Prospective Single-arm Clinical Trial Research Articles

Interim analysis of robot-assisted radical hysterectomy in Japan: a multicenter, prospective interventional single-arm clinical trial

ObjectiveTo investigate the efficacy and safety of robot-assisted radical hysterectomy (RARH) as a minimally invasive procedure in patients with cervical cancer that is curable by surgery.Materials and methodsThis study was a multicenter, open-label, single-arm clinical trial. The short-term outcome of open radical hysterectomy was used as the historical control. The primary endpoint was successful surgery with minimal blood loss (300 mL or less) and negative surgical margins. Secondary endpoints included surgical outcomes, recurrence-free survival (RFS), and overall survival (OS) rates.ResultsOverall, 101 cases were enrolled in this study at 10 participating medical institutions and 100 underwent RARH. Among these cases, 89 met the primary endpoint, exceeding the threshold of 0.75 set by the lower limit. At 2 years postoperatively, 17 cases had recurrences, 4 were classified as International federation of Obstetrics and Gynecology Stage IB1 or lower, while 13 as IB2 or higher. There were three deaths, including one in Stage IB1 and two in Stage IIB in the second postoperative year, all of which had lymph node metastasis. The oncological outcomes for all cases showed RFS and OS rates of 82.7% and 96.9%, respectively, over a median observation period of 37 months. For cases with Stage IB1, RFS and OS were 94.1% and 98.5%, respectively.ConclusionRARH demonstrated a significant reduction in blood loss while ensuring radicality, indicating the safety and efficacy of this procedure compared to conventional RH. Although it is conceivable that the results of this oncological analysis could change, as the data collection has not been fully completed, we plan to further evaluate the oncologic outcomes of RARH in future studies.Trial registrationUMIN-CTR: UMIN000022278, registered on 11th May 2016.

Metal-Free Custom-Made Zirconia Implants-A Prospective 5-Year Follow-Up Single-Arm Clinical Trial.

Dental implants made of zirconia (ZrO2) are a potential alternative for titanium implants in dentistry because of their good biocompatibility, mechanical properties and excellent aesthetic results. However, solid long-term scientific data to prove clinical success of ZrO2 implants are scarce. The aim of this study was to describe and to examine the clinical performance of custom-made two-piece ZrO2 implants, to identify possible influencing factors: a) manipulation of the implant after placement and b) the occlusal scheme on the survival rate, and to evaluate the performance of the implant-supported crown. This follow-up study collected and examined the 5-year data to answer the main question: What are the survival and the success rates of custom-made ZrO2 implants in the maxillary premolar region after 5 years? Of the 31 included patients in this prospective 5-year follow-up single-arm clinical trial, 30 received a custom-made ZrO2 implant to replace a missing single maxillary premolar, which was subsequently restored with a lithium disilicate crown. Parameters regarding clinical performance, marginal bone-level (MBL) changes, and patient-related outcome measures (PROMs) were assessed preoperatively, at the baseline, as well as 1 and 5 years after crown placement. Chances of survival and success of the implant were calculated and displayed using Kaplan-Meier statistics. Kaplan-Meier survival analysis was also performed with stratification based on the variables "manipulation of the implant prior to impression taking" and "occlusal scheme" and compared using log-rank tests. Bone-level moderation in time was compared using a paired samples t-test. Patient's expectations and satisfaction after 5 years were compared as a measure of fulfilled expectations, using a Wilcoxon signed-rank test. Performance of the implant-supported crowns was evaluated using validated criteria. Survival and success probabilities after 5 years were, respectively, 75.8% (95% CI [60.0%; 91.0%]) and 71.0% (95% CI [54.0%; 88.0%]) for the custom-made ZV3 implants. No significant differences in survival rate were found after stratification on "manipulation of the implant" and on "occlusal scheme." Mean bone-level alteration between baseline and the first follow-up was +0.06 mm (95% CI [-0.23 mm; 0.12 mm]; SD = 0.42 mm) and between baseline and the second follow-up was +0.04 mm (95% CI [-0.35 mm; 0.26 mm]; SD = 0.54 mm). Patients' satisfaction for patients with implants still in function after 5 years was 91.7% (IQR = [90.5%-97.3%]), indicating satisfaction with the treatment. Pooled satisfaction in patients with successful implants after 5 years was significantly higher than patients' expressed expectations before treatment. None of the crowns failed, and no interventions were required. Survival rate of these particular ZV3 implants in our study was lower than expected and clinically not acceptable. Hence, ZV3 implant placement as applied in this study cannot be recommended for clinical practice. Further research on the different appearances of mechanical failure in ZrO2 implants would be highly recommended before a larger prospective randomized clinical trial is conducted to evaluate treatment with custom-made ZrO2 dental implants.

857P Safety and efficacy of neoadjuvant immunochemotherapy in patients with locally advanced head and neck squamous cell carcinoma: A prospective single-arm clinical trial

857P Safety and efficacy of neoadjuvant immunochemotherapy in patients with locally advanced head and neck squamous cell carcinoma: A prospective single-arm clinical trial

Outcomes of a Novel Single Branched Aortic Stent Graft for Treatment of Type B Aortic Dissection

Intervention on Type B dissection frequently requires landing the proximal edge of the stent graft between the left common carotid artery and left subclavian artery (LSA). The Gore® TAG® Thoracic Branch Endoprosthesis (TBE) is a technology which allows LSA preservation with a single internal branch. This study was a prospective non-randomized single-arm clinical trial of patients with type B aortic dissection that were treated with the single branched device. Patients with operative indications for acute, chronic or residual Type B dissections that originated distal to the origin of a left subclavian artery suitable for branch graft placement were eligible for the study. Native aortic and surgical graft proximal landing zones were eligible. Among the 132 patients, there were 25 (18.9%) acute type B dissections, 79 (59.8%) of chronic type B dissections and 28 (21.1%) of residual dissections after previous open Type A repair. Percutaneous access was used in 105 (79.5%) patients. Overall, 30-day mortality occurred in 6 patients (4.5%). The overall 30 day stroke rate was 2/132(1.5%) and the one-year freedom from stroke was 96.8%. Device Technical Success and Procedural Success was achieved in 129/132(97.7%) and 110/132(83.3%) of subjects, respectively and there was one instance of loss of side branch patency. There was no persistent antegrade false lumen flow observed. In this study of a novel branched endograft device to preserve the LSA in patients with type B dissection undergoing TEVAR, we demonstrate acceptable safety and efficacy outcomes at one year.

Infinity: A Prospective Trial for Safety and Accuracy of Navigated Posterior Cervical and Thoracic Instrumentation in long-segment Fusions.

Unblinded single-arm prospective clinical trial. Evaluate safety and accuracy of navigation for placement of posterior cervicothoracic instrumentation. Computer assisted stereotactic navigation for placement of spinal instrumentation has been widely studied and implemented in the thoracic and lumbar spine. However less literature exists regarding the use of computer assisted navigation for posterior cervical instrumentation, particularly with lateral mass fixation. Here we present the first prospective study of navigated cervical lateral mass screw placement for cervicothoracic fusion. Patients who met indications for posterior cervical fusion were screened, consented, and enrolled preoperatively for instrumentation with Medtronic Infinity Occipital-Cervical-Thoracic implants, with use of intraoperative O-arm and stereotactic Stealth navigation. Postoperative CTs of the instrumented levels were obtained during the same hospital admission. Primary outcome of the trial was safety. Secondary outcomes were screw accuracy assessed by Gertzbein-Robbins grade, neurologic exams, and patient reported outcomes on the PROMIS 29 questionnaire. A total of 50 patients underwent surgery, and 557 screws were placed. There were no adverse events related to the use of navigation or screw malposition. Gertzbein-Robbins grade A or B placement comprised 95% of navigated screws. There was a decrease in positive Hoffmann sign rate postoperatively, and sensory and motor exams remained stable. There was improvement in patient reported pain and sleep domains. Navigation for cervicothoracic instrumentation is safe overall and leads to high rates of accurately placed screws. Longer term follow up could provide more insight to whether the use of this technology results in durable improvement in spinal alignment parameters and patient reported outcomes. 3.

A novel single-port robotic system in urology: a prospective multicenter single-arm clinical trial evaluating feasibility and efficacy of first 50 cases

ObjectiveThis study aimed to assess the feasibility and safety of the SHURUI single-port robotic surgical system for a range of major urological surgeries. MethodsIn this prospective, multicenter clinical trial, we examined the effectiveness of the SHURUI surgical system in urological interventions. The first 50 patients from four centers in China underwent single-port surgeries including partial nephrectomy, radical prostatectomy, partial adrenalectomy, and pyeloureteroplasty, exclusively by the SHURUI system. The study's primary endpoints focused on the success of surgeries, gauging this by the absence of deviations from planned procedures, the need for additional ports, or re-operations within a 24-hour period post-surgery. Secondary endpoints encompassed a range of surgical metrics, functional outcomes, and patient demographic data. Clinical assessments were conducted before surgery, before discharge, and 1-month following discharge. ResultsThe surgical procedures were executed successfully without requiring intraoperative conversions or transfusions. Both estimated blood loss and operation durations were maintained within satisfactory limits. For each type of surgery, the mean console times and estimated blood loss were 179.8 (SD 39.4) min and 125.6 (SD 126.0) mL for radical prostatectomy, 126.7 (SD 47.8) min and 39.2 (SD 54.4) mL for partial nephrectomy, 112.6 (SD 37.4) min and 20.0 (SD 13.2) mL for partial adrenalectomy, and 148.0 (SD 18.2) min and 18.0 (SD 17.9) mL for pyeloureteroplasty, respectively. Across the cohort, 17 patients experienced a total of 25 adverse events, while 10 postoperative complications, all rated as Clavien–Dindo Grade I, were encountered by eight patients. All patients had shown recovery or improvement from these events before the end of this trial. ConclusionThe SHURUI single-port robotic system demonstrated feasibility and safety in the performance of major urological surgeries. These initial findings highlight the system's potential, though further research and longer follow-up are required to assess long-term outcomes.

Posterior two-unit cantilevered zirconia resin-bonded fixed partial dentures: A 3-year prospective single-arm clinical trial

ObjectivesTo evaluate the longevity of cantilevered zirconia-based resin-bonded fixed partial dentures (RBFPDs) in replacing missing posterior teeth, as well as the quality of life and patient satisfaction experienced by those receiving zirconia RBFPDs. MethodsA prospective single-arm uncontrolled clinical trial was conducted to replace one or more missing premolars or molars with a span of 5 to 8 mm using cantilevered zirconia RBFPDs. Thirty-six participants with 40 prostheses were recruited and underwent a 3-year clinical evaluation. The retainer designs included a minimum thickness of 0.8 mm, a minimum of 200° circumferential wraparound with an occlusal bar, and a connector dimension of 3 × 3 mm. Patient-reported outcomes, including patient satisfaction and Oral Health Impact Profile (OHIP), were assessed. ResultsThe average age of participants was 45.8 years, and 72.5 % were women. The success rate of the posterior zirconia RBFPDs was 76.2 %, with an estimated mean success duration of 46.1 months. The survival rate was 88.1 %, with an estimated mean survival duration of 49.4 months. Participants were highly satisfied with the treatment, achieving an average satisfaction score of 80.8 ± 11.9. Participants' total OHIP scores decreased from 52.3 to 39.6 after 3 years, indicating a significant improvement in oral health-related quality of life (P = 0.009). ConclusionsAfter 3 years, a moderately high survival rate and favourable patient-reported outcomes of posterior cantilevered zirconia RBFPDs were achieved. Therefore, it can be recommended as a conservative treatment option to replace missing posterior teeth, provided that retainer design considerations are taken into account. Clinical significanceCantilevered zirconia RBFPDs for posterior teeth can serve as a conservative treatment option that is both aesthetically pleasing and biocompatible. It offers a more cost-effective alternative compared to dental implants, which are often prohibitively expensive for the majority of patients. This approach has the potential to greatly improve patient-reported outcomes.

A prospective single-arm clinical trial to assess the safety and efficacy of monofilament polydioxanone barbed suture, MONOFIX®, on abdominal fascial closure.

For abdominal fascial closure, the choice of optimal suture material and appropriate suture technique are of paramount importance to prevent the incidence of incisional hernia. Although barbed sutures are widely used in various surgical fields, their safety and feasibility on abdominal fascial closure which requires the most tensile strength for security have not been established yet. We conducted a prospective, single-arm, interventional clinical trial to present the postoperative outcomes of using barbed sutures in abdominal fascial closure between April 2021 and August 2021. Patients with colorectal cancer who underwent minimally invasive surgery in elective setting were included. For all participants, monofilament polydioxanone barbed suture, MONOFIX®, was used to secure the abdominal fasica. The primary outcome was the 1-year incidence of incisional hernia assessed by computed tomography. A total of 30 patients were included. The median fascial incision length and suture length were 6.5cm (range, 6-7.5cm) and 31cm (range, 27.5-39.0cm), respectively. The median procedure time of abdominal fascial closure was 4min (range, 3-9min). There was no incidence of unexpected event related to suturing including suture cutting, stopper separation from threads, and suture loosening. One case of superficial surgical site infection occurred during postoperative hospital stays. There was no fascial dehiscence, incisional hernia, and adhesive ileus during a median follow-up period of 17.5months. Monofilament polydioxanone barbed suture, MONOFIX®, may be used safely and effectively on abdominal fascial closure. NCT05872334.

Covalent FAPI PET enables accurate management of medullary thyroid carcinoma: A prospective single-arm comparative clinical trial.

LBA6018 Background: Localizing medullary thyroid carcinoma (MTC) lesions is crucial for treatment decision, but the detection using the current imaging modalities is unsatisfied. Previously, we reported a 68Ga-labeled targeted covalent radiopharmaceutical fibroblast activation protein inhibitor (68Ga-TCR-FAPI), which demonstrated improved and sustained tumor targeting. This study aimed to head-to-head compare the 68Ga-TCR-FAPI PET-CT and the currently approved 18F-FDG PET-CT in detecting MTC. Methods: This was a prospective, single-center, open-labeled, single-arm comparative imaging trial. MTC patients with serum calcitonin>10 pg/ml and without targeted therapy were eligible. Serum calcitonin level, 68Ga-TCR-FAPI PET-CT and 18F-FDG PET-CT were acquired within a maximum interval of 30 days. Images were independently interpreted by 3 readers to calculate the patient-based and region-based detection rate. Quantitative PET parameters were calculated from the lesion ROI and compared between 68Ga-TCR-FAPI and 18F-FDG PET-CT. The accuracy of imaging findings was validated on lesions with histopathology or calcitonin-based follow-up. The primary outcome was patient-based detection rate, and the secondary outcome included region-based detection rates, metabolic parameters comparison and diagnostic accuracy. Results: 50 patients were enrolled between May 11th, 2023 and Feb. 1st, 2024. 68Ga-TCR-FAPI exhibited significantly higher patient-based detection rate than 18F-FDG PET-CT (98% vs. 66%, p=0.0002). Detection rates were also superior for 68Ga-TCR-FAPI in head and neck (72% vs. 50%, p=0.0098), thorax (50% vs. 34%, p=0.0269), abdomen (28% vs. 10%, p=0.0077) and skeleton (54% vs. 16%, p<0.0001). On quantitative analysis, SUVmax was significantly higher in 68Ga-TCR-FAPI PET-CT than 18F-FDG PET-CT (11.71±9.16 vs. 2.55±1.73, p<0.0001). Diagnostic accuracy was substantially greater with 68Ga-TCR-FAPI PET-CT than 18F-FDG PET-CT (96.7% vs. 43.3%, p<0.0001) based on 60 histopathological validated lesions from 15 patients who underwent surgery. Notably, 60% (30/50) patients directly benefited from 68Ga-TCR-FAPI PET-CT, with 66.7% (10/15) experiencing changes in surgical plans, and 100% (6/6) of the newly diagnosed MTC with R0 resection achieved biochemical cure at 1-month post-surgery. Conclusions: 68Ga-TCR-FAPI PET-CT displayed higher detection rate, metabolic value and diagnostic accuracy than 18F-FDG PET-CT in MTC patients, and should be integrated into MTC evaluation at initial diagnosis and persistent disease. Clinical trial information: NCT06084767 . [Table: see text]

Ocular Surface Changes in Glaucomatous Patients Undergoing Cataract Surgery Combined with Micro Invasive Glaucoma Surgery (2nd Generation Trabecular Stents Istent Inject ®): A Study about 69 Eyes

Introduction: The purpose of this study was to evaluate ocular surface changes and dry eyes symptoms in patients undergoing cataract surgery by phacoemulsification combined with implantation of two trabecular stents (Istent Inject®). Methods: This single-arm prospective interventional clinical trial enrolled 69 patients with mild-to-moderate open-angle glaucoma taking 1 to 4 glaucoma medications that underwent phacoemulsification combined with implantation of two trabecular stents (Istent). We explored several key data about ocular surface and glaucoma evolution throughout the follow-up, including the Ocular Surface Disease Index score, the Oxford score, the Efron conjunctival score, and the Fluorescein Tear Break-up Time (FTBUT). Results: Mean OSDI scores improved from 40.1 ± 21.6 (severe dry eye) preoperatively to 17.5 ± 15.3 (mild dry eye) at 3 months. While 73% of eyes had moderate or severe OSDI scores preoperatively, only 29% had such scores at 3 months. The mean FTBUT increased from 4.3 ±2.4 seconds preoperatively to 6.4 ±2.5 seconds at 3 months; the average Oxford staining score decreased from 1.4 ± 1.0 preoperatively to 0.4 ± 0.6 at 3 months. There was a reduction in the number of glaucoma medications from 1.5 to 0.6 medications. Mean IOP decreased from 17.4 ± 4.2mmHg to 14.5 ± 3.2mmHg at the 3 months follow-up. The safety profile of the surgery was excellent. Conclusion: The implantation of two trabecular stents (Istent inject®) combined with cataract surgery resulted in clinical and functional improvements in ocular surface health, as well as significant reductions in IOP and medications in patients with open-angle glaucoma.

Quality of life (QoL) benefits following 177Lu-DOTATATE therapy in patients (pts) with 68Ga-DOTATATE PET positive primary site agnostic neuroendocrine tumors (NET).

e16291 Background: The QoL experience during the 1st year of follow up for 68Ga-DOTATATE PET positive primary site agnostic pts with progressive metastatic NET enrolled in a prospective single arm clinical trial of 177Lu-DOTATATE therapy (OZM 067) is described here. Methods: Pts with progressive NET, Ki67 Index < 30%, adequate organ function & ECOG £2 were eligible. Only pts demonstrating positive disease (Krenning score 3-4) on 68Ga-DOTATATE PET were eligible to proceed to 177Lu-DOTATATE therapy (4 cycles at 8- to 12- week intervals. Primary outcome was progression free survival (PFS) at 12 mths. QoL (EORTC QLQ 30 and GINET21) at baseline, 6, 12, 18, 24, 30 months were recorded. Summary scores at time point of interest, and their change from baseline were estimated using a mixed model repeated measure, with baseline assessment included in the model as covariate. Data were normalized with a range of 0-100. A positive change score for Global Summary Status, Functioning Domains, and a negative change score for Symptom Scales and Items represent improvement. A ≥5 point change score is used as a threshold for Minimal Clinically Important Difference (MCID). Results: 195 pts were enrolled. 13 pts were 68Ga-DOTATATE PET negative while 5 pts withdrew consent. 177 pts received at least one dose of 177Lu-DOTATATE. All pts enrolled were eligible for a minimum of 12 mths follow up at time of data lock. The primary site was GEPNET in 143 (81%) and non GEPNET in 34 (19%). At 12 mths, the median follow-up was 33 (range 3-71) mths. PFS and OS were 81 (95% CI: 75-86)% and 92 (87-95)% respectively. QoL data at the following timepoints baseline, 6 & 12 (±2) mths were available in 174,128 & 111 pts respectively. The top three symptoms captured in EORTC QLQ 30 was Fatigue (32.5 SD 23.8) , Insomnia (26.7 SD 28.1) and Diarrhea (22.1 SD 29.4). At 12 mths, an improvement in mean score of ≥MCID in Global Health status (GHS) (+5.4), Role Fc Scale (+7,1), Social Fc Scale (+8.7) and multiple symptoms (Fatigue, Pain, Appetite, Constipation, Diarrhea, Financial Difficulties), Sexual fc, Social, Body image (Table 1) were captured. Conclusions: Patients with primary site agnostic 68Ga-DOTATATE PET positive NET experienced improvement in multiple quality of life domains including multiple symptoms post 177Lu-DOTATATE at 12 mths. Sexual fc and body image had the largest improvement. Clinical trial information: NCT02743741 . [Table: see text]

First in Human Phase 1 Clinical Trial of Stereotactic Irradiation to Achieve Lung Volume Reduction (SILVR) in Severe Emphysema

PurposeOnly a subset of patients with severe emphysema qualify for lung volume reduction surgery or endobronchial valves. We previously demonstrated that Stereotactic Ablative Radiotherapy (SABR) of lung tumors reduces lung volume in treated lobes by creating localized lung fibrosis. We aimed to determine the safety and, secondarily, explore the efficacy of Stereotactic Irradiation for Lung Volume Reduction (SILVR) over 18 months following intervention in patients with severe emphysema. Methods and materialsWe conducted a single-arm prospective clinical trial in eligible patients with severe emphysema treated with unilateral SABR (45 Gy in three fractions) to a target within the most emphysematous region. Primary outcome was safety i.e., incidence of grade≥3 adverse events. Secondary outcomes of efficacy were also explored. ResultsEight subjects received the intervention. Median (range) baseline characteristics were age 73 years (63-78), FEV1% 28.5% (19.0-42.0), DLCO% 40% (24.0-67.0), and BODE index 5.5 (5-9). The incidence of grade≥3 adverse events was 3/8 (37.5%). The relative Δtarget lobe volume was -23.1% (-1.6,-41.5) and -26.5% (-20.6,-40.8) at six and 18 months, respectively. Absolute ΔFEV1% was greater in subjects with BODE index ≤5 vs. ≥6 (+12.0% vs. -2.0%). The mean baseline lung density (in Hounsfield units, reflecting the amount of preserved parenchyma) within the intermediate dose volume (V60BED3) correlated with the absolute Δtarget lobe volume at 18 months. ConclusionsStereotactic Irradiation for Lung Volume Reduction appears to be safe, with a signal for efficacy as a novel therapeutic alternative for patients with severe emphysema. SILVR may be most safe/effective in patients with lower BODE index and/or less parenchymal destruction.

The effect of feeding on serum concentrations of cobalamin, folate, trypsin-like immunoreactivity, and pancreatic lipase immunoreactivity in dogs with signs of chronic gastrointestinal disease.

It is unknown if serum concentrations of cobalamin, folate, canine pancreatic lipase immunoreactivity (cPLI), and canine trypsin-like immunoreactivity (cTLI) obtained postprandially are equivalent to measurements obtained after withholding food in dogs with suspected gastrointestinal disease. Measurements of serum concentrations of cobalamin, folate, cPLI, and cTLI postprandially will be equivalent to measurements after 12 hours of withholding food in dogs with signs of chronic gastrointestinal disease. Changes observed will not alter clinical interpretation. 51 client-owned dogs with signs of gastrointestinal disease. Prospective single arm clinical trial. Serum concentrations of cobalamin, folate, cPLI and cTLI 2, 4, and 8 hours postprandially were compared by equivalence testing to values after withholding food for 12 hours (baseline). Mean serum cobalamin concentrations 2 hours (498.1 ± 213.1 ng/L; P = 0.024) and 4 hours (501.9 ± 207.4 ng/L; P = 0.008) postprandial were equivalent to baseline (517.3 ± 211.5 ng/L). Mean serum cTLI 2 hours (31.3 ± 14 μg/L; P < 0.001) and 4 hours (29.6 ± 13.1 μg/L; P = 0.027) postprandial were equivalent to baseline (31.1 ± 15 μg/L). Mean serum folate concentration 2 hours postprandial (15 ± 7.7 μg/L) was equivalent to baseline (13.7 ± 8.3 μg/L; P < 0.001). Equivalence could not be assessed for cPLI due to results below the lower limit of quantification. Feeding altered the clinical interpretation in 27% (cobalamin), 35% (folate), 20% (cTLI), and 12% (cPLI) of dogs. The clinical interpretation for a substantial number of samples changed after feeding, therefore withholding food before sample collection is prudent.

CD19-Specific CAR-T Cell Treatment of 115 Children and Young Adults with Acute B Lymphoblastic Leukemia: Long-term Follow-up.

Chemotherapy has been the primary treatment for patients with B-cell acute lymphoblastic leukemia (B-ALL). However, there are still patients who are not sensitive to chemotherapy, including those with refractory/relapse (R/R) disease and those experiencing minimal residual disease (MRD) re-emergence. Chimeric antigen receptor-T lymphocytes (CAR-T) therapy may provide a new treatment option for these patients. Our institution conducted a single-arm prospective clinical trial (ChiCTR-OPN-17013507) using CAR-T-19 to treat R/R B-ALL and MRD re-emergent patients. One hundred and fifteen patients, aged 1-25 years (median age, 8 years), were enrolled, including 67 R/R and 48 MRD re-emergent CD19-positive B-ALL patients. All patients achieved morphologic complete remission (CR), and within 1 month after infusion, 111 out of 115 (96.5%) patients achieved MRD-negative CR. With a median follow-up time of 48.4 months, the estimated 4-year leukemia-free survival (LFS) rate and overall survival (OS) rate were 68.7%±4.5% and 70.7%±4.3%, respectively. There were no significant differences in long-term efficacy observed among patients with different disease statuses before infusion (4-year OS: MRD re-emergence vs. R/R B-ALL, 70.6%±6.6% vs. 66.5%±6.1%, p=0.755; 4-year LFS: MRD re-emergence vs. R/R B-ALL, 67.3%±7.0% vs. 63.8%±6.2%, p=0.704). R/R B-ALL patients bridging to transplantation after CAR-T treatment had a superior OS and LFS compared to those who did not. However, for MRD re-emergent patients, there was no significant difference in OS and LFS, regardless of whether they underwent hematopoietic stem cell transplantation or not. CD19 CAR-T therapy effectively and safely cures both R/R B-ALL and MRD re-emergent patients.

Celiac plexus radiosurgery - an introduction to the method and a practical manual.

Celiac plexus radioablation (CPR) is an emerging non-invasive interventional treatment for severe pain associated with cancer-related damage to the celiac plexus. Due to its complex aetiology, such pain often responds poorly to conventional analgesics, and high doses of these medications can cause toxicity. Celiac plexus radiosurgery employs advanced radiotherapy techniques to administer a high single dose of 25 Gy to the anatomically defined celiac plexus, aiming to reduce pain intensity and enhance patients' quality of life. The safety and efficacy of CPR have been validated in a prospective single-arm clinical trial that included 125 patients. The positive outcomes of this trial led to the integration of CPR into pain management guidelines; however, the novel approach to radiotherapy planning might be initially challenging to grasp. In this article, we provide a brief overview of the method along with a comprehensive, Polish and English-language guide on how to perform CPR and manage patients, based on our clinical experience.

Mitoxantrone Hydrochloride Liposome Injection Combined with Carmustine, Etoposide, and Cytarabine As Conditioning of Autologous Hematopoietic Stem Cell Transplantation in NHL Patients：a Prospective Single-Arm Clinical Trial

Background：High-dose chemotherapy and autologous stem-cell transplantation (ASCT) is standard consolidation therapy for aggressive lymphoma.Choosing the most effective conditioning regimen prior to ASCT can lead to longer survival in these patients.Mitoxantrone liposome is an anthraquinone antibiotic anti-tumor drug. Previous studies have shown that mitoxantrone liposome monotherapy or combined with other drugs has achieved good efficacy for T-cell lymphoma, but there are no reports of its application in conditioning. Objective:This is a prospective single-arm clinical study to evaluate the efficacy and safety of mitoxantrone hydrochloride liposome injection combined with carmustine, etoposide, cytarabine (modified BEAM protocol) as conditioning of autologous hematopoietic stem cell transplantation for NHL patients (NCT05681403). Methods: Patients with non-Hodgkin lymphoma who planned to undergo ASCT were eligible to participate in the trial if they were 18 to 60 years of age.The patients received mitoxantrone hydrochloride liposome injection 24 mg/m 2,ivgtt,d-7, carmustine 300 mg/m 2,ivgtt,d-6, etoposide200 mg/m 2,ivgtt,d-5~ -2,cytarabine 200 mg/m 2 q12h,ivgtt,d-5~ -2 as conditioning regimen.The primary end point was the relapse rate within three years and the secondary end point was adverse events of modified BEAM protocol. Results：Twenty-five NHL patients (median age 39 years old,17 males and 8 females) were enrolled,including 40% DLBCL, 12% MCL, 4% primary mediastinal B-cell lymphoma,4%B lymphoblastic lymphoma,4%Marginal zone B-cell lymphoma,12% PTCL-NOS, 8% ALK +ALCL,8% NK/T lymphoma, 8% AITL,4% ALK -ALCL and 4% Sézary syndrome. 18 cases achieved complete remission before ASCT, while 7 cases received partial remission before ASCT. The median of neutrophil recovery time was 11 days(7-15) and the median of platelet recovery was 12days (7-60).Nausea,vomit,constipation,blue skin and cough were the most frequently reported conditioning related AEs (88%,16%,12%,12% and 8% of patients,respectively), and other AE included 1 case of hypoxemia, 1 case of hypotension, 1 case of palpitation, 1 case of rash. Except one patient experienced a grade 3 vomit ,the others were grade 1-2 and improved after symptomatic treatment. Nine patients experienced febrile neutropenia and 2 cases of sepsis, 4 cases of respiratory infection, and 3 cases of oral mucositis. All partial remission patients achieved complete remission post-HSCT and one of them relapsed 7 months after ASCT.The others were all in complete remission during follow-up. Conclusion:Mitoxantrone hydrochloride liposome injection combined with carmustine, etoposide, cytarabine (modified BEAM protocol) was a well-tolerated and effective conditioning regimen for NHL and the study is ongoing and updated results will be presented in the future.

Effect of Voice and Articulation Parameters of a Home-Based Serious Game for Speech Therapy in Children With Articulation Disorder: Prospective Single-Arm Clinical Trial.

Articulation disorder decreases the clarity of language and causes a decrease in children's learning and social ability. The demand for non-face-to-face treatment is increasing owing to the limited number of therapists and geographical or economic constraints. Non-face-to-face speech therapy programs using serious games have been proposed as an alternative. The aim of this study is to investigate the efficacy of home therapy on logopedic and phoniatric abilities in children with articulation disorder using the Smart Speech game interface. This study is a prospective single-arm clinical trial. Children with articulation disorders, whose Urimal Test of Articulation and Phonology (U-TAP) was -2 SDs or less and the Receptive and Expressive Vocabulary Test score was -1 SD or more, were enrolled. A preliminary evaluation (E0) was conducted to check whether the children had articulation disorders, and for the next 4 weeks, they lived their usual lifestyle without other treatments. Prior to the beginning of the training, a pre-evaluation (E1) was performed, and the children trained at home for ≥30 minutes per day, ≥5 times a week, over 4 weeks (a total of 20 sessions). The Smart Speech program comprised oral exercise training, breathing training, and speech training; the difficulty and type of the training were configured differently according to the participants' articulation error, exercise, and vocal ability. After the training, postevaluation (E2) was performed using the same method. Finally, 8 weeks later, postevaluation (E3) was performed as a follow-up. A voice evaluation included parameters such as maximum phonation time (MPT), fundamental frequency (F0), jitter, peak air pressure (relative average perturbation), pitch, intensity, and voice onset time. Articulation parameters included a percentage of correct consonants (PCC; U-TAP word-unit PCC, U-TAP sentence-unit PCC, and three-position articulation test) and alternate motion evaluation (diadochokinesis, DDK). Data obtained during each evaluation (E1-E2-E3) were compared. A total of 13 children with articulation disorders aged 4-10 years were enrolled in the study. In voice parameters, MPT, jitter, and pitch showed significant changes in repeated-measures ANOVA. However, only MPT showed significant changes during E1-E2 (P=.007) and E1-E3 (P=.004) in post hoc tests. Other voice parameters did not show significant changes. In articulation parameters, U-TAP, three-position articulation test (TA), and DDK showed significant changes in repeated-measures ANOVA. In post hoc tests, U-TAP (word, sentence) and TA showed significant changes during E1-E2 (P=.003, .04, and .01) and E1-E3 (P=.001, .03, and .003), and DDK showed significant changes during E1-E2 only (P=.03). Home-based serious games can be considered an alternative treatment method to improve language function. Clinical Research Information Service KCT0006448; https://cris.nih.go.kr/cris/search/detailSearch.do/20119.

Liquid Nitrogen Cryoballoon Ablation System for Paroxysmal Atrial Fibrillation: A Multicenter, Prospective, Single-Arm Clinical Trial

BackgroundCryoballoon ablation (CBA) has emerged as an effective treatment for atrial fibrillation (AF). ObjectivesThis study sought to assess the performance of a novel liquid nitrogen–driven CBA system and evaluate its safety and efficacy in the treatment of drug-resistant paroxysmal atrial fibrillation (PAF). MethodsThis was a prospective multicenter single-arm clinical trial with 10 participating tertiary hospitals enrolling 176 patients with PAF. All participants received liquid nitrogen–driven CBA developed by the Cryofocus Medtech Company. Scheduled follow-up was performed before discharge and 3 months, 6 months, and 12 months after CBA. The primary endpoints were defined as 1) treatment success (freedom from antiarrhythmic drugs and atrial tachycardia at 12 months after CBA); and 2) immediate success rate of pulmonary vein isolation. The safety endpoint was the incidence of device- and procedure-related adverse events (AEs) and all-cause mortality. ResultsA total of 172 participants were included, with an average age of 59.22 ± 9.25 years and 99 (57.56%) of them men. Immediate success rate was 97.67% (95% CI: 94.15%-99.36%) and 12-month treatment success rate was 82.56% (95% CI: 76.89%-88.23%), including a late recurrence rate of 13.61%. Incidences of device- and procedure-related AEs were 2.27% and 25.00%, respectively. Phrenic nerve palsy (PNP) occurred in 6 patients, of which 5 recovered during follow-up. Although the incidence of total severe AEs was 17.05%, including an all-cause mortality of 0.57%, only 1 case of permanent PNP was related to the CBA procedure. ConclusionsThis premarketing prospective multicenter single-arm clinical trial demonstrated that the liquid nitrogen cryoablation system is safe and effective in the treatment of PAF.

Initial experience of laparoendoscopic single-site radical prostatectomy with a novel purpose-built robotic system

ObjectiveThis prospective single-arm clinical trial aimed to evaluated the feasibility and safety of the application of the SHURUI system (Beijing Surgerii Technology Co., Ltd., Beijing, China), a novel purpose-built robotic system, in single-port robotic radical prostatectomy. MethodsSixteen patients diagnosed with prostate cancer were prospectively enrolled in and underwent robotic radical prostatectomy from October 2021 to August 2022 by the SHURUI single-port robotic surgical system. The demographic and baseline data, surgical, oncological, and functional outcomes as well as follow-up data were recorded. ResultsThe mean operative time was 226.3 (standard deviation [SD] 52.0) min, and the mean console time was 183.4 (SD 48.3) min, with the mean estimated blood loss of 116.3 (SD 90.0) mL. The mean length of postoperative hospital stay was 4.50 (SD 0.97) days. Two patients had postoperative complications (Clavien-Dindo Grade II), and both patients improved after conservative treatment. All patients’ postoperative prostate-specific antigen levels decreased to below 0.2 ng/mL 1 month after discharge. The mean prostate-specific antigen level further decreased to a mean of 0.0219 (SD 0.0641) ng/mL 6 months after surgery. Thirty days postoperatively, 12 out of 16 patients reported using no more than one urinary pad per day, and all patients reported satisfactory urinary control without the need for pads 6 months after surgery. ConclusionThe SHURUI system is safe and feasible in performing radical prostatectomy via both transperitoneal and extraperitoneal approaches. Tumor control and urinary continence were satisfying for patients enrolled in. The next phase involves conducting a large-scale, multicenter randomized controlled trial to thoroughly assess the effectiveness and safety of the new technology in a broader population.

Evaluation of Effects of Bimaxillary Anchored Fixed Functional Appliance on Temporomandibular Joint and Maxillomandibular Complex in Late Adolescents: An MRI Study

Objective To evaluate and assess changes in temporomandibular joint (TMJ), dental, skeletal and soft tissue changes following bimaxillary anchored fixed functional appliance (FFA) treatment of skeletal Class II malocclusion using Magnetic Resonance Imaging. Methods The prospective single-arm clinical trial included 15 patients (8 males, 7 females; mean age 15.71 + 1.81years) with Class II Division 1 malocclusion treated with bimaxillary anchored Forsus FRD. Four miniplates were placed bilaterally in maxilla and mandible. Then Forsus FRD L pin module was attached to miniplates without levelling of the arches. Pre-treatment (T1) and post-functional (T2) lateral cephalograms and MRI of TMJ were recorded. A total of 7 parameters were used to assess TMJ in all the 3 planes using MRI. Student’s t-test was carried out to compare pre- and post-treatment-induced changes. Results The mandible significantly moved forward (SNB, 3.71 + 0.91°; SND, 3.21 + 1.25°; Pg-OLp, 2.61 + 0.66 mm, p &lt; 0.001) and there was distalizing effect on maxilla (SNA, –0.79 + 0.89°; A-OLp, –0.57 + 0.47mm, &amp;lt;0.001). Mean overjet correction of 4.43mm was achieved, of which 71.8% were skeletal changes. 65% of skeletal changes contributed to molar relationship correction. The forward positioning of mandible seems to be because of condylar and glenoid fossa remodelling, with condyle moving in anterior position within glenoid fossa (3.28 + 2.29) and articular disc moved posteriorly relative to condylar head (2.27 + 1.62°). Conclusion Significant skeletal changes and TMJ remodelling were observed with bimaxillary anchored FFA in correcting skeletal Class II malocclusion.