Prospective Randomized Trial Research Articles

Effectiveness of methylene blue as a local anesthetic and analgesic in perianal operations: A prospective double-blind randomized control trial

BackgroundPerianal operations often result in significant postoperative pain, which negatively affects patient comfort and recovery. The search for effective pain relief options has led to the investigation of methylene blue, a biological stain with potential analgesic properties. AimsThis study aimed to evaluate the analgesic and anaesthetic effects of a mixture of methylene blue and lidocaine compared to plain lidocaine in the management of postoperative pain after perianal operations. MethodsA prospective, double-blinded, randomized controlled trial was conducted at a single center between 2015 and 2023. A total of 727 adult patients undergoing perianal surgical operations were randomly assigned to two groups: the experimental group received a solution of methylene blue and lidocaine, while the control group received plain lidocaine. Pain levels were assessed using the Visual Analog Scale (VAS), and follow-up visits and phone calls were conducted. The analysis included 727 participants who underwent operations for perianal abscess, fistula, fissure, and haemorrhoid. The participants were divided into the experimental group (N=329) and the control group (N=398). The data were analyzed using SPSS version 28, applying descriptive and inferential statistical methods. ResultsThe study included a total of 727 patients, with a mean age of 47 years (ranging from 18 to 90 years). Among the patients, 56.5% were males and 43.5% were females. The two groups showed significant differences in terms of postoperative analgesic use and pain-free days (p<0.001). Specifically, the methylene blue group had lower Visual Analog Scale (VAS) scores compared to the control group (p<0.05, p<0.001), respectively. No significant differences in immediate complications were observed between the two groups. ConclusionMethylene blue is an effective intervention for reducing postoperative pain after perianal operations, potentially decreasing the need for additional pain medication. The findings of this study suggest that methylene blue has a promising role in pain management without an increase in complications.

Flat dose intravenous immunoglobulin (IVIG) for primary infection prophylaxis after CAR-T for B-cell non-Hodgkin lymphoma (B-NHL).

e19004 Background: Prolonged hypogammaglobulinemia is a common side effect of CD19 chimeric antigen receptor (CAR) T-cell therapy for B-NHL. Average infection rates 1 year (yr) post CAR-T are 44-53% (Kampouri, Tran Infect Dis 2023). Prophylactic IVIG is typically dosed by weight; however, optimal dosing strategy remains unknown. We explored the efficacy of reduced flat IVIG dose on infection rates and non-relapse mortality (NRM) post CAR-T. Methods: B-NHL pts who received commercial CD19 CAR-T therapy from Nov 2017 to Mar 2023 at Vanderbilt Medical Center were included. All pts were on trimethoprim-sulfamethoxazole and valacyclovir for prophylaxis. IVIG at a flat dose of 10 grams was given for IgG &lt; 400 mg/dL. Relevant clinical variables were collected from day 30 to 1 yr. Infections were defined as mild (treated outpatient), moderate (required admission), or severe (required intensive care unit) and by CTCAE v5 criteria. Severe neutropenia was defined as ANC&lt;500 and severe lymphopenia was ALC&lt;500. NRM was defined by death without progression or relapse. Estimated cost of therapy was $140/gram of IVIG based on previously published data. Results: A total of 43 pts (35 large cell lymphoma, 7 mantle cell lymphoma, and 1 follicular lymphoma) with median follow up of 445 days (range 134-2141) were included. Axicabtagene ciloleucel was given to 34 pts (79%), tisagenlecleucel to 2 pts (5%), and brexucabtagene autoleucel to 7 pts (16%). Median age was 58 (range 22-81). Median number of pre CAR-T therapies was 3 (range 1-7). There were 52 total infections with median time to first infection of 165 days (range 31-365). Of all infections, 21 (40%) were viral, 29 (56%) bacterial, and 2 (4%) fungal. There were 31 (60%) mild infections, 19 (36%) moderate, and 2 (4%) severe. Multiple G≥3 infections occurred in 14 pts (33%). At first infection, 4 pts (10%) had severeneutropenia and 13 pts (31%) had severelymphopenia. IVIG was given to 27 pts (63%). Median IgG at D30 was 438 mg/dL (range 143–1099) and 414 mg/dL (range 133–842) at D60. Prolonged IgG≤400 at 6 months occurred in 15 pts (35%). Median IVIG cost using flat dosing was $2800 (range $0-12,600) compared to a median cost of $8,075 (range $0-76,642) if weight-based dosing was utilized. NRM was 9% (4 pts). Of those pts, only 1 had a G≥3 infection during the first-year post CAR-T. Conclusions: We demonstrate comparable infection rates 1 yr post CD19 CAR-T and low NRM with the use of 10g flat IVIG dosing for consecutively treated pts. In addition, only 1 of 4 pts with NRM had severe infection within 1 yr. Notably, 35% of pts had persistent hypogammaglobulinemia at 6 mo and use of a flat dosing schedule provided substantial cost reduction. These findings should be validated in a prospective randomized trial.

Effect of fluorescent imaging using indocyanine green on surgical morbidity during minimally invasive surgery for esophageal cancer (IndoCinMIE).

e16115 Background: Anastomotic leak following Esophagectomy is associated with significant morbidity and mortality. A major determinant of anastomotic success is good vascular perfusion of the gastric conduit. Indocyanine Green fluorescence angiography (ICG-FA) provides real-time intraoperative evaluation of the vascular perfusion of the gastric conduit but its efficacy in reducing in anastomotic failure has not been proven so far in a prospective randomized trial. The aim of this study was to determine the impact of ICG during minimally invasive esophagectomy (MIE) in reducing the rates of anastomotic failure. Methods: It is a single centre Phase-II RCT with an allocation ratio of 1:1 with accrual beginning from September 2023 with planned sample size of 15 patients in each arm. All consenting patients above 18 years with histologically proven esophageal cancer (treatment naïve/neoadjuvant therapy) fit to undergo a major surgery were included. The patients were randomized into the ICG arm and Non-ICG arm. The anastomotic leak rates (studied at POD 7 with an oral contrast study and POD 30), in both arms was the primary endpoint. The utility of ICG in deciding the site of esophago-gastric anastomosis for the patients in the ICG arm was compared to the patients in the control arm where site of anastomosis was decided based on the surgeon’s subjective assessment of the most appropriate site for the same. The role of ICG-FA in bringing about a change of anastomotic site against the surgeon’s subjective assessment was noted in the test arm as one of the secondary end points. A near-infrared camera system was be used for detecting the ICG fluorescence. Evaluation with fluorescence was performed in real-time. Approximately 20 seconds after IV ICG injection, blood flow was confirmed by ICG-FA as it passed through the right gastroepiploic vessels. If vascular perfusion via ICG-FA was well visualized within 60 s, it was defined as a good perfusion zone, while no vascular perfusion or perfusion times &gt; 60 s would indicate a poor perfusion zone. The anastomotic perfusion result using ICG-FA was evaluated by the surgical team and the anastomosis was performed within the good perfusion zone. Results: A total of 30 patients were accrued for the trial, 15 in each arm. Overall, 3 out of 30 patients had an anastomotic leak (10%), all of which were from the Non-ICG arm (20%). There were no leaks noted in the ICG arm. The rate of anastomotic leak within the non-ICG arm was significantly higher than the ICG arm (p = 0.0726). Within the ICG arm, the use of ICG-FA led to a revision in the site of anastomosis in 6 of the 15 patients (40%). Conclusions: The use of ICG-FA has the potential to reduce anastomotic leaks and improve outcomes in MIE while also allowing for enhanced discretion in choosing the optimal site of anastomosis. Its feasibility concludes phase II of the trial and will begin accrual for Phase III. Clinical trial information: CTRI/2023/09/058118 .

The clinical utility of plasma cell-free DNA (cfDNA) in NET-02: Randomised, phase II trial of liposomal irinotecan (nal-IRI)/5-fluorouracil (5-FU)/folinic acid or docetaxel as second-line (2L) therapy in patients (pts) with progressive poorly differentiated extra-pulmonary neuroendocrine carcinoma (PD-EP-NEC).

4130 Background: In NET-02, nal-IRI/5-FU, but not docetaxel, met the primary endpoint of 6-month (mo) progression-free survival (PFS) rate in pts with progressive PD-EP-NEC (1). The prognostic potential of cfDNA in progressive PD-EP-NEC has not been explored in a prospective randomised trial. Methods: NET-02 was a multi-centre, randomised (1:1), phase II trial of IV nal-IRI/5-FU/folinic acid, Q14 days (ARM A), or IV docetaxel, Q21 days (ARM B), as 2L therapy in pts with progressive PD-EP-NEC. Plasma samples were taken at baseline (T0), following 6 weeks of treatment (T1) and at progression (T2). Samples were analysed using a multi-omic next-generation sequencing (NGS) approach (T7-MBD-seq) (measures genome-wide methylation and low pass whole genome copy number alterations (CNA)). The tumour fraction (TF) of cfDNA was determined using ichorCNA and correlated with clinical outcomes using Cox proportional hazards model and Logistic regression. Results: Of 56 pts evaluable for efficacy, there were 54 (96%) T0 samples (48 passed quality control), 31 (55%) at T1 and 20 (36%) at T2. At T0, 36/48 (75%) samples had detectable TF by copy number (using 3% TF cut-off). For the entire cohort, T0 TF was negatively prognostic for overall survival (OS) (Hazard Ratio (HR) 1.17, 95% Confidence interval (CI) 1.00-1.37, P=.044), but not for 6 mo PFS rate (Odds ratio (OR) 1.25, 95% CI 0.91-1.73, P=.17), response rate (RR) (OR 1.11, 95% CI 0.67-1.76, P=.65) or PFS (HR 1.04, 95%CI 0.91-1.20, P=.53). In the entire cohort, median OS split by TF (N=16 each) was 10.2 mo (95% CI 4.1-not available (NA)) for low (TF≤8.6%), 6.9 mo (95% CI 3.4-14.8) for medium (8.6&lt;TF≤24.3%) and 3.7 mo (95% CI 2.8-NA) for high (TF&gt;24.3%). T0 TF was also negatively prognostic for 6 mo PFS rate and OS in ARM A (P=.02, P=.03), but not ARM B (P=.61, P=.48), but was not prognostic for RR or PFS (Table). TF correlated with the presence of liver metastases (Wilcoxon Rank Sum P=.009), but not with ECOG PS (P=.14), sex (P=.10), Ki-67 (P=.39) or age (Spearman rank correlation P=.45). Longitudinal copy number and methylation cfDNA analysis is on-going. Conclusions: These results suggest that it may be possible to stratify prognosis based on amount of baseline TF in patients with progressive PD-EP-NEC, and may also identify patients who would benefit most from the nal-IRI combination. 1. McNamara 2023, EClin Med. Clinical trial information: 03837977. [Table: see text]

SNF-CLIMEDIN: A prospective randomized trial of digital intervention in patients with advanced NSCLC—A HeCOG study.

1520 Background: The purpose of this trial is to investigate the effectiveness of online digital intervention to NSCLC patients in terms of quality of life (QoL), cost and the interrelation with clinical and molecular characteristics. Methods: This prospective randomized trial recruited 200 advanced NSCLC patients (3/22-10/23). All had NGS tissue analysis for 161 genes and received standard treatment (predominantly immuno-chemotherapy). Through the CareAcross online platform they received information about their disease and treatment, and periodically reported any of 22 preplanned adverse events (AEs). Patients were randomized 1:1 in the intervention (A) and control (B) arm; patients in arm A received digitally, additionally, evidence-based guidance for the reported AEs. The study was designed to assess QoL improvement (measured per patient as reduction of the number of AEs reported at last contact, compared to those previously reported). EQ5D-5L scores were collected. Patient-case level hospitalizations data were collected and costs were estimated based on reimbursed costs as defined by the Ministry of Health. Results were correlated with patients’ clinical and molecular characteristics. Results: Clinical and molecular characteristics will be presented during ASCO Congress. For all patients, responses were: CR: 2%, PR: 35.5%, SD: 35%, PD: 10.5%. Median PFS was 7.0 months (95%CI: 5-8), 1-year 18% (38%-55%). Median OS: 12 months (11-14), 1-year 47% (38%-55%). No difference was found between the two arms in any of the above, nor in OS in relation to clinical and molecular characteristics. The most common AEs that patients reported were fatigue, cough, anorexia, nausea. More patients submitted AE reports online than their clinicians (89% vs 68% of patients, p&lt;0.01); more AEs were reported per submission, compared to their clinicians. Patients in arm Α reported marginally higher improvement compared to B (77.2% vs 75.7%); 15 of 22 AEs were associated with higher (14) or same (1) improvement in arm A vs B (not statistically significant); of the most common: fatigue (61.3% vs 48.6%), anorexia (86.5% vs 70.2%; p&lt;0.05) and nausea (93.0% vs 87.2%). Baseline EQ5D was similar in both arms; comparing post-treatment (6th cycle) results shows higher improvement in all 5 dimensions in arm A vs B, especially in Anxiety/Depression (final values: 1.9 vs 2.2). The mean AE-related costs in Euros in arm A vs B were: hospitalization: 455.4 (95%CI: 91.9-941.5) vs 779.5 (346.6-1328.5) (p&lt;0.001); diagnostics: 20.3 (0.5-50.8) vs 73.3 (1.3-186.1) (p&lt;0.001). Follow up is ongoing. Conclusions: Digital oncology is feasible, cost-effective by reducing hospitalizations, improves certain AEs and tends to improve QoL of NSCLC patients regardless of clinical and molecular status. Patients report digitally more informative AEs for clinical and research analysis. Online platforms can complement the Oncology team. Clinical trial information: NCT05372081 .

A phase II study of lurbinectedin with or without avelumab in small cell carcinoma of the bladder (LASER).

TPS4629 Background: Small cell carcinoma of the bladder (SCCB) is a rare, aggressive malignancy accounting for &lt;1% of all bladder malignancies. Given its rarity, few prospective randomized trials have been completed in SCCB. Most therapeutic evidence comes from retrospective case series and due to its histologic similarity to small cell lung cancer (SCLC), current guidelines recommend bladder cancers with any component of small cell histology be treated similarly to SCLC. Lurbinectedin is a novel alkylating agent which recently received accelerated approval from the FDA as a second line treatment for SCLC after demonstrating an overall response rate (ORR) of 35.2% and median duration of response (DoR) of 5.3 months (Trigo et al., Lancet Oncol, 2020). Avelumab is an anti-PD-L1 antibody FDA approved as maintenance treatment for patients with locally advanced or metastatic urothelial cancer (UC) without progression on frontline chemotherapy. Case reports have demonstrated that second line options in SCLC, including immunotherapy, appear to have some efficacy in SCCB. The purpose of this study is to assess the efficacy of lurbinectedin, either alone or in combination with avelumab, in participants with SCCB or other high grade neuroendocrine tumors (HGNETs) of the urinary tract. Methods: LASER (NCT06228066) is a phase II, multisite, open label, nonrandomized study with two cohorts. Eligible patients must have pathologically confirmed SCCB or other HGNETs of the urinary tract. Patients with mixed histologies, with any component of neuroendocrine tumor, are eligible. Patients must have received or be ineligible/refused frontline platinum/etoposide therapy. Participants in Cohort 1 must have received prior immune checkpoint inhibitors (ICIs) or be ineligible for treatment with ICI. These patients will receive lurbinectedin 3.2mg/m2 IV every 21 days. Participants in Cohort 2 must be ICI naïve but eligible to receive them. These patients will receive lurbinectedin 3.2mg/m2 IV and avelumab 800mg IV every 21 days. The primary endpoint for both cohorts is ORR, with key secondary endpoints including clinical benefit rate, PFS, OS, and DoR. The study will be conducted using a Simon minimax two stage design to rule out an ORR of 5% in favor of an ORR of 25% or greater in each cohort. If 1 of the first 12 patients has a response accrual will continue up to 16 evaluable patients per cohort. Accrual ceiling will be set at 35 patients. Exploratory objectives include analyzing peripheral immune subsets, DNA and RNA sequencing of tumors, and measurement of ctDNA and CTCs. Clinical trial information: NCT06228066 .

Chemotherapy and liver transplantation versus chemotherapy alone in patients with definitively unresectable colorectal liver metastases: A prospective multicentric randomized trial (TRANSMET).

3500 Background: Despite the increasing efficacy of chemotherapy (CT) and advances in surgical techniques for initially unresectable colorectal liver metastases (uCLM), secondary resection rate remains low. For definitively uCLM, CT remains the standard of care but liver transplantation (LT) has shown promising results. This first randomized trial aimed to assess the efficacy of CT combined to LT for uCLM. Methods: Patients with definitively uCLM from resected BRAF non mutated colorectal cancer, having responded to CT (≥ 3 months and ≤ 3 lines) in the absence of extrahepatic disease, were validated by an independent experts’ committee and randomly assigned (1:1) to receive CT and LT (CT+LT arm) or CT alone (CT arm). The primary endpoint was 5-year overall survival (OS). Secondary endpoints were progression free survival (PFS) and patterns of recurrence. In order to detect a 40% difference in OS from 10% (CT) to 50% (CT+LT) (2-sided α level 5% - 90% power), 29 events were initially needed, secondly re-estimated to 50 according to the rate of patients not receiving LT in the CT+LT arm during the study. Results: Between February 2016 and July 2021, 94 patients (median age 54 years, IQR 47-59) were randomly assigned to CT+LT arm (n = 47) or CT arm (n = 47). Median number and maximal diameter of uCLM at diagnosis were 20 (13-25) and 51.5 (37-78) mm, respectively. At randomization, objective response was obtained after a median number of 20 (14-27) CT cycles during 1 (44%), 2 (40%) or 3 (16%) lines. Median delay between primary tumour resection and randomisation was 14.6 (10.6-22.3) months. In CT+LT arm, 38 (81%) underwent LT after a median of 51 (30-65) days from randomization. Nine patients did not receive LT because of tumour progression during the waiting time or intraoperative finding of extrahepatic disease. Three (8%) of the 38 transplanted patients were retransplanted, one of whom (3%) died postoperatively. Post-transplant CT was administered in 26 (68%) patients. In CT arm, 9 (19%) patients unexpectedly underwent partial hepatectomy (7) or LT (2). In intent-to-treat analysis, 5-year OS was 57% in CT+LT arm and 13% in CT alone arm (log-rank test: p = 0.0003 - HR 0.37; 95%CI 0.21-0.65). In per protocol analysis, 5-year OS rate was 73% and 9%, respectively (HR 0.16; 95%CI 0.07-0.33). Median PFS was 17.4 months versus 6.4 months (HR 0.34; 95%CI 0.20-0.58), respectively. Among transplanted patients, 28 (74%) had lung (39%), liver (3%), other (21%) or multisite (11%) recurrence, optionally treated by surgery (36%) or local ablation (11%). Fifteen (40%) patients were ultimately disease-free. Conclusions: LT combined with CT significantly improved survival in selected patients with uCLM compared to CT alone. These results argue for validating LT as a new standard option that may change the treatment strategy for liver-only uCLM patients. Clinical trial information: NCT02597348 .

Outcomes of patients with intrahepatic cholangiocarcinoma with a focus on the interaction between tumor stage and age on mortality over the past decade.

e16201 Background: Intrahepatic cholangiocarcinoma(iCCA) is the second most prevalent liver tumor and originates from the epithelial cells of the bile duct . The purpose of this study is to assess to the extent independent prognostic factors influence mortality in iCCA. We also investigated the clinical characteristics and survival outcomes of patients with iCCA between 2010 and 2017. Methods: Data from the Surveillance, Epidemiology, and End Results (SEER) database provided information on 5083 iCCA patients in the USA, between 2010 and 2017. Demographics, clinical features, overall mortality (OM), cancer-specific mortality (CSM), and the interaction between age and tumor stage were analyzed. Variables with p &lt; 0.1 in univariate Cox regression were included in the multivariate model, with a hazard ratio (HR) &gt; 1 indicating adverse prognostic factors. Results: Multivariate Cox proportional hazard regression analyses showed higher OM in males (HR = 1.19), metropolitan counties with 250,000 population (HR = 1.15), and lower in the age groups 40-59 (HR = 0.58) and 60-79 (HR = 0.65). Patients who underwent radiation therapy (HR = 0.78), chemotherapy (HR = 0.54), and surgery (HR = 0.29) had lower OM. Similarly, CSM was higher in males (HR = 1.17) and metropolitan counties (HR = 1.18), but lower in age groups 40-59 (HR = 0.52) and 60-79 (HR = 0.57). Interaction analysis revealed higher OM in stage III tumors with lymph node involvement aged 40-59 (HR = 2.30). CSM was higher in ages 40-59 with stage III iCCA (HR = 2.60) and stage IV (HR = 2.81), as well as in 60-79 with stage III (HR = 2.24) and stage IV tumors (HR = 2.93). OM and CSM were higher in all age groups &gt; 40 compared to the younger population. Conclusions: In this large retrospective study using the SEER database, we unfolded an aspect of iCCA mortality that has not been previously studied. We found a significant interaction between two independent prognostic factors that enhance mortality. This data may assist treating oncologists in selecting patients that would benefit from early aggressive treatment modalities which proved to be beneficial as seen in our study. This study paves the way for future prospective randomized clinical trials to further understand the impact of such interactions in patients with iCCA, especially in the era of precision oncology.

Comparison of the Efficacy of Indwelling Gastric Tubes in Preoperative and Postoperative Patients With Oral and Maxillofacial Malignancies

PurposeTo explore the optimal plan for the timing of indwelling gastric tube placement in oral and maxillofacial malignant tumor patients. DesignA prospective randomized controlled trial. Methods80 patients with oral and maxillofacial tumor were selected, and 40 patients were Pre-operative group. The remaining 40 patients were the control group, called Postoperative group. The body weight and hospital stay of the two groups were observed before and after surgery. Blood samples were taken before surgery and 1, 3 and 7 days after surgery to detect hemoglobin and plasma albumin. FindingsThe number of postoperative hospitalization days in the pre-operative group was significantly lower than that in the post-operative group; postoperative hemoglobin and plasma albumins were lower in both groups compared with the preoperative level. ConclusionsPreoperative nasogastric tube ensured early postoperative administration of gastrointestinal nutrition, promoted postoperative plasma albumin recovery, and shortened the days of hospitalization.

Effects of peer-education training on cardiopulmonary resuscitation knowledge and skill retention of secondary school students: a feasibility study

ObjectivesThe need for cardiopulmonary resuscitation (CPR) training dissemination in the community could be resolved by mass school training programmes. However, the availability of instructors remains an unsolved problem. Our purpose...

Re-irradiation in recurrent glioblastoma: PET- or MRI-based? Results of a prospective randomized clinical trial.

2021 Background: Re-irradiation is an important treatment option for recurrent glioblastoma (rGBM). Here, we aimed to compare the oncological outcome of a re-irradiation target volume delineation based on O-(2-[18F]fluoroethyl)-L-tyrosine (FET) positron emission tomography (PET) with the one of a treatment based on contrast enhanced T1-weighted magnetic resonance imaging (T1Gd-MRI). Methods: GLIAA was a prospective, multicenter, randomized trial (NOA 10/ARO 2013-1, DKTK-a.). Patients with rGBM recurrence of 1-6 cm following initial radiotherapy were recruited at 14 centers in Germany and randomized 1:1 between a FET-PET- (arm A) and a T1Gd-MRI-based target volume delineation (arm B). The treatment consisted in a high-precision stereotactic re-irradiation with 39 Gy in 13 fractions. The primary endpoint was progression-free survival (PFS) from randomization. Secondary endpoints included overall survival (OS), local tumor control, and toxicity. Results: From November 26, 2013, to September 2, 2021, 271 patients were assessed for eligibility and 200 were randomized. 98 patients in the FET-PET arm and 97 patients in the T1Gd-MRI arm were treated per protocol. Median PFS was 4.0 months (95% confidence interval [CI] 3.7-5.2) in the FET-PET arm and 4.9 months (95% CI 3.7-6.0) in the GdT1-MRI arm (one-sided stratified log-rank test p=0.98; adjusted HR for the experimental versus the control arm 1.14 [95% CI 0.85-1.52], p=0.39). Median OS was 9.4 months (95% CI 7.8-11.1) in arm A and 9.0 months (95% CI 7.6-10.5) in arm B (HR 1.01 [95% CI 0.75-1.37], p=0.92). Local control rate at 12 months was 22% in the FET-PET arm (95% CI 14%-31%) and 20% in the GdT1-MRI arm (95% CI 12%-29%). Radiation necrosis as adverse event was documented in 25.5% of cases in arm A and in 21.6% in arm B. Of the 239 patients who received the FET tracer, 3 reported 5 severe adverse events in the timespan of 7 days after PET. No event was related to the application of the tracer. Conclusions: In this trial, FET-PET-based re-irradiation of rGBM was not superior to the GdT1-MRI-based treatment. Consequently, both options remain valid in this setting. Stereotactic re-irradiation with 39 Gy in 3 Gy fractions was shown to be safe and the FET-PET investigation was well tolerated in all cases. Due to the inclusion of FET-PET-positive patients only, our results do not impact the known diagnostic role of FET-PET in differentiating rGBM progression from post-therapeutic changes. Clinical trial information: NCT01252459 .

A Prospective Randomized Pilot Study: One-Year Outcomes of Ligament Reconstruction Tendon Interposition Versus Suture Tape Suspensionplasty for Thumb Carpometacarpal Joint Arthritis

We performed a randomized controlled trial assessing patient-reported outcome measures following trapeziectomy with ligament reconstruction and tendon interposition (LRTI) or suture tape suspensionplasty (STS) for treatment of thumb carpometacarpal joint osteoarthritis. Patients undergoing surgery for thumb carpometacarpal joint osteoarthritis were prospectively randomized to LRTI or STS. Outcome measures were collected at 2 weeks, 4 weeks, 3 months, and 1 year and included visual analog scale pain, Patient-Reported Outcomes Measurement Information System (PROMIS) Upper Extremity, return to work/activity, range of motion, grip/pinch strength, and complications. Thirty-one patients (32 thumbs) were randomized from 51 patients offered participation over two years. One-year follow-up was 97%. Both groups had a decrease in visual analog scale pain scores at all postoperative time points. The trajectory of postoperative Patient-Reported Outcomes Measurement Information System Upper Extremity scores was similar, and both groups achieved the meaningful clinically important difference for improvement in PROMIS Upper Extremity by three months. Grip strength was substantially increased in both groups at one year. Return to work/activity and surgical complications favored the LRTI group. Our study did not suggest any clinically relevant differences in the postoperative patient-reported outcome measures or objective clinical measurements between LRTI and STS, although LRTI patients had a faster return to work/activity and lower complication rates. Therapeutic IIB.

Can Verbal Interview Decrease Preoperative Anxiety and Postoperative Discomfort in Oral and Maxillofacial Surgery Patients?: A Randomized Clinical Trial

BackgroundPreoperative anxiety is a condition that can be seen frequently in oral and maxillofacial surgery patients and affects the recovery process. PurposeThe aim of this study was to determine the effect of preoperative educational/informative interviews on preoperative anxiety levels and postoperative discomfort in patients undergoing oral and maxillofacial surgery. Study design, setting, sampleThis prospective randomized clinical trial involved patients who underwent oral and maxillofacial surgery at Aydın-Adnan-Menderes University, Oral and Maxillofacial Surgery Hospital. Patients with neurological or psychological disorders, a history of previous psychiatric drug use, those who used anxiolytic or sedative drugs before surgery, those who required postoperative anxiolytic and opioid administration, or patients who underwent nonstandard surgical and anesthesia protocols were excluded. Exposure VariablePreoperative educational/informative interview is the exposure variable. Subjects were randomly assigned to the intervention and control groups. Main outcome variablesThe primary outcome variable was preoperative anxiety measured by the Spielberger State-Trait Anxiety Inventory (STAI) and the Amsterdam Preoperative Anxiety and Information scale (APAIS). The secondary outcome variables were postoperative pain measured by Visual Analog Scale (VAS) at the first and sixth hours, postoperative nausea (repeated gagging or spitting), and postoperative vomiting (active vomiting)were observed within 6 hours following general anaesthesia. CovariatesThe study’s covariates were age, weight, sex, American Society of Anes-thesiologists Physical Status Classification System (ASA) score, marital status, edicational background, surgery procedure, anesthesia procedure, duration of surgery, recovery time. AnalysesThe chi-square and student t-tests were used to compare primary predictor and covariates against outcome variables. A p-value <.05 was considered significant. ResultsA total of 92 patients were included in this study, with 46 randomized to intervention group and 46 to control group. The mean age (37.78±13.94 years vs 33.34±15.17 years, p=0.16) and sex differences (female/male: 16/30(34.8/65.2) vs 26/20(56.5/43.5), p=0.06) were comparable between groups. While higher values were recorded in the average anxiety scores in the control group than in the study group, statistically significant differences were found [STAI-S (37.36±10.87 vs 52.39±12.13) (p<0.01), APAIS-T (15.82±5.35 vs 21.39±6.69) (p<0.01), APAIS-A (4.17±2.12 vs 6.47±2.15) (p<0.01), APAIS-B (5.76±2.03 vs 7.65±2.60) (p<0.01), and APAIS-C (6.04±2.47 vs 7.21±2.38), (p<0.05)]. At the same time, there was also a significant difference in terms of early postoperative pain [(2.08±2.77 vs 3.43±2.86), (p=0.02)] and postoperative nausea [12/34 (26.1/73.9) vs 25/21(54.3/45.7), (p=0.01)]. Conclusions and RelevanceOral and maxillofacial surgery causes significant situational anxiety. This study showed that preoperative educational/informative interviews reduced preoperative anxiety levels and postoperative discomfort such as early postoperative pain, nausea, and vomiting.

Comparison of adjuvant targeted and anti-PD1 immunotherapy in BRAF-mutated stage III cutaneous melanoma: Retrospective, single center cohort study.

e21558 Background: Targeted therapy (TT) and anti-PD1 immunotherapy (IT) are standard of adjuvant stage III melanoma treatment. However, no comparative prospective randomized trials (head-to-head) were conducted. Data limited to a few retrospective studies. Both treatment regimens were registered in Russia in 2019. We aimed to compare adjuvant options in Russian melanoma pts. Methods: We conducted a single-center retrospective observational study approved by the IRB. We included all pts age 18 and older (one patient, female, was 14) with BRAF-mutated stage III melanoma who were treated at the N.N.Blokhin NMRC of Oncology MoH and received adjuvant therapy between Jan 2019 and Dec 2022. The primary endpoint was RFS, the secondary endpoint - OS. Cox regression analysis was used to identify prognostic factors for RFS (including substage, thickness and ulceration of primary tumor). Results: A total of 209 pts were included, mostly BRAF V600E/K, 92 (44%) male and 117 (56%) female. Median age was 50,6 years (range: 14-81). 93 (44,4%) pts received TT, 103 (49,3%) pts received IT and 13 (6,3%) didn’t receive adjuvant therapy (observation only). The observation group wasn’t analyzed due to a small number of pts. At a median follow-up of 27 mo, median RFS was 30 mo (95% CI 23-56) in TT group and wasn’t reached in IT group; median OS wasn’t reached in both groups. There weren’t statistical differences between TT and IT groups in RFS (HR 0,84, 95% CI 0,53-1,34, p = 0,47) and OS (HR 0,59, 95% CI 0,26-1,34, p = 0,21), even though at 12 mo, the rate of RFS was higher in the TT group (91.4%) compared IT group (67%), at 18 mo – 79,5% and 63,1%, 24 mo – 68,8% and 61,1% respectively. TT group had numeric but not significant RFS benefit in most subgroups. HR values for substage, thickness and ulceration are presented in the table below. Tx+T0 pts (TT, n = 7; IT, n = 13) and unknown status of ulceration (TT, n = 7; IT, n = 16) was not presented for some pts. Conclusions: Differences between TT and IT wasn't reached at a median follow-up of 27 mo. But IT-treated pts had more and earlier recurrences than TT pts. In BRAF mutated pts, adjuvant TT might prevent early recurrences more effectively than IT. These results need to be interpreted with caution given its retrospective and non-randomized nature and potential selection biases. Additional time to follow-up and biomarker analysis was planned. [Table: see text]

Real-world impact of KRAS mutations on clinical outcomes in metastatic colorectal cancer treated with trifluridine-tipiracil in the USA.

e15566 Background: Defining the impact of KRAS mutation status on outcomes to standard of care treatments in metastatic colorectal cancer (mCRC) is of increasing clinical relevance. We interrogated a large real-world genomic database to further explore the association between KRAS mutations and benefit to trifluridine-tipiracil (FTD-TPI) in patients with mCRC. Methods: 19,364 patients with mCRC and known KRAS mutation status were analyzed by next-generation sequencing (NextSeq, 592 Genes; NovaSeq, whole exome sequencing (WES)) at Caris Life Sciences. Real-world overall survival (rwOS) and time on treatment (ToT) was inferred from insurance claims data and calculated from time of start of treatment with FTD-TPI to last contact and time from first to last treatment with FTD-TPI with comparison done by the Kaplan-Meier test, respectively. Chi-square test was applied where appropriate, with p-value adjusted for multiple comparisons (p &lt; 0.05). Results: 764 of 10,571 (7.2%) patients with wild-type (WT) KRAS, 768 of 6,984 (11%) with KRAS G12 mutation, and 170 of 1,809 (9.4%) with KRAS G13 mutation received FTD-TPI. Age distribution was similar among groups. Sidedness of primary site was reported in 692 (40.3%) patients; an increased proportion of right-sided tumors was observed in KRAS G12 (53.4% vs. 28.3%, p &lt; 0.0001) and G13 (56% vs 28.3%, p &lt; 0.0001) groups compared to KRAS WT. An increased proportion of TP53 mutations in KRAS WT was observed compared to KRAS G12 mutation (87% vs. 70%, p &lt; 0.0001) and KRAS G13 mutation groups (87% vs. 75%, p &lt; 0.0001). KRAS G12 mutation was associated with shorter median rwOS compared to KRAS WT (7.33 vs. 8.43 months (mo), HR 1.13 (95% CI 1.11-1.42), p = 0.041). KRAS G13 mutation was associated with similar rwOS to KRAS WT. Median ToT was shorter in patients with KRAS G12 mutations than KRAS WT (1.8 vs. 2 mo, HR of 1.22 (95% CI 1.11-1.42), p &lt; 0.001). Median ToT was longer in patients with KRAS G13 versus KRAS G12 (2.3 vs. 1.8 mo, HR 0.82 (95% CI 0.68-0.98), p = 0.032). Conclusions: To our knowledge, this is the largest primarily US-based cohort of mCRC treated with FTD-TPI to be reported. KRAS G12 mutation, but not KRAS G13 mutation, was associated with shorter rwOS and ToT compared to KRAS WT, despite enrichment of TP53 and BRAF mutations in the KRAS WT group. This finding is consistent with previously published analyses of large randomized prospective trials of FTD-TPI in mCRC and further support KRAS mutation status as a predictive biomarker in this setting. [Table: see text]

Comparison between outcome of early and delayed laparoscopic surgery in patients with acute cholecystitis – A prospective randomized controlled trial.

Comparison between outcome of early and delayed laparoscopic surgery in patients with acute cholecystitis – A prospective randomized controlled trial.

Effect of glenosphere diameter and lateralization in primary reverse shoulder arthroplasty: a randomized clinical trial

BackgroundWithin reverse total shoulder arthroplasty (RSA), prior studies have suggested that smaller glenosphere diameters may result in higher rates of scapular notching and polyethylene wear, while lateralized glenospheres may allow for better range of motion (ROM); however, supportive data remains limited. Therefore, the purpose of this study was to report the outcomes of a prospective randomized clinical trial comparing 4 different glenosphere configurations based on diameter and lateral offset. MethodsBetween 2016 and 2020, 113 primary RSAs with a diagnosis of either rotator cuff tear arthropathy (n = 48, 42%), irreparable rotator cuff tears (n = 22, 19%), or primary glenohumeral osteoarthritis with subluxation or glenoid bone loss (n = 43, 38%) were enrolled into a blinded prospective randomized clinical trial. The mean age of the patients included in the study was 73 ± 7 (range, 50-89) years, and 58 (51.3%) were males. All procedures were performed by two surgeons utilizing the ReUnion RSA system (Stryker, Mahwah, NJ, USA). Patients were randomized into four possible groups based on the diameter and lateral offset of the glenosphere implanted: 36 mm diameter with 2 mm (n = 34, 30.1%) or 6 mm (n = 28, 24.8%) of lateralization and 40 mm diameter with 2 mm (n = 29, 25.7%) or 6 mm (n = 22, 19.5%) of lateralization. Outcomes collected included pain, active ROM, strength, satisfaction, patient-reported outcome measures (PROMs), complications, reoperations, and revisions. PROMs included the Oxford Shoulder Score, the American Shoulder and Elbow Surgeons, and the quick Disabilities of the Arm, Shoulder and Hand questionnaire. All patients were followed for a minimum of 2 years. ResultsWith the numbers available, glenosphere diameter and lateralization resulted in no differences in pain, ROM, strength, satisfaction, and PROMs at 1 year, 2 years, or final follow-up (All P > .05). However, all 3 complications (10.7% vs. 0% vs. 0% vs. 0%; P = .025) and 2 revision surgeries (7.1% vs. 0% vs. 0% vs. 0%; P = .103) occurred in males, with the 36 + 6 cohort. ConclusionsUsing this particular RSA design, implantation of glenospheres with 36 mm or 40 mm of diameter and 2 mm or 6 mm of sphere lateralization did not translate into significant differences when primary RSA was performed in shoulders with rotator cuff tear arthropathy, irreparable cuff tears, or primary glenohumeral osteoarthritis. However, all observed complications occurred in males with the smallest diameter and lateralized glenosphere.

How long does it take to read a mammogram? Investigating the reading time of digital breast tomosynthesis and digital mammography

PurposeTo analyse digital breast tomosynthesis (DBT) reading times in the screening setting, compared to 2D full-field digital mammography (FFDM), and investigate the impact of reader experience and professional group on interpretation times. MethodReading time data were recorded in the PROSPECTS Trial, a prospective randomised trial comparing DBT plus FFDM or synthetic 2D mammography (S2D) to FFDM alone, in the National Health Service (NHS) breast screening programme, from January 2019-February 2023. Time to read DBT+FFDM or DBT+S2D and FFDM alone was calculated per case and reading times were compared between modalities using dependent T-tests. Reading times were compared between readers from different professional groups (radiologists and radiographer readers) and experience levels using independent T-tests. The learning curve effect of using DBT in screening on reading time was investigated using a Kruskal-Wallis test. ResultsForty-eight readers interpreted 1,242 FFDM batches (34,210 FFDM cases) and 973 DBT batches (13,983 DBT cases). DBT reading time was doubled compared to FFDM (2.09 ± 0.64 min vs. 0.98 ± 0.30 min; p < 0.001), and DBT+S2D reading was longer than DBT + FFDM (2.24 ± 0.62 min vs. 2.04 ± 0.46 min; p = 0.006). No difference was identified in reading time between radiologists and radiographers (2.06 ± 0.71 min vs. 2.14 ± 0.46 min, respectively; p = 0.71). Readers with five or more years of experience reading DBT were quicker than those with less experience (1.86 ± 0.56 min vs. 2.37 ± 0.65 min; p = 0.008), and DBT reading time decreased after less than 9 months accrued screening experience (p = 0.01). ConclusionsDBT reading times were double those of FFDM in the screening setting, but there was a short learning curve effect with readers showing significant improvements in reading times within the first nine months of DBT experience.ClinicalTrials.gov Identifier: NCT03733106.

Metabolomic and Physiological Effects of a Cardiorenal Protective Diet Intervention in African American Adults with Chronic Kidney Disease.

Chronic kidney disease (CKD) impacts 14% of adults in the United States, and African American (AA) individuals are disproportionately affected, with more than 3 times higher risk of kidney failure as compared to White individuals. This study evaluated the effects of base-producing fruit and vegetables (FVs) on cardiorenal outcomes in AA persons with CKD and hypertension (HTN) in a low socioeconomic area. The "Cardiorenal Protective Diet" prospective randomized trial evaluated the effects of a 6-week, community-based FV intervention compared to a waitlist control (WL) in 91 AA adults (age = 58.3 ± 10.1 years, 66% female, 48% income ≤ USD 25K). Biometric and metabolomic variables were collected at baseline and 6 weeks post-intervention. The change in health outcomes for both groups was statistically insignificant (p > 0.05), though small reductions in albumin to creatinine ratio, body mass index, total cholesterol, and systolic blood pressure were observed in the FV group. Metabolomic profiling identified key markers (p < 0.05), including C3, C5, 1-Met-His, kynurenine, PC ae 38:5, and choline, indicating kidney function decline in the WL group. Overall, delivering a directed cardiorenal protective diet intervention improved cardiorenal outcomes in AA adults with CKD and HTN. Additionally, metabolomic profiling may serve as a prognostic technique for the early identification of biomarkers as indicators for worsening CKD and increased CVD risk.

Tranexamic Acid Subcutaneously Administered with Epinephrine and Lidocaine in Upper Blepharoplasty: A Randomized Double-Blind Control Trial

BackgroundEyelid surgery is one of the top five aesthetic procedures. It is performed to improve both appearance and function, but intraoperative bleeding leads to adverse events which perturb patients. The objective of this study was to demonstrate the efficacy of TXA combined with epinephrine in decreasing intraoperative blood loss and postoperative inflammation.MethodsThis prospective randomized control trial was performed on the 30 eyelids of 15 patients who underwent upper blepharoplasty. One of each patient’s eyes was randomly assigned to the TXA group, and the other eye was in the control group. Eyes in the TXA group were given 2% lidocaine with epinephrine (1:100000) mixed with TXA (50 mg/ml) in 1:1 mixture subcutaneously as a local anesthetic. The eyes in the control group received 2% lidocaine with epinephrine (1:100000) diluted with normal saline in 1:1 mixture. Intraoperative blood loss and postoperative swelling were compared between the two groups.ResultsIntraoperative blood loss was significantly higher in the TXA group [4.86 (1.83) ml] than it was in the control group [2.53 (1.49) ml] (p < 0.001). There was no statistically significant difference between the two groups in operative time (p = 0.645), pain score (p = 0.498), lid crease (p = 0.548), or MRD1 (p = 0.626). On postoperative day 7, there was no difference in lid crease (p = 0.879), MRD1 (p = 0.463), pain score (p = 0.934), or ecchymosis (p = 0.976) between two groups.ConclusionsTXA in lidocaine with epinephrine was found to increase intraoperative bleeding compared to lidocaine with epinephrine alone, but there was no difference in postoperative swelling or ecchymosis. TXA combined with lidocaine and epinephrine injected subcutaneously should be avoided until additional relevant data are obtained. Further drug interaction study is needed.Level of Evidence IIThis journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.