Prospective Multicenter Clinical Trial Research Articles

Polymer-free sirolimus- and probucol-eluting stents versus durable polymer-based everolimus-eluting stents for percutaneous coronary revascularization: A prospective multicenter randomized clinical trial

Polymer-free sirolimus- and probucol-eluting stents versus durable polymer-based everolimus-eluting stents for percutaneous coronary revascularization: A prospective multicenter randomized clinical trial

When specific exercise is more effective than medication - Sensorimotor training is currently the most promising option to treat and prevent chemotherapy-induced peripheral neuropathy (CIPN).

Introduction Chemotherapy-induced peripheral neuropathy (CIPN) is a highly prevalent and clinically relevant adverse effect of chemotherapy, negatively impacting patient quality of life. The lack of effective preventive or therapeutic options regarding CIPN often requires changes in cancer therapy, potentially resulting in reduced survival. Meanwhile 10 studies have shown that specific exercise can reduce relevant symptoms of CIPN (Streckmann eu al. 2021). In our most recent study (Streckmann et al. 2024) we have been able to show that CIPN can even be prevented by up to 70%. Methods we performed a prospective multicenter randomized clinical trial (STOP) and followed up patients over 5 years (May 2014 – Nov. 2020) at 4 centers and around Cologne, Germany. Patients undergoing treatment with oxaliplatin or vinca alkaloids were recruited. Participants in the intervention groups performed supervised sensorimotor training (SMT) or whole-body vibration training (WBV), twice a week, concomitant to medical therapy. The primary end point was the incidence of CIPN. Secondary end points included subjective neuropathy symptoms, balance control, physical activity levels, quality of life, and clinical outcome. For cross-stratum evaluations, the Mantel-Haenszel test (MH) was used, and within individual strata, Fisher exact test was used for analysis. Results A total 158 patients (mean [SD] age, 49.1 [18.0-82.0] years; 93 [58.9%] male) were randomized into 1 of 3 groups: 55 (34.8%) in SMT, 53 (33.5%) in WBV, and 50 (31.6%) in treatment as usual (TAU). The incidence of CIPN in participants was significantly lower in both intervention groups compared to the control group (TAU): (SMT, 12 of 40 [30.0%; 95% CI, 17.9%-42.1%] and WBV, 14 of 34 [41.2%; 95% CI, 27.9%-54.5%] vs TAU, 24 of 34 [70.6%; 95% CI, 58.0%-83.2%]; P = .002 for intention to treat–MH). Improvements in favor of SMT compared to TAU were furthermore found for balance control bipedal with eyes open; bipedal with eyes closed; monopedal, vibration sensitivity, sense of touch, lower leg strength, pain reduction, burning sensation, chemotherapy dose reductions, and mortality. Discussion/Conclusion Specific exercise can reduce and even prevent the symptoms of a neuropathy. Sensorimotor training seems essential. More high-quality research is needed to derive evidence-based recommendations. Overall, it seems that sensorimotor training has great potential to target most neuropathies and is therefore currently the best treatment option for neuropathies.

ChatGPT-Assisted Machine Learning for Chronic Disease Classification and Prediction: A Developmental and Validation Study.

Background Chronic diseases such as chronic kidney disease (CKD), chronic liver disease (CLD), tuberculosis (TB), dementia, and heart disease are global health concerns of significant importance, representing major causes of morbidity and mortality worldwide. Early diagnosis and interventions are critical to improve patient outcomes and reduce healthcare costs. Methods This prospective observational study analyzed clinical data from 270 patients (calculated using G*Power 3.1.9.7 analysis (Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany), α = 0.05, power = 0.80), with 260 (96.3%) completing the protocol. The cohort comprised 149 (55.2%) males and 121 (44.8%) females, distributed across CKD (n=55, 21.2%), CLD (n=52, 20.0%), TB (n=51, 19.6%), dementia (n=50, 19.2%), and heart disease (n=52, 20.0%). Three ML models were employed with ChatGPT version 3.5 assistance (OpenAI, San Francisco, CA, USA) in feature selection and hyperparameter optimization: logistic regression, random forest, and support vector machines. Model performance was evaluated using accuracy, sensitivity, specificity, precision, recall, F1-score, and AUC-ROC metrics. Ten-fold cross-validation was applied to ensure robustness. Results The random forest model demonstrated superior performance, achieving the highest accuracy in predicting CKD (47/55, 85.3%, p < 0.001, sensitivity 45/55, 82.5%, specificity 48/55, 87.2%) and heart disease (46/52, 88.2%, p < 0.001, sensitivity 45/52, 85.7%, specificity 47/52, 90.1%). Logistic regression effectively predicted TB (41/51, 80.1%, p < 0.01) and dementia (41/50, 82.4%, p < 0.01). Key predictive parameters included hemoglobin (median 10.2 g/dL, IQR 8.4-12.6) and erythrocyte sedimentation rate (median 42.0 mm/hr, IQR 20.0-65.0). Model validation showed high consistency, with positive acid-fast bacilli in 40/51 (78.4%) TB cases and characteristic radiological findings in 43/51 (84.3%) cases. Conclusion ML algorithms, particularly random forest, show promising potential in chronic disease classification and prediction. The integration of ChatGPT enhanced model development through optimized feature selection and hyperparameter tuning. Future research should focus on external validation through multi-center studies and prospective clinical trials.

Effects of valsartan vs amlodipine and achieved lower blood pressure on the incidence of end-stage kidney disease: The VALUE Trial.

There is a paucity of data investigating the impact of antihypertensive drug classes and blood pressure (BP) treatment targets on the incidence of end-stage kidney disease (ESKD). In patients with high-risk hypertension aged 50-80 years or above, we aimed to, 1) compare effects of valsartan, an angiotensin receptor blocker, with amlodipine, a calcium channel blocker and, 2) assess the effect of achieving systolic BP <135 vs ≥135 mmHg on the ESKD incidence. The VALUE Trial was a multicenter prospective double-blinded randomized clinical trial in patients with essential hypertension and high cardiovascular risk including known coronary disease, left ventricular hypertrophy and previous stroke, in which ESKD was a secondary endpoint defined as progression to kidney transplant and/or dialysis. Patients were randomized to either valsartan or amlodipine, with other anti-hypertensive medications as add-on if needed to reach the systolic BP target of <140 mmHg. Cox proportional hazards ratio (HR) was used to compare different treatment groups and achieved systolic BP <135 with ≥135 mmHg, during 3-6 years of follow-up. 15,245 patients were randomized and followed until 63,631 patient-years with only 90 patients lost to follow-up. The primary outcome, a composite of cardiac morbidity and mortality, was neutral between valsartan and amlodipine. On valsartan 47 patients (0.61 %) and on amlodipine 50 patients (0.66 %) developed ESKD (HR=1.02, 95 % CI 0.68-1.52, p =0.94). Achieved SBP <135 mmHg was strongly related to less ESKD (n =9/5036 patients, 0.2 %) compared with achieved SBP ≥135 mmHg (n =73/8766 patients, 0.8 %) (HR=0.28, CI 0.14-0.58, p <0.001). In hypertensive patients with a high cardiovascular risk, valsartan and amlodipine have a similar impact on the incidence of end-stage kidney disease. Achieving SBP <135 mmHg, averaging 128.8/77.3 mm, is highly efficacious in kidney protection.

Prospective multicentric randomised clinical trial among early stage tongue cancer patients- evaluating effect of peritumoural infiltration of local anaesthetic agent prior to surgery on local control

Prospective multicentric randomised clinical trial among early stage tongue cancer patients- evaluating effect of peritumoural infiltration of local anaesthetic agent prior to surgery on local control

Risk factors of level Ib lymph node metastasis and clinical outcome of its selectively prophylactic irradiation in nasopharyngeal carcinoma: A real-world study

PurposeTo evaluate the risk factor of level Ib lymph node metastasis (LNM) and the clinical outcome of its selectively prophylactic irradiation (pRT) in nasopharyngeal carcinoma (NPC) patients treated with IMRT. Methods518 NPC patients receiving radical IMRT were collected. The structures of primary tumor invasions and neck LNM levels were analyzed bilaterally to estimate the risk factors of level Ib LNM. Patients with level Ib LNM and submandibular gland (SMG) invasion received level Ib pRT. The level Ib recurrence-free survival (RFSIb), regional recurrence-free survival (RRFS), and the incidence of ≥ grade 2 xerostomia at 1-year post-IMRT were compared in negative level Ib LNM patients who omitted, received unilateral, or bilateral level Ib pRT. ResultsThirteen (2.5 %) patients with 18 sides had level Ib LNM. Ipsilateral SMG invasion was an independent risk factor for level Ib LNM. With a median follow-up time of 98.0 months, the 5-year RFSIb, 5-year RRFS and the incidence of xerostomia ≥ grade 2 at 1-year post-IMRT in negative level Ib LNM patients who omitted pRT, received unilateral, bilateral pRT to the level Ib were 99.7 % vs.100 % vs. 97.5 % (P = 0.110), 98.0 % vs. 92.1 % vs. 95.1 % (P = 0.120) and 28.0 % vs. 38.3 % vs. 90.0 % (P < 0.001), respectively. ConclusionsOur study revealed that ipsilateral SMG invasion was the independent risk factor for the level Ib LNM. Omitting pRT in patients without ipsilateral level Ib LNM and SMG invasion did not increase the RFSIB and RRFS, and reduced the incidence of xerostomia. Further multi-center prospective randomized clinical trial is warranted.

Sirolimus Plus Roxadustat in Patients with Pure Red Cell Aplasia: Results from a Prospective Multi-Center Clinical Trial

Sirolimus Plus Roxadustat in Patients with Pure Red Cell Aplasia: Results from a Prospective Multi-Center Clinical Trial

Usefulness of a dedicated laser-cut metal stent with an anchoring hook and thin delivery system for endoscopic ultrasound-guided hepaticogastrostomy in malignant biliary obstruction: a prospective multicenter trial (with video).

Background and AimsEUS-guided hepaticogastrostomy (EUS-HGS) carries a risk of serious adverse events (AEs). A newly designed, partially covered laser-cut stent with antimigration anchoring hooks and a thin tapered tip (7.2F), called a Hook stent, has been developed to prevent serious AEs associated with EUS-HGS. The present prospective multicenter clinical trial evaluated the efficacy and safety of the Hook stent for EUS-HGS after failure of ERCP in patients with unresectable malignant biliary obstruction. MethodsThe primary endpoint was the rate of clinical success, and the secondary endpoints were the rates of technical success, AEs, recurrent biliary obstruction (RBO), procedure success without using a tract dilation device, re-intervention for RBO, time to RBO (TRBO) and overall survival (OS). ResultsA total of 38 patients underwent EUS-HGS using the Hook stent. Its technical and clinical success rates in patients undergoing EUS-HGS were 100% and 92.1%, respectively. The procedure success rate without using a tract dilation device was 94.7%. Four (10.5%) patients developed early AEs, but there were no severe AEs such as stent migration. RBO developed in 26.3% of patients. Re-intervention for RBO had a 100% success rate. The median TRBO was not reached, and the median OS was 191 days. ConclusionsEUS-HGS using the Hook stent demonstrated a high clinical success rate, a low rate of early AEs, and an acceptable stent patency. The Hook stent is safe and feasible for use in patients undergoing EUS-HGS.

Clinical improvements after endoscopic lung volume reduction with valves in patients with advanced emphysema and a 6-min walk test ≤140 m at baseline.

Data regarding the effectiveness and safety of endoscopic lung volume reduction with valves (ELVR) in emphysema patients with a very low 6-min walk test (6MWT) are limited. Patients with severe emphysema and very low exercise capacity, as indicated by a 6MWT ≤140 m, are often excluded from clinical studies on ELVR, assuming limited therapeutic benefits and increased complication risk. This study utilised data from the Lungenemphysemregister e.V., a large German national multi-centre prospective open-label clinical trial, and aimed to assess the outcomes of ELVR in patients with a baseline 6MWT ≤140 m and dyspnoea primarily attributed to hyperinflation. 54 patients with a baseline 6MWT ≤140 m and 365 patients with a baseline 6MWT between 140 and 450 m were included in the study. Baseline characteristics were representative for patients with advanced lung emphysema. Patients with a 6MWT ≤140 m at baseline had a lower forced expiratory volume in 1 s and diffusing capacity of the lung for carbon monoxide and higher symptom burden. In the 3-month follow-up, patients of both groups showed statistically significant improvements in lung function parameters, exercise capacity and quality of life parameters compared to baseline. Patients with a 6MWT ≤140 m at baseline showed significantly more 6MWT improvement compared to patients with baseline 6MWT between 140 and 450 m. Moreover, complication rates were similar in both groups. In summary, the data indicate that ELVR may be an effective and safe treatment for emphysema patients with a very low 6MWT of ≤140 m if very limited exercise capacity is predominately caused by lung emphysema. Therefore future studies should include emphysema patients with a very low 6MWT.

Evaluation of safety and effectiveness of the LISTENT LCI-20PI cochlear implant in prelingually deafened children

ObjectivesThis prospective multicenter clinical trial was to evaluate the safety and effectiveness of a novel cochlear implant (CI) system, the LISTENT LCI-20PI device in prelingually deafened children (<6 years old). DesignThe LCI-20PI CI system was implanted in 70 prelingually deafened children (<6 years old). The median age (interquartile range) at implantation was 3 years old (2–4 years old). The status of the LCI-20PI devices was evaluated through CI device testing and fitting including measurement of electrically evoked compound action potential (ECAP), electrode impedances, subjective thresholds (T levels), and subjective comfort levels (C levels). The safety and effectiveness of the devices were evaluated during 1-year follow-up. The clinical trial registration number is ChiCTR2200067092. ResultsECAPs were successfully measured in 92.8% (64/70) recipients intraoperatively and in 94.3% (66/70) recipients during device activation. Most of the impedances (99.7%) were within normal limits of 0.7–20 kOhm. The median (interquartile ranges) Meaningful Auditory Integration Scale/Infant-Toddler Meaningful Auditory Integration Scale (MAIS/IT-MAIS) was 95% (85%–97.5%) at 12-month post-activation testing. Median (interquartile range) close-set monosyllabic-word recognition score (MRS) and disyllabic-word recognition score (DRS) in children 3–6 years old at 12-month post-activation testing were 86% (77%–97%) and 90% (70%–100%), respectively. ConclusionsThe new developed LCI-20PI CI device proved safe and effective in prelingually deafened children (<6 years old) in the clinical trial. This CI system could be a cost-effective alternative for prelingually deafened children.

The sixth sense: how much does interictal intracranial EEG add to determining the focality of epileptic networks?

Intracranial EEG is used for two main purposes: to determine (i) if epileptic networks are amenable to focal treatment and (ii) where to intervene. Currently, these questions are answered qualitatively and differently across centres. There is a need to quantify the focality of epileptic networks systematically, which may guide surgical decision-making, enable large-scale data analysis and facilitate multi-centre prospective clinical trials. We analysed interictal data from 101 patients with drug-resistant epilepsy who underwent pre-surgical evaluation with intracranial EEG at a single centre. We chose interictal data because of its potential to reduce the morbidity and cost associated with ictal recording. Sixty-five patients had unifocal seizure onset on intracranial EEG, and 36 were non-focal or multi-focal. We quantified the spatial dispersion of implanted electrodes and interictal intracranial EEG abnormalities for each patient. We compared these measures against the '5 Sense Score,' a pre-implant prediction of the likelihood of focal seizure onset, assessed the ability to predict unifocal seizure onset by combining these metrics and evaluated how predicted focality relates to subsequent treatment and outcomes. The spatial dispersion of intracranial EEG electrodes predicted network focality with similar performance to the 5-SENSE score [area under the receiver operating characteristic curve = 0.68 (95% confidence interval 0.57, 0.78)], indicating that electrode placement accurately reflected pre-implant information. A cross-validated model combining the 5-SENSE score and the spatial dispersion of interictal intracranial EEG abnormalities significantly improved this prediction [area under the receiver operating characteristic curve = 0.79 (95% confidence interval 0.70, 0.88); P < 0.05]. Predictions from this combined model differed between surgical- from device-treated patients with an area under the receiver operating characteristic curve of 0.81 (95% confidence interval 0.68, 0.85) and between patients with good and poor post-surgical outcome at 2 years with an area under the receiver operating characteristic curve of 0.70 (95% confidence interval 0.56, 0.85). Spatial measures of interictal intracranial EEG abnormality significantly improved upon pre-implant predictions of network focality by area under the receiver operating characteristic curve and increased sensitivity in a single-centre study. Quantified focality predictions related to ultimate treatment strategy and surgical outcomes. While the 5-SENSE score weighed for specificity in their multi-centre validation to prevent unnecessary implantation, sensitivity improvement found in our single-centre study by including intracranial EEG may aid the decision on whom to perform the focal intervention. We present this study as an important step in building standardized, quantitative tools to guide epilepsy surgery.

Correlation of tracer uptake in sentinel lymph nodes as measured on SPECT/CT and during intra-operative gamma tracing with SENSEI: the UZ Leuven experience

PurposeThis retrospective analysis aims to study the relationship between tracer uptake in sentinel lymph nodes (SLNs) as measured on SPECT/CT and during intra-operative gamma tracing with a drop-in gamma probe (SENSEI®) in patients who participated in the UZ Leuven cohort of a prospective multicentre clinical trial evaluating the SENSEI® probe for minimally-invasive SLN biopsy (SLNB) in prostate cancer. Correlation of pre- and intraoperative imaging can allow for improved surgical planning, providing important information to guide intraoperative findings.MethodsNine patients with histologically proven prostate cancer scheduled for radical prostatectomy (RP) with extended pelvic lymph node dissection (ePLND) were prospectively selected for preoperative lymphoscintigraphy with SPECT/CT the day before surgery after intra-prostatic injection of 240 MBq of 99mTc-nanocolloid under ultrasound guidance. SLNB was performed with the SENSEI® drop-in gamma probe during standard of care RP with ePLND. SLN detection and counts on SPECT/CT and in vivo and ex vivo probe measurements were compared.ResultsThe patient-based detection rate of at least one SLN was 100% on SPECT/CT and 100% intraoperatively with the drop-in gamma probe. In total, 29 SLNs were detected with the probe and 32 SLNs on SPECT/CT. The correlation between SPECT/CT counts and in vivo and ex vivo probe measurements was significant but moderate (Pearson r = 0.57, p = 0.002 and r = 0.64, p = 0.0003, respectively).ConclusionsDrop-in gamma probe measurements showed a moderate correlation with the SPECT/CT counts. SPECT/CT uptake values can be used as an estimate for in vivo detection of SLNs with the probe.

The impact of time to postoperative recurrence on the prognosis of patients with esophageal cancer post recurrence: exploratory analysis of OGSG 1003.

The association between recurrence timing and prognosis in patients with locally advanced resectable esophageal cancer undergoing neoadjuvant chemotherapy (NAC) followed by esophagectomy remains unclear. This study aimed to clarify this association using multicenter prospective clinical trial data. Among 162 patients enrolled in a NAC phase II study comparing the efficacy of cisplatin and fluorouracil plus docetaxel with cisplatin and fluorouracil plus adriamycin, 64 patients with recurrence after R0 resection were included in this study. We evaluated the association between recurrence timing and overall survival after recurrence (OSr), along with clinicopathological factors associated with recurrence timing and OSr. Among 64 patients, 46 (71.9%) and 59 (92.2%) experienced recurrence within 1 and 2years after surgery, respectively. Groups based on recurrence timing, including ≤ 6, 6-12, and > 12 months, had median OSr of 3.6, 13.9, and 13.4 months, respectively. The prognosis was significantly poorer for patients with recurrence ≤ 6 months after surgery than for other patients (P < 0.001). Multivariate analysis revealed pathological lymph node staging as an independent factor associated with early recurrence (odds ratio: 3.46, 95% confidence interval: 1.47-8.02, P = 0.0045). On the other hand, multivariate analysis for factors associated with OSr revealed pT (hazard ratio [HR]: 1.91, 95%CI 1.26-2.88, P = 0.0022), early recurrence (HR: 6.88, 95%CI 2.68-17.6, P < 0.001), and treatment after recurrence, with both local treatment (HR: 0.47, 95%CI 0.22-0.98, P = 0.043) and chemotherapy (HR: 0.25, 95%CI 0.11-0.58, P = 0.0011) as independent prognostic factors. Patients with advanced esophageal cancer experiencing recurrence within 6 months after esophagectomy following NAC have an extremely poor prognosis, suggesting that an advanced pN stage is associated with early recurrence.

Tackling challenges in rare diseases: The ISGACA approach on non-pancreatic cancers in the periampullary region

ObjectiveRare but aggressive cancer types like non-pancreatic periampullary cancers pose unique challenges for cancer research due to their low incidence rates and lack of consensus on optimal treatment strategies, therefore necessitating a collaborative approach. The International Study Group on non-pancreatic peri-Ampullary CAncer (ISGACA) aimed to build a collaborative initiative to pool expertise, funding opportunities, and data from over 60 medical centers, in order to improve outcomes for underrepresented patients with rare cancers. MethodsThe ISGACA approach predefined a stepwise approach including a research scope, establishing a dedicated steering committee, creating a recognizable brand, identifying research gaps, following a well-defined timeline, ensuring robust data collection, addressing legal and ethical considerations, securing financial resources, investing in research ethics training and statistical expertise, raising awareness, creating uniformity, and initiating prospective studies. ResultsOverall, 60 medical centers joined the ISGACA consortium (41 in Europe, 15 in North-America, three in Asia, one in Australia). The database includes 4309 patients. Nine publications and several ongoing studies which in turn allowed for a successful application of research grants. Subsequently, an international consensus meeting established uniform definitions and classifications, and one prospective multicenter international clinical trial has been initiated. ConclusionBy sharing knowledge, expertise, and clinical data, the ISGACA approach has not only gathered sufficient evidence to secure grants and ethical approvals for prospective studies, but also demonstrates options for standardizing patient care and improving outcomes for patients with rare cancers. The ISGACA approach offers a detailed methodology for initiating research on rare cancers and could serve as a replicable model for future research initiatives.

Tumor microenvironment RNA test to predict immunotherapy outcomes in advanced gastric cancer: The TIMES001 trial

Clinical trials support the efficacy of immune checkpoint blockades (ICBs) plus chemotherapy in a subset of patients with metastatic gastric cancer (mGC). To identify the determinants of response, we developed a TMEscore model to assess tumor microenvironment (TME), which was previously proven to be a biomarker for ICBs. A reference database of TMEscore assays was established using PCR assay kits containing 30 TME genes. This multi-center prospective clinical trial (NCT#04850716) included patients with mGC who were administered ICB combined with chemotherapy as a first-line regimen. Eighty-six tumor samples extracted from five medical centers before treatment were used to estimate the TMEscore, PD-L1 (CPS), and mismatch repair deficiency. The objective response rate (ORR) and median PFS of the cohort were 31.4% and six months. Enhanced ORR was observed in TMEscore-high mGC patients (ORR= 59%). The survival analysis demonstrated that high TMEscore was significantly associated with a more favorable PFS and OS. Moreover, TMEscore was found to be a predictive biomarker that surpassed MSI and CPS (AUC= 0.873, 0.511, and 0.524, respectively). By integrating the TMEscore and clinical variables, the fused model further enhances the predictive efficiency and translational application in a clinical setting. This prospective clinical study indicates that the TMEscore assay is a robust biomarker for screening patients with mGC who may derive survival benefits from ICB plus chemotherapy. Guangdong Basic and Applied Basic Research Foundation (2023A1515011214), Science and Technology Program of Guangzhou (202206080011), and Guangzhou Science and Technology Project (2023A03J0722 and 2023A04J2357).

A multicenter prospective clinical trial on the effect of domestic bone level implants on single tooth implantation and restoration

Objective: To evaluate the clinical application effects of a domestic bone-level implant system for restoring single tooth loss, and provide clinical evidence for the promotion and application of domestic implants. Methods: A prospective, multicenter clinical trial was conducted from April 2018 to January 2020 in three institutions: Department of Oral Implantology, School & Hospital of Stomatology, Wuhan University, Department of Stomatology, The First Affiliated Hospital of Zhejiang University School of Medicine, and Department of Stomatology, The Third Hospital of Hebei Medical University. The trial planned to include 100 patients for single tooth implantation and restoration, followed up for 1 year, to evaluate the implantation success rate and other related outcomes. Results: This study screened a total of 142 patients and ultimately included 100, comprising 43 males and 57 females with age of (47.0±12.2) years. Ninety-eight out of 100 patients completed a one-year follow-up (98.0%), while 2 patients terminated the trial early due to implant loosening (2.0%). After a one-year follow-up, the implants of the 98 patients were all functioning successfully, with a success rate of 98.0% (98/100). The patients were satisfied with the overall restoration effect. Conclusions: This study indicates that the domestic bone-level implant system has achieved favorable short-term clinical outcomes for single-tooth implantation and restoration.

Comparison of the effect of combined usage of povidone-iodine irrigation and topical vancomycin powder to the use of povidone-iodine irrigation alone on the periprosthetic joint infection incidence rate in patients undergoing primary total hip and knee arthroplasty: a protocol for multicenter prospective randomized clinical trial

BackgroundWith the increasing number of joint replacement surgeries, periprosthetic joint infection (PJI) has become a significant concern in orthopedic practice, making research on PJI prevention paramount. Therefore, the study will aim to compare the effect of combined usage of povidone-iodine and topical vancomycin powder to the use of povidone-iodine alone on the PJI incidence rate in patients undergoing primary total hip (THA) and total knee arthroplasty (TKA).MethodsThe prospective randomized clinical trial will be conducted in two independent voivodeship hospitals with extensive experience in lower limb arthroplasties. The studied material will comprise 840 patients referred to hospitals for primary THA or TKA. The patients will be randomly allocated to two equal groups, receiving two different interventions during joint replacement. In group I, povidone-iodine irrigation and consecutively topical vancomycin powder will be used before wound closure. In group II, only povidone-iodine lavage irrigation will be used before wound closure. The primary outcome will be the incidence rate of PJI based on the number of patients with PJI occurrence within 90 days after arthroplasty. The occurrence will be determined using a combined approach, including reviewing hospital records for readmissions and follow-up phone interviews with patients. The infection will be diagnosed based on Musculoskeletal Infection Society criteria. The chi-square test will be used to compare the infection rates between the two studied groups. Risk and odds ratios for the between-groups comparison purposes will also be estimated. Medical cost analysis will also be performed.DiscussionA randomized clinical trial comparing the effect of combined usage of povidone-iodine irrigation and vancomycin powder to the use of povidone-iodine irrigation alone in preventing PJIs after primary arthroplasty is crucial to advancing knowledge in orthopedic surgery, improving patient outcomes, and guiding evidence-based clinical practices.Trial registrationClinicalTrials.gov NCT05972603. Registered on 2 August 2023.

Preventive Effect of Neuromuscular Training on Chemotherapy-Induced Neuropathy

Chemotherapy-induced peripheral neuropathy (CIPN) is a highly prevalent and clinically relevant adverse effect of chemotherapy, negatively impacting patient quality of life. The lack of effective preventive or therapeutic options regarding CIPN often requires changes in cancer therapy, potentially resulting in reduced survival. To determine whether sensorimotor training (SMT) and whole-body vibration (WBV) training reduce symptoms and decrease the onset of CIPN. This prospective multicenter randomized clinical trial (STOP) followed up patients over 5 years at 4 centers in or near Cologne, Germany. Patients undergoing treatment with oxaliplatin or vinca alkaloids were recruited. Participants were recruited from May 2014 to November 2020. Data were last analyzed in June 2021. Participants in the intervention groups performed supervised SMT or WBV training sessions twice a week, each lasting approximately 15 to 30 minutes, concomitant to medical therapy. The primary end point was the incidence of CIPN. Secondary end points included subjective neuropathy symptoms, balance control, physical activity levels, quality of life, and clinical outcome. For cross-stratum evaluations, the Mantel-Haenszel test (MH) was used, and within individual strata, Fisher exact test was used for analysis. A total of 1605 patients were screened, and 1196 patients did not meet all inclusion criteria, with 251 further excluded or declining participation. A total of 158 patients (mean [SD] age, 49.1 [18.0-82.0] years; 93 [58.9%] male) were randomized into 1 of 3 groups: 55 (34.8%) in SMT, 53 (33.5%) in WBV, and 50 (31.6%) in treatment as usual (TAU). The incidence of CIPN in participants was significantly lower in both intervention groups compared to the control group (TAU): (SMT, 12 of 40 [30.0%; 95% CI, 17.9%-42.1%] and WBV, 14 of 34 [41.2%; 95% CI, 27.9%-54.5%] vs TAU, 24 of 34 [70.6%; 95% CI, 58.0%-83.2%]; P = .002 for intention to treat-MH). Patients receiving vinca alkaloids and performing SMT benefited the most. Results were more pronounced in a per-protocol analysis (>75% participation in the intervention) (SMT, 8 of 28 [28.6%; 95% CI, 16.6%-40.5%] and WBV, 9 of 24 [37.5%; 95% CI, 24.4%-50.5%] vs TAU, 22 of 30 [73.3%; 95% CI, 61.6%-85.6%]). Improvements in favor of SMT compared to TAU were found for balance control bipedal with eyes open; bipedal with eyes closed; monopedal, vibration sensitivity, sense of touch, lower leg strength, pain reduction, burning sensation, chemotherapy dose reductions, and mortality. This randomized clinical trial provides initial evidence that neuromuscular training decreases the onset of CIPN. German Clinical Trials Register: DRKS00006088.

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

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

Post-transplant cyclophosphamide-based graft-versus-host disease prophylaxis following mismatched unrelated donor peripheral blood stem cell (PBSC) transplantation.

6503 Background: Our prior prospective multi-center clinical trial (15-MMUD; NCT02793544) estimated 79% overall survival (OS) at one year in adult patients with hematological malignancies undergoing reduced intensity conditioning (RIC), receiving bone marrow (BM) grafts from HLA-mismatched unrelated donors (MMUD), and post-transplant cyclophosphamide (PTCy)-based graft- versus-host disease (GVHD) prophylaxis (Shaw et al, J Clin Oncol 2021). We sought to determine whether OS in adults receiving mobilized PBSC from MMUD would be comparable. Methods: We conducted a prospective, multi-center Phase II study (ACCESS; NCT04904588) to assess the impact of PTCy-based GVHD prophylaxis on OS following MMUD transplantation in adults and children with advanced hematological malignancies. The study included three strata: two for adults based on conditioning regimen intensity [myeloablative (MAC) or RIC] using PBSC, and one pediatric cohort using MAC and BM. Eligible donors were matched at 4-7/8 HLA-loci (HLA -A, -B, -C, and -DRB1) and &lt; 35 years. The primary endpoint was OS at one year following transplantation. We report the results of a planned interim analysis of the first 70 adult patients enrolled on the RIC PBSC stratum. Results: Thirteen sites enrolled 70 patients with the following demographics: median age of 65 years (range 24-77); 50% male; diagnoses: AML (53%), MDS (26%), ALL (7%), other heme malignancies (14%); and patient race/ethnicity: non-Hispanic white (48%). Donor characteristics included: median age 25y (range 18-35); male (44%); and HLA match level: 7/8: 67%; 6/8: 27%; 5/8: 6%. Conditioning regimens included fludarabine (flu) and melphalan (63%), flu/busulfan (20%), other (17%). OS at one year post HCT was 79% (95% confidence interval (CI): 68-87%). Secondary endpoints are provided in the table. Conclusions: Encouraging OS was observed at one year following MMUD PBSC in patients receiving RIC and PTCy. Notably, half of enrolled patients were people of color. OS was similar to our prior study using BM grafts. Rates of GVHD and other complications appear comparable to those in HLA-matched donor recipients, suggesting MMUD HCT could expand access to a potentially life-saving therapy. Accrual to both adult strata of ACCESS is complete, with over 200 patients in follow-up. Accrual to the pediatric stratum continues. Clinical trial information: NCT04904588 . [Table: see text]