A multicenter, randomized, active-controlled, clinical trial study to evaluate the efficacy and safety of navigation guided balloon Eustachian tuboplasty

To assess the safety and efficacy of navigation-guided balloon Eustachian tuboplasty (BET) compared to medical management (MM) alone in patients with chronic Eustachian tube dilatory dysfunction (ETD). This is a prospective, multicenter, 1:1 parallel-group, randomized controlled trial (RCT). It aims to assess the efficacy of navigation-guided BET compared to MM alone in patients with chronic ETD. The primary outcome measure was an improvement in the Eustachian tube dysfunction questionnaire (ETDQ)-7 score at the 6-week follow-up compared with baseline. Secondary outcome measures included changes in the signs and symptoms during the follow-up, changes in the score for each subcategory of ETDQ-7, type of tympanometry, pure tone audiometry, and the availability of a positive modified Valsalva maneuver. Navigation-guided BET was safely performed in all patients. A total of 38 ears of 31 patients (19 ears of 16 patients in the BET group and 19 ears of 15 patients in the control group) completed the planned treatment and 6 weeks of follow-up. More patients in the BET group (1.99 ± 0.85) had less symptomatic dysfunction than in the control group (3.40 ± 1.29) at 6 weeks post-procedure (P = 0.001). More patients experienced tympanogram improvement in the BET group at 6 weeks compared to the control group (36.5% vs. 15.8%) with a positive modified Valsalva maneuver (36.6% vs. 15.8%, P = 0.014). Additionally, air–bone gap change was significantly decreased in the BET group compared to the control group at the 6-week follow-up visit (P = 0.037). This prospective, multicenter, RCT study suggests that navigation-guided BET is a safe and superior treatment option compared to MM alone in patients with chronic ETD.

A Systematic Review: Topical Sucralfate for Burn Wound

BACKGROUND: Topical sucralfate has been used for burn and non-burn skin and mucosal lesion with remarkable results. The healing rate of mucosa is faster than skin lesion. AIM: A current systematic review was conducted to objectively evaluate wound healing benefits of topical sucralfate for burn wound and to show on which degree of burn wound it works compare with another topical agents of burn wound therapy. METHODS: Databases were searched for relevant studies: Google Scholar, PUBMED, and ProQuest. Data sources were searched using MeSH terms: “topical sucralfate” and “burn wound” for all publications up to December 2018. All English papers were included. Only studies performed in humans were included in this study. A total of 2437 publications were found, of which 3 studies met the inclusion criteria and were relevant to be used in this systematic review. The primary outcome was burn wound healing. DATA EXTRACTION: Data from retrieved studies were reviewed and tabulated according to year of publication, study design, human or animal studies, characteristics of the population, and outcomes. DATA SYNTHESIS: A total of 2 randomized controlled trials (RCTs) and 1 observational comparative study were found. All trials are on second degree burn wound patients. Jadad score was used to assess the methodological quality of the RCTs. One RCT and one comparative study demonstrated favorable outcomes with the use of topical sucralfate. There is one publication with no significant differences. CONCLUSIONS: This systematic review shows a noticeably beneficial effect of topical sucralfate for burn wound. It is better than other topical agent in wound healing rate, decreased infection rate and enhancement of epithelialization also granulation with no local or systemic adverse reactions. However, multicenter RCT with larger sample size are needed to make recommendation for burn wound treatment.

RTID-01. PHASE III MULTICENTER RCT OF POST-SURGICAL STEREOTACTIC RADIOTHERAPY VERSUS SURGICALLY TARGETED RADIATION THERAPY FOR THE TREATMENT OF LARGE NEWLY DIAGNOSED BRAIN METASTASES – TRIAL IN PROGRESS

BACKGROUND Resection (R) followed by single- or multi-fraction stereotactic radiosurgery (SRT) of brain metastases (BMs) lowers resection bed recurrence compared to R alone. Nevertheless, for larger BMs, 12-month recurrence rates after R+SRT can exceed 20–30%. Aiming to improve outcomes, a permanently implanted collagen tile brachytherapy device (GammaTile, GT Medical Technologies, Tempe, AZ) utilizing Cs-131 seeds embedded within a bioresorbable collagen tile was developed and is described as Surgically Targeted Radiation Therapy (STaRT) to distinguish it from external beam radiotherapy. STaRT allows rapid, intense localized radiation dose delivery directly to the tumor bed with predictable dosimetry immediately at the time of R, which may confer reduced risk for radiation necrosis compared to other therapies. It is hypothesized that R+ STaRT will increase surgical bed recurrence-free survival (SB-RFS), while reducing impact on functional and neurocognitive status compared to R+SRT. METHODS Multicenter, randomized, comparison trial of patients with resectable, previously untreated “index” BMs (≥ 2.5–5cm), and 0–3 other tumors, will be preoperatively randomized 1:1 to undergo R+SRT or R+STaRT to the index lesion; unresected tumors in both groups will receive SRT. Planned sample size is 180 from 14 sites. Enrollment opened 03/31/2021. First subject was enrolled 04/07/2021. Primary endpoint is SB-RFS. Secondary endpoints include overall survival, quality of life, neurocognition, functional status, imaging findings and adverse events. Follow-up will be through 24 months. This will be the first randomized trial comparing R+SRT versus R+STaRT delivered by Cs-131 sources in permanently implanted resorbable collagen tile carriers. Primary and secondary outcome measures captured will elucidate the potential risks and benefits of these two RT delivery methods in the setting of newly diagnosed BMs. We will present trial accrual progress, available data, experience and lessons learned.

Adjunctive ketamine for sedation in critically ill mechanically ventilated patients: an active-controlled, pilot, feasibility clinical trial

Objective Ketamine has been shown to decrease sedative requirements in intensive care unit (ICU). Randomized trials are limited on patient-centered outcomes. We designed this pilot trial to evaluate the feasibility of a large randomized controlled trial (RCT) testing the effect of ketamine as an adjunct analgosedative compared with standard of care alone as a control group (CG) in critically ill patients with mechanical ventilation (MV). We also provided preliminary evidence on clinically relevant outcomes to plan a larger trial. Material and methods Pilot, active-controlled, open-label RCT was conducted at medical, surgical, and transplant ICUs at a large tertiary and quaternary care medical institution (King Faisal Specialist Hospital and Research Center, Saudi Arabia). The study included adult patients who were intubated within 24 h, expected to require MV for the next calendar day, and had institutional pain and sedation protocol initiated. Patients were randomized in a 1:1 ratio to adjunct ketamine infusion 1–2 μg/kg/min for 48 h or CG alone. Results Of 437 patients screened from September 2019 through November 2020, 83 (18.9%) patients were included (43 in CG and 40 in ketamine) and 352 (80.5%) were excluded. Average enrollment rate was 3–4 patients/month. Consent and protocol adherence rates were adequate (89.24% and 76%, respectively). Demographics were balanced between groups. Median MV duration was 7 (interquartile range [IQR] 3–9.25 days) in ketamine and 5 (IQR 2–8 days) in CG. Median VFDs was 19 (IQR 0–24.75 days) in ketamine and 19 (IQR 0–24 days) in the CG (p = 0.70). More patients attained goal Richmond Agitation–Sedation Scale at 24 and 48 h in ketamine (67.5% and 73.5%, respectively) compared with CG (52.4% and 66.7%, respectively). Sedatives and vasopressors cumulative use, and hemodynamic changes were similar. ICU length-of-stay was 12.5 (IQR 6–21.2 days) in ketamine, compared with 12 (IQR 5.5–23 days) in CG. No serious adverse events were observed in either group. Conclusions Ketamine as an adjunct analgosedative agent appeared to be feasible and safe with no negative impact on outcomes, including hemodynamics. This pilot RCT identified areas of improvement in study protocol before conducting a large, adequately powered, multicenter RCT which is likely justified to investigate ketamine association with patient-centered outcomes further. Trial registration ClinicalTrials.gov: NCT04075006. Registered on 30 August 2019. Current controlled trials: ISRCTN14730035. Registered on 3 February 2020

External validity in a multicenter randomized clinical trial of proximal humeral fractures: the DelPhi trial

Background Randomized controlled trials (RCT) are regarded as the gold standard for effect evaluation in clinical interventions. However, RCTs may not produce relevant results to all patient groups. We aimed to assess the external validity of a multicenter RCT (DelPhi trial). Methods The DelPhi RCT investigated whether elderly patients with displaced proximal humeral fractures (PHFs) receiving reversed total shoulder prosthetic replacement (RTSA) gained better functional outcomes compared to open reduction and internal fixation (ORIF) using an proximal humerus locking plate (PHILOS). Eligible patients were between 65 and 85 years old with severely displaced 11-B2 or 11-C2 fractures (AO/OTA-classification, 2007). We compared baseline and follow-up data of patients for two of the seven hospitals that were included in the DelPhi trial (n = 54) with non-included patients (n = 69). Comparisons were made based on reviewing medical records regarding demographic, health and fracture parameters. Results Forty-four percent of the eligible patients were included in the DelPhi trial. Comparing included and non-included patients indicated higher incidences of serious heart disease (P = 0.044) and a tendency toward higher tobacco intake (P = 0.067) in non-included patients. Furthermore, non-included patients were older (P = 0.040) and had higher ASA classification (P < 0.001) and were in more need for resident aid (in-home assistance) (P = 0.022) than included patients. The cause of PHF was more frequently related to fall indoors in non-included vs. included patients (P = 0.018) and non-included patients were more prone to other concomitant fractures (P = 0.004). Having concomitant fractures was associated with osteoporosis (P = 0.014). We observed no significant differences in rates of complications or deaths between included and non-included patients within 3 months after treatment. In descending order, non-included patients were treated conservatively, with PHILOS, RTSA, anatomic hemi-prothesis or an alternative type of ORIF. RTSA was the preferred treatment choice for C2-type fractures (P < 0.001). Conclusions Results from the DelPhi RCT may not directly apply to older PHFs patients with lower health status or concomitant fractures. Level of evidence Level 4.

T2 One Year Follow up Results of the DETECT Enzymatic Debridement Multicenter RCT

Introduction Bromelain Based Debridement (BBD) of deep thermal burns has been approved for use in Europe, Argentina, Russia, South Korea, Peru, and Israel, and is an investigational product in the United States. Topline results of acute stage endpoints of the DETECT Phase 3 multicenter RCT have been reported previously. The aim of this abstract is to present the 12-month follow-up of predefined endpoints of scar quality, function and quality of life (QoL). Methods One-hundred and seventy-five adult patients with deep burns were randomized in a Phase 3 clinical trial to one of 3 treatment arms – BBD, Standard of Care (SOC), or Gel vehicle (placebo control) in a 3:3:1 ratio (75 BBD, 75 SOC, and 25 Gel). Scar quality (cosmesis) and function data were analyzed for longer-term data collected at 3, 6, 12 (and 24 - data not yet final) months. Cosmesis and function were measured using Modified Vancouver Scar Scale (MVSS) and Patient and Observer Scar Assessment Scale (POSAS) to demonstrate that BBD treatment was non-inferior to SOC treatment, as measured at 12 months from wound closure date, evaluated by assessors blinded to the treatment arm. QoL was measured by the EQ-5D (EuroQol 5 Dimensions), VAS (Visual Analog Scale) and BSHS-B (Burn Specific Health Scale – Brief) scales. Missing values were imputed in the analysis using multiple imputation, with best case-worst case imputations as sensitivity analyses. Results The 12-month follow-up mean MVSS scores were lower (better) for the BBD group (3.70±2.10) than for the SOC (5.08±3.11) and Gel groups (5.63±2.99). A regression analysis showed that BBD has a 1.36 MVSS point advantage over SOC after adjustment for all other variables in the model (p-value = 0.0027). The 95% CI for this treatment effect was -2.24 to -0.48, excluding the pre-defined non-inferiority margin of +1.9 points, thus establishing non-inferiority of BBD treatment compared with SOC. Note that the interval also excludes 0, indicating superiority of BBD over SOC. The 3- and 6-month follow-up MVSS scores are also lower for the BBD group (5.51±3.09, 4.43±2.59) than for the SOC (6.63±3.44, 5.43±3.75) and Gel (7.56±2.67, 8.89±3.37) groups. POSAS total scores followed similar trends to MVSS scores but did not reach statistical significance at 12 months. QOL was generally similar among the treatment arms. Conclusions In addition to the significant acute stage results presented previously, the long-term results of this RCT further demonstrate the safety of BBD treatment, including significantly better 12-month follow-up MVSS scores.

Use of Intra-Aortic Balloon Pump During Coronary Artery Bypass Graft Surgery. Current Questions and Few Answers.

The intra-aortic balloon pump (IABP) is used to prevent complications after coronary artery bypass grafting (CABG) surgery; although some results are controversial nowadays even contradictory. A new article on this field is published in this edition and shows that the risk factors for in-hospital mortality are the preoperative plasma creatinine level and cardiopulmonary bypass time in 177 patients. About the prophylactic use of the IABP regarding mortality the results reflected so far in meta-analyses have been highly contradictory between them, and the risk factors associated with it have been several and different. This lack of evidence has resulted in the continued variation of IABP use in these procedures. A large, multicenter RCT is certainly required to take the next step towards more definitive evidence, either for or against, the use of IABP in high-risk CABG. Until then, the unanswered questions regarding this topic will remain.

The Landmark Series: Minimally Invasive Pancreatic Resection

Background Pancreatic resections are among the most technically demanding procedures, including a high risk of potentially life-threatening complications and outcomes strongly correlated to hospital volume and individual surgeon experience. Minimally invasive pancreatic resections (MIPRs) have become a part of standard surgical practice worldwide over the last decade; however, in comparison with other surgical procedures, the implementation of minimally invasive approaches into clinical practice has been rather slow. Objective The aim of this study was to highlight and summarize the available randomized controlled trials (RCTs) evaluating the role of minimally invasive approaches in pancreatic surgery. Methods A WHO trial registry and Pubmed database literature search was performed to identify all RCTs comparing MIPRs (robot-assisted and/or laparoscopic distal pancreatectomy [DP] or pancreatoduodenectomy [PD]) with open pancreatic resections (OPRs). Results Overall, five RCTs on MIPR versus OPR have been published and seven RCTs are currently recruiting. For DP, the results of two RCTs were in favor of minimally invasive distal pancreatectomy (MIDP) in terms of shorter hospital stay and less intraoperative blood loss, with comparable morbidity and mortality. Regarding PD, two RCTs showed similar advantages for MIPD. However, concerns were raised after the early termination of the third multicenter RCT on MIPD versus open PD due to higher complication-related mortality in the laparoscopic group and no clear other demonstrable advantages. No RCTs on robot-assisted pancreatic procedures are available as yet. Conclusion At the current level of evidence, MIDP is thought to be safe and feasible, although oncological safety should be further evaluated. Based on the results of the RCTs conducted for PD, MIPD cannot be proclaimed as the superior alternative to open PD, although promising outcomes have been demonstrated by experienced centers. Future studies should provide answers to the role of robotic approaches in pancreatic surgery and aim to identity the subgroups of patients or indications with the greatest benefit of MIPRs.

Functional Disability in Adolescents with Chronic Pain: Comparing an Interdisciplinary Exposure Program to Usual Care

(1) Background: Chronic musculoskeletal pain (CMP) in adolescents can negatively affect physical, psychological, and social functioning, resulting in functional disability. This randomized controlled trial (RCT) aimed to evaluate the effectiveness of an outpatient rehabilitation program based on graded exposure in vivo (EP) compared with care as usual (CAU: interdisciplinary outpatient rehabilitation care). Both EP and CAU aim to improve functional ability in adolescents with CMP. (2) Methods: Pragmatic multicenter RCT with 12-month follow-up. Adolescents (12–21 years) with CMP were invited to participate. Primary outcome: functional disability; secondary outcomes: perceived harmfulness; pain catastrophizing; pain intensity. Data analysis: intention-to-treat linear mixed model. (3) Results: Sixty adolescents (mean 16 years) were randomized; data for 53 were analyzed. Adolescents in EP showed relevant and significant decreases in functional disability (estimated mean difference at least −8.81, p ≤ 0.01) compared with CAU at all times. Significant differences in favor of EP were found for perceived harmfulness at all times (p ≤ 0.002), for pain catastrophizing at 2 months (p = 0.039) and for pain intensity at 4 and 10 months (p ≤ 0.028). (4) Conclusion: EP leads to a significant and clinically relevant decrease in functional disability compared with usual care.