Single-arm Prospective Observational Study Research Articles

Chemotherapy effects on bone mineral density and microstructure in women with breast cancer.

Chemotherapy involves the administration of steroids to prevent nausea and vomiting; however, its effect on bone microstructure remains unknown. This study aimed to evaluate the changes in bone mineral density (BMD) and bone microstructure associated with chemotherapy using high-resolution peripheral quantitative computed tomography (HR-pQCT) in women with early breast cancer. This prospective single-arm observational study included non-osteoporotic, postmenopausal women with breast cancer. The patients underwent dual-energy X-ray absorptiometry (DXA), HR-pQCT, and tartrate-resistant acid phosphatase-5b (TRACP-5b) or procollagen type-I N-terminal propeptide (P1NP) measurements at baseline, end of chemotherapy, and 6months after chemotherapy. The primary endpoint was the change in total volumetric BMD at the distal tibia and radius. Eighteen women were included in the study (median age: 57years; range: 55-62years). At 6months after chemotherapy, HR-pQCT indicated a significant decrease in total volumetric BMD (median: distal tibia -4.5%, p < 0.01; distal radius -2.3%, p < 0.01), cortical volumetric BMD (-1.9%, p < 0.01; -0.8%, p = 0.07, respectively), and trabecular volumetric BMD (-1.1%, p = 0.09; -3.0%, p < 0.01, respectively). The DXA BMD also showed a significant decrease in the lumbar spine (median: -4.5%, p < 0.01), total hip (-5.5%, p < 0.01), and femoral neck (-4.2%, p < 0.01). TRACP-5b and P1NP levels were significantly increased at the end of chemotherapy compared to baseline. Postmenopausal women undergoing chemotherapy for early breast cancer experienced significant BMD deterioration in weight-bearing bone, which was further reduced 6months after chemotherapy.

Therapeutic efficacy and safety of artemether-lumefantrine combination therapy for the treatment of uncomplicated Plasmodium falciparum malaria at Teda Health Centre, Northwest Ethiopia, 2022/23

BackgroundThe emergence of Plasmodium falciparum drug resistance against artemisinin-based combination therapy has threatened malaria control efforts. Since malaria control and elimination plans are dependent on these drugs, they must remain efficacious. However, resistance to these drugs was detected in low-transmission settings and is predicted to emerge in high-transmission settings, including in unspecified areas of Ethiopia. Therefore, this study aimed to assess the therapeutic efficacy and safety of artemether-lumefantrine for the treatment of uncomplicated P. falciparum malaria.MethodsA single-arm prospective observational study was conducted at Teda Health Centre, Northwest Ethiopia, by following the 2009 World Health Organization efficacy study guidelines from September 2022 to February 2023. Patients with uncomplicated falciparum malaria were conveniently selected and treated with a standard dose of artemether-lumefantrine, along with a single low dose of primaquine. Then clinical and parasitological responses and haemoglobin levels were assessed during the 28-day scheduled follow-up. Blood films were examined and asexual parasites were quantified; axillary temperature was measured; and drug adverse events were assessed throughout the follow-up. Finally, the drug efficacy (adequate clinical and parasitological response) was determined by Kaplan–Meier and per-protocol analyses. The data were analysed using the WHO Excel spreadsheet and SPSS version 25 software.ResultsThe success rates of PCR uncorrected and corrected Kaplan–Meier analysis on day 28 were 95.8% (95% CI 87.5–98.6) and 97.3% (95% CI 89.4–99.3), respectively. The per-protocol PCR uncorrected and corrected adequate clinical and parasitological responses were 95.5% (95% CI 87.5–99.1) and 97% (95% CI 89.5–99.6), respectively. On day-3, 97% of study participants were free of asexual parasitaemia, and all of them were fever-free on day-2. All of the gametocyte-positive patients at baseline were found to be negative for gametocytes on day-2. Moreover, the baseline mean hemoglobin of 13.10 g/dl increased slightly on day-14 to 13.27 g/dl but significantly on day-28 to 13.69 g/dl in a paired sample t test. All adverse events reported were mild.ConclusionArtemether-lumefantrine continued to be an efficacious and safe drug for the treatment of uncomplicated Plasmodium falciparum malaria at the Teda Health Centre.Trial registration: unique ID# PACTR202309773069812 at https://pactr.samrc.ac.za on September 1, 2023.

Docetaxel, Oxaliplatin with Capecitabine (TEX Regimen) in Metastatic Gastric and Gastroesophageal Adenocarcinoma: A Prospective Single-Arm Observational Study from a Tertiary Cancer Center in Kashmir

Abstract Background Metastatic gastric and gastroesophageal adenocarcinoma (MGGEAC) is a challenging disease with limited treatment options. The Taxotere, Eloxatin, and Xeloda (TEX) regimen has shown promising results in several clinical trials. There exists a dearth of data pertaining to the efficacy and tolerance of the treatment approach in the populace of Kashmir. Methods This study was performed at the Department of Medical Oncology, Sher-I-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir. Patients with MGGEAC received treatment with biweekly TEX regimen that included docetaxel 50 mg/m2-D1, oxaliplatin 85 mg/m2-D1, and capecitabine 1250 mg/m2/day, twice daily orally, for 14 days. The effectiveness of the regimen was assessed based on the overall response rate (ORR), progression-free survival (PFS), and overall survival (OS), along with the prognostic factors, safety, and tolerability of the regimen. Results The ORR was 63.5% after four cycles. The median PFS and OS were 9.1 and 13 months, respectively. Univariate and multivariate analysis showed that a higher number of sites of metastases is associated with poor PFS. The TEX regimen was well tolerated. The most observed grade 3 to 4 toxicities were neutropenia (36.7%), anemia (20%), fatigue (20%), and febrile neutropenia (16.7%). Conclusion Using the TEX regimen in MGGEAC showed better response rates and a slightly longer PFS. A higher number of sites of metastases is a poor prognostic factor in MGGEAC, as seen in our study. The toxicity profile shows that the regimen is tolerable. We recommend a randomized controlled study comparing CapeOx with TEX to test this regimen further.

Visual Outcomes and Patient Satisfaction of Trifocal or Trifocal Toric IOLs in Chinese Cataract Patients: Focus on Near Vision at 33 cm.

To examine the visual outcomes, particularly at 33 cm, and assess patient satisfaction following the implantation of a diffractive trifocal intraocular lens (IOL) and its toric variant. This prospective single-arm observational study involved 45 Chinese patients (90 eyes) underwent bilateral cataract surgery and PanOptix or PanOptix toric intraocular lenses (IOLs) implantation. Postoperatively, visual acuity was evaluated at various distances, including 40 cm and 33 cm, for both monocular and binocular outcomes. Patient satisfaction was evaluated using the VF-14 questionnaire. 72 eyes underwent PanOptix IOLs implantation, and 18 eyes received PanOptix toric IOLs. At 3-month postoperative mark, the mean monocular UDVA, UIVA, and UNVA at 40 cm and 33 cm were -0.02±0.09, 0.00±0.07, 0.02±0.07, and 0.07±0.14 logMAR, respectively, with proportions of visual acuity exceeding 0.1 logMAR were 96.7%, 96.7%, 94.4%, and 74.4%, respectively. The mean binocular UDVA, UIVA, and UNVA at 40 cm and 33 cm were -0.05±0.06, -0.03±0.05, 0.00±0.05, and 0.04±0.07 logMAR, respectively, with proportions of visual acuity exceeding 0.1 logMAR were 97.8%, 100.0%, 100.0%, and 91.1%, respectively. When the near point shifted from 40cm to 33cm, some patients showed a decline for UDVA, but the average reduction was less than one line. The overall VF-14 questionnaire score was 4.02±4.19. PanOptix can provide Chinese patients with a full range of satisfying visual acuity, near to 33cm. Though the visual acuity of some patients at 33 cm did not match the level at 40 cm, the gap of one line may not carry clinical significant.

Novel adaptation of the KCC-questionnaire for cardiomyopathy screening in a racially diverse obstetric population

Cardiomyopathy occurring during pregnancy or postpartum represents a leading cause of maternal mortality. An overlap between pregnancy-associated symptoms and symptoms of cardiomyopathy contributes to delays in diagnosis. To address the need for screening and improve the diagnosis of pregnancy-related cardiomyopathy, we sought to evaluate the association between cardiovascular symptoms, an adapted version of the 12-item Kansas City Cardiomyopathy Questionnaire for pregnancy (KCCQ-P) and left ventricular systolic dysfunction (LVSD). We conducted a single-arm prospective observational study of pregnant and postpartum participants enrolled between October 2021 and October 2022. A symptom questionnaire, KCCQ-P, and a resting echocardiogram were performed. The primary study outcome was LVSD, defined as left ventricular ejection fraction (LVEF) < 50%. We sub-divided those with LVEF (≥50%) into subclinical LVSD (left ventricular global longitudinal strain (GLS) > –18), and no LVSD (GLS ≤ −18). Ninety women were included in the final analysis. The median age was 31 years (Q1: 28, Q3: 35), 37% identified as Non-Hispanic White, 30% as Non-Hispanic Black, and 23% as Hispanic or Latino. KCCQ-P total scores were markedly lower with LVSD (median: 30.2; Q1: 22.9, Q3: 61.5) vs. subclinical LVSD (median: 60.7; Q1: 47.0, Q3: 76.2) vs. no LVSD (median: 86.5; Q1: 62.5, Q3: 95.8) p < 0.001. KCCQ-P score was able to detect LVSD with an AUC of 0.848. While individual cardiovascular symptoms were not associated with LVSD, KCCQ-P scores were significantly lower in those with apparent and subclinical LVSD and may be useful as a screening tool pending additional evaluation in larger cohorts.

A leadless ventricular pacemaker providing atrioventricular synchronous pacing in the real-world setting: results from the Micra AV post-approval registry

Abstract Introduction Advances in leadless pacemaker technology have enabled accelerometer based atrioventricular synchronous (AVS) pacing by sensing atrial mechanical contraction. However, longer-term performance of these devices in real-world clinical practice has not been assessed. Objectives To report the performance of the Micra AV transcatheter pacemaker from the worldwide Micra AV post-approval registry (PAR) through 1-year post-implant. Methods The Micra AV PAR is an ongoing prospective single-arm observational study designed to assess the safety and effectiveness of the Micra AV system in the real-world setting. Patients enrolled in the Micra AV PAR will be followed for 3 years. For the present interim analysis, baseline characteristics, total AV synchrony index (sum of %AM-VP, %AM-VS, and AV conduction mode switch percentage), major complications, and system revisions through 12-months of implant were summarized and compared to a historical cohort of 2,667 transvenous dual chamber (TV-DC) pacing patients. Results The device was successfully implanted in 797 of 801 patients (99.4%) at 98 centers in 19 countries between February 2020 and April 2022. Mean age was 74.1±15.1 years, 42.2% were female, and 31.3% were precluded from transvenous device therapy. Micra AV patients were on average older (74.1 vs. 71.1 yrs, P&amp;lt;0.0001) and had a significantly higher incidence of renal disease (22.3% vs. 9.8%, P&amp;lt;0.0001) compared with TV-DC patients. Mean follow-up was 7.7±6.4 months. Through 12-months, the major complication rate was 4.2% in Micra AV patients compared to 8.8% TV-DC patients (HR: 0.48, P&amp;lt;0.001, Figure). At 12-months, the system revision rate was 1.9% in Micra AV patients compared to 5.5% for TV-DC patients (HR: 0.28, P&amp;lt;0.001). The reduction in system revisions was largely driven by the absence of lead dislodgements requiring revision. Of the 397 patients with device interrogation files available for analysis, 315 (79.4%) were programmed to VDD mode at last follow-up and had a median AV synchrony index of 86.4% (IQR: 68.8% - 97.4%). Conclusions The Micra AV leadless pacemaker was implanted with a high rate of success in patients with a high co-morbidity burden, with a significantly lower rate of complications and system revisions through 12-months compared to dual-chamber transvenous pacemakers despite patients being older and having a higher incidence of renal disease. Longer-term performance will continue to be assessed in this ongoing trial.Major Complications Through 12-months

Abstract 15771: Cardiosphere-Derived Cell Extracellular Vesicles (CDC-EVs) Alter C-C Chemokine Receptor Type 2 (CCR2) Mediated Monocyte Pro-Inflammatory Signaling Following Cardiac Injury

Background: Following cardiac damage, CCL2 (a cytokine released by the injured cardiac tissue) recruits CCR2+ monocytes to the site of injury. Heightened CCL2 levels, however, can over activate the CCR2+ mediated pro-inflammatory response leading to poor cardiac healing. Cardiosphere-derived cell extracellular vesicles (CDC-EVs) have been shown to suppress the inflammatory response by decreasing CCR2 monocyte expression. We hypothesized that treatment with CDC-EVs would suppress CCR2 expression of peripheral monocyte in patients with acute MI. Methods: A prospective single arm observational study was performed. Inpatients at Buffalo General Medical Center were recruited following these criteria: 1) &gt;18 years of age AND 2) a type I MI. Subjects were excluded for the following: 1) fever in last 2 days/infection, 2) is or may be pregnant, or 3) currently undergoing cancer treatment. Monocytes were isolated from peripheral blood samples using Ficoll/centrifugation followed by magnetic activated cell sorting. Isolated monocytes were incubated with either PBS, normal human dermal fibroblast EVs (NHDF-EVs) or CDC-EVs. Monocytes then were analyzed for CCR2 expression by flow cytometry. Multi-variate analysis was performed. Results: CDC-EVs significantly reduced classical monocyte expression of CCR2 by 23% as quantified by flow cytometry compared with PBS (p&lt;0.05, one way ANOVA, n=23) and by 13% compared with NHDF-EVs (p&lt;0.05, one way ANOVA, n=23) in patients with recent MI. This reduction was seen regardless of patients’ pre-existing co-morbidities, medications, LVEF, or history of PCI. Smoking was associated with decreased response to CDC-EV mediated CCR2 suppression (Linear regression model R -0.93, p&lt;0.05, n=23). Conclusions: CDC-EVs effectively downregulate CCR2 expression in patients with recent MI, representing a potential adjunct to current clinical therapies in patients with a heightened pro-inflammatory response post-MI.

Autonomic Neuropathy in Ambulatory Type 2 Diabetes Mellitus Patients: A Single-arm Prospective, Observational Study

Abstract Introduction: Diabetic autonomic neuropathy (DAN), a serious complication of diabetes, is a significant contributor to increased morbidity and mortality. Although DAN often coexists with different peripheral neuropathies and other complications, it may also present in isolation. The present study aimed to understand the DAN status of a cohort of ambulatory type 2 diabetics in a tertiary care setting. Methods: A single-arm prospective observational study was carried out, where enrolled patients were interviewed for basic demographics and comorbidities, screened for symptoms of autonomic dysregulation, and other risk factors such as smoking and alcoholism. Based on the presence of overt symptoms, they were divided into two groups with or without any overt symptoms of autonomic neuropathy. Both groups were subjected to a battery of autonomic neuropathy tests, and their DAN status was characterized based on the observed scores. Results: The overall prevalence of DAN, as observed in our study, was 36%. Of 108 patients, 97 presented with one or more symptoms of autonomic dysregulation, whereas the rest, 10.1%, were without any symptoms. Among heart rate-based tests, a significant (P &lt; 0.001) decrease followed by an increase in the Valsalva ratio was observed in 6 months and 12 months, respectively. A significant decrease (P &lt; 0.001) in deep breathing test (E: I) values was observed in the 12th month. Most of the DAN patients presented with moderate autonomic dysfunction, followed by mild and severe, respectively. However, no significant change in DAN severity was noted with time. Conclusion: Using simple cardiovascular tests, DAN can be detected during the asymptomatic phase of the disease.

Treatment of sinus headache using a device that combines acoustic vibration with oscillating expiratory pressure.

To determine if simultaneous administration of acoustic vibration and oscillating expiratory pressure affects the severity of facial pain among patients with complaint of "sinus headache". This is a prospective single-arm observational study performed at a tertiary care medical center. Subjects with complaint of sinus headache without evidence of chronic rhinosinusitis on exam or computed tomography participated in a clinical study applying simultaneous acoustic vibrations and positive expiratory pressure to the nasal cavity twice daily over 4 weeks. Efficacy was assessed using three validated pain metrics-pain visual analog scale (VAS), brief pain inventory-short form (BPI-SF), and McGill pain questionnaire-short form (MPQ-SF). Device safety and patient satisfaction were also assessed using questionnaires. Twenty-nine patients (mean age 49 years, 55% female) completed the study without any major adverse events. At the 4 week follow-up, facial pain VAS improved from mean ± SD of 59.6 ± 15.7 to 34.6 ± 21.7 (p < .001), BPI mean pain (mean ± standard deviation) improved from 4.4 ± 2.0 to 2.9 ± 1.9 (p = .007), and MPQ-SF total improved from 12.2 ± 6.5 to 6.5 ± 5.2 (p < .001) with approximately 70% of patients achieving a minimal clinically important difference (MCID) across all metrics. Additionally, pain VAS was assessed 5 min after a single use at baseline with significant improvement (p < .001). Eighty-six percent of subjects would both use device again and recommend it to others. Simultaneous administration of acoustic vibration and oscillating expiratory pressure appears to be a safe treatment for sinus headaches in patients without objective evidence of chronic sinusitis. Results from this initial study are promising with regard to efficacy in treatment of sinus headaches but will require further study. 2c.

A leadless ventricular pacemaker providing atrioventricular synchronous pacing in the real-world setting: acute results from the Micra AV post-approval registry

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Medtronic, inc. Introduction Advances in leadless pacemaker technology have enabled accelerometer based atrioventricular synchronous (AVS) pacing by sensing atrial mechanical contraction. However, acute safety performance of these devices in real-world clinical practice has not been assessed. Objectives To report the acute performance of the Micra AV transcatheter pacemaker from the worldwide Micra AV post-approval registry (PAR). Methods The Micra AV PAR is an ongoing prospective single-arm observational study designed to assess the safety and effectiveness of the Micra AV system in the real-world setting. Patients enrolled in the Micra AV PAR will be followed for 3 years. For the present interim analysis, baseline characteristics, total AV synchrony index (sum of %AM-VP, %AM-VS, and AV conduction mode switch percentage), and major complications occurring within 30-days of implant were summarized and compared to a historical cohort of 2,667 transvenous dual chamber (TV-DC) pacing patients. Results The device was successfully implanted in 797 of 802 patients (99.4%) at 99 centers. Mean age was 74.1±15.1 years and 42.3% were female. The most common pacing indication was AV block (55.7%). Comorbidities included diabetes (29.7%), CAD (22.8%), and heart failure (12.1%), with 31.3% precluded from transvenous device therapy. Micra AV patients were on average older (74.1 vs. 71.1 yrs, P&amp;lt;0.0001) and had a significantly higher incidence of renal disease (22.3% vs. 9.8%, P&amp;lt;0.0001). Major complications occurred in 2.6% of Micra AV patients and in 7.1% TV-DC patients (P&amp;lt;0.001, Figure). The reduction in major complications was largely driven by the absence of pneumothoraces and lead dislodgements among Micra AV patients. Of the 309 patients programmed to VDD mode with at least 30 days of device follow-up, the median AV synchrony index was 86.0% (IQR: 69.2% - 97.2%). Mean A4 amplitude was 2.1±1.6 m/s2 post-implant and 2.2±1.7 m/s2 at follow-up (P=0.57) in 308 patients with paired assessments. Conclusions The Micra AV leadless pacemaker was implanted with a high rate of success in patients with a high co-morbidity burden, with a significantly lower rate of acute complications relative to dual-chamber transvenous pacemakers despite patients being older and having a higher incidence of renal disease. Longer-term performance will continue to be assessed in this ongoing trial.

P783 Symptom Improvement of ulceRative colitis after an Injection dose of Ustekinumab in Japanese clinical practice, measured using patient-reported outcomes (SIRIUS) study, Interim Analysis

Abstract Background Ustekinumab (UST) is treated to moderate to severe adult ulcerative colitis (UC) patients. We conducted the SIRIUS study (Symptom Improvement of ulceRative colitis after an Injection dose of UStekinumab in Japanese clinical practice, measured using patient-reported outcomes (PRO)) to record daily symptoms for 8 weeks after the introduction of intravenous ustekinumab in moderate to severe UC patients, which aimed to reveal early response patterns of symptoms during the induction of remission period with ustekinumab, and to explore symptoms suitable for monitoring and predicting treatment effect. This interim analysis focuses on stool frequency (SF) and rectal bleeding (RB) scores in the PRO-2 during the 8-week induction period. Methods This single-arm prospective observational study conducted in 23 centers in Japan aimed to recruit 140 patients with moderate-to-severe UC between July 2021 and July 2022. RB score, SF score, abdominal pain, nocturnal diarrhea, tenesmus, and patient perception of improvement were recorded daily using a smartphone app. To be eligible for the study, participants must have a documented diagnosis of UC, be ≥16 years of age, have UC (partial Mayo score of 5~9), have had an inadequate response or intolerance to prior UC therapies, and be able to understand and complete PRO instruments using a smartphone. Patients who had prior exposure to UST, history of extensive colectomy, or were hospitalized when UST was started were excluded. Results In this analysis,137 patients were included. Seventy-four (54.4%) patients were male and the median age was 35 years. Seventy-six (55.9%) patients were Bio-naïve. This high proportion of Bio-naïve patients reflects the fact that UST can be used for Bio-naive patients without restrictions in the Japanese health insurance. At weeks 2 and 4, 56 (41.2%) and 57 (41.9%) patients attended outpatient clinics, respectively. The data collection rate of the PROs was 95%. Mean SF and RB scores were demonstrated stratified by prior treatment with Bio (Figure 1&amp;3). Significant decreases in mean SF and RB scores were observed within 1 week in both Bio-naïve and -experienced patients. the time-course change in SF was similar between Bio-naïve and -experienced patients, but the decrease in RB scores was greater in the Bio-naïve patients than the Bio-experienced patients. Conclusion A daily PRO-based analysis was conducted in the Sirius study to monitor symptoms during the first 8 weeks after the introduction of UST in patients with moderate-to-severe UC. This interim analysis revealed that SF and RB scores started to decrease within 1 week, demonstrating a rapid symptomatic response to UST. The analysis of the other PROs and predictors of efficacy will be performed in further studies.

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.

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.

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.

Molecular Cytology by One-Step Nucleic Acid Amplification (OSNA) Assay of Peritoneal Washings during D2 Gastrectomy in Advanced Gastric Cancer Patients: Preliminary Results.

The presence of peritoneal free cancer cells (FCC) in gastric cancer (GC) patients is a poor prognostic factor. D2 gastrectomy may induce exfoliated FCC spread from the primary tumour or involved lymph nodes (LN). Conventional cytology for FCC detection has several limitations, whereas 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 intraoperative increase of FCC in peritoneal fluid. Twenty-seven 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 mL of saline was performed twice: (1) after gastrectomy with D2 lymphadenectomy and (2) after alimentary tract reconstruction. The IPL samples were analysed by initial cytology and four (1–4) consecutive OSNA assays. Initial OSNA measurement (1) revealed positive results (≥24.6 cCP/μL) in 7 (29.6%) patients. Subsequent OSNA measurements showed a significant decrease in the FCC level after D2 gastrectomy (1 vs. 2; p = 0.0012). The first IPL induced a non-significant increase in the FCCs (2 vs. 3, p = 0.3300), but the second IPL reversed it to normal levels (3 vs. 4, p = 0.0.0574). The OSNA assay indicates a temporal intraoperative increase in the peritoneal FCC in advanced GC patients undergoing D2 gastrectomy. Two consecutive IPLs are necessary to reverse the increase of CK19 mRNA level in peritoneal washings.

Immunological mechanism of postherpetic neuralgia and effect of pregabalin treatment on the mechanism: a prospective single-arm observational study.

BackgroundAlthough neuropathic pain is a severe and common pain, its pathophysiology has not been elucidated yet. Studies in recent years have focused on the immune system’s role in the pathogenesis of neuropathic pain. The aim of this study was to investigate the role of immunological mechanisms in neuropathic pain and the effect of pregabalin by measuring immunological marker levels in peripheral blood before and after pregabalin treatment in postherpetic neuralgia (PHN) patients with neuropathic pain.MethodsForty patients diagnosed with PHN were included in the study. CD4, T follicular cells (Tfh CD4+CXCR5+PD1+), Th17 (CD4+CCR6+ and CD4+IL17A+), regulatory T cells (Treg CD4+ CD25+foxp3+), Th1 (CD4+ CXCR3+ and CD4+ IFN-γ+) and Th2 (CD4+ IL-4+) cell ratios were measured in peripheral blood samples before treatment and after 3 months of treatment.ResultsWhen immunological marker and inflammation parameter levels were compared before and after treatment, the helper T cell ratio (CD3+, CD4+) was 30.28 ± 12.27% before treatment and 34.93 ± 11.70% after treatment, so there was a statistically significant increase (P = 0.028). Th17 was 4.75 ± 5.02% before treatment and 5.80 ± 3.13% after treatment, and there was a statistically significant increase (P = 0.036).ConclusionsImmunological mechanisms play an essential role in the pathogenesis of neuropathic pain, immunologically based treatment approach will be the critical point of treatment.