insulin pumps and various levels of patient knowledge were being noted by perioperative staff. <h3>Identification of the problem</h3> The plan of care was found to be inconsistent for these patients and there was no standardized treatment guideline in place to manage practice. <h3>Objectives of project</h3> The objective of this project was to 1) Standardize the perioperative process of insulin pump management, 2) Create a clinical practice guideline specific for this population, and 3) Systematically educate staff of the new process and guideline. <h3>Method</h3> A multidisciplinary team was assembled and the current practice was analyzed to identify gaps. Multiple areas of practice were identified. Monthly meetings were held with leaders from each area contributing to the practice guideline development. <h3>Outcomes</h3> A multidisciplinary clinical practice guideline was developed in conjunction with endocrinology physicians, hospitalists, anesthesiologists, nurses and pharmacists to standardize the process from pre-admission screening to discharge. A new process was created in the electronic medical record to record the patients pump, basal rate and bolus amounts given. Education for staff was developed and distributed hospital wide. <h3>Discussion</h3> This QI project targeted a clinical gap and created a team from nursing, medicine, pharmacy, nutrition, anesthesiology and informatics to standardize practice for a low volume, high risk process. This project ensures that patients with insulin pumps are identified in the pre-screening unit and are assessed for their independence in pump management. <h3>Conclusion and implications</h3> Patients with insulin pumps are now admitted day of surgery with a detailed plan of care from an endocrinologist. Accurate documentation of patient's insulin pump and activity is now standardized. This assists with communication between nursing staff and anesthesia, and aides in promoting positive outcomes for surgical patients. <h3>Future Research</h3> Comparison of glucose levels pre and post practice guideline implementation for effectiveness of change.

An Integrative Review of Team Nursing and Delegation: Implications for Nurse Staffing during COVID-19.

BackgroundDuring the COVID‐19 pandemic, providing care for critically ill patients has been challenging due to the limited number of skilled nurses, rapid transmission of the virus, and increased patient acuity in relation to the virus. These factors have led to the implementation of team nursing as a model of nursing care out of necessity for resource allocation. Nurses can use prior evidence to inform the model of nursing care and reimagine patient care responsibilities during a crisis.PurposeTo review the evidence for team nursing as a model of patient care and delegation and determine how it affects patient, nurse, and organizational outcomes.MethodsWe conducted an integrative review of team nursing and delegation using Whittemore and Knafl’s (2005) methodology.ResultsWe identified 22 team nursing articles, 21 delegation articles, and two papers about U.S. nursing laws and scopes of practice for delegation. Overall, team nursing had varied effects on patient, nursing, and organizational outcomes compared with other nursing care models. Education regarding delegation is critical for team nursing, and evidence indicates that it improves nurses’ delegation knowledge, decision‐making, and competency.Linking evidence to actionTeam nursing had both positive and negative outcomes for patients, nurses, and the organization. Delegation education improved team nursing care.

An Evidence-Based Approach to Nursing Recognition and Management of Early Sepsis in Percutaneous Transhepatic Biliary Drainage (PTBD)

<h3>Introduction</h3> Percutaneous Transhepatic Biliary Drainage (PTBD) is an interventional radiology (IR) procedure indicated for relief of biliary obstructive symptoms: pruritus, jaundice ang cholangitis cause by benign or malignant conditions. Gallstones, cholangiocarcinoma and hepatobiliary malignancy are frequently seen to cause sepsis. <h3>Identification of the Problem</h3> Although PTBD is generally a safe procedure, significant complications manifest as systemic inflammatory response syndrome (SIRS) that leads to mortality. Early post anesthesia care unit (PACU) nursing recognition is critical in effectively managing these high risk patients. <h3>EBP Question/Purpose: PICO question. Databases utilized</h3> What is the best practice for patients post biliary drain placement presenting symptoms of systemic inflammatory response syndrome (SIRS)? (P) Patients post PTBD; (I) Early recognition of SIRS; (C) Prompt/early management of SIRS compare to standard care in alleviating sepsis (O). The evidence-based practice (EBP) searches were conducted using PUBMED/CINAHL databases. <h3>Methods/Evidence</h3> The evidence reviewed from PUBMED/CINAHL ranged from 2013 to 2019. Mesh terms were: interventional, biliary drainage, PTBD, pathophysiology, cholangitis, symptoms, complications, sepsis and SIRS. The first search yielded eight out of 36 articles that met PICO criteria. The second and final search included eight additional articles with terms of mortality and patient outcomes. <h3>Significance of Findings/Outcomes</h3> EBP appraisal revealed compelling science for recognizing and managing early SIRS in PTBD patients. Team created an EBP algorithm (see poster) that was effective for PACU nurses in early recognition of SIRS and prompt PACU nursing management to mitigate deteriorating symptoms of increased heart rates and rigors followed by fevers to improve quality patient care. <h3>Implications for perianesthesia nurses and future research</h3> Post PTBD SIRS can be challenging for PACU nurses to manage life-threatening complications. Evidence supports the development of an algorithm tool that focuses on recognition, assessment, and appropriate management of SIRS in this population. The science recommends easy accessibility of standing physician order sets, including medications, such as intravenous (IV) fluids, IV antibiotics, and acetaminophen as SIRS management in PACU strategies to facilitate positive patient outcomes.

Operationalization of heart failure patients engagement with mHealth

Abstract Funding Acknowledgements Type of funding sources: None. Introduction The computing and communication features of mobile devices have been leveraged in mobile Health (mHealth) interventions to provide comprehensive and tailored support that may have positive outcomes in patients with heart failure (HF. However, the effects of the interventions have shown mixed evidence. Considering that patients’ engagement is a prerequisite for the effectiveness of the interventions, understanding how patients engage with the interventions, and the effects of patients’ engagement on HF outcomes may explain the mixed findings. Objective This study aimed to synthesize current evidence on measures of HF patients’ engagement with mHealth interventions, and the effects of the interventions on HF outcomes. Method In accordance with the Arksey and O’Malley framework for scoping review, a comprehensive search of the literature was conducted in 7 databases for relevant studies published in the English language from 2009 to Feb. 2021. The descriptive characteristics of the studies were reported. Thematic analysis was conducted to identify themes that described patients’ engagement in the qualitative studies included in the review. Results The review synthesized 29 studies that operationalized engagement with mHealth interventions in 3665 patients with HF, ranging from a sample of 7 to 1571, with a median of 80 patients. Patients’ engagement with mHealth interventions was measured quantitively based on system usage data (82.7%, 24/29), qualitatively by semi-structured interviews and focus groups (10.3%, 3/29), and by mixed methods or combination of qualitative and system usage data (17.2%, 5/29). System usage data were evaluated using 7 metrics: (1) number of physiological parameters measured (88.5%, 3/26); (2) duration of use or time spent (3.8%, 6/26); (3) features accessed/screen viewed (11.5%, 3/26); (4) number of HF educational videos viewed (7.7%, 2/26); (5) number of SMS response (3.8%, 1/26); (6) number of HF questionnaire completed (3.8%, 1/26; (7)numbers of logins (5%, 1/19). There is a lack of consistency in how system usage metrics were reported across the studies; 73.7 % of the studies reported only the descriptive statistics of the System usage data. Intervention usage was the most identified subtheme in the qualitative measure. The effect of patients’ engagement with mHealth interventions on HF-related outcomes was inconclusive. Conclusion The operational definitions of patients’ engagement with mHealth interventions are underreported and lack consistency. The application of inferential analytical methods to the engagement data is extremely limited, which indicates a gap in mHealth research in patients with HF. More research focusing on developing optimal and standardized measures of patients’ engagement that may be applied across different study designs is warranted

Epilepsy and COVID-19: predictors of a positive outcome in patients with epilepsy (based on analysis of clinical cases)

Background. Many patients with neurological disorders have an increased risk of infection and the severe course of COVID-19. Studies on positive predictors of seizure outcomes with the 2019 novel coronavirus disease remain limited.The objective is to study predictors for positive health outcomes after COVID infection in patients with epilepsy based on analysis of clinical observations.Design and Methods. Study design - the work is a part of a prospective observational study of seizure dynamics after COVID infection in patients with epilepsy.Results. The presented clinical observation demonstrates a positive health outcome after COVID infection in a young patient with the genetic generalized epilepsy with sustained clinical and electroencephalographic seizure remission on the next generation AED monotherapy (brivaracetam).Conclusion. Predictors for positive health outcome after the 2019 novel coronavirus disease in patients with epilepsy include a young age, absence of somatic comorbidities, seizure remission, modern drug use with no interaction among AEDs and antibiotics and antivirals for the coronavirus disease treatment. Despite the encouraging data on the favourable course of epilepsy in cases of developing COVID-19, further research is needed to continue.

Home-based primary care: A systematic review of the literature, 2010-2020.

Although more than seven million older adults struggle or are unable to leave their homes independently, only a small minority access home-based primary care (HBPC). Despite substantial growth of HBPC, fueled by growing evidence supporting positive patient outcomes and cost savings, the population remains dramatically underserved and many evidence gaps still exist around scope of practice and key issues in care delivery and quality. Understanding the current state of the field is critical to the delivery of high-quality home-based care. We conducted a systematic search of the peer-reviewed literature on HBPC, published between January 2010 and January 2020, using Medline, CINAHL, Embase, Web of Science, and Scopus online libraries. All studies were evaluated by two members of the research team, and key findings were extracted. The initial search yielded 1730 unique studies for screening. Of these initial results, 1322 were deemed not relevant to this review. Of the 408 studies deemed potentially relevant, 79 were included in the study. Researchers identified five overarching themes: the provision of HBPC, the composition of care teams, HBPC outcomes, the role of telehealth, and emergency preparedness efforts. The need and desire for growth of HBPC has been highlighted by the recent COVID-19 pandemic. Current research on HBPC finds a diverse scope of practice, successful use of interdisciplinary teams, positive outcomes, and increasing interest in telehealth with many areas ripe for further research.

Individualised care in Flemish and Dutch hospitals: Comparing patients' and nurses' perceptions.

Patient-centred care has been recognised as vital for today's healthcare quality. This type of care puts patients at the centre, contributing to positive patient outcomes such as patient autonomy. Empirical research comparing nurses' and patients' perceptions of the support and provision of patient-centred care is limited and focuses solely on nurses and patients working and staying on surgical wards. Comparing patients' and nurses' perceptions of patient-centred care on different types of hospital wards, and exploring if patient empowerment, health literacy, and certain sociodemographic and context-related variables are associated with these perceptions. Cross-sectional design. Data were collected in ten Flemish (February-June 2016) and two Dutch (December 2014-May 2015) hospitals using the Individualised Care Scale (ICS). A linear mixed model was fitted. Data from 845 patients and 569 nurses were analysed. As the ICS was used to measure the concept of patient-centred care, it is described using the term 'individualised care.' Nurses perceived that they supported and provided individualised care more compared with patients as they scored significantly higher on the ICS compared with patients. Patients with higher empowerment scores, higher health literacy, a degree lower than bachelor, a longer hospital stay, and patients who were employed and who were admitted to Dutch hospitals scored significantly higher on some of the ICS subscales/subsections. Nurses who were older and more experienced and those working in Dutch hospitals, regional hospitals and maternity wards scored significantly higher on some of the ICS subscales/subsections. Nurses perceived that they supported and provided individualised care more compared with patients. Creating a shared understanding towards the support and provision of individualised care should be a priority as this could generate more effective nursing care that takes into account the individuality of the patient.

Oxygen Economics: The Use of Heated High-Flow Nasal Oxygen in Air Medical Transport of the Adult Patient

The use of oxygen via a heated high-flow nasal cannula (HHFNC) in transport of the adult patient experiencing hypoxemic respiratory failure is an emerging and successful adjunct. Although early intubation was thought to be the safest intervention early in the coronavirus disease 2019 pandemic, what we have learned over the past year was that it would serve the patient best to avoid intubation. We discuss an individual case study of a coronavirus disease 2019–infected patient who required subsequent interfacility air transport to our quaternary care facility. This patient presented to the receiving air medical team on HHFNC. Before January 2021, the capability of this program to transport these patients on HHFNC was not possible because our current ventilation platforms had to be upgraded to include the high-flow option and because of the relative infancy of the HHFNC platforms available for adult air transport. The previously noted approach to not intubate these patients, or to certainly use caution when making the decision to intubate, was not the common theme until late in 2020. Presented in this case discussion will be pertinent positive and negatives as they relate to transporting the patient on HHFNC to include the all-important issue of oxygen supply and demand. The authors would emphasize that the named products in this case are simply products used by the receiving air medical program and do not in any way support an endorsement of these products over any other platforms used to provide positive patient interventions and outcomes.

Building ad-hoc team social capital through simulation

The concept of high functioning healthcare teams is complex and competencies have been developed primarily from aviation. High-functioning healthcare teams, including those formed in an ad-hoc manner, are crucial to positive patient outcomes. Social capital theory identifies structural, cognitive and relational dimensions involved in the formation of trusting, cohesive relationships. Theories of social capital can be used to advise the development of interprofessional simulation-based education. Interprofessional simulation-based education curricula development must focus on the social sciences if it is to promote strong, healthy team relationships. Simulation-based education should take place in learning environments that promote the development of social capital between team members, especially where teams are formed ad hoc.

Abstract 1393: PSMA-Targeted Thorium Conjugate (BAY 2315497) and olaparib combination show synergistic anti-tumor activity in prostate cancer models

Abstract The PSMA targeted thorium-227 conjugate PSMA-TTC (BAY 2315497) is a novel targeted alpha therapy (TAT) approach which is currently under investigation in a FiH trial in patients with metastatic castration resistant prostate cancer (mCRPC; NCT03724747). It consists of the alpha emitter thorium-227 complexed to a 3,2-HOPO chelator conjugated to a PSMA targeting antibody delivering radiation to PSMA expressing tumor cells and their microenvironment resulting in the induction of potentially cytotoxic DNA double-strand breaks (DBS). Combining with the PARP inhibitor olaparib may act synergistically via inhibition of DDR pathways. Here we evaluated the efficacy of PSMA-TTC in combination with olaparib that demonstrated a positive outcome in patients with homologous recombination repair-mutated mCRPC. We explored potential synergies of the combination treatment in prostate cancer models in vitro and in vivo and studied the mode of action by protein and RNA analysis. In vitro, synergy of the combination of PSMA-TTC with olaparib with a combination index (CI) of 0.7 was observed in three cell lines, namely LNCaP, 22Rv1 and MDA-PCa2b. with the first two (LNCaP and 22Rv1) carrying mutations in BRCA2. Only moderate synergy with a CI of 0.8 was seen in BRCA2 wt VCaP cells. In vivo, dose dependent anti-tumor activity with single i.v. injections of PSMA-TTC at 150 and 300 kBq/kg was seen in the LNCaP prostate cancer model resulting in a tumor/control (T/C) ratio of 0.3 and 0.09 at day 28, respectively. In contrast, olaparib given at 50 mg/kg QD did not show activity at day 28. The 300 kBq/kg PSMA-TTC dose combined with olaparib showed the most pronounced anti-tumor activity (T/C=0.04) and significantly increased the number of animals with complete tumor regressions compared to high dose PSMA-TTC alone (6 CRs vs 2 CRs, p = 0.0397, Chi-square) on day 28. At the end of the consecutive surveillance period on day 117, 7/8 (87.5%) animals remained tumor-free (putatively cured) in the combination group vs 4/10 (40%) mice in the PMSA-TTC monotherapy group (Chi-square test, P = 0.0400). Additive or synergistic toxicological effects for the combination treatment were not seen based on body weight loss and fatal tox rate. At the 117-day time point both the 300 kBq/kg PSMA-TTC monotherapy and combination with olaparib group demonstrated 0.3% and 9.3% body weight gain indicating good tolerability. Changes in markers of DNA damage response following treatment will be presented. In summary, combination of PSMA-TTC with olaparib shows synergistic preclinical anti-tumor activity and support further clinical investigation of this combination treatment in prostate cancer patients. Citation Format: Christoph A. Schatz, Stefanie Hammer, Antje Wengner, Urs B. Hagemann, Dominik Mumberg, Arne Scholz. PSMA-Targeted Thorium Conjugate (BAY 2315497) and olaparib combination show synergistic anti-tumor activity in prostate cancer models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1393.

Association of Abnormal Brachial Index with Diabetic Nephropathy as an Independent Risk Factor for Coronary Arterial Disease in Type 2 Diabetic Patients - A Retrospective Single Centre Real-World Evidence Study in Indian Population

Objective: To study the association between ankle brachial index (ABI) and microvascular complications in Type 2 diabetes (T2DM) patients with the coronary arterial disease (CAD). Methodology: A retrospective study was carried out on 3,458 T2DM patients reportedly with CAD, G1 (n=33), and without CAD, G2 (n=3125), who had given the ABI test. ABI was defined as normal (1.0 - 1.4) and abnormal (&lt;1.0 and &gt;1.4). The logistic regression analysis was used to identify the determinants of CAD positive outcomes in T2DM patients. Results: Overall, patient percentage-wise CAD 10% (333), abnormal ABI 26% (913), neuropathy 37% (1278), nephropathy, 8% (293), and retinopathy &lt;1% (24). The ABI abnormality and CAD positives were higher in patients with nephropathy (32 and 20%) than in neuropathy (28 and 13%). Age-wise, 52 and 62% of neuropathy and nephropathy patients, respectively, were &gt;60 years and had shown increased ABI abnormality from age 50 years onwards. The logistic model had shown nephropathy patients, [OR-1.8 [1.26-2.58], - p-0.001] in association with abnormal ABI, [OR-1.27 [95% CI, 0.99–1.63], p- 0.057] predicted to have CAD positive outcomes. While neuropathy, OR-0.69, [0.54 - 0.90], and hypertension, OR-0.43 [0.33 - 0.57] were not contributing towards CAD in our study population. Conclusion: Type 2 diabetes patients with abnormal ABI were predicted to have a 27% increased odds ratio of CAD outcome and 80% in the presence of nephropathy. Thus, as part of comprehensive diabetes care, albuminuria screening along with ABI measurement is being suggested.

Management of incisional hernias in liver transplant patients

PURPOSE: The purpose of this study is to describe an optimal management strategy for incisional hernias in liver transplant patients. METHODS: Patients were identified who underwent open preperitoneal hernia repair for incisional hernia following liver transplantation. Perioperative management and surgical technique were described; wound complications and hernia recurrence were the primary outcomes assessed. RESULTS: A total of 17 patients met our criteria. All patients were on immunosuppression, and one patient (5.9%) had sirolimus stopped prior to the operation. One patient (5.9%) quit smoking, and two patients (11.8%) required optimization of their diabetes to have an A1c ≤7.2. Two patients (11.8%) received botulinum toxin A preoperatively due to significant loss of domain. The mean size of the biologic mesh was 818.8 ± 210 cm2, one patient (5.9%) received an anterior component separation and four (23.5%) received a panniculectomy. Postoperatively, three patients (17.7%) developed wound complications and one patient required reoperation for seroma. There were no 30-day readmissions and no hernia recurrences with mean follow-up time of 21.6 ± 11.6 months. CONCLUSION: The use of preperitoneal biologic mesh is an effective method for the management of incisional hernia in liver transplant patients; perioperative optimization and care are also influential in assuring positive outcomes for patients.

Mid-term outcomes of posterior stabilized total knee arthroplasty in severe osteoarthritis

Aim: The purpose of this study was to reveal mid-term outcomes by retrospectively investigating patients who underwent total knee arthroplasty with a posterior stabilized design.&#x0D; Material and methods: The study included a total of 68 knees of 52 patients with completed follow-up data who underwent PCL substituting (PS) total knee arthroplasty due to a diagnosis of primary or secondary osteoarthritis. The 52 patients comprised 45 (86.5%) females and 7 (13.5%) males with a mean age of 65.2±9.32 years (range, 30-82 years). The American Knee Society criteria were adopted for assessment of patient knee scores and functional knee scores. The Total Knee Prosthesis Radiological Evaluation criteria were applied for radiological evaluation of the patients.&#x0D; Results: The mean follow-up period of the patients was 32.1 ± 9.85 months (range: 18-60 months) and the Knee Society Scores (KSS) were 41.5 (range: 26 - 58) preoperatively, and 84.3 (range: 51 - 97) postoperatively. The mean preoperative and postoperative range of motion was 88.2º (range: 60º - 100º), and 106.7º (range: 90º - 120º), respectively. Two-stage revision surgery was applied to one patient due to deep infection. No cases of aseptic loosening were observed. Implant survivorship, and excellent and good results according to the functional knee score were reported as 98.8%, 41.1%, and 32.3%, respectively.&#x0D; Conclusion: Positive patient outcomes were obtained with the use of PS total knee arthroplasty in patients with severe osteoarthritis and there was no evidence of loss in mid-term follow-up.