Single-arm Observational Study Research Articles

Impact of minimally invasive surgery on surgeon health (ISSUE) study: protocol of a single-arm observational study conducted in the live surgery setting

IntroductionThe rapid evolution of minimally invasive surgery has had a positive impact on patient outcomes; however, it is reported to be associated with work-related musculoskeletal symptoms (WMS) in surgeons. Currently...

Effectiveness and Safety of Atezolizumab Monotherapy in Previously Treated Japanese Patients With Unresectable Advanced or Recurrent NSCLC: A Multicenter, Prospective, Observational Study (J-TAIL)

IntroductionThe efficacy and safety of atezolizumab in previously treated patients with NSCLC have been established in the registrational phase 3 OAK trial. In this study, we evaluated the effectiveness and safety of atezolizumab monotherapy in a large real-world cohort to confirm the reproducibility of the results of the registrational trial. MethodsThis was a multicenter, prospective, single-arm observational study. Consecutive patients with previously treated NSCLC scheduled to receive atezolizumab monotherapy were enrolled. The primary end point was the 18-month overall survival (OS) rate. The incidence of adverse events (AEs) and immune-related AEs was evaluated. ResultsOverall, 1002 patients were included in the safety analysis set and 1000 in the full analysis set. Median follow-up was 11.5 months. Of the full analysis set, 62% were ineligible for the OAK trial (OAK-unlike subpopulation). The 18-month OS rate was 41.1%, with a median OS of 13.0 months (95% confidence interval: 12.2–15.1). The 18-month OS rate was 49.4% and 36.1% in OAK-like and OAK-unlike subpopulations, respectively; that in patients with Eastern Cooperative Oncology Group performance status greater than or equal to 2 was 14.3%. The incidence of AEs overall, in the OAK-like, and OAK-unlike subpopulations was 43.9%, 46.2%, and 42.5%; that of immune-related AEs was 19.0%, 20.1%, and 18.3%, respectively. ConclusionsThe findings suggest that atezolizumab may be effective and safe for previously treated patients with NSCLC in real-world settings; however, atezolizumab administration should be considered carefully regarding the benefit–risk balance for the OAK-unlike subpopulation, especially in patients with Eastern Cooperative Oncology Group performance status greater than or equal to 2.

Patient-specific virtual three-dimensional surgical navigation for gastric cancer surgery: A prospective study for preoperative planning and intraoperative guidance.

Abdominal computed tomography (CT) can accurately demonstrate organs and vascular structures around the stomach, and its potential role for image guidance is becoming increasingly established. However, solely using two-dimensional CT images to identify critical anatomical structures is undeniably challenging and not surgeon-friendly. To validate the feasibility of a patient-specific 3-D surgical navigation system for preoperative planning and intraoperative guidance during robotic gastric cancer surgery. A prospective single-arm open-label observational study was conducted. Thirty participants underwent robotic distal gastrectomy for gastric cancer using a virtual surgical navigation system that provides patient-specific 3-D anatomical information with a pneumoperitoneum model using preoperative CT-angiography. Turnaround time and the accuracy of detecting vascular anatomy with its variations were measured, and perioperative outcomes were compared with a control group after propensity-score matching during the same study period. Among 36 registered patients, 6 were excluded from the study. Patient-specific 3-D anatomy reconstruction was successfully implemented without any problems in all 30 patients using preoperative CT. All vessels encountered during gastric cancer surgery were successfully reconstructed, and all vascular origins and variations were identical to operative findings. The operative data and short-term outcomes between the experimental and control group were comparable. The experimental group showed shorter anesthesia time (218.6 min vs. 230.3 min; P=0.299), operative time (177.1 min vs. 193.9 min; P=0.137), and console time (129.3 min vs. 147.4 min; P=0.101) than the control group, although the differences were not statistically significant. Patient-specific 3-D surgical navigation system for robotic gastrectomy for gastric cancer is clinically feasible and applicable with an acceptable turnaround time. This system enables patient-specific preoperative planning and intraoperative navigation by visualizing all the anatomy required for gastrectomy in 3-D models without any error. Clinicaltrials.gov, identifier NCT05039333.

Real-World Data on the Usage of Hemopatch® as a Hemostat and Dural Sealant in Cranial and Spinal Neurosurgery.

Background and objectives Cerebrospinal fluid (CSF) leakage is a significant complication in cranial and spinal interventions. Hemostatic patches such as Hemopatch® are therefore used to support the watertight closure of the dura mater. Recently, we published the results of a large registry documenting the effectiveness and safety of Hemopatch® in various surgical specialties, including neurosurgery. Here we aimed to analyze the outcomes from the neurological/spinal cohort of this registry in more detail. Methods Based on the data from the original registry, we performed a post hoc analysis for the neurological/spinal cohort. The Hemopatch® registry was designed as a prospective, multicenter, single-arm observational study. All surgeons were familiar with the application of Hemopatch® and it was used at the discretion of the responsible surgeon. The neurological/spinal cohort was open for patients of any age if they had received Hemopatch® during an open or minimally invasive cranial or spinal procedure. Patients with known hypersensitivity to bovine proteins or brilliant blue, intraoperative pulsatile severe bleeding, or an active infection at the potential target application site (TAS) were excluded from the registry. For the posthoc evaluation, we stratified the patients of the neurological/spinal cohort into two sub-cohorts: cranial and spinal. We collected information about the TAS, intraoperative achievement of watertight closure of the dura, and occurrence of postoperative CSF leaks. Results The registry comprised 148 patients in the neurological/spinal cohort when enrolment was stopped. The dura was the application site for Hemopatch® in 147 patients (in one patient in the sacral region after tumor excision), of which 123 underwent a cranial procedure. Twenty-four patients underwent a spinal procedure. Intraoperatively, watertight closure was achieved in 130 patients (cranial sub-cohort: 119; spinal sub-cohort: 11). Postoperative CSF leakage occurred in 11 patients (cranial sub-cohort: nine; spinal sub-cohort: two). We observed no serious adverse events related to Hemopatch®. Conclusion Our post hoc analysis of real-world data from a European registry confirms the safe and effective use of Hemopatch® in neurosurgery, including cranial and spinal procedures, as also observed in some case series.

Treatment Effect of Phototherapy with Low-Level Energy in Patients with Allergic Rhinitis: A Single-Arm Observational Study.

Allergic rhinitis is one of the most common health challenges and has a chronic and repetitive course that requires symptomatic treatment. We aimed to investigate the effect of phototherapy on allergic rhinitis and how long it takes to demonstrate treatment effect. Twenty-one patients who were diagnosed with allergic rhinitis using the skin prick test were enrolled. Red light (660 nm) and infrared light (940 nm) with a low power energy of 5 mW were used three times a day at intervals of at least 5 h. The Rhinoconjuntivitis Quality of Life Questionnaire (RQLQ) and a visual analog scale (VAS) were used to measure the changes in symptoms. The median RQLQ and VAS scores before treatment were 62 (49-81.5) and 3 (2-5) points, respectively. The RQLQ score improved significantly at two and four weeks after treatment (52 [39-62.5]) and 46.0 [30.5-57.0], respectively). The VAS scores also improved significantly at two and four weeks after treatment. Nasal obstruction and rhinorrhea improved significantly at one week after the procedure. Low-power (5 mW) light irradiation (660 nm red light and 940 nm infrared) was effective in improving the symptoms of allergic rhinitis. In addition, symptom improvement became clear approximately a week after use. Further studies are required to reach a definitive conclusion.

Rescue Intracranial Balloon Angioplasty with or without Stent Placement in Acute Strokes with Intracranial Atherosclerotic Disease

Optimal management of acute ischemic stroke (AIS) secondary to intracranial atherosclerotic disease (ICAD) refractory to conventional mechanical thrombectomy remains unclear. We aimed to investigate the clinical outcome of patients undergoing rescue intracranial balloon angioplasty with or without stent placement in the setting of AIS in our institution. This is a retrospective single-arm observational study to evaluate the efficacy and safety of rescue balloon angioplasty with or without stent placement in emergent large vessel occlusion (EVLO) strokes with underlying ICAD. We included all patients undergoing such rescue intervention within 24hours of AIS presentation with EVLO between 2017 and 2021. We further evaluated stent or vessel reocclusion. Of 20 patients undergoing rescue intervention, 3 cases achieved adequate recanalization of artery using balloon angioplasty alone. Seventeen patients required stent placement. Fourteen (70%) procedures resulted in National Institutes of Health Stroke Scale improvement in postprocedure and upon discharge. Among 6 (30%) procedures with worsening neurological measures, 3 had reoccluded stent 24-48hours after procedure, 2 had symptomatic hemorrhagic conversion, and 1 had perforator occlusion. Nine patients (45%) had favorable functional outcome (modified Rankin Scale ≤2) at discharge, unchanged or improved at 3-month follow-up. The median modified Rankin Scale score was 4 (Interquartile range: 1.75-4) at discharge, improving to 3 (Interquartile range: 0-4) at 3-month follow-up. Two patients (10%) died during hospital stay. Rescue angioplasty with or without stenting can lead to significant clinical improvement in patients with ICAD presenting with ELVO and refractory to thrombectomy; however, this procedure is associated with a high rate of morbidity in acute setting.

WeWalk: walking with a buddy after stroke—a pilot study evaluating feasibility and acceptability of a person-centred dyadic behaviour change intervention

BackgroundEvidence for benefits of physical activity after stroke is unequivocal. However, many people with stroke are inactive, spending > 80% of waking hours sedentary even when they have physical capacity for activity, indicating barriers to physical activity participation that are not physical. WeWalk is a 12-week person-centred dyadic behaviour change intervention in which a person with stroke (PWS) and a walking buddy form a dyad to work together to support the PWS to increase their physical activity by walking outdoors. This pilot study examined the feasibility of recruiting dyads, explored their perceptions of acceptability and their experiences using WeWalk, to identify required refinements before progression to a clinical trial.MethodsDesign: A single-arm observational pilot study with qualitative evaluation.Intervention: WeWalk involved facilitated face-to-face and telephone sessions with a researcher who was also a behaviour change practitioner, supported by intervention handbooks and diaries, in which dyads agreed walking goals and plans, monitored progress, and developed strategies for maintaining walking.Evaluation: Descriptive data on recruitment and retention were collected. Interview data were collected through semi-structured interviews and analysed using thematic analysis, guided by a theoretical framework of acceptability.ResultsWe recruited 21 dyads comprising community dwelling PWS and their walking buddies. Ten dyads fully completed WeWalk before government-imposed COVID-19 lockdown. Despite lockdown, 18 dyads completed exit interviews. We identified three themes: acceptability evolves with experience, mutuality, and person-centredness with personally relevant tailoring. As dyads recognised how WeWalk components supported walking, perceptions of acceptability grew. Effort receded as goals and enjoyment of walking together were realised. The dyadic structure provided accountability, and participants’ confidence developed as they experienced physical and psychological benefits of walking. WeWalk worked best when dyads exhibited relational connectivity and mutuality in setting and achieving goals. Tailoring intervention components to individual circumstances and values supported dyads in participation and achieving meaningful goals.ConclusionRecruiting dyads was feasible and most engaged with WeWalk. Participants viewed the dyadic structure and intervention components as acceptable for promoting outdoor walking and valued the personally tailored nature of WeWalk. Developing buddy support skills and community delivery pathways are required refinements. ISCTRN number: 34488928.

A Prospective Observational Pilot Study on the Effects of the Activity-Based Stress Release Program on the Mental State and Autonomic Nervous System in Psychiatric Patients.

In our pilot study, we investigated the psychological (well-being and personal coping strategies) and physiological (assessed by heart rate variability (HRV)) effects of the newly developed activity-based stress release (ABSR) program for people with depressive disorders, also in combination with burnout symptoms and/or anxiety disorders. A single-arm prospective observational study was carried out. Twenty participants diagnosed with depression and burnout or anxiety disorders were invited to participate in the 8-week ABSR program. All participants filled in two questionnaires (the multidimensional mental state questionnaire and the Ehrenfeld inventory on coping style) before, directly after and 2 months after the 8-week ABSR program. In addition, all participants were offered a 24-hour Holter ECG measurement before, directly after and 2 months after the 8-week ABSR program to measure HRV. Calmness and serenity showed a statistically significant improvement after the 8-week ABSR program. However, complete questionnaire sets were not available from all of the participants. In the four individuals who had agreed to a 24-hour Holter ECG, the overall HRV and parasympathetic activity increased. The ABSR program is an encouraging novel therapeutic approach: A significant improvement in calmness and serenity was observed after ABSR. A larger and controlled trial of this treatment option in depression and burnout is recommended. It should be further investigated how ABSR affects task-evoked and resting brain activity, and what effects it has on the cardiovascular system in general (better blood flow and normalization of activity are to be expected).

628. Utilizing Cefepime Therapeutic Drug Monitoring for Patients at Risk of or Exhibiting Signs of Neurotoxicity

Abstract Background Increasing risk of neurotoxicity has been observed with increasing cefepime levels, potentially due to the competitive inhibition of GABA receptors in the central nervous system (CNS). The suggested threshold is ≥20 mg/dL. Risk factors include decreased clearance with renal impairment, or increased CNS penetration with blood-brain barrier dysfunction. This study analyzes the association between high trough levels and risk factors for cefepime-induced neurotoxicity (CIN), and the utility of therapeutic drug monitoring (TDM) in guiding cefepime therapy. Methods This was a prospective single-arm observational study. Eligible patients had signs of potential CIN or had risk factors including cefepime ≥4 g/day for ≥4 days, renal impairment, CNS disease, and/or co-administration of neurotoxic medications. Interventions for discontinuation or dose adjustment were made for levels ≥20. The primary outcome was the incidence of troughs ≥20 in patients with possible signs of or risk factors for CIN. The secondary outcome was the proportion of patients whose therapy is altered in response to TDM. Results A total of 20 patients were included. Reasons for inclusion were 15 with renal impairment, 10 had signs of neurotoxicity, and 5 were included to confirm therapeutic dosing. Patients could have multiple risk factors for CIN. Ten of 20 had a trough ≥20 (median 19). Six of 10 with signs of neurotoxicity had a trough ≥20 (OR 2.25, 95% CI 0.38-13.47; p=0.66) and 10 of 15 with renal impairment had a trough ≥20 (RD 0.67, 95% CI 0.13-0.89; p=0.0325). Cefepime was renally dose adjusted in 7 of 10 with a trough ≥20. Of the total 20 patients, 16 required interventions of which 12 were confirmed by the trough result. Conclusion Renal impairment was found to be a statistically significant risk factor for CIN, even when cefepime was renally dose adjusted. These patients may benefit from TDM. TDM allowed for confirmation of interventions and further interventions were made based on trough levels. Despite a small sample size, cefepime TDM has the potential to identify patients at risk for CIN and may assist in making dose adjustments to improve patient safety. Disclosures All Authors: No reported disclosures.

The Effect of Painless Delivery with Intrathecal Sufentanil on Labor Progress and Neonatal Outcomes: A Single Center Study on Pregnant Women.

Delivery pain is the most unbearable pain and can be relieved with intrathecal opioids. This study aimed to investigate the effect of intrathecal sufentanil for painless delivery on labor progress and neonatal outcomes in pregnant women. This was a single-arm observational cohort study on 1055 pregnant women candidates for vaginal delivery with spinal analgesia referred to the Akbarabadi Hospital. First, 0.1 µg/kg of intrathecal sufentanil was used, and maternal blood pressure and maternal and fetal heart rates were recorded after analgesia. During delivery, the mothers were monitored for nausea, pruritus, motor block, apnea, urinary retention, or the possibility of an emergency cesarean section. The duration of the analgesia, the duration of the second stages of labor, and the mother's pain scores were recorded based on the Visual Analogue Scale (VAS). 1- and 5-minute Apgar scores and arterial blood gas (ABG) of the umbilical cord were also recorded. The most common station was -3 for 723 women, followed by -2 for 229 women. Fifty-two women underwent cesarean section, and fetal distress was the most common reason for cesarean section (57.7%). The mean time for initiating analgesia was 5.93 ± 2.87 minutes, and the mean visual analog scale was 1.08 ± 0.16. The mean Apgar was 9.0 ± 0.47; the mean weight at birth was 2917.39 ± 449.90 gr; PH was 7.31 ± 2.03; HCO3 was 22.67 ± 3.08mEq/liter, and PaCo2 was 43.36 ± 7.06 mmHg. Regarding complications, the patients just developed itching (n = 78), and hypotension, bradycardia, apnea, and decreased consciousness were overlooked. Intrathecal sufentanil is safe and efficient in painless delivery, resulting in normal Apgar and normal PH with no specific side-effect.

Response to Hypomethylating Agents Plus Venetoclax in Patients with Acute Myeloid Leukemia and Myelodysplastic Syndrome: Real World Data from a Developing Country

Background: Myelodysplastic syndrome (MDS) is a pre-malignant condition characterized by ineffective hematopoiesis, cytopenias and potential to transform into acute leukemia. Acute myeloid leukemia (AML) is a hematological malignancy deriving from myeloid progenitor cells. About one quarter of patients fail to respond to initial therapy (refractory AML). In addition, around 50% of initial responders relapse after a transient remission (relapsed AML). Commonly used salvage chemotherapy regimens include FLAG, FLAG-Ida, HIDAC and Hypomethylating agents (HMA) with or without Venetoclax. In patients who are ineligible for transplant or with poor functional status and in relapsed/refractory cases, treatment options are minimal. However recent data from Western countries has shown promising results with HMA plus Venetoclax in such patients. No such data is available from Pakistan. Objectives: To assess response of HMA plus Venetoclax in patients with AML and MDS treated at Armed Forces Bone Marrow Transplant Center, Rawalpindi, Pakistan. Methods: Study design: Single arm observational prospective study Research Setting: Armed Forces Bone Marrow Transplant Center, Rawalpindi, Pakistan. Study population: Cases included in study were patients of AML and MDS who received HMA plus Venetoclax. A total of 35 patients (25 AML, 10 MDS) were found eligible and included in the final analysis. The primary outcome measured was response to HMA plus Venetoclax. Results: Out of 25 AML patients 17 (68%) were male and 8 (32%) were female. Median age of patients was 44 (range 20-67). Six (24%) patients had AML MRC, 18 (72%) had AML NOS which included 2 (8%) AML-M0, 1 (4%) AML-M1, 9 (36%) AML-M2, 3 (12%) AML-M4 and 3 (12%) patients with AML-M5 while other 3 patients included 1 (4%) patient each of t-AML and AML transformed from Fanconi anemia and aplastic anemia. One (4%) AML-M2 patient had Monosomy 7 and 1 (4%) AML-M5 had trisomy 8. Three (12%), 16 (64%) and 6 (24%) patients were categorized into favorable, intermediate and high risk respectively. Nine (36%) had relapsed disease including 3 (12%) who had relapsed after allogenic HSCT, 8 (32%) had refractory disease while 7 (28%) were unfit for intensive chemotherapy due to advanced age or poor functional status. Median number of HMA+ Venetoclax cycles given were 3 (range 1-16). Overall response rate (ORR) was 44% (n=11), including 9 (36%) patients with CR and 1 (4%) with CRi. One (4%) patient had partial response (PR). Fourteen (56%) patients were non-responders. Of the 10 patients who responded, 6 (24%) achieved remission after 2 cycles while other 4 achieved remission, 1 (4%) patient each, after 1, 3, 5 and 6 cycles. Two (8%) patients underwent allogenic HSCT after achieving remission, including 1 (4%) who had relapsed after first HSCT and underwent second HSCT after achieving CR with HMA+Venetoclax. Out of 10 MDS patients 8 (80%) were male and 2 (20%) were female. Median age of patients was 51 (range 29-71). Two (25%) patients had MDS-MLD, 6 (60%) MDS-EB2 and 2 (20%) had fibrotic MDS. One (10%), 7 (70%) and 2 (20%) patients had intermediate, high and very high risk disease (as per R-IPSS score) respectively. One (10%) patient had relapsed after allogenic HSCT. Median no of cycles of HMA+Venetoclax given were 2 (range 1-6). Three (30%) patients achieved CR (after 2 cycles each), 2 (20%) had stable disease and 5 (50%) patients were non-responders. Two (20%) patients underwent allogenic HSCT after receiving HMA+Venetoclax (Table:1) Common side effects noted were prolonged cytopenias, febrile neutropenia and infections (cellulitis, perianal infections and fungal infections). No treatment related mortality was noted. Conclusion: HMA plus Venetoclax is effective treatment regimen in relapsed/ refractory AML and MDS, however our population shows inferior results as compared to Western population and further large randomized controlled trials are needed to validate this observation. Key Words: Relapsed AML, refractory AML, MDS, salvage chemotherapy, Hypomethylating agents, Venetoclax Research funding: None Word count: 691 Presentation type: Oral Category: Acute Leukemia/ Myelodysplastic syndrome Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Lesion Index-guided workflow for the treatment of paroxysmal atrial fibrillation is safe and effective - Final results from the LSI Workflow Study.

Pulmonary vein isolation (PVI) ablation is a standard therapy for paroxysmal atrial fibrillation (PAF). Lesion Index (LSI) is a metric to guide radiofrequency (RF) ablation using the TactiCath Ablation Catheter, Sensor Enabled with the EnSite Cardiac Mapping System (Abbott). This study (NCT-03906461) was designed to capture best practices using LSI-guided catheter ablation to treat PAF subjects in a real-world setting. This prospective single-arm observational study enrolled 143 PAF subjects in the United States, Europe, and Japan undergoing de novo PVI with RF ablation. PVI lesions were assigned to 10 anatomically defined segments. Mean LSIs achieved for all lesions were analyzed. Follow-up was conducted between 3-6 months and 12 months after the procedure. Pulmonary veins were isolated in all subjects. The mean achieved LSI was 4.9, with lower values in Europe (4.4) and Japan (4.5) than the United States (5.5). First-pass success, defined as no gaps requiring touch-up ablation after 20 minutes post isolation, was achieved in 76.2% of subjects. Use of high LSI (≥5) resulted in shorter procedure, RF, and fluoroscopy times and fewer touch-up ablations compared to low LSI (<5). At 12 months, 99.3% of subjects were free from procedure- or device-related serious adverse events and 95.7% (112/117) (35.0% on antiarrhythmic drugs) were free from recurrence and/or a repeat ablation procedure for atrial fibrillation / atrial flutter / atrial tachycardia. LSI-guided ablation strategies proved safe and effective despite differences in LSI workflows. Use of high LSI values resulted in shorter procedure, RF, and fluoroscopy times and fewer touch-up ablations compared to low LSI.

Intraoperative adjustment of implantable collamer lens vault by lens rotation aided by intraoperative OCT.

To assess the use of intraoperative optical coherence tomography (OCT) to detect high vault during implantation surgery and guide intraoperative vault adjustment by implantable collamer lens (ICL) rotation. Instituto Zaldivar SA. Mendoza, Argentina. Prospective single-arm observational study. 25 eyes of 25 consecutive patients showing high intraoperative vault who had undergone ICL rotation from horizontal to vertical or oblique position were evaluated. Central ICL vault was measured both intraoperatively using the microscope-integrated iOCT mounted on a standard surgical microscope (HS Hi-R NEO 900A NIR) and postoperatively using the Casia 2 swept-source OCT at 4 hours, 1 day, and 1 month. 25 eyes of 25 consecutive patients showing high intraoperative vault who had undergone ICL rotation from horizontal to vertical or oblique position were evaluated. The mean vault value obtained intraoperatively was 1147.88 ± 188.36 μm and changed significantly to 739.76 ± 194.97 μm after lens rotation to either vertical (n = 19, 76% of cases) or oblique (n = 6, 24% of cases) positions (mean difference 408.12 ± 213.57 μm, P < .001). The amount of change due to lens rotation was significantly correlated with white-to-white distance ( r = -0.480, P = .015) and vault before rotation ( r = -0.564, P = .003). The mean vault values were 758.40 ± 187.10 μm, 729.73 ± 227.86 μm, and 661.88 ± 275.17 μm at 4 hours, 24 hours, and 1 month postsurgery, respectively. Intraoperative adjustment of ICL vault by lens rotation using intraoperative OCT was an effective procedure to obtain an optimal vault.

A 12-week personalised physical activity and dietary protein intervention for older adults undergoing peritoneal dialysis: A feasibility study

This single-arm observational study explored the feasibility and efficacy of a 12-week personalised physical activity and dietary protein intervention programme for older adults undergoing peritoneal dialysis. Older adults undergoing peritoneal dialysis received eight individualised nutrition and physical activity advice sessions provided by trained nurses. Protein intake and physical activity were regarded as primary outcomes. All data were collected at baseline and at week 12. The enrolment rate was 78.4%. Twenty-nine patients participated in the study. Of these, 86.2% (25/29) completed the intervention. There was a significant increase in protein intake (t = -4.453, P< 0.001) and physical activity levels (Z = -2.929, P = 0.004). Of the participants, 56.0% achieved the targeted protein goal, and 41.4% met the physical activity goal. The timed up-and-go performance (t = 4.135, P = 0.001) increased after intervention. Trained nurses can successfully implement personalised diet and physical activity advice, and achieve promising patient outcomes.

Ten-year outcomes of surgical aortic valve replacement with a contemporary supra-annular porcine valve in a Medicare population

ObjectiveBioprosthetic surgical aortic valve replacement remains an important treatment option in the era of transcatheter interventions. Real-world outcomes are not well characterized because of limited prospective follow-up studies. We present the 10-year clinical outcomes of Medicare beneficiaries undergoing surgical aortic valve replacement with a contemporary supra-annular porcine valve. MethodsThis is a single-arm observational study using Medicare fee-for-service claims data. De-identified patients undergoing surgical aortic valve replacement with the Epic Supra valve (Abbott) in the United States between January 1, 2008, and December 31, 2019, were selected by International Classification of Diseases 9th and 10th Revision procedure codes and then linked to a manufacturer device tracking database. All-cause mortality, heart failure rehospitalization, and aortic valve reintervention (surgical or transcatheter valve-in-valve) were evaluated at 10 years using the Kaplan–Meier method. ResultsAmong 272,591 Medicare beneficiaries undergoing surgical aortic valve replacement during the study period, 11,685 received the Epic Supra valve, of whom 51.6% (6029) had underlying heart failure. Mean age was 76 ± 7 years. Survival at 10 years in patients without preoperative heart failure was 43.5% (95% confidence interval, 41.8-45.2) compared with 24.1% (95% confidence interval, 22.6-25.5) for patients with heart failure (P < .001). The 10-year freedom from heart failure rehospitalization was 64.0% (95% confidence interval, 62.6-65.3). Freedom from aortic valve reintervention was 94.6% (95% confidence interval, 93.8-95.3) at 10 years. ConclusionsThis real-world nationwide study of US Medicare beneficiaries receiving the Epic Supra valve demonstrates more than 94% freedom from all-cause valve reintervention and 64% freedom from heart failure rehospitalization at 10 years postimplant. Long-term survival and heart failure rehospitalization in this population with aortic valve disease undergoing surgical aortic valve replacement were found to be impacted by underlying heart failure.

A systematic review of retinoic acid in the journey of spermatogonium to spermatozoa: From basic to clinical application

Background: Retinoic acid plays an essential role in testicular development and functions, especially spermatogenesis. We have reviewed the role of retinoic acid from basic (molecular) to clinical application. Methods: A search was conducted in the online database including PubMed, Google Scholar, and Scopus for English studies published in the last eight years about this issue. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines in assessing the studies we are going to investigate. Results: Studies indicated that retinoic acid plays an essential role during pluripotent stem cell migration and lineage commitment, cell differentiation, apoptosis, stem cell number regulation, and maturation arrest in spermatogenic cells. Retinoic acid can also affect related protein expression and signaling pathways at different stages of spermatogenesis. Four studies have applied retinoic acid to humans, all of them in the single-arm observational study. The results look promising but need further research with more controlled study methods, randomization, and large samples. Conclusions: This current systematic review emphasizes a novel retinoic acid mechanism that has not been well described in the literature previously on its functions during the first seven days of spermatogenesis, leading to new directions or explanations of male infertility cause and treatments as a part of reproductive health care.

Role of Cardiosphere‐Derived Cell Extracellular Vesicles (CDC‐EVs) in Modulating CCR2 Mediated Pro‐inflammatory Signaling following Cardiac Injury

BackgroundFollowing myocardial injury, CCL2 (a cytokine released by the injured cardiac tissue) recruits CCR2+ monocytes to the site of injury to begin the repair process. Heightened CCL2 levels, however, over‐activate the CCR2+ mediated pro‐inflammatory response which in turn leads to poor cardiac healing and gives rise to downstream complications like congestive heart failure (CHF) and arrhythmias. Cardiosphere‐derived cell extracellular vesicles (CDC‐EVs) have been shown to down regulate this CCL2‐mediated inflammatory response by decreasing CCR2 expression on monocytes in healthy patients. We hypothesized that patients with acute myocardial infarction (MI) and decompensated heart failure would have higher levels of peripheral monocyte CCR2 expression compared with healthy controls and treatment with CDC‐EVs would suppress CCR2 expression regardless of patient presentation.MethodsA prospective single arm observational study was performed to investigate the immune response in patients presenting with cardiac injury. We recruited inpatients at Buffalo General Medical Center who met the following inclusion criteria: 1) &gt; 18 years of age AND 2) a type I MI or 3) acute on chronic CHF exacerbation or 4) chronic compensated CHF. Subjects were excluded from the study for the following: 1) fever in last 2 days/infection, 2) is or may be pregnant, and 3) currently undergoing cancer treatment. For part 1 of the study, blood samples from 32 patients with recent MI, acute CHF, or compensated CHF (between day 1 to 3 of admission) were drawn. Human monocytes were isolated from peripheral blood using Ficoll/centrifugation followed by magnetically activated cell sorting. Isolated monocytes were incubated with either PBS, normal human dermal fibroblast‐EVs (NHDF‐EVs) or CDC‐EVs and analyzed for CCR2 expression by flow cytometry. Multi‐variate analysis was performed to investigate the relationship of CCR2 expression and specific clinical risk factors for heart disease.ResultsCDC‐EVs significantly reduced classical monocyte (CD14hiCD16‐) surface expression of CCR2 expression by 35% as quantified by flow cytometry when compared with PBS and NHDF‐EVs (p&lt;0.005, Kruskal‐Wallis, n=31) in patients with recent MI, acute CHF exacerbation and chronic compensated CHF. This reduction was seen regardless of patients’ pre‐existing co‐morbidities like hypertension, diabetes, hyperlipidemia, chronic kidney disease, ongoing treatment with chronic medications (Aspirin, statins or ACE inhibitors), cardiac ejection fraction, prior history of coronary stents, CCR2 genotype, sex, or age. Smoking was associated with decreased response to CDC‐EV mediated CCR2 suppression when compared to PBS (linear regression model R ‐0.93, p&lt;0.05, n=26).ConclusionsCDC‐EVs down regulated CCR2 expression in non‐smoking patients with recent MI, acute CHF, or chronic compensated CHF. This immune‐modulatory effect of CDC‐EVs may be used in the future as an adjunct to current clinical therapy to improve cardiac healing.

CI-525-01 EARLY EXPERIENCE WITH A LEADLESS VENTRICULAR PACEMAKER PROVIDING ATRIOVENTRICULAR SYNCHRONOUS PACING IN THE REAL-WORLD SETTING: RESULTS FROM THE MICRA AV POST-APPROVAL REGISTRY

Advances in leadless pacemaker technology have enabled accelerometer based atrioventricular synchronous (AVS) pacing by sensing atrial mechanical contraction. However, performance of these devices in real-world clinical practice has not been assessed. To report the acute performance of the Micra AV leadless pacemaker from the global Micra AV post-approval registry (PAR). The Micra AV PAR is an ongoing prospective single-arm observational study designed to assess the safety and effectiveness of Micra AV in the real-world setting. The registry will enroll approximately 750 patients and follow them for 3-years. For this analysis, baseline characteristics, device performance, and pericardial effusion events were summarized. The device was successfully implanted in 400 of 402 patients (99.5%) at 77 centers (mean age 75.4±14.1 years, 43.8% female). The most common pacing indication was AV block (49.0%), followed by sinus node dysfunction (17.9%), and bradyarrhythmia with AF (16.2%). Co-morbidities included diabetes (33.6%), heart failure (14.7%), and COPD (9.0%) with 33.3% precluded from transvenous devices. Pericardial effusion occurred in 5 patients (1.24%). Of the 153 patients programmed to VDD mode with ≥30 days of device follow-up, median pacing percentage was 70.7% with 43.1% of patients having >90% pacing. The median percentage of ventricular paces preceded by atrial mechanical detection was 75% in the 66 patients with >90% ventricular pacing (Figure). The Micra AV leadless pacemaker was implanted with a high rate of success among patients with a high co-morbidity burden. Longer-term performance of the device will continue to be assessed in this ongoing trial.

105: SURGICAL DISSECTION DOES NOT INCREASE FREE CANCER CELLS (FCC) IN PERITONEAL LAVAGE OF PATIENTS FOLLOWING D2 GASTRECTOMY

Abstract Background and aim Peritoneal free cancer cells (FCC) in patients with gastric cancer (GC) is poor prognostic factor. D2 gastrectomy dissection may induce exfoliated FCC spread from primary tumour or involved lymph nodes (LN). Conventional cytology for FCC detection has several limitations, and prophylactic use of extensive intraoperative peritoneal lavage (IPL) does not improve survival. A prospective single-arm observational study was conducted to verify whether D2 gastrectomy causes an increase of FCC in peritoneal lavage as in patients with GC following D2 gastrectomy. Methods Thirty GC patients underwent D2 gastrectomy, followed by objective quantitative measurements of CK19 mRNA level reflecting FCC with One-Step Nucleic Acid Amplification (OSNA) assay. The IPL with 3000 cc of saline was performed twice after: (1) gastrectomy with D2 lymphadenectomy; and (2) alimentary tract reconstruction. The IPL samples were analysed by initial cytology and four (1–4) consecutive OSNA assays (Figure 1). Three patients were excluded due to positive cytology in samples obtained after laparotomy. Results Initial OSNA measurement (1) revealed positive results (≥24.6 cCP/μl) in 7 (29.6%) patients. Subsequent OSNA measurements revealed a significant decrease in the FCC level after removal of the primary tumour with regional LNs (D2 gastrectomy) (1 vs 2; medians [95%CI]: 4.6 [1.1–18.5] vs. 0.00004 [0–0.2] cCP/μl; P = 0.0012). The first IPL induced non-significant increase in the FCCs (2 vs 3, medians [95%CI]: 0.00004 [0–0.2] vs 0 [0–0.5] cCP/μl; P = 0.3300), but the second IPL reversed it to normal levels (3 vs 4, medians [95%CI]: 0 [0–0.5] vs 0 [0–0] cCP/μl; P = 0.0.0574). At this point of operation, additional finding was a trend toward temporal increase of FCC in patients with LN involvement (pN1–3)(2 vs 3; medians [95%CI]: 0 [0–0.2] vs 0 [0–42.8] cCP/μl; P = 0.0674). One patient was still positive (FCC) at the end of operation as measured by OSNA (4). Conclusion D2 Gastrectomy does not induce increase in the peritoneal FCCs. Temporal intraoperative increase in peritoneal FCC after the IPL may be observed, especially in tumours with LN metastases. At least two consecutive IPLs (with min. 3000 mL of saline) are necessary to reverse temporal increase of peritoneal FCC.

Tissue characterisation and primary percutaneous coronary intervention guidance using intravascular ultrasound: rationale and design of the SPECTRUM study

IntroductionIntravascular ultrasound (IVUS) improves clinical outcome in patients undergoing percutaneous coronary intervention (PCI) but dedicated prospective studies assessing the safety and efficacy of IVUS guidance during primary PCI are lacking.Methods...