Late Follow-up Research Articles

Therapeutic Outcomes of 177Lu-PSMA Targeted Therapy in Patients with Metastatic Castration-Resistant Prostate Cancer: A Single-Center Study.

This study aimed to evaluate the therapeutic outcomes of 177Lutetium (177Lu)-PSMA-617 in metastatic castrate-resistant prostate cancer (mCRPC) patients, based on post-treatment imaging findings. All post-therapeutic scans were collected retrospectively from patients treated with 100-200 mCi 177Lu-PSMA-617 from March 2018 to December 2020 for mCRPC. Two independent readers interpreted the scans and visually categorized them into three strata: responsive, stable, and progressive. The responses were defined based on changes in the number of detected lesions, as well as the intensity of the hottest lesion. Data were registered, and the trend of changes was descriptively discussed. Out of 36 patients (aged 67±8.8 years), 23 underwent at least two treatment cycles. Nineteen patients (82.6%) had bone metastases, 12 (52.2%) had nodal metastases, 5 (21.7%) had liver metastases, and 3 (13.0%) had lung metastases. Eleven patients (47.8%) were considered responsive in the post-therapeutic scans, two of which experienced complete eradication of the metastatic sites. Three patients (13%) were categorized as progressive, and 9 (39.1%) patients remained stable. Regarding mortality, nine patients died during the late follow-up (median of 24 months). In the surviving population, 65% reported no or mild pain in the final follow-up, based on a 5-point scale pain assessment. The treatment of mCRPC patients with 177Lu-PSMA-617 may limit their disease progression and preserve their physical performance, which are important factors in their survival and quality of life.

Lithotripsy-Assisted Transcatheter Mitral Valve Replacement for Severe Mitral Annular and Valve Calcification: Late Follow-up.

The safety and effectiveness of transseptal transcatheter mitral valve replacement (TMVR) is being evaluated in clinical trials targeting patients with mitral regurgitation at a high surgical risk or unfavorable anatomy for edge-to-edge repair. Severe mitral leaflet and annular calcification (MAC) may be associated with incomplete expansion of self-expanding prostheses or trauma, including catastrophic annular rupture, following balloon-expandable valve implantation.

The Effectiveness of Coronary Artery Bypass Grafting in Patients with Left Ventricular Dysfunction.

Coronary artery bypass grafting (CABG) in patients with left ventricular dysfunction (LVD) remains a surgical challenge and is still controversial. The aim of this study was to evaluate the effectiveness of CABG in patients with LVD. This retrospective study included a total of 160 consecutive patients (133 males, 27 females, mean age 62.1±10.12 years [range 37 to 86 years]) who had a left ventricular ejection fraction (LVEF) ≤ 45% determined by echocardiography and underwent elective isolated CABG between September 2013 and December 2018. Preoperative echocardiographic data, such as ejection fraction, left ventricular (LV) end-systolic diameter, and LV end-diastolic diameter, were collected and evaluated. Preoperatively, 85 (53.13%) patients were in New York Heart Association functional class III or IV and the mean LVEF was 38.65±5.72% (range 20 to 45). The overall hospital mortality was 5% (eight patients). Late follow-up was obtained in 152 (90%) cases (median follow-up time was 56,5 [3-87] months postoperatively). During follow-up, mortality developed in 11.3% (16 patients). Mean LVEF increased significantly from 38.78±5.59% before surgery to 43.29±8.46% after surgery (P<0.01). Mean late survival, freedom from coronary reintervention, and congestive heart failure rates were 86.3±3.3%, 88.7±3.9%, and 89.4±3.1%, respectively. In patients with LVD, CABG can be performed with low postoperative morbidity and mortality rates. Patients with LVD could benefit from coronary bypass surgery regarding postoperative LV systolic function and higher quality of life.

Onyx Versus Particles for Middle Meningeal Artery Embolization in Chronic Subdural Hematoma.

Middle meningeal artery (MMA) embolization has recently emerged as a treatment option for chronic subdural hematoma (cSDH). It is considered a simple and potentially safe endovascular procedure. To compare between 2 different embolic agents; onyx (ethylene vinyl alcohol) and emboparticles (polyvinyl alcohol particles-PVA) for endovascular treatment of cSDH. A retrospective analysis of all patients who underwent MMA embolization for cSDH treatment in 2 comprehensive centers between August 2018 and December 2021. Primary outcomes were failure of embolization and need for rescue surgical evacuation. Among 97 MMA embolizations, 49 (50.5%) received onyx and 48 (49.5%) received PVA. The presence of acute or subacute on cSDH was higher in the PVA group 11/49 (22.5%) vs 30/48 (62.5%), respectively, P < .001. There were no significant differences between both groups regarding failure of embolization 6/49 (12.2%) vs 12/48 (25.0%), respectively, P = .112, and need of unplanned rescue surgical evacuation 5/49 (10.2%) vs 8/48 (16.7%), respectively, P = .354. Hematoma thickness at late follow-up was significantly smaller in the PVA group 7.8 mm vs 4.6 mm, respectively; P = .017. Both onyx and PVA as embolic agents for cSDH can be used safely and have comparable clinical and surgical outcomes.

2235. Discordance of Clinical and Microbiological Endpoints in Clinical Trials for Complicated Urinary Tract Infection (cUTI)

Abstract Background Complicated urinary tract infections (cUTI) are a clinical syndrome characterized by pyuria and a documented microbial pathogen on urine or blood culture, accompanied by local and systemic signs and symptoms, in the presence of urinary tract abnormalities or acute pyelonephritis. Current FDA guidance recommends that the primary endpoint for cUTI clinical trials be a composite of the clinical and microbiological responses, assessed at a fixed time after therapy. In recent trials, it has been noted that while some patients have clinical resolution of symptoms, they are considered failures due to positive urine cultures. These discordant outcomes have raised questions about the utility of the microbiological endpoint. Methods We analyzed patient data from 13 phase 3 clinical trials submitted to the FDA. We focused on the microbiological modified intent-to-treat (m-MITT) population, including patients who have at least 1 bacterial pathogen known to cause cUTI and received at least one dose of study drug (N=4842). Outcomes were determined at the Test of Cure (TOC) visit 7-10 days after therapy, and the Late Follow Up (LFU) visit 3-4 weeks after therapy. Clinical and microbiological success were defined as the resolution of cUTI symptoms present at entry, with no new symptoms (clinical cure), and reduction of the pathogen at entry to ≤ 103 CFU/mL on urine culture (microbiological eradication). Results Among all included patients, 70.7% were overall successes at the TOC, exhibiting clinical and microbiological success. 18.0% were discordant failures (clinical cure/microbiological persistence), and 6.7% were concordant failures (clinical failure/microbiological persistence). In a multivariate logistic regression model, discordance was associated with obesity, lithiasis, use of analgesics, and receipt of carbapenem antibiotics. Discordant patients were at an increased risk for clinical failure at the LFU visit, and the risk of late clinical failure increased with longer time between the TOC and LFU visits. Conclusion Microbiological persistence at the TOC visit despite resolution of symptoms was associated with an increased risk of late clinical failure. Microbiological outcomes appear to be an important component in the composite endpoint. Disclosures All Authors: No reported disclosures.

225. Efficacy and safety of sulbactam-durlobactam are consistent across regions in the global ATTACK phase 3 trial in the treatment of carbapenem-resistant Acinetobacter baumannii-calcoaceticus complex (CRABC) infections

Abstract Background ATTACK is a randomized, active-controlled, noninferiority trial that evaluated the efficacy and safety of sulbactam-durlobactam (SUL-DUR) compared to colistin for CRABC infections. The primary efficacy endpoint of all-cause mortality (ACM) at day 28 and the primary safety objective of incidence of nephrotoxicity based on RIFLE criteria were met. Due to the global variation of carbapenem and multi-drug resistance, geographic subgroups were evaluated to explore consistency of efficacy and safety across regions. Methods Patients were randomized to SUL-DUR or colistin treatment for 7-14 days and all patients received imipenem/cilastatin as background therapy. The primary efficacy analysis in the CRABC population consisted of 125 patients: SUL-DUR (N=63) and colistin (N=62). The primary safety population included 177 patients who received any amount of drug. Secondary efficacy endpoints included ACM at day 14, clinical cure and microbiological favorable assessment at end-of treatment (EOT), test-of-cure (TOC) and late follow-up (LFU). Results are described geographically by the following regions: the Americas, Asia-Pacific and Europe. Results Overall, ACM at day 28 in the SUL-DUR arm and colistin arm was 12/63 (19.0%) vs. 20/62 (32.3%), respectively; ACM at day 14 overall in the SUL-DUR arm and colistin arm was 4/63 (6.3%) vs. 12/62 (19.4%), respectively (Table 1). Day 28 ACM, and secondary endpoints were similar across the geographic regions and consistent with overall findings (Table 1). Criteria for RIFLE nephrotoxicity were met more often in the colistin arm than the SUL-DUR arm in all regions (Table 1). Conclusion ACM, clinical outcomes, microbiological favorable assessment, and RIFLE-assessed nephrotoxicity were consistently favorable in patients treated with SUL-DUR versus colistin across regions. These findings suggest, that if approved, SUL-DUR could be an important global therapeutic option for Acinetobacter infections including carbapenem-resistant and multidrug-resistant strains. Disclosures Alita Miller, PhD, Entasis Therapeutics: Ownership Interest|Entasis Therapeutics: Stocks/Bonds Adam B. Shapiro, Ph.D, Entasis Therapeutics: Employee|Entasis Therapeutics: Stocks/Bonds Sarah McLeod, PhD, Entasis Therapeutics: Employee|Entasis Therapeutics: Stocks/Bonds Khurram Rana, PharmD, Entasis Therapeutics: Employee|Entasis Therapeutics: Ownership Interest|Entasis Therapeutics: Stocks/Bonds Drew Lewis, MD, MTM&amp;H, Entasis Therapeutics: employee|Entasis Therapeutics: employee|Entasis Therapeutics: Stocks/Bonds|Entasis Therapeutics: Stocks/Bonds David Altarac, MD, MPA, Entasis Therapeutics: Ownership Interest|Entasis Therapeutics: Stocks/Bonds.

732. Microbiologic and clinical outcome concordance in the global phase 3 ATTACK trial: Sulbactam-durlobactam (SUL-DUR) versus colistin therapy in patients with Acinetobacter baumannii-calcoaceticus complex (ABC) infections

Abstract Background SUL-DUR is a β-lactam/β-lactamase inhibitor combination in development for the treatment of ABC, which is a cause of severe infections with substantial mortality. ATTACK evaluated the efficacy and safety of SUL-DUR versus colistin (COL) in patients with serious ABC infections. Methods Part A was a randomized, blinded non-inferiority study (SUL-DUR versus COL) in ABC pneumonia or bacteremia; Part B was an open label study (SUL-DUR only) that enrolled patients with ABC infections who did not tolerate COL or whose pathogens were resistant to COL (COL-R). All subjects received imipenem/cilastatin as background therapy. Primary endpoint included 28-day all-cause mortality (ACM) in Part A patients with carbapenem-resistant ABC at baseline (CRABC m-MITT). Clinical and microbiologic outcomes were measured at the End of Therapy (EOT), Test of Cure (TOC) and Late Follow-up (LFU) visits in CRABC m-MITT patients. In this study, COL-R was defined as MIC ≥ 4 µg/ml and SUL-DUR-non-susceptible (NS) was defined as MIC ≥ 8 µg/ml. Results SUL-DUR was non-inferior to COL in 28-day ACM; 19.0% SUL-DUR versus 32.3% in the COL group (Table 1). SUL-DUR therapy resulted in statistically significant higher clinical cures at EOT and TOC. Similarly, a significant treatment difference in microbiological favorable assessment was observed at EOT and TOC (24.4% and 26.3%, respectively, in Part A). Similar mortality differences were observed in subgroups including infection type, severity of illness, mechanical ventilation, and duration of stay of at least 5 days in the ICU prior to starting study treatment (Table 2). All 149 baseline ABC isolates from CRABC m-MITT patients were multi-drug resistant; the SUL-DUR MIC50/90 was 2/4 µg/ml (range of 0.25 – 8 µg/ml). At baseline 33% of ABC infections were polymicrobial. Conclusion In ATTACK, patients treated with SUL-DUR had lower mortality, higher clinical cure rates and significantly greater microbiologically favorable outcomes than those treated with COL. The correlation between clinical and microbiologic outcomes provides additional evidence that, if approved, SUL-DUR could be an important therapeutic option for Acinetobacter infections including carbapenem-resistant and multidrug-resistant strains. Disclosures David Altarac, MD, MPA, Entasis Therapeutics: Ownership Interest|Entasis Therapeutics: Stocks/Bonds Alita Miller, PhD, Entasis Therapeutics: Employee Sarah McLeod, PhD, Entasis Therapeutics: Employee Adam B. Shapiro, Ph.D, Entasis Therapeutics: Employee|Entasis Therapeutics: Stocks/Bonds Khurram Rana, PharmD, Entasis Therapeutics: Employee|Entasis Therapeutics: Ownership Interest|Entasis Therapeutics: Stocks/Bonds Drew Lewis, MD, MTM&amp;H, Entasis Therapeutics: employee|Entasis Therapeutics: employee|Entasis Therapeutics: Stocks/Bonds|Entasis Therapeutics: Stocks/Bonds Gabrielle Poirier, BS, Entasis Therapeutics: Ownership Interest|Entasis Therapeutics: Stocks/Bonds Daria Chabas, BS, Entasis Therapeutics: Ownership Interest|Entasis Therapeutics: Stocks/Bonds.

734. Efficacy of sulbactam-durlobactam (SUL-DUR) versus colistin in patients with extensively drug-resistant (XDR) and pan-drug resistant (PDR) Acinetobacter baumannii-calcoaceticus complex (ABC) infections

Abstract Background Acinetobacter baumannii-calcoaceticus complex (ABC) is a group of closely related species that cause serious infections associated with substantial mortality due in large part to very high antibiotic resistance rates and, consequently, a lack of effective therapies (Lancet 2022: 399;629–655). ATTACK was a global, active-controlled Phase 3 trial conducted to evaluate the efficacy and safety of SUL-DUR versus colistin (COL) for patients with ABC infections. Clinical and microbiological outcomes of all CRABC m-MITT patients vs. those with XDR or PDR ABC infections in ATTACK. Methods Part A was a blinded, randomized, non-inferiority study in ABC pneumonia or bacteremia. In Part B, patients who did not tolerate COL or had COL-resistant (R) ABC infections received SUL-DUR. All patients received imipenem/cilastatin as background therapy. Primary endpoint included 28-day all-cause mortality in Part A patients with carbapenem-resistant ABC at baseline (CRABC m-MITT). Clinical and microbiological outcomes were evaluated at End of Therapy (EOT), Test of Cure (TOC) and late follow-up (LFU) visits. COL-R was defined as MIC ≥ 4 µg/ml. MDR and XDR were defined according to Magiorakis et al (2012) CMI: 18, 268–81; PDR was defined as non-susceptibility to all approved agents (7 antibiotic classes) tested. Results Of 149 baseline ABC isolates from CRABC m-MITT patients, 100% were (MDR), 129 (87%) were XDR and 14 (9.4%) were PDR. 19 (15%) of XDR and 10 (71%) of PDR ABC infections were in patients with bacteremia. 51% of XDR (N = 66) and all PDR ABC infections were in European patients. The SUL-DUR MIC50/90 against the XDR set was 2/4 µg/ml (range = 0.25 – 8 µg/ml). 13 (93%) PDR ABC were susceptible to SUL-DUR at ≤ 4 µg/mL, its preliminary breakpoint. Clinical and microbiological outcomes favoring SUL-DUR over COL were nearly identical in patients with XDR ABC infections as in the total population (Table 1). Of the 13 evaluable patients with PDR ABC infections treated with SUL-DUR in Part B, only one (7.7%) did not survive to Day 28 and 12 (92%) experienced clinical and microbiological cure at TOC. Conclusion Patients enrolled in ATTACK had very high rates of XDR and PDR ABC infections, consistent with emerging global trends. Patients treated with SUL-DUR experienced better clinical and microbiological outcomes than those treated with COL, including those infected with XDR and PDR ABC. Disclosures Alita Miller, PhD, Entasis Therapeutics: Employee Sarah McLeod, PhD, Entasis Therapeutics: Employee Adam B. Shapiro, Ph.D, Entasis Therapeutics: Employee|Entasis Therapeutics: Stocks/Bonds Khurram Rana, PharmD, Entasis Therapeutics: Employee|Entasis Therapeutics: Ownership Interest|Entasis Therapeutics: Stocks/Bonds Drew Lewis, MD, MTM&amp;H, Entasis Therapeutics: employee|Entasis Therapeutics: employee|Entasis Therapeutics: Stocks/Bonds|Entasis Therapeutics: Stocks/Bonds Gabrielle Poirier, BS, Entasis Therapeutics: Ownership Interest|Entasis Therapeutics: Stocks/Bonds Daria Chabas, BS, Entasis Therapeutics: Ownership Interest|Entasis Therapeutics: Stocks/Bonds David Altarac, MD, MPA, Entasis Therapeutics: Ownership Interest|Entasis Therapeutics: Stocks/Bonds.

Unveiling the Biological Role of Peripheral Blood Human Circulating Hematopoietic Stem and Progenitor Cells

Although most hematopoietic stem/progenitor cells (HSPC) reside in the bone marrow (BM), few circulating HSPC (cHSPC) can be also found in the peripheral blood (PB) at steady state. The biological role and relationship with BM-resident counterpart in humans remain still not fully elucidated. In the present study, we phenotypically characterized cHSPC composition by applying multi-parametric flow cytometry on 110 PB and, as control, 48 BM samples of healthy donors (HD) of different age groups. These analyses were combined with cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) and ad hoc designed in vitro and in vivo assays to investigate the transcriptional and functional properties of steady-state cHSPC subpopulations with respect to BM counterpart. Moreover, to study circulating vs. resident HSPC differentiation potential in vivo in humans, we exploited integration site (IS) clonal tracking of cHSPC, BM HSPC and mature PB lineages isolated from patients treated with autologous HSPC-gene therapy (GT) at late follow-ups post-treatment (>2 years), once steady-state hematopoiesis is established. We observed that cHSPC show a progressive reduction in number during aging and a different composition than BM counterpart, with Multi Lymphoid Progenitors (MLP) displaying the highest PB circulation propensity. cHSPC were endowed with BM homing capability and multilineage differentiation potential both in vitro and in vivo, showing an early skewing toward erythroid differentiation after transplantation. Moreover, we detected a reduced long-term human cell engraftment in cHSPC- than BM HSPC-transplanted mice. This latter finding might be explained by the low primitive Hematopoietic Stem Cell (HSC) content and the transcriptional pre-activated state observed in steady-state PB HSC, as assessed in our single-cell RNA-sequencing analyses. Indeed, applying CITE-seq on PB- and BM-derived HSPC, we identified a unique transcriptional profile of both primitive and lineage-committed cHSPC subpopulations, characterized by lower replicative, metabolic and transcriptional activity, but increased differentiation-, adhesion- and immune response-priming than BM counterpart. Furthermore, we observed that PB phenotypic primitive HSC and Multipotent Progenitors (MPP) and Committed Myeloid Progenitors (CMP) were transcriptionally and functionally skewed toward erythroid lineages as compared to BM-resident counterpart. Finally, since upon gene correction each HSPC and its progeny became univocally marked by distinct IS, we exploited IS analyses from 5 patients treated with HSPC-GT at >2 years after GT to investigate the steady-state hematopoietic output of PB and BM HSPC in vivo in humans. In line with the enrichment of lymphoid transcriptional signature observed in trafficking HSPC, we found a higher IS sharing between PB mature lymphoid compartment and steady-state PB-derived HSPC. Moreover, a substantial fraction of trafficking HSPC displayed an enriched expression of the gene signature associated with thymus seeding progenitor type 1 (TSP1), a group of low-cycling immature lymphoid progenitors with thymus-emigrant properties. Although at lower level with respect to PB cells, we detected a TSP1 signature also in BM dataset, thus suggesting that few thymus-emigrant lymphoid progenitors originate in the BM and preferentially egress into the PB in order to seed lymphoid organs. Altogether, our findings indicate PB trafficking HSPC as a peculiar steady-state reservoir of low-cycling, pre-activated hematopoietic progenitors, which are endowed with BM homing and repopulation potential. The enrichment of phenotypic and functional erythroid-committed progenitors in cHSPC suggest a supportive role of these cells in sustaining extramedullary erythropoiesis. Furthermore, our results of IS analyses combined with the higher expression of TSP1 signature in PB vs. BM HSPC indicate the key function of steady-state trafficking HSPC in the seeding of the thymus, with the aim of locally differentiating into lymphoid progeny. Overall, our work represents one of the most comprehensive studies on cHSPC, unveiling fundamental insights on their biological role in humans.

Outcomes After Prolonged ICU Stays in Postoperative Cardiac Surgery Patients.

Prolonged postoperative intensive care unit (ICU) stays are common after cardiac surgery and are associated with poor outcomes. There are few studies evaluating how risk factors associated with mortality may change during prolonged ICU stays or how mortality may vary with length of stay. We evaluated operative and long-term mortality in post-cardiac surgery patients after prolonged ICU stays at 7, 14, 21, and 28 days and factors associated with mortality. We included University of Michigan Medical Center cardiac surgery patients with ≥ 7 postoperative days in the ICU. We determined factors associated with hospital mortality at 7, 14, 21, and 28 days of ICU stay using logistic regression, and among hospital survivors, we determined the factors associated with long-term mortality using Cox regression. Of 8309 ICU admissions from cardiac surgery, 1174 (14%) had ICU stays > 7 days. Operative mortality was 11%, 18%, 22%, and 35% for the 7-, 14-, 21-, and 28-day groups, respectively. Mechanical ventilation on the day of assessment was associated with increased odds ratios of operative mortality in all models. Of the 1049 (89%) hospital survivors, 420 (40%) died by late follow-up. Median (IQR) Cox model survival was 10.7 (0.7) years. Longer ICU stays, postoperative pneumonia, and elevated discharge blood urea nitrogen were associated with increased hazard of dying; whereas higher discharge platelet count and cardiac transplant were protective. Both operative and late mortality increased as the duration of a ICU stay increased after cardiac surgery.

Outpatient Mental Health Follow-up and Recurrent Self-harm and Suicide Among Patients Admitted to the ICU for Self-harm: A Population-based Cohort Study

Patients surviving an ICU admission for deliberate self-harm are at high risk of recurrent self-harm or suicide after discharge. It is unknown whether mental health follow-up after discharge (with either a family physician or psychiatrist) reduces this risk. What is the association between mental health follow-up after discharge and recurrent self-harm among patients admitted to the ICU for intentional self-harm? Population-based cohort study of consecutive adults (≥ 18 years of age) from Ontario, Canada, who were admitted to ICU because of intentional self-harm between 2009 and 2017. We categorized patients according to follow-up, with 'early follow-up' indicating 1 to 21days after discharge, 'late follow-up' indicating 22 to 60days after discharge, and 'no follow-up' indicating no follow-up within 60days of discharge. We conducted analyses using a cause-specific extended Cox regression model to account for varying time for mental health follow-up relative to the outcomes of interest. The primary outcome was recurrent ICU admission for self-harm within 1 year of discharge. We included 9,569 consecutive adults admitted to the ICU for deliberate self-harm. Compared with receiving no mental health follow-up, both early follow-up (hazard ratio [HR], 1.37; 95%CI, 1.07-1.75) and late follow-up (HR, 1.69; 95%CI, 1.22-2.35) were associated with increased risk in recurrent ICU admission for self-harm. As compared with no follow-up, neither early follow-up (HR, 1.10; 95% CI, 0.70-1.73) nor late follow-up (HR, 1.54; 95% CI, 0.84-2.83) were associated with increased risk of death by suicide. Among adults admitted to the ICU for deliberate self-harm, mental health follow-up after discharge was not associated with reduced risk of recurrent ICU admission for self-harm or death resulting from suicide, and patients seeking outpatient follow-up may be those at highest risk of these outcomes. Future research should focus on additional and novel methods of risk mitigation in this vulnerable population.

Extraperitoneal tissue retraction technique: An effective assistant of extraperitoneal pure single-port robotic-assisted radical prostatectomy with the da Vinci Si surgical system.

The limitations of tissue retraction and the amount of surgical working space have a great impact on extraperitoneal single-port robotic-assisted radical prostatectomy (sp-RARP) with the multiport robotic surgical system. We used an extraperitoneal tissue retraction technique to achieve tissue exposure and working space expansion. This study evaluated the safety, feasibility, and efficacy of the extraperitoneal tissue retraction technique in extraperitoneal pure sp-RARP with the da Vinci Si surgical system. Data from 42 patients were analyzed retrospectively from December 2018 to February 2020. The extraperitoneal tissue retraction technique was not used in 20 patients (group I) and was used in 22 patients (group II). Preoperative, intraoperative, and postoperative data were collected. The oncological and functional data during late follow-up were recorded. All patients successfully underwent extraperitoneal pure sp-RARP. No patients required conversion to a multiport surgery or placement of additional assistant ports. The two groups were similar regarding baseline features. The median operation time in group I was significantly longer than that in group II (P < 0.001). The estimated blood loss volume in group I was significantly higher than that in group II (P < 0.001). There were no serious complications in either group. There were four cases of peritoneal tears in group I and none in group II (P = 0.043). The surgical margin and lymph nodes were negative in both groups. The oncological and functional outcomes were similar between the two groups 6 months after the procedure. The extraperitoneal tissue retraction technique is safe and feasible. The technique promotes tissue exposure and expands the surgical working space, which is important for achieving extraperitoneal pure sp-RARP with the da Vinci Si surgical system, especially for beginners. The short-term oncological and functional outcomes were within acceptable ranges. The long-term effects of this technique need further evaluation.

Comparative Clinical Trial Between Conventional Treatment and Treatment with Rich Plasma Implants in Platelets (PRP) in Patients with Pseudarthrosis in the Tibia

The objective of this work was to carry out a comparative clinical study of the cost between the Conventional Treatment and the Treatment with Platelet Rich Plasma (PRP) in patients with Pseudarthrosis in the Tibia. At human bone fractures, mainly at arising in accidents in traffic and others and your complications, represent one important condition what has jeopardized health and quality of life, in addition to crescents for the Unified Health System (SUS), so much in the treatment primary, how much of us care with their grievances. One there, the Pseudarthrosis, entity gives Orthopedics already quite known, it is one complication of fractures Where o bone no it presents features in consolidation and regeneration. This is mainly due to poor vascularization at the fracture site, inadequate or late treatment and follow-up of the fracture, or the presence of a gap between the bone fragments. Surgical treatment is the most common for Pseudoarthrosis and it may be necessary for the patient to have a vascularized bone graft in the affected region. Against in a scenery, in what if observe o increase in costs hospital at the treatment surgical of fractures, so as pension expenses at the costing in pensions and retirements, resulting in loss gives activity work and loss of Health and Quality of Life with great repercussion at economy of country, was performed a study with essay Clinical Cats Comparison of Treatment Surgical Conventional for Pseudarthrosis gives Tibia, with o use in new technologies like the injection in Plasma Rich in Platelets (PRP) at the focus gives referred lesion, in patients attended fur System single of Health (SUS). The results obtained demonstrate that treatment with Platelet Rich Plasma (PRP) is less expensive, less traumatic, effective and allows for a shorter hospital stay, in addition to improving the Quality of Life.

Quantifying Donor Deficits Following Nerve Transfer Surgery in Tetraplegia

Nerve transfer (NT) surgery can improve function in people with cervical spinal cord injury (SCI). However, the impact of donor nerve deficits remains unclear. The purpose of this study was to quantify donor deficits experienced by individuals with cervical SCI following NT. This prospective single-arm, comparative study included people with SCI undergoing upper extremity NTs. Myometry was used to assess muscle strength at baseline and follow-up. The Spinal Cord Independence Measure was used to measure the ability to perform activities of daily living. Ten individuals underwent 20 NTs to restore elbow extension (donor, posterior deltoid; n= 2), hand opening (donor, supinator; n= 7), and hand closing (donor, brachialis; n= 11). Shoulder abduction strength decreased (-5.6% at early and-4.5% late follow-up) in the elbow extension NT. Wrist extension strength decreased at early (-46.9% ± 30.3) and increased by late (76.4% ± 154.0) follow-up in the hand opening NT. No statistically significant change in elbow flexion strength was noted in the hand closing NT. Spinal Cord Independence Measure scores did not change significantly between baseline and early postoperative follow-up; they improved at late follow-up. Use of expendable donor nerves with redundant function to perform NT surgery has relatively little impact on strength or capacity to perform activities of daily living, even in the unique and highly vulnerable SCI population. Early, temporary loss in wrist extension strength can be seen after the supinator to posterior interosseous nerve transfer. This study offers quantitative data about possible diminution of donor function after NT, enabling hand surgeons to better counsel individuals contemplating upper extremity reconstruction. Prognostic I.

Clinical Implications of the “Broken Line” Angiographic Pattern in Patients With Spontaneous Coronary Artery Dissection

Spontaneous coronary artery dissection (SCAD) is a rare but increasingly recognized cause of acute myocardial infarction. Coronary angiography remains the best diagnostic tool; however, clinical suspicion and experience is required to interpret angiographic findings. This study sought to assess the clinical implications of the "broken line" (BKL) angiographic pattern in a large, nationwide, cohort of patients with SCAD. The Spanish SCAD registry (NCT03607981) prospectively enrolled consecutive patients with SCAD. All angiograms were centrally analyzed and the BKL pattern was systematically assessed. The BKL angiographic pattern was found in 64 of 389 patients (16%). Patients with the BKL appearance were more frequently female (97 vs 87%, p <0.05), presented more often as intramural hematoma (83 vs 58%, p <0.001), had longer lesions (47 ± 29 vs 36 ± 22 mm, p <0.01), and had severe tortuosity (25 vs 10%, p <0.01) but showed better initial coronary flow (thrombolysis in myocardial infarction flow 2.6 ± 0.8 vs 2.1 ± 1.2, p <0.01). Patients with BKL received more frequently conservative medical management (91 vs 76%, p <0.01). At late clinical follow-up (median 29 months, interquartile range 17 to 38) predefined adverse events (death, myocardial infarction, revascularization, recurrent SCAD, or stroke) occurred less frequently (3.5 vs 15%, p <0.05) in patients with the BKL appearance. The better clinical outcomes of patients in the BKL group persisted after adjusting for potential confounders (adjusted hazard ratio 0.2, 95% confidence interval 0.1 to 0.9, p <0.05). In conclusion, patients with SCAD presenting the BKL angiographic pattern are more frequently female and present more often as intramural hematoma with longer lesions and severe vessel tortuosity but have better coronary flow. Patients with the BKL morphology have a favorable prognosis (NCT03607981).

Long-Term Aesthetic and Functional Evaluation of Intramuscular Augmentation Gluteoplasty with Implants.

The insertion of gluteal silicone implants by intramuscular technique leads patients to develop gluteus maximus muscle atrophy. The objective of the present study was to correlate the muscular atrophy of the gluteus maximus proportional to the volume of the silicone implants used. The secondary objectives were to assess volumetry of the gluteus maximus muscle in the late follow-up, to assess the positioning of the implants, and to verify the association between volumetric muscle recovery and practice of physical exercise. This is a prospective study. The sample was composed of 22 patients who were operated and followed up on an outpatient basis and through gluteus computed tomography at three different moments: preoperatively, 12 months postoperatively, and late postoperatively (≥96 months). Computed tomographic three-dimensional reconstruction and volumetric analysis showed a median atrophy of 6.68% of the gluteus maximus muscle volume in 12 months and 7.47% in the late postoperative period. The correlation between relative volume of the implant and atrophy percentage of the gluteus maximus did not present statistically significant results. There was an association between the practice of physical exercise and volumetry recovery of the gluteus maximus. No patient presented gluteal implant rotation. There is no correlation between proportional volume of implants and atrophy percentage of gluteus maximus muscle, when using implants up to 400 cm 3 . The gluteus maximus muscle presents atrophy in the late follow-up of augmentation gluteoplasty with implants. There is recovery of muscle volumetry in the patients who practice physical activities. Intramuscular plane implants demonstrated stability in their long-term positioning. Therapeutic, IV.

Aortic remodelling and late outcomes following thoracic endovascular repair with a bare-metal stent distal extension among patients with complicated type-B aortic dissection

OBJECTIVESThe goal of this study was to describe the factors affecting mid and late aortic remodelling following thoracic endovascular aortic repair with the PETTICOAT (Provisional Extension To Induce Complete Attachment) technique among patients with complicated acute or subacute type B aortic dissection.METHODSA retrospective single-centre study that evaluates clinical and morphological outcomes among 65 consecutive patients. The area and diameter of the true and false lumen, overall aortic diameter and false lumen perfusion were evaluated.RESULTSConcomitant direct visceral artery stenting was successfully conducted in 32 (49%) patients. There was one (1.5%) postoperative stroke; three (4.6%) patients developed spinal cord ischaemia; two (3%) patients suffered retrograde type A dissection; and two (3%) patients had mesenteric ischaemia, despite successful reperfusion, that required a bowel resection. Median postoperative follow-up was 63.1 (interquartile range, 32.1– 91.8) months. The probability of survival was 96.9% [95% confidence interval (CI) 88.3%–99.2%] at 30 days, 93.9% (95% CI 84.4%–97.6%) at 1 year, 78.0 (95% CI 64.2%–87.0%) at 5 years and 72.8% (95% CI at 57.9%–83.2%) at 10 years postoperatively. There was a statistically significant postoperative increase in true-lumen area, diameter and true-lumen index in all five aortic levels measured. Complete false lumen (FL) thrombosis at the coeliac trunk, renal arteries and aortic bifurcation levels was observed in 47%, 15% and 24% of patients at midterm (6–15 months) and in 29%, 21% and 29% on late (later than 21 months) computed tomography angiograms (CTA). Persistent false lumen (FL) perfusion at the coeliac level on midterm CTA was associated with a larger extent of late aortic growth (P = 0.042) and was, in the majority of cases, caused by iliac re-entries either alone (28.57) or in combination with visceral and lumbar (28.57%) or distal aortic (10.71%) re-entries. A larger abdominal aortic diameter at midterm was associated with an increased probability of distal aortic reinterventions (hazard ratio 7.26, 95% CI 2.41–21.9, P < 0.001).CONCLUSIONSPersistent FL perfusion of the distal aorta at midterm following TEVAR with the PETTICOAT technique among patients with acute and subacute type B dissection is caused mainly by iliac, visceral, lumber and distal aorta re-entries. Patients with persistent FL perfusion have an increased risk of aortic aneurysmal growth at late follow-up.

Catastrophic Vascular Injury After Total Knee Arthroplasty.

Vascular injury is a feared complication of any surgical procedure. This study examined the incidence of vascular injury during total knee arthroplasty (TKA), the circumstances and timing of injury intraoperatively, and acute management. Eighteen cases of catastrophic vascular injury after primary TKA (12 of 19,577; 0.06%) or revision TKA (6 of 4453; 0.1%) were identified. Catastrophic injury was defined as any vascular injury requiring vascular surgery. Chart review was performed to identify the timing of vascular injury, the injured blood vessel, and acute management. The Knee Society Score (KSS) was calculated. Mean follow-up was 8 years. Surgical indications included primary osteoarthritis for 12 cases, reimplantation for infection for 3 cases, and aseptic revision for 3 cases. Vessel injury included the popliteal artery in 10 cases, the popliteal artery and vein in 5 cases, and the popliteal vein in 3 cases. Thirteen injuries occurred during tibial preparation. Management included thrombectomy and reanastomosis in 15 cases and vessel bypass in 3 cases. One patient had thrombosis and limb ischemia 2 days after repair, requiring bypass. No amputations had occurred at late follow-up. Mean KSS was 74 at latest follow-up. Catastrophic vascular injury is more common after revision TKA (1 of 1000) than after primary TKA (6 of 10,000). Most injuries occur during tibial preparation. If identified quickly and addressed promptly by vascular surgery, limb salvage is likely. [Orthopedics. 2022;45(6):340-344.].

Sirolimus-Coated Balloon With a Microsphere-Based Technology for the Treatment of De Novo or Restenotic Coronary Lesions

BackgroundNon stent-based local drug delivery with drug-coated balloon (DCB) is an alternative to drug-eluting stent with favorable clinical applicability in the treatment of selected coronary lesions. Our purpose was to report the initial performance, safety and efficacy evaluations of a novel sirolimus-coated balloon in the treatment of coronary lesions. MethodsThis was a phase I (first-in-man), prospective, multicenter, single-arm trial evaluating the novel SELUTION SLR™ DCB (M.A. Med Alliance SA, Nyon, Switzerland), which incorporates a polymeric microsphere-based technology for controlled and continuous release of sirolimus, in the treatment of de novo or restenotic lesions. ResultsA total of 56 patients/lesions were enrolled between November/2018 and March/2019. Diabetes was found in 46.6 %, and de novo lesions represented 79.6 % of cases. Device and procedural/clinical success were 100 % and 96.4 %, respectively. There was only one major adverse cardiac event (target lesion revascularization) reported at late follow-up. By quantitative coronary angiography analysis, mean % diameter stenosis was 30.5 ± 16.7 %, late lumen loss was 0.26 ± 0.45 mm and angiographic binary restenosis occurred in 4 of 45 cases at 6-month angiographic follow-up. ConclusionThe novel SELUTION sirolimus-coated balloon demonstrated safety and efficacy in the treatment of diseased coronary vessels, including absence of mortality and relatively low late lumen loss at late follow-up.

142. Loss of sagittal correction >3 years after adult spinal deformity surgery

<h3>BACKGROUND CONTEXT</h3> The durability of adult spinal deformity (ASD) surgery is key for cost-effective treatment. Malalignment is one of the main reasons for revision surgery. <h3>PURPOSE</h3> To investigate risk factors for loss of correction within the instrumented lumbar spine following ASD surgery. <h3>STUDY DESIGN/SETTING</h3> Retrospective cohort study of a prospective database. <h3>PATIENT SAMPLE</h3> This study included 321 ASD patients with minimum 3 -year follow-up. <h3>OUTCOME MEASURES</h3> L1-S1, L4-S1 and L1-L4 lumbar lordosis. <h3>METHODS</h3> A total of 321 patients who underwent fusion of the lumbar spine (=5 levels, LIV S1/ilium) with a revision-free follow-up =3 years were identified. Patients were stratified by the change in PI-LL from 6 weeks to 3 years postop as Maintained vs Loss > 5°. Those with a loss due to instrumentation failure (broken rod, screw pullout, etc.) were excluded before comparisons. Changes in regional and focal lordosis over time were investigated with repeated measures ANOVA and factor comparison. <h3>RESULTS</h3> Mean age 64 yrs, BMI 28 kg/m², 80% female. The baseline alignment (PI-LL=21±19°, T1PA=26±12°) was corrected to PI-LL=3±13°, and T1PA=18±10° at 3 yrs (mean 3Y follow-up: 45±11m, with 44±11 mo between early and late follow-up). Eighty-two patients (25.5%) lost >5° of PI-LL correction (mean loss 10±5°). After exclusion of patients with instrumentation failure, 52 patients (Loss) with a mean loss of correction of 8.6±2.9 were compared to 222 controls with maintained LL correction. Demographics were similar between groups (age: 63 vs 61 p=0.15; Sex: 78.4% F vs 88.5% p=0.10). There were no significant differences in use of osteotomy, 3CO, and IBF between Loss and Maintained LL (all p >0.1). There was no significant difference in number of levels fused (11 vs 12 p=0.39), rod material (CoCr 59.4% vs 58.8% p=0.34), and BMP use (88.7% vs 84.6% p=0.41) but Loss had less supplemental rod use (5.8% vs 23.4% p=0.004). Comparison between Maintained and Loss revealed a similar PI-LL mismatch at pre-op (16.7±18.7 vs 20.9±18.3 p=0.14) and final postop (1.8±12.5 vs 5.1±14.5 p=0.11) but a significantly smaller PI-LL for Loss at early postop (0.6±12.8 vs -3.5±13.7 p=0.41). Distally, Maintained had a significant improvement in L4-S1 lordosis from preop to early postop (p=0.013), with no significant difference from early to final follow-up. In contrast, patients in the Loss group had no difference in L4-S1 from preop to early postop (p=0.14), but showed a significant loss of correction at 3 years (p <0.001). Proximally, significant increase between pre and early postop in L1-L4 (all p <0.001), with Loss and Maintained reaching similar early postop value (p=0.34). However, from early postop to final follow up, Loss showed a significant decrease in proximal lordosis (p <0.001) while Maintained did not (p=0.08), corresponding with a smaller absolute L1-L4 in the Loss cohort at 3 yrs (p=0.002). Screw orientation showed a significant decrease from early to late follow-up between the L1 and S1 screws for Loss (1.3±4.1 p=0.031), without any changes across the L4-S1 segment (-0.1±2.9 p=0.97). <h3>CONCLUSIONS</h3> Approximately a quarter of patients lose an average of 10° of their 6-week correction by 3 years. Lordosis is lost proximally through the instrumentation (ie, tulip/shank angle shifts and/or rod bending), but lost distally through bone "settling" through the instrumentation itself. The use of supplemental rods and avoiding sagittal overcorrection may help mitigate this loss. <h3>FDA DEVICE/DRUG STATUS</h3> This abstract does not discuss or include any applicable devices or drugs.