Multicenter Clinical Study Research Articles

Long-term Responders to Nanoparticle Albumin-bound Paclitaxel Following Immune Checkpoint Inhibitor in Non-small Cell Lung Cancer.

The efficacy of cytotoxic chemo-therapy has been reported to improve after immune checkpoint inhibitor (ICI) administration. We previously conducted a multicenter prospective clinical study to evaluate the efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-PTX) after ICI treatment. In that study, some patients showed a long-term response to nab-PTX, which is not usually observed with single-agent chemotherapy. The present study aimed to evaluate the clinical characteristics of these patients. We retrospectively analyzed updated data from 29 patients enrolled in our clinical study who received nab-PTX monotherapy after ICI treatment. We defined a "long-term responder" as a patient who achieved a 1-year progression-free survival (PFS). Among the 29 patients, 10 (34.5%) were long-term responders, two of whom achieved a 5-year PFS. A key difference between long-term and non-long-term responders was that the long-term responders had a significantly higher number of patients with Eastern Cooperative Oncology Group-performance status of 0 (70.0% versus 10.5%; p=0.002). Furthermore, median cycles of previous ICIs and median treatment cycles were significantly higher in long-term responders than in non-long-term responders (8 cycles versus 3 cycles; p=0.03) (5.9 months versus 2.0 months; p=0.02). In the 10 long-term responders, six patients required at least a one-stage dose reduction owing to adverse events, and four patients required a two-stage dose reduction. Nab-PTX administration after ICI treatment may elicit a long-term response. A long-term response can be achieved even with a dose reduction due to adverse events.

Inter-Reader Agreement for Contrast-Enhanced Ultrasound Liver Imaging Reporting and Data System Major Features and Final Categorization: A Subanalysis From a Prospective Multicenter Study.

Contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS) is used to definitively diagnose hepatocellular carcinoma (HCC) in patients at risk. However, the user variability associated with CEUS LI-RADS has not been validated in North American and European patients. This study aims to evaluate the inter-reader agreements of CEUS LI-RADS features for, and final categorization of, HCC in patients at risk. This retrospective multicenter clinical study used the database of a previous prospective multinational study, evaluating the accuracy of CEUS LI-RADS for HCC diagnosis in patients at risk. All cases were first evaluated by a site physician performing/supervising the CEUS examination. Randomly selected cases were re-evaluated by a blinded central reader. Final diagnosis was confirmed with the reference standard, which was a composite of imaging tests and histology. Cohen's kappa test was used to evaluate inter-reader agreement. This study included 150 liver nodules and 58.0% (87/150) were confirmed as HCC, 4.7% (7/150) non-HCC malignancies, 22.7% (34/150) had no confirmed final diagnosis, and 14.7% (22/150) were nonmalignant. Inter-reader agreements were substantial for CEUS LI-RADS categorization (κ = 0.61; 95% confidence interval [CI]: 0.51-0.71) and major features assessment (ranged κ = 0.64-0.78), LR-5 (κ = 0.65; 95% CI: 0.52-0.77), and LR-M (κ = 0.67; 95% CI: 0.44-0.90), while for LR-1 and LR-2 categorization was almost perfect (κ = 0.85; 95% CI: 0.65-1.00). Our study reported a substantial inter-reader agreement for overall CEUS LI-RADS categorization, especially for LR-5 and LR-M, and major imaging features of HCC, further confirming CEUS LI-RADS as a valuable and reliable tool for diagnosis of HCC.

Effects of Chios Mastiha essential oil on cholesterol levels of healthy volunteers: a prospective, randomized, placebo-controlled study

Abstract Introduction Chios Mastiha essential oil (CMO) is a natural product extracted from the resin of Mastiha, possessing antioxidant, anti-microbial, anti-ulcer, anti-neoplasmatic and cholesterol lowering capabilities in vitro, and its hypolipidemic effect was confirmed in animal studies. Yet, there are no randomized, placebo-controlled clinical studies in the literature regarding CMO’s hypolipidemic effects in humans. A prospective, randomized, placebo-controlled study was designed to study the hypolipidemic effect of CMO capsules on healthy volunteers with elevated cholesterol. Methods 192 healthy volunteers were screened and 160 of them with total cholesterol> 200 mg/dl participated in the study. They were randomized with a 2:1 ratio of receiving CMO capsules (200 mg mastiha-oil/capsule) and placebo for 8 weeks respectively. 113 patients received CMO and 47 were randomized in the control group, and all of them completed the follow-up period. Results After 8 weeks of CMO administration, total and LDL cholesterol were significantly lower in the CMO compared to the placebo group 215.2±27.5 vs 237.0±27.9 mg/dl (p<0.001) and 135.0±26.1 vs 153.0±23.3 mg/dl (p<0.001) respectively. No gastrointestinal adverse events, liver or renal toxicity were reported. Additionally, in the CMO group total cholesterol was significantly decreased by 20.6 mg/dl (9%) and LDL by 18.1 mg/dl (12%), triglycerides by 21.8 mg/dl (15%) and glucose by 4.6 mg/dl (5%) and HDL was increased by 2.4 mg/dl (5%), compared to their baseline values. Conclusion MASTIHA-OIL study showed the efficacy and safety of CMO in reduction of Total and LDL-cholesterol after 8 weeks of administration in healthy volunteers with elevated cholesterol levels. Multicenter clinical studies are needed to further study its hypolipidemic effect and establish CMO as a treatment choice for patients with dyslipidemia, given its safety, efficacy and multiple beneficial biologic effects.

Could piano music therapy alleviate high sinus rhythm in subjects with controlled hypertension?

Abstract Background/Introduction With a millenary tradition, music is rediscovered nowadays, as adjuvant therapy. The number of beats per minute (bpm) is the common factor of cardiology – representing heart rate (HR), and music – reprezentative for tempo. Purpose Our goal was the HR modulation in patients (pts) with moderate tachycardia using three piano kits: K1 – Adagio by Albinoni, K2 – Piano Concerto nr. 21 by Mozart, second part; and K3 – Liebestraum by Liszt. Methods During 1st January – 31st December 2023, we identified by ambulatory screening 288 pts adequate for our goal. As exclusion criterion, we considered any type of rhythm or conduction dysturbances. All selected pts were controlled with antihypertensive agents not altering HR, usually thiazide/thiazide-like diuretics and/or ACEis/ARBs. The study group consisted in 144 hypertensive pts controlled at least six months, without any other cardiac diseases. The control group consisted in 144 pts with normal cardiologic examination. Both groups were demographically balanced. The HR at admission was between 84 and 120 bpm, the pts being stratified in three bpm subcategories. All pts have done three visits consisting in: physical examination, ECG, lab markers, TTE for V1 at initiation and EoS at six months, and respectively, physical exam and ECG for V2 at 3 months. Results (in bpm): Inside the group with HR 84-96 treated with K1, the Controlled HTN group (CHG) and the Normal Cardiac group (NCG) alleviated HR from 85,8 +/- 12,6 to 82,6 +/- 12,2; and from 85,7 +/- 12,6 to 80,8 +/- 11,9, respectively. For pts inside the interval 97-108 treated with K1, the CHG group and the NCG alleviated HR from 94,3 +/- 14,1 to 90,9 +/- 13,7 and, respectively, from 94,4 +/- 14,1 to 89,7 +/- 13,6. In pts from HR spectrum 97-108 treated with K2, the CHG and the NCG alleviated HR from 98,4 +/- 14,6 to 95,7 +/- 14,1; and from 98,5 +/- 14,6 to 94,1 +/- 13,8; respectively. Inside the group with HR spectrum 109-120 treated with K1, the CHG and the NCG alleviated HR from 97,1 +/- 14,3 to 94,8 +/- 13,9; and, respectively, from 97,0 +/- 14,3 to 93,9 +/- 13,7. For pts inside the interval 109-120 treated with K2, the CHG and the NCG alleviated HR from 101,7 +/- 14,6 to 99,3 +/- 14,2; and from 101,8 +/- 14,6 to 97,3 +/- 14,1; respectively. In pts from HR spectrum 109-120 treated with K3, the CHG and the NCG alleviated HR from 106,1 +/- 14,7 to 103,8 +/- 14,6; and from 106,5 +/- 14,4 to 103,6 +/- 14,4; respectively. Conclusions The effect of piano music on HR seems favorable in controlled hypertensive pts without major comorbidities, probably by interfering the sympathetic vegetative nervous system. In this regard, it could be used as adjuvant in optimizing this cardiac parameter. However, a multicentered randomized clinical study will be needed.

Application of anticoagulants in the perioperative period of pci for patients with a history of atrial fibrillation and NSTEMI: a real-world, large multicenter retrospective clinical study

Abstract Backgrounds The optimal management for patients with atrial fibrillation (AF) and concomitant coronary artery disease (CAD) remains unclear, particularly regarding anticoagulants use and ischemia-bleeding balance risks. This study aims to investigate the impact of perioperative anticoagulant use on patients with AF and acute non-ST-segment elevation myocardial infarction (NSTEMI). Methods Data for this study were obtained from a retrospective cohort of patients admitted to and discharged from 72 secondary and tertiary hospitals from 2010 to 2023. A total of 150,530 patients were enrolled, including 74,373 NSTEMI patients. Patients were divided into anticoagulants and non-anticoagulants groups. A total of 1,358 patients were included in the non-anticoagulant group, and 3,541 patients were included in the anticoagulant group. Patients in each group were one-to-one matched based on propensity scores using the nearest available pair matching (PSM) method with a caliper width equal to 0.01. The primary endpoints were major adverse cardiovascular and cerebrovascular adverse events (MACCE), including cardiovascular death, recurrent myocardial infarction, and stroke. Secondary endpoints included cardiovascular death, recurrent myocardial infarction, BARC type 3 bleeding, and cerebral hemorrhage. Follow-up time points were set at 1 month,3 months, and 6 months. Multivariate Cox regression models were used to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI). Results After PSM matching, each group consisted of 809 patients. The anticoagulant group had a higher proportion of males, a higher prevalence of patients with a history of Percutaneous Coronary Intervention, and hyperlipidemia, while proportions of patients with Killips classification of III/IV and history of chronic kidney disease were lower. Anticoagulant use during the perioperative period significantly reduced the occurrence of MACCE at the primary endpoint at 1 month (aHR 0.57; P < 0.001), 3 months (aHR 0.57; P = 0.023), and 6 months (aHR 0.57; P < 0.001). At the secondary endpoint, anticoagulants use was associated with a lower incidence of cardiogenic death at 1 month,3 months, and 6 months (aHR 0.55; P <0.001), (aHR 0.55; P <0.001), (aHR 0.56; P <0.001), lower risk of myocardial infarction recurrence at 3 months and 6 months (aHR 0.47; P = 0.02), (aHR 0.44; P <0.001), without increasing the risk of bleeding events, including BARC type 3 bleeding and cerebral hemorrhage. Conclusion Perioperative anticoagulant use during PCI can reduce the occurrence of cardiac death, myocardial infarction, and stroke recurrence within 6 months post-surgery without increasing bleeding events in AF and NSTEMI patients. Therefore, for patients with AF, it is recommended to consider combining anticoagulant therapy with dual antiplatelet therapy during the perioperative period, if no contraindications.

Outcomes of bilateral temporomandibular joint arthroscopy: an international multicentric prospective study including 524 joints.

This study aimed to evaluate the efficacy of bilateral TMJ arthroscopy in patients with different Wilkes stages, comparing the results obtained in different arthroscopic levels on a larger scale, unifying similar populations. A multicentric prospective clinical study was conducted in three TMJ departments performing temporomandibular joint surgery in Portugal and Brazil, with an enrolling window active from January 1, 2019, to December 1, 2022. The primary clinical outcome was TMJ pain evaluated through a visual analogue scale. The secondary clinical outcome was the maximum mouth opening (MMO). TMJ arthroscopy was performed with a 1.9-mm arthroscope, including a video system with a 2.8-mm outer protective cannula. 262 patients, representing a total of 524 operated joints were enrolled. The mean age was 35.3 years. A significant decrease postoperatively in VAS pain was observed for all Wilkes stages. The lowest value of VAS pain was observed in Wilkes II compared to Wilkes III and IV. In the secondary outcome, MMO was observed to have a significant improvement in all Wilkes stages. In this multicentric study, bilateral TMJ arthroscopy was shown to be an effective procedure to reduce pain and increase maximum mouth opening in patients with different Wilkes stages, representing a valid minimally invasive solution.

Efficacy and Safety of Rivaroxaban, Apixaban, and Edoxaban for Nonvalvular Atrial Fibrillation Based on Blood Coagulation Activity and Drug Plasma Concentration: SETtsu and North Osaka Multicenter Direct Oral AntiCoagulant (SET DOAC) Registry

Background: The therapeutic effects of oral anticoagulant drugs for nonvalvular atrial fibrillation (NVAF) suggest that the three factor Xa (FXa) inhibitors may have distinct safety profiles, though this is not yet fully conclusive. This study investigated the current dosing of rivaroxaban, apixaban, and edoxaban by monitoring drug plasma concentration (PC) and coagulation activity from the viewpoint of the safety. Methods and results: This multicenter clinical study monitored the drug PC and two coagulation biomarkers (fibrinogen and fibrin monomer complex [FMC]) at peak and trough timing in 268 outpatients taking rivaroxaban (n = 72), apixaban (n = 71), and edoxaban (n = 125) for NVAF. Doses were adjusted based on the dose-adjustment criteria of each drug. Referencing our previous study, peak drug PC remained below the cut-off level for predicting bleeding events except in eight patients (rivaroxaban, n = 3; apixaban, n = 2; edoxaban, n = 3) in whom bleeding events occurred. Among them, two (one each on rivaroxaban and edoxaban) had a peak drug PC below the cut-off level. Drug PCs widely varied from peak to trough, whereas FMC levels, reflecting thrombin activity, remained within the normal range (<6.1 µg/mL) regardless of PC variations. These results indicated that the anticoagulant effects of these drugs persisted throughout the day regardless of the drug PC levels, dosage, and dosing frequency. Regarding the change over time in peak PC, the elevation over time developed more in rivaroxaban (29/57; 50.9%, p < 0.05) than in edoxaban (32/101; 31.7%), and rivaroxaban tended to accumulate more than edoxaban. Conclusions: Although drug PC levels of once-daily FXa inhibitors widely varied from peak to trough, FMC levels were maintained within the normal range without daily variations. Rivaroxaban also tended to accumulate over time. The results indicate the low risk of thrombotic events with once-daily FXa inhibitors and its correspondence to the twice-daily regimen.

Practice and reflections on regional mutual recognition of clinical research ethics review——based on survey results from medical and health institutions in Jiangsu Province

With the continuous advancement of medical research, the number of multi-center clinical studies has been steadily increasing, bringing about significant challenges to ethical review. Improving the efficiency and quality of ethical review has become a necessity driven by national policies and the development of the industry. Mutual recognition of ethical reviews is one of the most effective ways to enhance the efficiency of ethical review in multi-center clinical trials. The promotion of mutual recognition of ethical reviews is both feasible and practically significant; however, progress has been less than ideal. Through conducting surveys, this study attempts to understand the status of mutual recognition of ethical reviews in Jiangsu Province, identify the reasons hindering the implementation of mutual recognition, and propose possible solutions. The results indicate that while most medical and health institutions are aware of the policies related to mutual recognition of ethical reviews, the majority remain in a wait-and-see attitude. Ensuring policy guarantees and the high quality and homogeneity of ethical review across institutions are considered necessary conditions for achieving mutual recognition of ethical reviews.

Predictive value of radiomics for intracranial aneurysm rupture: a systematic review and meta-analysis.

To systematically review the literature on radiomics for predicting intracranial aneurysm rupture and conduct a meta-analysis to obtain evidence confirming the value of radiomics in this prediction. A systematic literature search was conducted in PubMed, Web of Science, Embase, and The Cochrane Library databases up to March 2024. The QUADAS-2 tool was used to assess study quality. Stata 15.0 and Review Manager 5.4.1 were used for statistical analysis. Outcomes included combined sensitivity (Sen), specificity (Spe), positive likelihood ratio (+LR), negative likelihood ratio (-LR), diagnostic odds ratio (DOR), and their 95% confidence intervals (CI), as well as pre-test and post-test probabilities. The SROC curve was plotted, and the area under the curve (AUC) was calculated. Publication bias and small-study effects were assessed using the Deeks' funnel plot. The 9 included studies reported 4,284 patients, with 1,411 patients with intracranial aneurysm rupture (prevalence 32.9%). The overall performance of radiomics for predicting intracranial aneurysm rupture showed a combined Sen of 0.78 (95% CI: 0.74-0.82), Spe of 0.74 (95% CI: 0.70-0.78), +LR of 3.0 (95% CI: 2.7-3.4), -LR of 0.29 (95% CI: 0.25-0.35), DOR of 10 (95% CI: 9-12), and AUC of 0.83 (95% CI: 0.79-0.86). Significant heterogeneity was observed in both Sen (I2 = 90.93, 95% CI: 89.00-92.87%) and Spe (I2 = 94.28, 95% CI: 93.21-95.34%). Radiomics can improve the diagnostic efficacy of intracranial aneurysm rupture. More large-sample, prospective, multicenter clinical studies are needed to further evaluate its predictive value. https://www.crd.york.ac.uk/PROSPERO/.

Global trends and performance of dry needling from 2004 to 2024: a bibliometric analysis.

Many doctors are incorporating dry needling into their clinical practice. Despite this growing trend, there has not been a comprehensive bibliometric analysis conducted in this field. Thus, this study aims to investigate the current research landscape, key research contributors, and popular research topics in dry needling, and to analyze the developmental trends within this area of study. The study utilized the Web of Science Core Collection (WoSCC) as the main data source. Scientific literature was gathered through title (TI) searches for original clinical research papers on dry needling published between 2004 and 2024, using 'dry needling' or 'dry needle' as the search term. Statistical analyses and visualizations of the literature information, such as keywords, countries, research institutions, and authors, were conducted using the bibliometric.com online platform and VOSviewer. This approach aimed to statistically analyze and visualize the key research entities, hotspots, and frontiers in dry needling research. Additionally, the study delved into collaborative networks, research outputs, hot topics, and trends within the field of dry needling. This investigation encompassed 468 publications, with the year 2021 topping the charts for the highest publication output, amassing a total of 271 articles. The journal "Acupuncture in Medicine" emerged as the most frequently cited publication. The most impactful article was titled "Acupuncture and dry-needling for low back pain: An updated systematic review within the framework of the Cochrane Collaboration." Spain took the lead as the most productive country in this domain, with the United States closely following. Cesar Fernández-de-las-Peñas emerged as the most prolific author in the field. The Universidad Rey Juan Carlos in Spain was recognized as the most productive institution for research in dry needling. As for journal keywords, "dry needling," "trigger point," and "myofascial pain syn-drome" were the triumvirate of terms most recurrently encountered. The field of dry needling research has witnessed significant growth in recent years, characterized by the emergence of novel trends such as comparative studies with acupuncture, exploration into the mechanisms of action, and a transition toward interdisciplinary approaches. As medical models evolve, the focus is expanding from the exclusive treatment of muscle pain to broader applications. Despite this progress, the domain is underscored by a paucity of large-scale, multicenter clinical trials and animal studies. There exists an imperative for enhanced collaboration among academic and research institutions. A more profound exploration and comprehensive research endeavors are essential to enhance our understanding and broaden the clinical application of dry needling techniques.

Evaluation of a plasma cell-free DNA methylation test for colorectal cancer diagnosis: a multicenter clinical study.

A blood-based diagnostic test is a promising strategy for colorectal cancer (CRC). The MethyDT test (IColohunter), which detects methylation levels of NTMT1 and MAP3K14-AS1, exhibited potential in discriminating CRC, but its clinical performance needs to be validated in large-scale populations. A multicenter, double-blinded, cross-sectional study that enrolled 1194 participants was performed. Plasma samples were collected to detect methylation levels of NTMT1 and MAP3K14-AS1 using quantitative methylation-specific PCR with the MethyDT test, and the accuracy was further evaluated by Sanger sequencing. The sensitivities of the MethyDT test for detecting CRC, early stages of CRC (I and II), advanced adenoma (AA), and high-grade intraepithelial neoplasia (HGIN) were 91.2% (95% confidence interval [CI], 88.4-94.0), 87.4% (95% CI, 82.5-92.2), 43.5% (95% CI, 35.7-51.4), and 72.7% (95% CI, 57.5-87.9), respectively. The specificities for participants with non-AA, interfering diseases (ID), and no evidence of disease (NED) were 85.0% (95% CI, 78.8-91.3), 93.7% (95% CI, 91.4-95.9) and 97.3% (95% CI, 90.5-99.7), respectively, and its overall specificity for all-controls was 92.4% (95% CI, 90.3-94.4). The consistency of the MethyDT test with pathology for CRC was high with a kappa value of 0.830 (95% CI, 0.795-0.865). Additionally, the MethyDT test was comparable to Sanger sequencing for detecting methylation with kappa values > 0.97. The MethyDT test demonstrates excellent sensitivity and specificity for CRC and high consistency with Sanger sequencing for methylation, suggesting it may serve as a potential noninvasive diagnostic tool for the detection of CRC. This clinical trial has been registered in ClinicalTrials.gov (NCT05508503).

Diagnostic accuracy of rapid antigen tests for detection of Delta and Omicron variants of severe acute respiratory syndrome coronavirus 2: Direct evidence from prospective clinical settings.

Despite widespread application during the coronavirus disease-19 pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection using patient-performed rapid antigen tests (RATs) is limited, especially regarding the Delta and Omicron variants. Therefore, in this study, we evaluated the performance of RATs in identifying Delta and Omicron infections in self-test settings. In this multicenter clinical performance study conducted in Korea between November 2021 and February 2022, we included participants without prior diagnostic device experience. Using 2 RAT types, we compared the results with real-time reverse transcriptase-polymerase chain reaction testing, focusing on clinical sensitivity and specificity. Reverse transcriptase-polymerase chain reaction helped confirm 77 SARS-CoV-2 infections among 280 participants. RATs exhibited high positive agreement for Omicron detection but lower rates for Delta, especially among partially vaccinated individuals. This study provides direct evidence that RATs, originally developed for ancestral strains of SARS-CoV-2, effectively detect major variants such as Delta and Omicron in real patient/clinical settings. By confirming variant presence through sequencing, our research offers significant and novel insights into the performance of RATs, particularly in the context of breakthrough infections postvaccination, with precise data on vaccination status and timing obtained from government records.

A multicenter clinical study on the incidence and influencing factors of cephalosporin-induced anaphylaxis

To investigate the incidence and influencing factors of allergic reactions to cephalosporins. A cross-sectional study of 29 medical institutions in Zhejiang Province was conducted from April 2021 to June 2021. The incidence of allergic reactions to cephalosporins was investigated, and the influencing factors of cephalosporin-induced allergic reactions were analyzed by Poisson regression. A total of 56 155 patients were included in this study. The total incidence of allergic reactions to cephalosporin was 1.67‰, the highest incidence of anaphylaxis occurred for ceftizoxime (4.27‰), followed by ceftriaxone (3.49‰) and cefotaxime (2.40‰). There was no significant difference in the incidence of allergic reactions between patients with negative skin tests and those without skin tests (1.75‰ vs. 1.63‰, RR=1.07, 95%CI: 0.70-1.63, P>0.05). Poisson regression showed that body mass index (BMI) <18.5 kg/m2 (RR=2.43, 95%CI: 1.23-4.82, P<0.05) and history of β-lactam antibiotics allergy (RR=33.88, 95%CI: 1.47-781.12, P<0.05) increased cephalosporin-induced anaphylaxis. Compared with cefuroxime, the risk of allergic reactions was increased for ceftriaxone (RR=3.08, 95%CI: 1.70-5.59, P<0.01), ceftazidime (RR=1.89, 95%CI: 1.03-3.47, P<0.05), and ceftizoxime (RR=3.74, 95%CI: 1.64-8.50, P<0.01). Lower BMI and history of β-lactam antibiotics allergy increase the risk of cephalosporin allergic reactions. The routine skin test may not reduce the occurrence of allergic reactions to cephalosporins.

Effects of different forced-air warming systems on the core temperature of patients: a manikin and multi-center clinical study

BackgroundThe use of forced-air warming (FAW) blankets is widely recognized for preventing shivering and hypothermia in patients under general anesthesia. Various types of products are currently available for hospitals, and we have conducted a preliminary evaluation of insulation equipment based on expert opinions and initial parameters. However, we lack real-world experiments and accurate clinical data to validate these parameters and the accuracy of our decision-making results. This study aims to confirm the effectiveness of different FAW systems by assessing the thermal protection and operational characteristics of the equipment in both experimental and clinical settings, thereby enhancing our evaluation database.MethodsIn the manikin test, we conducted six tests including heat distribution and heating rate, heater outlet temperature stability, etc. In the clinical study, patients were randomly assigned to four groups [Group A (Bair Hugger Therapy, 3 M, St. Paul, MN, USA; 63500); Group B (EQUATOR® level I, Smith Medical ASD, MN, USA; Snuggle Warm, SW-2013); Group C (Jiang Men Da Cheng Medical Devices Co., Ltd, China; IOB-006); and Group D (Shang Hai Nest Tech Medical Materials Co., Ltd, China; BH-017)], with each group comprising 30 individuals. At the start of anesthesia induction, the FAW blanket was activated and set to 43 °C until the completion of surgery. The primary endpoint was the average core body temperature during surgery. Secondary endpoints included hemodynamic and surgical variables, adverse events, and recovery metrics.ResultsIn the manikin test, the observed results of the experimental parameters (heat distribution, air pressure difference, and hole observation test) for Group A are superior to those of the other groups. In the clinical study, although the mean perioperative core body temperature remained above 36 °C across all groups [Group A: 36.31 ± 0.04; Group B: 36.26 ± 0.06; Group C: 36.17 ± 0.03; Group D: 36.25 ± 0.05], patients in Group A maintained higher temperatures compared to the other groups (p < 0.001).ConclusionsAmong patients undergoing laparoscopic radical resection of colorectal cancer with general anesthesia, all four FAW systems effectively prevented perioperative hypothermia. However, the system in Group A minimized heat loss more effectively than the others, providing superior thermal protection.Trial registrationChiCTR2200065394, 03/11/2022.

307 - Correlation of Early Postpartum Anal/Faecal Incontinence with Endoanal Ultrasound, Digital Rectal Examination, Machine Learning-supported Electric Impedance Spectroscopy, and High-Resolution Anorectal Manometry Results: Exploratory Results from a Prospective, Comparative, Multicentre Clinical Study

307 - Correlation of Early Postpartum Anal/Faecal Incontinence with Endoanal Ultrasound, Digital Rectal Examination, Machine Learning-supported Electric Impedance Spectroscopy, and High-Resolution Anorectal Manometry Results: Exploratory Results from a Prospective, Comparative, Multicentre Clinical Study

Lung Ultrasound Spectroscopy Applied to the Differential Diagnosis of Pulmonary Diseases: An In Vivo Multicenter Clinical Study.

Lung ultrasound (LUS) is an important imaging modality to assess the state of the lung surface. However, current LUS approaches are based on subjective interpretation of imaging artifacts, which results in poor specificity as quantitative evaluation lacks. The latter could be improved by adopting LUS spectroscopy of vertical artifacts. Indeed, parameterizing these artifacts with native frequency, bandwidth, and total intensity ( [Formula: see text]) already showed potentials in differentiating pulmonary fibrosis (PF). In this study, we acquired radio frequency (RF) data from 114 patients. These data (representing the largest LUS RF dataset worldwide) were acquired by utilizing a multifrequency approach, implemented with an ULtrasound Advanced Open Platform (ULA-OP). Convex (CA631) and linear (LA533) probes (Esaote, Florence, Italy) were utilized to acquire RF data at three (2, 3, and 4 MHz), and four (3, 4, 5, and 6 MHz) imaging frequencies. A multifrequency analysis was conducted on vertical artifacts detected in patients having cardiogenic pulmonary edema (CPE), pneumonia, or PF. These artifacts were characterized by the three abovementioned parameters, and their mean values were used to project each patient into a feature space having up to three dimensions. Binary classifiers were used to evaluate the performance of these three mean features in differentiating patients affected by CPE, pneumonia, and PF. Acquisitions of multifrequency data performed with linear probe lead to accuracies up to 85.43% in the differential diagnosis of these diseases (convex probes' maximum accuracy was 74.51%). Moreover, the results showed high potentials of mean [Formula: see text] (by itself or combined with other features) in improving LUS specificity.

Horizontal Guided Bone Regeneration of the Posterior Mandible to Allow Implant Placement: 1-Year Prospective Study Results.

Assess whether horizontal ridge augmentation with guided bone regeneration (GBR) using deproteinized bovine bone mineral (DBBM), autologous bone, and a resorbable collagen membrane supports successful implant placement. This open, prospective, single-cohort, multicenter clinical study included patients with ridge defects that required GBR prior to implant insertion. The primary endpoint was radiologically assessed bone gain after 8 months post-GBR, measured at the center of planned implant sites. Secondary endpoints included implant survival and success, marginal bone levels (MBLs), MBL changes, and soft tissue health. Of 45 patients evaluated 8 months post-GBR, nine experienced dehiscence in the first 3 weeks of the healing period. GBR led to radiologically determined mean bone width gain of 4.0 ± 1.5 mm and 4.8 ± 1.7 mm, measured 1 and 3 mm from the top of the crest, respectively, allowing successful implant placement in 44 patients (97.8%). The cumulative implant survival and success rates were 98.9% and 95.5%, respectively. MBLs were stable: -1.18 ± 0.64 mm at definitive prosthesis placement (DPP) and - 1.07 ± 0.74 mm at 1 year. Soft tissue health and esthetics (plaque and bleeding indices, papilla, keratinized mucosa, and pink esthetic score) improved from DPP to 1 year. Patients were highly satisfied with implant function and esthetics, and their oral health-related quality of life improved. GBR using DBBM and a collagen membrane offered a safe and effective treatment option for horizontal ridge augmentation sufficient to support implant-based tooth rehabilitation. Registered at ClinicalTrials.gov NCT03028922 (registrations sites, as above listed affiliations, first posted January 23, 2017).

Evaluating culture-free targeted next-generation sequencing for diagnosing drug-resistant tuberculosis: a multicentre clinical study of two end-to-end commercial workflows.

Drug-resistant tuberculosis remains a major obstacle in ending the global tuberculosis epidemic. Deployment of molecular tools for comprehensive drug resistance profiling is imperative for successful detection and characterisation of tuberculosis drug resistance. We aimed to assess the diagnostic accuracy of a new class of molecular diagnostics for drug-resistant tuberculosis. We conducted a prospective, cross-sectional, multicentre clinical evaluation of the performance of two targeted next-generation sequencing (tNGS) assays for drug-resistant tuberculosis at reference laboratories in three countries (Georgia, India, and South Africa) to assess diagnostic accuracy and index test failure rates. Eligible participants were aged 18 years or older, with molecularly confirmed pulmonary tuberculosis, and at risk for rifampicin-resistant tuberculosis. Sensitivity and specificity for both tNGS index tests (GenoScreen Deeplex Myc-TB and Oxford Nanopore Technologies [ONT] Tuberculosis Drug Resistance Test) were calculated for rifampicin, isoniazid, fluoroquinolones (moxifloxacin, levofloxacin), second line-injectables (amikacin, kanamycin, capreomycin), pyrazinamide, bedaquiline, linezolid, clofazimine, ethambutol, and streptomycin against a composite reference standard of phenotypic drug susceptibility testing and whole-genome sequencing. Between April 1, 2021, and June 30, 2022, 832 individuals were invited to participate in the study, of whom 720 were included in the final analysis (212, 376, and 132 participants in Georgia, India, and South Africa, respectively). Of 720 clinical sediment samples evaluated, 658 (91%) and 684 (95%) produced complete or partial results on the GenoScreen and ONT tNGS workflows, respectively, with 593 (96%) and 603 (98%) of 616 smear-positive samples producing tNGS sequence data. Both workflows had sensitivities and specificities of more than 95% for rifampicin and isoniazid, and high accuracy for fluoroquinolones (sensitivity approximately ≥94%) and second line-injectables (sensitivity 80%) compared with the composite reference standard. Importantly, these assays also detected mutations associated with resistance to critical new and repurposed drugs (bedaquiline, linezolid) not currently detectable by any other WHO-recommended rapid diagnostics on the market. We note that the current format of assays have low sensitivity (≤50%) for linezolid and more work on mutations associated with drug resistance is needed. This multicentre evaluation demonstrates that culture-free tNGS can provide accurate sequencing results for detection and characterisation of drug resistance from Mycobacterium tuberculosis clinical sediment samples for timely, comprehensive profiling of drug-resistant tuberculosis. Unitaid.

Chest CT features and risk factors for patients with Omicron variant pneumonia: a multicenter retrospective clinical study

Introduction: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Omicron variant infection has become widespread in China as a result of the alterations in epidemic control and prevention policies. We identified the clinical characteristics and lung computed tomography (CT) imaging characteristics of patients infected during the early stage of the Omicron BA.5 wave in Shanghai to provide a guide to the diagnosis, treatment, and prognosis of infection. Methodology: Clinical information and lung CT imaging characteristics of patients with Omicron variant infection admitted to three designated hospitals in Shanghai from March to June 2022 were analyzed retrospectively. Results: A total of 958 patients were included in the analysis. Among the patients, 169 (17.64%) had pneumonia confirmed by CT, of whom 70.41% (119/169) had lesions in &lt; 10% of the lung area. Older age, unvaccinated status, and comorbid chronic lung disease, cerebrovascular disease, kidney disease, or Alzheimer`s disease were associated with poor prognosis. In patients with coronavirus disease 2019 (COVID-19) pneumonia, a large lesion size was associated with a poor prognosis. Age ≥ 65 years, unvaccinated status, fever &gt; 5 days, and lymphocyte count &lt; 0.5×109/L were risk factors for pneumonia. Conclusions: Age ≥ 65 years, unvaccinated status, fever &gt; 5 days, and lymphocyte count &lt; 0.5×109/L can be used to identify high-risk individuals who warrant a CT scan to screen for COVID-19 pneumonia, especially during the period of Omicron variant predominance. Concurrently, the importance of immunization should be emphasized to help people withstand the effects of Omicron variant infection.

Inetetamab combined with sirolimus and chemotherapy for the treatment of HER2‐positive metastatic breast cancer patients with abnormal activation of the PI3K/Akt/mTOR pathway after trastuzumab treatment

AbstractBackgroundWe explored the efficacy and safety of inetetamab combined with sirolimus and chemotherapy for the treatment of human epidermal factor receptor 2 (HER2)‐positive metastatic breast cancer patients with abnormal activation of the PI3K/Akt/mTOR (PAM) pathway after trastuzumab treatment.MethodsFor this prospective multicenter clinical study, HER2‐positive metastatic breast cancer patients with PAM pathway mutations confirmed by histology or peripheral blood genetic testing were enrolled from July 2021 to September 2022. Patients were randomly assigned to a trial or control group. The patients in the trial group received inetetamab combined with sirolimus and chemotherapy, while the control group patients received pyrotinib and chemotherapy. The RECIST v1.1 standard was used to evaluate efficacy. Descriptive statistics were used to summarize the clinicopathological features, and the Kaplan–Meier method was used to generate survival curves. The log‐rank test was used to compare progression‐free survival (PFS) between the two groups.ResultsA total of 59 HER2‐positive metastatic breast cancer patients with abnormal activation of the PAM pathway were included, of which 37 received inetetamab combined with sirolimus and chemotherapy treatment and 22 received pyrotinib and chemotherapy treatment. The median PFS was 4.64 months in the inetetamab group and 5.69 months in the pyrotinib group, with no statistically significant difference (p = 0.507). The objective response rates were 27.3% for the inetetamab group and 29.4% for the pyrotinib group. The safety assessment indicated that the adverse event (AE) incidences were 86.1% (31/36) in the inetetamab group and 78.9 (15/19) in the pyrotinib group, with 9 (25%) and four (21.1%) Grade 3/4 AEs in the inetetamab and pyrotinib groups, respectively.ConclusionsFor metastatic HER2‐positive breast cancer patients with abnormal PAM pathway activation and previous trastuzumab treatment, the combination of inetetamab with sirolimus and chemotherapy is equivalent to the combination of pyrotinib and chemotherapy. Therefore, this regimen could be a treatment option for PAM pathway‐activated metastatic HER2‐positive breast cancer patients.