Single Arm Research Articles

A perioperative study of Safusidenib in patients with IDH1-mutated glioma.

This is a single arm, open label perioperative trial to assess the feasibility, pharmacokinetics and pharmacodynamics of treatment with safusidenib following biopsy, and prior to surgical resection in patients with IDH1 mutated glioma who have not received radiation therapy or chemotherapy. Fifteen participants will receive treatment in two parts. First, biopsy followed by one cycle (28days) of safusidenib, an orally available, small molecular inhibitor of mutated IDH1, then maximal safe resection of the tumor (Part A). Second, after recovery from surgery, safusidenib until disease progression or unacceptable toxicity (Part B). This research will enable objective measurement of biological activity of safusidenib in patients with IDH1 mutated glioma. Anti-tumor activity will be assessed by progression free survival and time to next intervention.Clinical Trial Registration: NCT05577416 (ClinicalTrials.gov).

Treating acid reflux without compressing the food passageway: 4-year safety and clinical outcomes with the RefluxStop device in a prospective multicenter study

IntroductionRefluxStop is an implantable device for laparoscopic surgical treatment of gastroesophageal reflux disease (GERD) to restore and maintain lower esophageal sphincter and angle of His anatomy without encircling and putting pressure on the food passageway, thereby avoiding side effects such as dysphagia and bloating seen with traditional fundoplication. This study reports the clinical outcomes with RefluxStop at 4 years following implantation of the device.MethodsA prospective, single arm, multicenter clinical investigation analyzing safety and effectiveness of the RefluxStop device in 50 patients with chronic GERD.ResultsAvailable data are presented for 44 patients at 4 years with the addition of three patients at 3 years carried forward. At 4 years, median GERD-HRQL score was 90% reduced compared to baseline. Two patients (2/44) used regular daily proton pump inhibitors (PPIs) despite subsequent 24-h pH monitoring off PPI therapy yielding normal results. There were no device-related adverse events (AEs), esophageal dilations, migrations, or explants during the entire study period. AEs reported between 1 and 4 years were as follows: one subject with heartburn and a pathologic pH result with device positioned too low at surgery; one subject with dysphagia, thus, 46/47 patients reported no dysphagia-related AEs between years 1 and 4. Two patients (2/47) were dissatisfied with treatment despite normal 24-h pH monitoring, of whom one had manometry-verified dysmotility at 6 months, indicating dissatisfaction for reasons other than acid reflux.ConclusionThese results confirm the excellent and already published 1-year results as stable in the long-term, supporting the safety and effectiveness of the RefluxStop device in treating GERD for over 4 years. GERD-HRQL score, pH testing, and PPI usage indicate treatment success without dysphagia or gas-bloating and only minimal incidence of other AEs. This favorably low rate of AEs is likely attributable to RefluxStop’s dynamic physiologic interaction and non-encircling nature.

Resistance Training in Women Diagnosed with Breast Cancer: A Pilot Single Arm Pre-Post Intervention.

Background: Resistance training (RT) yields physical and psychological benefits for women living with and beyond breast cancer (WBC). This study examined the feasibility of a virtually delivered 8-week socially supportive RT intervention among WBC and assessed changes in physical activity and body image. Methods: A pilot single-arm 8-week pre-post intervention study design was implemented. Forty-one WBC were matched as exercise partners and asked to complete two RT sessions per week-one with a qualified exercise professional (QEP) and one with their peer. Data were collected at baseline (T1), post-intervention (T2), and 20 weeks post-baseline (T3). Results: The enrolment rate was 42%, the attendance rate for the QEP sessions was 63.8% and 40.0% for the peer sessions, and the retention rate was 87%. No adverse events were reported. Total weekly minutes of RT significantly (p < 0.05) increased by 42 minutes/week during the intervention and significantly decreased by 25 min/week at follow-up. Upper and lower body muscle strength increased (p < 0.01) during the intervention. Increased RT was associated with favorable activity self-perceptions. Conclusions: This pilot intervention study was feasible, safe, and demonstrated preliminary evidence for increasing RT time and strength among WBC. Virtually delivered socially supportive RT interventions can improve access for WBC.

A phase II study of oral chlorophyllin in haemorrhagic cystitis secondary to radiation therapy for pelvic malignancies (CLARITY).

48 Background: Chronic hemorrhagic cystitis (cHC) is seen in 5-15% of patients undergoing pelvic radiotherapy (pRT), often after a long cancer free survival. Hyperbaric oxygen therapy, the only modality with benefit proven in a randomized trial has limited utilization due of lack of availability, need of multiple sessions &amp; cost. In this phase II study, we aimed to evaluate the efficacy &amp; safety of Sodium-copper-chlorophyllin (CHL), a semi-synthetic mixture of sodium &amp; copper salts of chlorophyll, in pRT-induced cHC. This study was based on our preclinical findings where CHL offered radioprotection &amp; significantly reduced mortality &amp; morbidity in mice exposed to lethal doses of whole-body radiation.A subsequent phase 1 trial in adult healthy volunteers established the recommended phase 2 dose. Methods: This was a prospective, single centre, single arm, interventional phase II clinical trial (NCT05348239). Adult patients with grades II-IV hematuria (CTCAE v5.0) following pRT received at least 3 months prior were eligible. All patients received oral CHL 750 mg OD for a maximum of 3 months. A Simon two-stage minimax design with a type 1 error of 2.5% &amp; 80% power led to a sample size of 24 patients. The primary objective was the objective response rate (ORR), defined as the proportion of patients with complete response (CR) [resolution of gross hematuria] or partial response (PR) [decrease by at least one CTCAE grade of hematuria, but not complete resolution] from day 30-90 of starting the drug. At least seven objective responses were required to consider the drug for further development. Results: Thirty two patients were screened of whom 24 were enrolled, with median age of 63 (43-86) years. Indications for pRT included cervical (15), rectal (5) &amp; prostate cancer (4). The median time from RT to cHC was 45 (4-216) months. At enrolment, 6 (25%), 17 (70.8%) &amp; 1 (4.1%) patients had CTCAE grades 2, 3 &amp; 4 hematuria respectively, majority being refractory. An objective response occurred in 20 patients (83.3%; 95% CI, 62-95%), (Stable=1, PR=10, &amp; CR=10 as the best response).11 unrelated SAEs were observed in 8 patients. No treatment-related grade 4/5 adverse events were reported.No patient required angioembolisation, vesical artery ligation, or cystectomy.Proteomics studies indicated modulation of coagulation pathways and improved stem cell mediated regeneration and wound healing following chlorophyllin treatment. Conclusions: In this phase II study,oral CHL has shown objective &amp; sustained response in cHC related grade II-IV hematuria following pRT. A randomized, placebo-controlled, phase III trial assessing the efficacy of oral CHL is now planned. Clinical trial information: NCT05348239 .

SUNRAY-01, a pivotal, global study of olomorasib (LY3537982) in combination with pembrolizumab with or without chemotherapy for 1L treatment in KRAS G12C-mutant advanced NSCLC.

TPS218 Background: Mutations in KRAS are among the most frequent oncogenic drivers with the G12C variant found in ~13% of NSCLC. Outcomes for KRAS G12C-mutant NSCLC may be improved by combining KRAS G12C inhibitors with current 1L standard of care (SOC). Olomorasib is a potent and highly selective second-generation inhibitor of KRAS G12C, which delivers &gt;90% sustained target occupancy in preclinical models. In the LOXO-RAS-20001 phase 1/2 study, olomorasib in combination with pembrolizumab demonstrated preliminary efficacy and a favorable safety profile.1 Methods: SUNRAY-01 (NCT06119581) is a pivotal, global, phase 3 study in 1L advanced KRAS G12C-mutated NSCLC designed to seamlessly 1) optimize the dosing of olomorasib in combination with 1L SOC, and then 2) compare efficacy and safety of olomorasib plus SOC with placebo plus SOC. In the open-label randomized dose optimization (pembrolizumab plus olomorasib 50 mg vs 100 mg BID) and single arm safety lead-in (olomorasib plus pembrolizumab, pemetrexed, platinum), the optimal dose of olomorasib for combination therapy will be determined before the phase 3 study (parts A and B) is opened for enrollment. In part A, 384 participants with PD-L1 expression ≥50% are randomized (1:1) to pembrolizumab plus olomorasib or placebo. In part B, 552 participants are randomized (1:1) to pembrolizumab, pemetrexed, platinum plus olomorasib or placebo regardless of PD-L1 expression. Allocation of participants with PD-L1 expression ≥50% to either part A or part B will be at the discretion of the investigator. The primary objective is to compare efficacy based on PFS per RECIST v1.1 by blinded independent central review. Secondary endpoints include OS, ORR, DOR, DCR, TTR, PFS2, safety and tolerability, and patient-reported outcomes. Eligible participants (≥18 years) must have a KRAS G12C mutation in tumor or blood and known PD-L1 expression (0-100%), stage IIIB, IIIC, or IV NSCLC not suitable for curative intent radical surgery or radiation therapy, measurable disease per RECIST v1.1, and an ECOG PS 0-1. Participants can be enrolled based on local KRAS and PD-L1 testing results. Participants should not have received prior systemic therapy for advanced or metastatic NSCLC, however 1 cycle of SOC treatment prior to enrollment is allowed if immediate treatment is clinically indicated. Participants with asymptomatic (lesions ≤1.5 cm) or previously treated radiographically stable brain metastases are eligible. Key exclusion criteria include history of pneumonitis/interstitial lung disease and clinically significant active cardiovascular disease or malabsorption syndrome. The study opened for enrollment in December 2023. Reference: 1. Murciano-Goroff et al. 2023 Cancer Res 83 (8 Suppl): CT028. Clinical trial information: NCT06119581 .

A systematic review of physical activity and nutritional interventions for the management of normal weight and overweight obesity

AimsNormal Weight Obesity (NWO) and Overweight Obesity (OWO) are prevalent conditions, yet knowledge of management is limited. This review aims to assess the effectiveness of physical activity and nutritional interventions in the management of NWO and OWO (together defined as BMI <30 kg/m2 with raised body fat). Data synthesisClinical trials including any physical activity or nutritional interventions, published between 2012 and 2022, evaluating body fat change were selected. Seven trials met inclusion criteria, including one single arm intervention, and six RCTs. A high intensity interval training intervention (high risk of bias) had the largest effect on reducing percentage body fat (MD: −6.8%, SE: 0.06). High protein intake interventions were also found to be effective (MD: −2.8%, SE: 0.27, MD: −2.0%, SE: 0.05). These three interventions led to greater increases in fat free mass. Two energy restricted interventions resulted in the highest mean weight loss (MD: −3.10 kg, SD: 0.87 (intervention only), MD: −2.90 kg, SE: 0.06), but also loss of fat free mass, resulting in low reductions in percentage body fat (MD: −1.10%, SD: 0.57 (intervention only), MD: −0.8%, SE 0.30). There was considerable heterogeneity between studies. ConclusionsThere are physical activity and nutritional interventions that could be efficacious for the management of NWO and OWO. However, there was considerable heterogeneity between studies. The most promising nutritional intervention is high protein intake and the least is energy restriction (without increased protein intake). More high-quality trials are needed to evaluate interventions, and to determine the best tools to measure adiposity.

Profiling IgG and IgA antibody responses during vaccination and infection in a high-risk gonorrhoea population

Development of a vaccine against gonorrhoea is a global priority, driven by the rise in antibiotic resistance. Although Neisseria gonorrhoeae (Ng) infection does not induce substantial protective immunity, highly exposed individuals may develop immunity against re-infection with the same strain. Retrospective epidemiological studies have shown that vaccines containing Neisseria meningitidis (Nm) outer membrane vesicles (OMVs) provide a degree of cross-protection against Ng infection. We conducted a clinical trial (NCT04297436) of 4CMenB (Bexsero, GSK), a licensed Nm vaccine containing OMVs and recombinant antigens, comprising a single arm, open label study of two doses with 50 adults in coastal Kenya who have high exposure to Ng. Data from a Ng antigen microarray established that serum IgG and IgA reactivities against the gonococcal homologs of the recombinant antigens in the vaccine peaked at 10 but had declined by 24 weeks. For most reactive OMV-derived antigens, the reverse was the case. A cohort of similar individuals with laboratory-confirmed gonococcal infection were compared before, during, and after infection: their reactivities were weaker and differed from the vaccinated cohort. We conclude that the cross-protection of the 4CMenB vaccine against gonorrhoea could be explained by cross-reaction against a diverse selection of antigens derived from the OMV component.

Goldilocks mastectomy; a modified technique enhancing the aesthetic outcome presented as a single center single-arm prospective cohort study

BackgroundGoldilocks mastectomy represents a midway solution for breast reconstruction between flat chest and sophisticated reconstructive techniques. The literature lacks a standardization of the technique. In this study, we present a step-by-step approach with modifications in the original technique achieving better breast shape and contour within the context of standardization of the technique. MethodsA single arm prospective study was conducted at our center in which female patients with large ptotic breasts indicated for mastectomy were included. Patients with locally advanced skin changes, inflammatory carcinoma, stage IV disease as well as male patients were excluded. Recruited patients were subjected to the same surgical steps. Contralateral breast symmetrization was performed by reduction technique to patients who accepted this. All patients were requested to report their degree of satisfaction according to a simple 5-point Likert scale. Follow up mammogram was performed to all patients 1 year after the procedure. ResultsA total of 55 patients were included with a median (IQR) age of 56.0 (50.0–62.0) years. The median (IQR) BMI was 41.20 (36.55–44.35)Kg/m2. The median (IQR)operative time was 115.0 (105.0–120.0) minutes. Complications were encountered in 12 patients (21.8 %). The follow up period ranged from 19 to 66 months with a median (IQR) 36.0 (28.0–45.0)months. 98.2 % of the studied patients were either satisfied or extremely satisfied. ConclusionsGoldilocks mastectomy is a valid mastectomy option for selected patients with large ptotic breasts. Standardization of the surgical steps can help in improving the aesthetic outcome.

Effect of Infra Low Frequency (ILF) neurofeedback training on EEG in children with autism spectrum disorders.

To investigate whether Infra-low frequency Neurofeedback (ILF-NFB) training can improve brain electrical activity in children with autism spectrum disorders ASD. This single arm pre and post intervention study was carried out at IBMS (Institute of Basic Medical Sciences), Khyber Medical University, Peshawar and Shaheed Zulfiqar Ali Bhutto Medical University (SZABMU), Islamabad from January 2021 to December 2022. A purposive sampling technique was used. Thirty-five ASD children (male=24; female=11; 7-17 years) were provided with 30 sessions of infra low frequency (ILF) neurofeedback training for 15-20 minutes, during 10 weeks. Childhood Autism Rating Scale (CARS) scoring was done and electroencephalogram (EEG) activity was compared before and after ILF-NF training sessions. Around 62.9% participants had mild-moderate autism and 37.1% had severe autism. Wilcoxon Signed rank test revealed a significant decline in delta (Pre-test=47.31±19.22, Post-test=22.07±6.83; p=<0.001), theta (Pre-test=24.75±16.62, Post-test=12.37±3.59; p=<0.001) and alpha (Pre-test=12.01±9.81, Post-test=4.03±1.61; p=< 0.001) waves. Mann Whitney U test exhibited no significant gender differences in EEG pattern before and after neurofeedback except in theta waves (p=0.03) before the intervention. Decline in delta, theta, beta and alpha waves propose that ILF-NF training can be effective in improving the EEG activity. ILF-NFB can be perceived as a valuable non-invasive, non-pharmacological intervention for improving EEG pattern via reintegration of brain activity resulting in increased the attention and focus, enhanced mental stability and cognitive engagement.

Remote and local effects of ischemic preconditioning on vascular function: a case for cumulative benefit.

Brief, repeated cycles of limb ischemia and reperfusion [ischemic preconditioning (IPC)] can protect against vascular insult. Few papers have considered the effect of IPC on resting vascular function, and no single study has simultaneously considered the local (trained arm) and remote (untrained arm) effects of a single session of IPC and following repeated sessions. We determined macrovascular [allometrically scaled flow-mediated dilation (FMD)] and microvascular [cutaneous vascular conductance (CVC)] function in healthy adults before, immediately post, 20 min post, and 24 h post a single session of IPC (4 × 5 min of single arm ischemia). These outcomes also were remeasured 24 h after six IPC sessions, performed over 2 wk. FMD and CVC increased in both arms 20 min post [FMD mean difference (MD) 1.1%, P < 0.001; CVC MD 0.08 arbitrary units (AU), P = 0.004] but not 24 h post (FMD MD -0.2%, P = 0.459; CVC MD -0.02 AU, P = 0.526] a single session of IPC, with no differences between trained and untrained arms. Although FMD did not increase 24 h after one IPC session, it was elevated in both arms 24 h after the sixth session (MD 1.2%, P = 0.009). CVC was not altered in either arm 24 h after the last IPC session. These data indicate that the local and remote effects of IPC on vascular health may be equivalent and that the benefits to FMD may be greater with sustained training compared with a single IPC exposure.

Seated Pulmonary Artery Pressure Monitoring in Patients With Heart Failure: Results of the PROACTIVE-HF Trial

BackgroundMonitoring supine pulmonary artery pressures to guide heart failure (HF) management has reduced HF hospitalizations in select patients. ObjectivesThe purpose of this study was to evaluate the effect of managing seated mean pulmonary artery pressure (mPAP) with the Cordella Pulmonary Artery sensor on outcomes in patients with HF. MethodsFollowing GUIDE-HF (Hemodynamic-GUIDEd Management of Heart Failure Trial), with U.S. Food and Drug Administration input, PROACTIVE-HF (A Prospective, Multi-Center, Open Label, Single Arm Clinical Trial Evaluating the Safety and Efficacy of the Cordella Pulmonary Artery Sensor System in NYHA Class III Heart Failure Patients trial) was changed from a randomized to a single-arm, open label trial, conducted at 75 centers in the USA and Europe. Eligible patients had chronic HF with NYHA functional class III symptoms, irrespective of the ejection fraction, and recent HF hospitalization and/or elevated natriuretic peptides. The primary effectiveness endpoint at 6 months required the HF hospitalization or all-cause mortality rate to be lower than a performance goal of 0.43 events/patient, established from previous hemodynamic monitoring trials. Primary safety endpoints at 6 months were freedom from device- or system-related complications or pressure sensor failure. ResultsBetween February 7, 2020, and March 31, 2023, 456 patients were successfully implanted in modified intent-to-treat cohort. The 6-month event rate was 0.15 (95% CI: 0.12-0.20) which was significantly lower than performance goal (0.15 vs 0.43; P < 0.0001). Freedom from device- or system-related complications was 99.2% and freedom from sensor failure was 99.8% through 6 months. ConclusionsRemote management of seated mPAP is safe and results in a low rate of HF hospitalizations and mortality. These results support the use of seated mPAP monitoring and extend the growing body of evidence that pulmonary artery pressure–guided management improves outcomes in heart failure. (Multi-Center, Open Label, Single Arm Clinical Trial Evaluating the Safety and Efficacy of the Cordella Pulmonary Artery Sensor System in NYHA Class III Heart Failure Patients trial [PROACTIVE-HF]; NCT04089059)

A prospective single arm cohort study: An analysis of the effectiveness of surgical treatment of locally advanced breast cancer

BackgroundBreast cancer stands as a globally significant contributor to both incidence rates and mortality among women. Approximately 10–15 % of women will face a diagnosis of an advanced yet potentially treatable stage of the disease. When individuals diagnosed with locally advanced breast cancer (LABC) exhibit resistance to preoperative chemotherapy and experience tumor progression, they unfortunately forfeit the opportunity for surgical intervention, thereby diminishing the prospects for a radical cure. MethodWe conducted a prospective, single-arm cohort study aimed at evaluating the feasibility of locally modified radical resection for LABC with skin invasion. The primary endpoints encompassed overall survival (OS) and disease-free survival (DFS), whereas the secondary endpoint focused on the quality of life (QoL) among breast cancer patients. ResultsBetween March 2018 and December 2022, a total of 38 eligible patients were enrolled in this study. The Kaplan-Meier estimates for 1-year, 3-year, and 5-year DFS among all patients were 69.8 %, 53.3 %, and 37.5 %, respectively. Correspondingly, the OS rates were 100.0 %, 85.6 %, and 68.0 %. Both univariate and multivariate analyses revealed that patients with a history of neoadjuvant chemotherapy who exhibited stable or progressive disease had inferior DFS outcomes. Notably, patients demonstrated clinically meaningful and statistically significant enhancements in functional status and overall QoL. However, no notable improvement was observed in specific symptom domains. ConclusionPatients with locally advanced breast cancer, specifically those presenting with T4 tumors, who undergo surgical intervention followed by postoperative adjuvant therapy, can attain favorable prognostic outcomes and experience an enhanced quality of life.

Efficacy and Safety of Combination Therapy of Sintilimab and Chemotherapy with Cryoablation in the First-Line Treatment of Advanced Non-Squamous Non-Small Cell Lung Cancer (NSCLC): a pilot study protocol for a single center, single arm, phase II study (Preprint)

Efficacy and Safety of Combination Therapy of Sintilimab and Chemotherapy with Cryoablation in the First-Line Treatment of Advanced Non-Squamous Non-Small Cell Lung Cancer (NSCLC): a pilot study protocol for a single center, single arm, phase II study (Preprint)

A randomised trial comparing 6-monthly adjuvant zoledronate with a single one-time dose in patients with early breast cancer.

While adjuvant bisphosphonate use in early breast cancer (EBC) is associated with improvements in breast cancer-specific outcomes, questions remain around optimal bisphosphonate type, dose and scheduling.We evaluated a single zoledronate infusion in a prospective randomised trial. Postmenopausalpatientswith EBC were randomised to receive a single infusion of zoledronate (4mg IV) or 6-monthly treatment for 3years. Outcomes measured were; Quality of Life (QoL; EQ-5D-5L), bisphosphonate-related toxicities, including acute phase reactions (APRs), recurrence-free survival (RFS), bone metastasis-free survival (BMFS) and overall survival (OS). 211 patients were randomized to either a single infusion (n = 107) or six-monthly treatment (n = 104).After 3years of follow up there were no significant differences between the arms for QoL and most toxicity endpoints. APRs following zoledronate occurred in 81% (171/211) of patients (77.6% in single infusion arm and 84.6% in the 6-monthly group).While the frequency of APRs decreased over 3years in the 6-monthly arm, they still remain common. Of 34/104 (32.7%) patients who discontinued zoledronateearlyin the 6-monthly treatment group, the most common reason was APRs (16/34, 47%). At the 3year follow up, there were no differences between arms for RFS, BMFS or OS. A single infusion of zoledronate was associated with increased patient convenience, less toxicity, and lower rates of treatment discontinuation. Despite the common clinical impression that APRs decrease with time, this was not observed when patients were specifically questioned. While the study is not powered for non-inferiority, longer-term follow-up for confirmation of RFS and OS rates is ongoing.

Safety & efficacy of a robotic hip exoskeleton on outpatient stroke rehabilitation

ObjectiveThe objective of this study was to analyze the safety and efficacy of using a robotic hip exoskeleton designed by Samsung Electronics Co., Ltd., Korea, called the Gait Enhancing and Motivating System-Hip (GEMS-H), in assistance mode only with the poststroke population in an outpatient-rehabilitation setting.MethodsForty-one participants with an average age of 60 and average stroke latency of 6.5 years completed this prospective, single arm, interventional, longitudinal study during the COVID-19 pandemic. Significant modifications to the traditional outpatient clinical environment were made to adhere to organizational physical distancing policies as well as guidelines from the Centers for Disease Control. All participants received gait training with the GEMS-H in assistance mode for 18 training sessions over the course of 6–8 weeks. Performance-based and self-reported clinical outcomes were assessed at four time points: baseline, midpoint (after 9 training sessions), post (after 18 training sessions), and 1-month follow up. Daily step count was also collected throughout the duration of the study using an ankle-worn actigraphy device. Additionally, corticomotor excitability was measured at baseline and post for 4 bilateral lower limb muscles using transcranial magnetic stimulation.ResultsBy the end of the training program, the primary outcome, walking speed, improved by 0.13 m/s (p < 0.001). Secondary outcomes of walking endurance, balance, and functional gait also improved as measured by the 6-Minute Walk Test (47 m, p < 0.001), Berg Balance Scale (2.93 points, p < 0.001), and Functional Gait Assessment (1.80 points, p < 0.001). Daily step count significantly improved with and average increase of 1,750 steps per day (p < 0.001). There was a 35% increase in detectable lower limb motor evoked potentials and a significant decrease in the active motor threshold in the medial gastrocnemius (-5.7, p < 0.05) after training with the device.ConclusionsGait training with the GEMS-H exoskeleton showed significant improvements in walking speed, walking endurance, and balance in persons with chronic stroke. Day-to-day activity also improved as evidenced by increased daily step count. Additionally, corticomotor excitability changes suggest that training with this device may help correct interhemispheric imbalance typically seen after stroke.Trial RegistrationThis study is registered with ClinicalTrials.gov (NCT04285060).

Efficacy of Traditional Chinese Medicine Combined Online Group Psychotherapy (TCM-eRhab) on improving quality of life and relieving psychological burden for colorectal cancer survivors: a study protocol for a phase-II randomized controlled trial

BackgroundMore than 50% of colorectal cancer(CRC) patients experience cancer-related psychological burden after radical surgery, which can seriously affect their physical wellness, quality of life and even survival outcomes. Our research team developed a six-week Traditional Chinese Medicine Combined Online Group Psychotherapy (TCM-eRhab) and proved its efficacy on relieving cancer-related anxiety, depression and fear of cancer recurrence though phase I single arm clinical trial (n = 40). Large sample size randomized controlled clinical trial(RCT) is necessary to further evaluate TCM-eRhab’s role on improving quality of life and survival outcomes among this population. MethodsWe design a phase II RCT study, in which 210 CRC patients who have received radical surgery (stage I-III) will be recruited. Eligible patients will be randomly assigned to TCM-eRhab group or usual care group by 2:1 ratio. Patients in the intervention group will receive the structured TCM-eRhab program for six weeks, while patients in control group will receive usual care only. The primary outcomes are quality of life, severity of anxiety, depression and fear of cancer recurrence. Cancer recurrence rate will also be calculated according to long term follow-up data.DiscussionAs one of the first RCTs to evaluate the impacts of TCM combined psychological therapy to improve CRC patients’ quality of life after surgery, the results from this study will provide innovative knowledge and evidence on integrating TCM into CRC survivorship care and mind–body intervention model.

Surgical outcomes of profunda artery perforator flap in head and neck reconstruction: A systematic review and meta-analysis.

This study aims to evaluate the efficacy of the profunda artery perforator (PAP) flap in head and neck reconstruction. A single arm meta-analysis was performed for flap survival rate (primary outcome), reoperation for major complication, and overall complication rates (secondary outcomes). The search strategy yielded a total of 295 potentially relevant publications, of which 13 were included. A total of 305 patients (males: 80.8%, n = 232/281), with a median age of 56.1 years (n = 305/305; 95% CI 53.9-63), who underwent a total of 307 PAP flap reconstructions for head and neck defects were included. Flap survival rate was 100% (n = 306/307; 95% CI 99.6%-100%), with a reoperation rate for major complications of 3.7% (n = 15/307; 95% CI 1.85%-6.1%) and an overall complication rate of 26.5% (n = 92/307; 95% CI 15.7%-38.9%). Notable postoperative complications included wound dehiscence (n = 15/307, 4.9%), delayed healing (n = 14/307, 4.6%), and wound infection (n = 12/307, 3.9%). Partial flap necrosis and hematoma occurred in 2.6% of cases (n = 8/307), while arterial and venous thrombosis were documented in 0.7% (n = 2/307) and 1.3%, respectively (n = 4/307). The application of the PAP flap in head and neck reconstructions showed several favorable aspects, such as an exceptionally low flap failure rate, versatility in achieving variable dimensions, and a relatively low incidence of complications. PAP flap might be considered as a compelling alternative to the traditionally employed soft tissue free flaps in head and neck reconstruction.

Efficacy and safety of an oral combination therapy of niraparib and etoposide in platinum resistant/refractory ovarian cancer: a single arm, prospective, phase II study

ObjectiveNon-platinum chemotherapy is used in platinum resistant/refractory ovarian cancer patients but offers limited efficacy, especially in those who develop platinum resistance after ≤2 lines of platinum based chemotherapy. This phase...

Comparative evaluation of CT and MRI in the preoperative staging of colon cancer

The aim of this study is to compare the diagnostic performance of magnetic resonance imaging (MRI) against computed tomography (CT) in various aspects of local staging in colon cancer patients. This study was a prospective single arm diagnostic accuracy study. All consecutive adult patients with confirmed colon cancer that met the current criteria for surgical resection were considered as eligible. Diagnostic performance assessment included T (T1/T2 vs T3/T4 and < T3ab vs > T3cd) and N (N positive) staging, serosa and retroperitoneal surgical margin (RSM) involvement and extramural vascular invasion (EMVI). Imaging was based on a 3 Tesla MRI system and the evaluation of all sequences (T1, T2 and diffusion-weighted imaging-DWI series) by two independent readers. CT scan was performed in a 128 row multidetector (MD) CT scanner (slice thickness: 1 mm) with intravenous contrast. Pathology report was considered as the gold standard for local staging. Sensitivity (SE), specificity (SP), and area under the curve (AUC) were calculated for both observers. MRI displayed a higher diagnostic performance over CT in terms of T1/T2 vs T3/T4 (SE: 100% vs 83.9%, SP: 96.6% vs 81%, AUC: 0.825 vs 0.983, p < 0.001), N positive (p < 0.001) and EMVI (p = 0.023) assessment. An excellent performance of MRI was noted in the T3ab vs T3cd (CT AUCReader1: 0.636, AUCReader2: 0.55 vs MRI AUCReader1: 0.829 AUCReader2 0.846, p = 0.01) and RSM invasion diagnosis. In contrast to these, MRI did not perform well in the identification of serosa invasion. MRI had a higher diagnostic yield than CT in several local staging parameters.

Pseudoephedrine for ejaculatory dysfunction after retroperitoneal lymph node dissection in testicular cancer.

To assess the impact of ejaculatory dysfunction (EjD; failure of emission or retrograde ejaculation) on health-related quality of life (HRQoL) after retroperitoneal lymph node dissection (RPLND) for testicular cancer and explore the efficacy of pseudoephedrine hydrochloride as treatment. In a single arm, phase II trial, patients at ≥6 months after RPLND were invited to complete patient-reported outcome measures (European Organisation for Research and Treatment of Cancer [EORTC] quality of life questionnaire [QLQ]-30-item core, EORTC QLQ-testicular cancer-26, and Brief Male Sexual Function Inventory) evaluating HRQoL and sexual function in follow-up (ACTRN12622000537752/12622000542796). If EjD was reported, post-ejaculatory urine ± semen analysis was undertaken. In eligible patients, pseudoephedrine hydrochloride 60 mg was administered orally every 6 h for six doses. The primary endpoint was sperm count >39 million sperm/ejaculate (>5th centile) following treatment. The trial was powered to detect a clinically relevant 36% achieving sperm count of >39 million sperm/ejaculate. Secondary endpoints included semen volume >1.5 mL, total motile sperm count, safety, and HRQoL impacts. Of the 58 patients enrolled, the median (interquartile range [IQR]) age was 35 (29-41) years, with a median (IQR) of 37 (18-60) months from RPLND. EjD was reported in 33 (57%), including 27/52 (52%) receiving follow-up at our centre. There were no differences in global HRQoL; however, role functioning (P = 0.045), sexual problems (P < 0.005), and sexual enjoyment (P = 0.005) was poorer if EjD was present. In all, 24/33 (73%) patients with EjD consented to pseudoephedrine treatment. Of 22 evaluable patients, four (18%) achieved a sperm count of >39 million/ejaculate (P = 0.20), and four (18%) had a semen volume of >1.5 mL (P = 0.20). There was a mean increase of 105 million sperm/ejaculate (P = 0.051) and 1.47 mL increase in semen volume (P = 0.01). No safety concerns arose. Ejaculatory dysfunction is common after RPLND but did not impact global HRQoL in our cohort. Pseudoephedrine improved EjD for some; however, its efficacy was lower than expected. Pseudoephedrine may be considered on an individualised basis.