Outcomes of Patients With Early and Locally Advanced Lung Cancer: Protocol for the Italian Lung Cancer Observational Study (LUCENT).

BACKGROUND: Lung cancer, predominantly non-small cell lung cancer (NSCLC), remains a formidable challenge, necessitating an in-depth understanding of evolving treatment paradigms. The Italian Lung Cancer Observational Study (LUCENT) addresses this need by investigating the outcomes of patients with early and locally advanced lung cancer in Italy. OBJECTIVE: With a focus on real-world data and patient registries, this study aims to provide comprehensive insights into clinical, psychosocial, and economic impacts, contributing to informed decision-making in health care. METHODS: LUCENT is a prospective observational multicenter cohort study enrolling patients eligible for minimally invasive manual, robot-assisted, or traditional open surgery. The study will develop a web-based registry to collect longitudinal surgical, oncological, and socioeconomic outcome data. The primary objectives include performance assessment through the establishment of national benchmarks based on risk-adjusted outcomes and processes of care indicators. The secondary objectives encompass economic and psychosocial impact assessments of innovative technologies and treatment pathways. The multicenter design ensures a diverse and representative study population. RESULTS: The evolving landscape of NSCLC treatment necessitates a nuanced approach with consideration of the dynamic shifts in therapeutic strategies. LUCENT strives to fill existing knowledge gaps by providing a platform for collecting and analyzing real-world data, emphasizing the importance of patient-reported outcomes in enhancing the understanding of the disease. By developing a web-based registry, the study not only facilitates efficient data collection but also addresses the limitations of traditional methods, such as suboptimal response rates and costs associated with paper-and-pencil questionnaires. Recruitment will be conducted from January 01, 2024, to December 31, 2026. Follow-up will be performed for a minimum of 2 years. The study will be completed in the year 2028. CONCLUSIONS: LUCENT's potential implications are substantial. Establishing national benchmarks will enable a thorough evaluation of outcomes and care processes, guiding clinicians and policymakers in optimizing patient management. Furthermore, the study's secondary objectives, focusing on economic and psychosocial impacts, align with the contemporary emphasis on holistic cancer care. Insights gained from this study may influence treatment strategies, resource utilization, and patient well-being, thereby contributing to the ongoing refinement of lung cancer management. TRIAL REGISTRATION: ClinicalTrials.gov NCT05851755; https://clinicaltrials.gov/study/NCT05851755. ISRCTN 67197140; https://www.isrctn.com/ISRCTN67197140. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/57183.

Development and Validation of a Computed Tomography-Based Model for Noninvasive Prediction of the T Stage in Gastric Cancer: Multicenter Retrospective Study.

BACKGROUND: As part of the TNM (tumor-node-metastasis) staging system, T staging based on tumor depth is crucial for developing treatment plans. Previous studies have constructed a deep learning model based on computed tomographic (CT) radiomic signatures to predict the number of lymph node metastases and survival in patients with resected gastric cancer (GC). However, few studies have reported the combination of deep learning and radiomics in predicting T staging in GC. OBJECTIVE: This study aimed to develop a CT-based model for automatic prediction of the T stage of GC via radiomics and deep learning. METHODS: A total of 771 GC patients from 3 centers were retrospectively enrolled and divided into training, validation, and testing cohorts. Patients with GC were classified into mild (stage T1 and T2), moderate (stage T3), and severe (stage T4) groups. Three predictive models based on the labeled CT images were constructed using the radiomics features (radiomics model), deep features (deep learning model), and a combination of both (hybrid model). RESULTS: The overall classification accuracy of the radiomics model was 64.3% in the internal testing data set. The deep learning model and hybrid model showed better performance than the radiomics model, with overall classification accuracies of 75.7% (P=.04) and 81.4% (P=.001), respectively. On the subtasks of binary classification of tumor severity, the areas under the curve of the radiomics, deep learning, and hybrid models were 0.875, 0.866, and 0.886 in the internal testing data set and 0.820, 0.818, and 0.972 in the external testing data set, respectively, for differentiating mild (stage T1~T2) from nonmild (stage T3~T4) patients, and were 0.815, 0.892, and 0.894 in the internal testing data set and 0.685, 0.808, and 0.897 in the external testing data set, respectively, for differentiating nonsevere (stage T1~T3) from severe (stage T4) patients. CONCLUSIONS: The hybrid model integrating radiomics features and deep features showed favorable performance in diagnosing the pathological stage of GC.

Clinical evaluation of direct composite versus zirconia resin-bonded fixed dental prostheses for a single missing anterior tooth: a short-term multicenter retrospective study.

OBJECTIVES: This study aimed to compare the outcome of a simplified direct composite resin-bonded fixed dental prostheses without reinforcing fibers (CR-RBFDP) and resin-bonded fixed dental prostheses using zirconia (Zr-RBFDP). METHODS: The clinical records of five private practice dental clinics and one university hospital were analyzed. Failure was defined as a RBFDP that was removed or remade for any reason. Survival analyses were performed using log-rank tests. RESULTS: A total of 45 patients (CR-RBFDP, n = 17; Zr-RBFDP, n = 28) were followed up for 3 years. Among the CR-RBFDP cases, 1 case of framework fracture and 2 cases of discoloration occurred, whereas among the Zr-RBFDP cases, 1 case of debonding occurred. The mean duration of observation was 21.9 months. The 3-year survival rate was 92.3% for CR-RBFDP and 91.7% for Zr-RBFDP. Log-rank test showed no significant difference (p = 0.78). CONCLUSIONS: Within the limitations of this short-term retrospective study, the survival rate of CR-RBFDP was not significantly different from that of Zr-RBFDP. Contrary to concerns regarding material strength, CR-RBFDP showed reliable results. This direct composite restoration has the advantages of being less invasive and being completed in a single visit. CLINICAL SIGNIFICANCE: Despite differences in material strength, CR-RBFDPs without fiber reinforcement showed reliable short-term clinical results. This direct composite restoration has the advantage of being less invasive and can be restored in a single visit.

Efficacy and safety of linaclotide in treatment-resistant chronic constipation: A multicenter, open-label study.

BACKGROUND: This study aimed to evaluate the efficacy and safety of linaclotide in patients with chronic constipation (CC) or irritable bowel syndrome with constipation (IBS-C) who did not respond to treatment with magnesium oxide (MgO). METHODS: This study was designed as a multicenter, open-label, single-arm, exploratory study. Patients with CC or IBS-C who took MgO and those meeting the medication initiation criteria were administered linaclotide at a daily dosage of 500 µg for 12 weeks. The primary endpoint was a change in the Japanese version of the Patient Assessment of Constipation Quality of Life (JPAC-QOL) score from baseline, which was evaluated by using a paired t-test. KEY RESULTS: The patients' mean age (± standard deviation) was 67.6 ± 13.82 years. The full analysis set included 61 patients. The JPAC-QOL total score was 1.60 at baseline and 0.70 at 12 weeks, with a significant mean change of -0.89 ± 0.721 (p < 0.001). Several secondary endpoints also showed improvement. The frequency of spontaneous bowel movement (SBM) and complete SBM increased by 2.70 ± 7.254 (p < 0.01) and 2.81 ± 5.254 times, respectively (p < 0.001). The Bristol Stool Form Scale, abdominal bloating severity, and straining severity scores improved by 1.33 ± 1.274 (p < 0.001), -0.16 ± 0.563 (p < 0.05), and -0.46 ± 0.795 (p < 0.001) points, respectively. The safety analysis set included 65 patients, 7 of whom had diarrhea, which improved with dose reduction and drug withdrawal. CONCLUSION & INFERENCES: The study was conducted in an older adult population, similar to real clinical practice. Linaclotide may be an option for treating CC that shows an inadequate response to conventional therapy.

Platelet count has a nonlinear association with 30-day in-hospital mortality in ICU end-stage kidney disease patients: a multicenter retrospective cohort study.

This study addresses the relationship between platelet count and 30-day in-hospital mortality in End-Stage Kidney Disease (ESRD) patients in the intensive care unit (ICU), a topic with limited existing evidence. Utilizing data from the US eICU-CRD v2.0 database (2014-2015), a retrospective cohort study was conducted involving 3700 ICU ESRD patients. We employed binary logistic regression, smooth curve fitting, and subgroup analyses to explore the association between platelet count and 30-day in-hospital mortality. The 30-day in-hospital mortality rate was 13.27% (491/3700), with a median platelet count of 188 × 109/L. After adjusting for covariates, we observed a relationship between platelet count and 30-day in-hospital mortality (OR = 0.98, 95% CI 0.97, 0.99). Subgroup analyses supported these findings. More importantly, a nonlinear association was detected, with an inflection point at 222 × 109/L. The effect sizes (OR) on the left and right sides of the inflection point were 0.94 (0.92, 0.96) and 1.03 (1.00, 1.05), respectively. The most significant finding of this study is the revelation of a nonlinear relationship between baseline platelet count and 30-day in-hospital mortality in ICU patients with ESRD. This discovery explicitly suggests that when ESRD patients are admitted to the ICU, a platelet level closer to 222 × 109/L may predict a lower 30-day in-hospital mortality risk.

Machine learning-based prediction of early neurological deterioration after intravenous thrombolysis for stroke: insights from a large multicenter study.

Background: This investigation seeks to ascertain the efficacy of various machine learning models in forecasting early neurological deterioration (END) following thrombolysis in patients with acute ischemic stroke (AIS). Methods: Employing data from the Shenyang Stroke Emergency Map database, this multicenter study compiled information on 7,570 AIS patients from 29 comprehensive hospitals who received thrombolytic therapy between January 2019 and December 2021. An independent testing cohort was constituted from 2,046 patients at the First People's Hospital of Shenyang. The dataset incorporated 15 pertinent clinical and therapeutic variables. The principal outcome assessed was the occurrence of END post-thrombolysis. Model development was executed using an 80/20 split for training and internal validation, employing classifiers like logistic regression with lasso regularization (lasso regression), support vector machine (SVM), random forest (RF), gradient-boosted decision tree (GBDT), and multi-layer perceptron (MLP). The model with the highest area under the curve (AUC) was utilized to delineate feature significance. Results: Baseline characteristics showed variability in END incidence between the training (n = 7,570; END incidence 22%) and external validation cohorts (n = 2,046; END incidence 10%; p < 0.001). Notably, all machine learning models demonstrated superior AUC values compared to the reference model, indicating their enhanced predictive capacity. The lasso regression model achieved the highest AUC at 0.829 (95% CI: 0.799-0.86; p < 0.001), closely followed by the MLP model with an AUC of 0.828 (95% CI: 0.799-0.858; p < 0.001). The SVM, RF, and GBDT models also showed commendable AUCs of 0.753, 0.797, and 0.774, respectively. Decision curve analysis revealed that the SVM and MLP models demonstrated a high net benefit. Feature importance analysis emphasized "Onset To Needle Time" and "Admission NIHSS Score" as significant predictors. Conclusion: Our research establishes the MLP and lasso regression as robust tools for predicting early neurological deterioration in acute ischemic stroke patients following thrombolysis. Their superior predictive accuracy, compared to traditional models, highlights the significant potential of machine learning approaches in refining prognosis and enhancing clinical decisions in stroke care management. This advancement paves the way for more tailored therapeutic strategies, ultimately aiming to improve patient outcomes in clinical practice.

Survival predictors in patients with pancreatic cancer on liposomal irinotecan plus fluorouracil/leucovorin: a multicenter observational study.

Background: Approximately half of the patients with advanced pancreatic ductal adenocarcinoma (PDAC) receive subsequent lines of chemotherapy. Recently, the liposomal irinotecan (nal-IRI) plus 5-fluorouracil/leucovorin (5-FU/LV) regimen is recommended as subsequent lines of chemotherapy. However, little is known about the predictive factors for the nal-IRI + 5-FU/LV regimen, especially in patients with previous irinotecan (IRI) exposure. Objectives: We investigated the predictive factors associated with nal-IRI + 5-FU/LV treatment in patients with PDAC. Design: Multicenter, retrospective cohort study. Methods: This study included patients with advanced PDAC who received the nal-IRI + 5-FU/LV regimen for palliative purposes. Results: Overall, 268 patients were treated with nal-IRI + 5-FU/LV. The median overall survival (OS) was 7.9 months (95% confidence interval (CI): 7.0-8.8), while the median progression-free survival (PFS) was 2.6 months (95% CI: 1.9-3.2). An albumin level of<4.0 g/dL, neutrophil-to-lymphocyte ratio (NLR) of ⩾3.5, liver or peritoneal metastasis, and a history of >3 lines of palliative chemotherapy were associated with worse OS. An NLR of ⩾3.5 and liver metastasis were significant predictive factors for worse PFS. Previous exposure to IRI was not a significant predictor. Patients without prior IRI (no-IRI) treatment showed relatively longer OS and PFS compared to IRI responders and nonresponders, but these differences were not significant when compared specifically to the responders (OS: 8.8 vs 8.1 months, p = 0.388; PFS: 3.6 vs 2.6 months, p = 0.126). Conclusion: An NLR of ⩾3.5 and liver metastasis were associated with worse PFS. Prior IRI exposure was not a significant predictive factor for OS and PFS, especially in IRI responders.

The German research consortium for the study of bipolar disorder (BipoLife): a quality assurance protocol for MR neuroimaging data.

BACKGROUND: The German multicenter research consortium BipoLife aims to investigate the mechanisms underlying bipolar disorders. It focuses in particular on people at high risk of developing the disorder and young patients in the early stages of the disease. Functional and structural magnetic resonance imaging (MRI) data was collected in all participating centers. The collection of neuroimaging data in a longitudinal, multicenter study requires the implementation of a comprehensive quality assurance (QA) protocol. Here, we outline this protocol and illustrate its application within the BipoLife consortium. METHODS: The QA protocol consisted of (1) a training of participating research staff, (2) regular phantom measurements to evaluate the MR scanner performance and its temporal stability across the course of the study, and (3) the assessment of the quality of human MRI data by evaluating a variety of image metrics (e.g., signal-to-noise ratio, ghosting level). In this article, we will provide an overview on these QA procedures and show exemplarily the influence of its application on the results of standard neuroimaging analysis pipelines. DISCUSSION: The QA protocol helped to characterize the various MR scanners, to record their performance over the course of the study and to detect possible malfunctions at an early stage. It also assessed the quality of the human MRI data systematically to characterize its influence on various analyses. Furthermore, by setting up and publishing this protocol, we define standards that must be considered when analyzing data from the BipoLife consortium. It further promotes a systematic evaluation of data quality and a definition of subject inclusion criteria. In the long term, it will help to increase the chance of achieving clinically relevant results.

Relationship between ultrasonographic findings and subscales of the Knee Injury and Osteoarthritis Outcome Score in patients with early knee osteoarthritis: a multicenter study.

PURPOSE: To characterize the ultrasonographic findings of patients with early knee osteoarthritis (KOA) and determine which findings were associated with the Knee Injury and Osteoarthritis Outcome Score (KOOS) subscale. METHODS: The study included 98 knees (35 men, 63 women, 60.3 ± 11.5 years) diagnosed with early KOA with no major deformity radiographically, but with pain during activity and tenderness in the medial knee. Synovial hyperplasia in the suprapatellar bursa, knee joint effusion, horizontal tear of the medial meniscus (MM), osteophytes of the medial condyle of the femur and tibia, blood flow signals in the synovium of the suprapatellar bursa, medial collateral ligament bursa, infrapatellar fat pad, MM extrusion (MME) in the supine and upright positions, and the amount of change in MME were observed using ultrasonography. RESULTS: Correlations (p < 0.05) were found between the presence of synovial hyperplasia of the suprapatellar bursa (r<-0.20) and amount of MME in the upright position (r< - 0.24) and all KOOS subscales. Presence of joint effusion and the four KOOS subscales except quality of life (QOL) were correlated (p < 0.05). Partial correlation coefficients showed correlations (p < 0.05) between knee joint effusion and symptoms (r = 0.299) and activities of daily living (ADL) (r = 0.254) of the KOOS subscales, and between MME in the upright position and symptoms (r= - 0.263), pain (r= - 0.256), and ADL (r= - 0.212). CONCLUSION: Quality and difficulty of life of patients with early KOA may be influenced by synovial hyperplasia in the suprapatellar bursa, joint effusion, and MME values in the upright position. Among them, synovial hyperplasia of the suprapatellar bursa and amount of MME in the upright position were independently associated with the KOOS subscales.

A multicenter evaluation of a novel microfluidic rapid AST assay for Gram-negative bloodstream infections.

Common phenotypic methods for antimicrobial susceptibility testing (AST) of bacteria are slow, labor intensive, and display considerable technical variability. The QuickMIC system provides rapid AST using a microfluidic linear gradient. Here, we evaluate the performance of QuickMIC at four different laboratories with regard to speed, precision, accuracy, and reproducibility in comparison to broth microdilution (BMD). Spiked (n = 411) and clinical blood cultures (n = 148) were tested with the QuickMIC Gram-negative panel and compared with BMD for the 12 on-panel antibiotics, and 10 defined strains were run at each site to measure reproducibility. Logistic and linear regression analysis was applied to explore factors affecting assay performance. The overall essential agreement and categorical agreement between QuickMIC and BMD were 95.6% and 96.0%, respectively. Very major error, major error, and minor error rates were 1.0%, 0.6%, and 2.4%, respectively. Inter-laboratory reproducibility between the sites was high at 98.9% using the acceptable standard of ±1 twofold dilution. The mean in-instrument analysis time overall was 3 h 13 min (SD: 29 min). Regression analysis indicated that QuickMIC is robust with regard to initial inoculum and delay time after blood culture positivity. We conclude that QuickMIC can be used to rapidly measure MIC directly from blood cultures in clinical settings with high reproducibility, precision, and accuracy. The microfluidics-generated linear gradient ensures high reproducibility between laboratories, thus allowing a high level of trust in MIC values from single testing, at the cost of reduced measurement range compared to BMD. IMPORTANCE: Increasing antimicrobial resistance underscores the need for new diagnostic solutions to guide therapy, but traditional antimicrobial susceptibility testing (AST) is often inadequate in time-critical diseases such as sepsis. This work presents a novel and rapid AST system with a rapid turnaround of results, which may help reduce the time to guided therapy, possibly allowing early de-escalation of broad-spectrum empirical therapy as well as rapid adjustments to treatments when coverage is lacking.

Development and validation of an open-source pipeline for automatic population of case report forms from electronic health records: a pediatric multi-center prospective study.

BACKGROUND: Clinical trials and registry studies are essential for advancing research and developing novel treatments. However, these studies rely on manual entry of thousands of variables for each patient. Repurposing real-world data can significantly simplify the data collection, reduce transcription errors, and make the data entry process more efficient, consistent, and cost-effective. METHODS: We developed an open-source computational pipeline to collect laboratory and medication information from the electronic health record (EHR) data and populate case report forms. The pipeline was developed and validated with data from two independent pediatric hospitals in the US as part of the Long-terM OUtcomes after Multisystem Inflammatory Syndrome In Children (MUSIC) study. Our pipeline allowed the completion of two of the most time-consuming forms. We compared automatically extracted results with manually entered values in one hospital and applied the pipeline to a second hospital, where the output served as the primary data source for case report forms. FINDINGS: We extracted and populated 51,845 laboratory and 4913 medication values for 159 patients in two hospitals participating in a prospective pediatric study. We evaluated pipeline performance against data for 104 patients manually entered by clinicians in one of the hospitals. The highest concordance was found during patient hospitalization, with 91.59% of the automatically extracted laboratory and medication values corresponding with the manually entered values. In addition to the successfully populated values, we identified an additional 13,396 laboratory and 567 medication values of interest for the study. INTERPRETATION: The automatic data entry of laboratory and medication values during admission is feasible and has a high concordance with the manually entered data. By implementing this proof of concept, we demonstrate the quality of automatic data extraction and highlight the potential of secondary use of EHR data to advance medical science by improving data entry efficiency and expediting clinical research. FUNDING: NIH Grant 1OT3HL147154-01, U24HL135691, UG1HL135685.

Multicenter exploration of specialist palliative care in patients with left ventricular assist devices - a retrospective study.

BACKGROUND: The number of advanced heart failure patients with left ventricular assist devices (LVAD) is increasing. Despite guideline-recommendations, little is known about specialist palliative care involvement in LVAD-patients, especially in Europe. This study aims to investigate timing and setting of specialist palliative care in LVAD-patients. METHODS: We conducted a retrospective multicenter study in 2022. Specialist palliative care services in German LVAD-centers were identified and invited to participate. Forty adult LVAD-patients (mean age 65 years (SD 7.9), 90% male) from seven centers that received a specialist palliative care consultation during hospitalization were included. RESULTS: In 37 (67.3%) of the 55 LVAD-centers, specialist palliative care was available. The median duration between LVAD-implantation and first specialist palliative care contact was 17 months (IQR 6.3-50.3 months). Median duration between consultation and death was seven days (IQR 3-28 days). 65% of consults took place in an intensive/intermediate care unit with half of the patients having a Do-Not-Resuscitate order. Care planning significantly increased during involvement (advance directives before: n = 15, after: n = 19, p < 0.001; DNR before: n = 20, after: n = 28, p < 0.001). Symptom burden as assessed at first specialist palliative care contact was higher compared to the consultation requests (request: median 3 symptoms (IQR 3-6); first contact: median 9 (IQR 6-10); p < 0.001) with a focus on weakness, anxiety, overburdening of next-of-kin and dyspnea. More than 70% of patients died during index hospitalization, one third of these in a palliative care unit. CONCLUSIONS: This largest European multicenter investigation of LVAD-patients receiving specialist palliative care shows a late integration and high physical and psychosocial symptom burden. This study highlights the urgent need for earlier integration to identify and address poorly controlled symptoms. Further studies and educational efforts are needed to close the gap between guideline-recommendations and the current status quo.

Impact of causative organism identification on clinical outcomes after minimally invasive posterior fixation for thoracolumbar pyogenic spondylitis: multicenter retrospective cohort study.

PURPOSE: This study aimed to evaluate the difference in treatment duration and unplanned additional surgeries between patients with unidentified causative organisms on empiric antibiotics and those with identified organisms on selective antibiotics in treating thoracolumbar pyogenic spondylitis with minimally invasive posterior fixation. METHODS: This multicenter retrospective cohort study included patients with thoracolumbar pyogenic spondylitis refractory to conservative treatment who underwent minimally invasive posterior fixation. Patients were divided into the identified (known causative organism) and unidentified groups (unknown causative organism). We analyzed data on demographics, antibiotic use, surgical outcomes, and infection control indicators. RESULTS: We included 74 patients, with 52 (70%) and 22 (30%) in the identified and unidentified groups, respectively. On admission, the identified group had higher C-reactive protein (CRP) levels and more iliopsoas abscesses. The duration to postoperative CRP negative was similar in the identified and unidentified groups (7.13 vs. 6.48 weeks, p = 0.74). Only the identified group had unplanned additional surgeries due to poor infection control, affecting 6 of 52 patients (12%). Advanced age and causative organism identification increased the additional surgery odds (odds ratio [OR], 8.25; p = 0.033 and OR, 6.83; p = 0.034, respectively). CONCLUSION: The use of empiric antibiotics in minimally invasive posterior fixation was effective without identifying the causative organism and did not prolong treatment duration. In patients with identified organisms, 12% required unplanned additional surgery, indicating a more challenging infection control. Causative organism identification was associated with the need for additional surgery, suggesting a more cautious treatment strategy for these patients.

A randomized, multicenter phase III Study of once-per-cycle administration of efbemalenograstim alfa (F-627), a novel long-acting rhG-CSF, for prophylaxis of chemotherapy-induced neutropenia in patients with breast cancer.

BACKGROUND: F-627 (efbemalenograstim alfa) is a novel long acting granulocyte colony-stimulating factor (G-CSF) that contains two human G-CSF fused to a human immunoglobulin G2 (hIgG2) -Fc fragment with a peptide linker. This studyevaluated the efficacy and safety of F-627, also known as efbemalenograstim alfa (Ryzneuta®) in reducing neutropenia compared with filgrastim (GRAN®). METHODS: This was a multicenter, randomized, open-label, active-controlled non-inferiority study. Two hundred thirty nine (239) patients were enrolled in thirteen centers and received the chemotherapy with epirubicin (100 mg/m2) and cyclophosphamide (600 mg/m2) on day 1 of each cycle for a maximum of four cycles. Patients were randomized to receive either a single 20 mg subcutaneous (s.c.) injection of F-627 on day 3 of each cycle or daily s.c. injection of filgrastim 5 µg/kg/d starting from day 3 of each cycle. The primary endpoint was the duration of grade 3 or 4 neutropenia in cycle 1. The safety profile was also evaluated. RESULTS: The mean (SD) duration of grade 3 or 4 neutropenia in cycle 1 was 0.68 (1.10) and 0.71 (0.95) days for the F-627 and the filgrastim groups, respectively. The Hodges-Lehmann estimate of the between-group median difference (F-627 vs filgrastim) in the duration of grade 3 or 4 neutropenia in cycle 1 was 0 day and the upper limit of the one-sided 97.5% CI was 0 day, which was within the prespecified non-inferiority margin of 1-day. Results for all efficacy endpoints in cycles 2 - 4 were consistent with the results in cycle 1, however a trend towards a lower incidence and a shorter duration of grade 3 or 4 neutropenia and grade 4 neutropenia was observed in the F-627 group compared with the filgrastim group. The ANC nadir in the F-627 group was significantly higher than that in the filgrastim group in each cycle. A single fixed dose of F-627 was well tolerated and as safe as standard daily filgrastim. CONCLUSIONS: A single fixed dose of 20 mg of F-627 in each cycle was as safe and effective as a daily dose of filgrastim 5 µg/kg/d in reducing neutropenia and its complications in patients who received four cycles of EC. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04174599, on 22/11/2019.

The presentation pattern and surgical strategies in bronchopulmonary carcinoid tumors: a multicenter experience in a low-income country.

Background: Bronchopulmonary carcinoid tumors include typical and atypical carcinoids, with typical carcinoids accounting for 80%-90% of these types of tumor. The primary curative treatment for these tumors is surgical resection. To our knowledge, there are limited studies on the presentation patterns and treatment strategies of bronchopulmonary carcinoid tumors in Africa. Objective: To determine the presentation patterns and surgical strategies in bronchopulmonary carcinoid tumors in patients treated at multicenters in Ethiopia from January 2018 to December 2023. Materials and methods: A 5-year retrospective cross-sectional study was conducted using medical records and pathology record reviews of patients operated on in Tikur Anbessa Specialized Hospital, Menelik II Hospital, and Saint Peter's Specialized Hospital from 1 January 2018 to 31 December 2023. The completeness of the data was checked before being entered into EpiData version 4.6.1, and analysis was conducted using SPSS version 29. Logistic regression was applied to depict the association of the histological pattern with its predictors. A P-value of <0.05 was considered significant for the association of variables. Results: A total of 62 patients with bronchopulmonary carcinoid tumors were included in the study with a mean age of 35.29 ± 12.26 years ranging from 14 to 67 years, in which more than half [37 (56.5%)] were females, with a male-to-female ratio of 1:1.3. The majority of the patients were non-smokers (90.3%) and symptomatic (98.4%), with a mean duration of symptoms of 29.7 ± 26 months, ranging from 3 to 156 months. Nearly half of the patients (48.4%) were treated for pulmonary tuberculosis before a diagnosis of carcinoid tumor was made. The majority of the patients underwent surgery by open posterolateral thoracotomy (98.4%), and pneumonectomy was the most common (38.7%) resection performed. Typical carcinoids were observed in 85.5% of patients. Age, smoking history, duration of symptoms, location of tumors, and lymph node status were statistically associated with histological patterns. Recommendation: Based on our study findings, improving physician awareness on the clinical presentation of carcinoid tumors, training for surgeons in less invasive surgical approaches, and further nationwide studies are recommended.

A multicenter study on deep learning for glioblastoma auto-segmentation with prior knowledge in multimodal imaging.

A precise radiotherapy plan is crucial to ensure accurate segmentation of glioblastomas (GBMs) for radiation therapy. However, the traditional manual segmentation process is labor-intensive and heavily reliant on the experience of radiation oncologists. In this retrospective study, a novel auto-segmentation method is proposed to address these problems. To assess the method's applicability across diverse scenarios, we conducted its development and evaluation using a cohort of 148 eligible patients drawn from four multicenter datasets and retrospective data collection including noncontrast CT, multisequence MRI scans, and corresponding medical records. All patients were diagnosed with histologically confirmed high-grade glioma (HGG). A deep learning-based method (PKMI-Net) for automatically segmenting gross tumor volume (GTV) and clinical target volumes (CTV1 and CTV2) of GBMs was proposed by leveraging prior knowledge from multimodal imaging. The proposed PKMI-Net demonstrated high accuracy in segmenting, respectively, GTV, CTV1, and CTV2 in an 11-patient test set, achieving Dice similarity coefficients (DSC) of 0.94, 0.95, and 0.92; 95% Hausdorff distances (HD95) of 2.07, 1.18, and 3.95 mm; average surface distances (ASD) of 0.69, 0.39, and 1.17 mm; and relative volume differences (RVD) of 5.50%, 9.68%, and 3.97%. Moreover, the vast majority of GTV, CTV1, and CTV2 produced by PKMI-Net are clinically acceptable and require no revision for clinical practice. In our multicenter evaluation, the PKMI-Net exhibited consistent and robust generalizability across the various datasets, demonstrating its effectiveness in automatically segmenting GBMs. The proposed method using prior knowledge in multimodal imaging can improve the contouring accuracy of GBMs, which holds the potential to improve the quality and efficiency of GBMs' radiotherapy.

Histological and immunohistochemical soft-tissue response to cylindrical and concave abutments: Multicenter randomized clinical trial.

BACKGROUND: This study aimed to analyze the influence of concave and cylindrical abutments on peri-implant soft tissue. Dimensions, collagen fiber orientation, and immunohistochemical data were assessed. METHODS: A multicenter, split-mouth, double-blind randomized clinical trial was conducted. Two groups were analyzed: cylindrical abutments and concave abutments. After a 12-week healing period, peri-implant soft tissue samples were collected, processed, and evaluated for dimensions, collagen fiber orientation, and immunohistochemical data. Inflammatory infiltration and vascularization were assessed, and the abutment surfaces were analyzed using scanning electron microscopy. The statistical analysis was performed using the SPSS version 20.0 statistical package. RESULTS: A total of 74 samples in 37 patients were evaluated. Histological evaluation of peri-implant soft tissue dimensions revealed significant differences between concave and cylindrical abutments. Concave abutments exhibited greater total height (concave: 3.57 ± 0.28 - cylindrical: 2.95 ± 0.27) and barrier epithelium extension (concave: 2.46 ± 0.17 - cylindrical: 1.89 ± 0.21) (p < 0.05), while the supracrestal connective tissue extension (concave: 1.11 ± 0.17 - cylindrical: 1.03 ± 0.16) was slightly greater (p > 0.05). Collagen fiber orientation favored concave abutments (23.76 ± 5.86), with significantly more transverse/perpendicular fibers than for cylindrical abutments (15.68 ± 4.57). The immunohistochemical analysis evidenced greater inflammatory and vascular intensity in the lower portion for both abutments, though concave abutments showed lower overall intensity (concave: 1.05 ± 0.78 - cylindrical: 1.97 ± 0.68) (p < 0.05). The abutment surface analysis demonstrated a higher percentage of tissue remnants on concave abutments (42.47 ± 1.32; 45.12 ± 3.03) (p < 0.05). CONCLUSIONS: Within the limitations of this study, concave abutments presented significantly greater peri-implant tissue height, linked to an extended barrier epithelium, versus cylindrical abutments in thick tissue phenotype. This enhanced soft tissue sealing, favoring a greater percentage of transversely oriented collagen fibers. The concave design reduced chronic inflammatory exudation with T and B cells, thus minimizing the risk of chronic inflammation. PLAIN LANGUAGE SUMMARY: This study looked at how 2 different shapes of dental implant abutments (the parts that connect the implant to the crown), specifically concave and cylindrical, affect the soft tissue around the implants. We wanted to see how these shapes influenced the tissue's size, structure, and health. We conducted a clinical trial with 37 patients, comparing the 2 types of abutments in the same mouth over 12 weeks. Our findings showed that the concave abutments led to a taller and more extensive layer of protective tissue around the implant compared to the cylindrical ones. This protective tissue had more favorable collagen fiber orientation, which is important for the strength and health of the tissue. Additionally, the concave abutments resulted in less inflammation and better tissue integration. In conclusion, concave abutments may provide better support and health for the soft tissue around dental implants, reducing the risk of chronic inflammation and potentially leading to better long-term outcomes for patients with dental implants.

One-year outcomes of a novel venous stent for symptomatic iliofemoral venous obstruction: prospective cohort study.

BACKGROUND: A stent with characteristics of a hybrid design may have advantages in improving the patency of symptomatic iliofemoral vein obstruction. This study assessed the safety and effectiveness of the V-Mixtent Venous Stent in treating symptomatic iliofemoral outflow obstruction. METHODS: Eligible patients had a Clinical-Etiologic-Anatomic-Physiologic (CEAP) C classification of ≥ 3 or a Venous Clinical Severity Score (VCSS) pain score of ≥ 2. The primary safety endpoint was the rate of major adverse events within 30 days. The primary effectiveness endpoint was the 12-month primary patency rate. Secondary endpoints included changes in VCSS from baseline to 6 and 12 months, alterations in CEAP C classification, Chronic Venous Disease Quality of Life Questionnaire (CIVIQ-14) scores at 12 months, and stent durability measures. RESULTS: Between December 2020 and November 2021, 171 patients were enrolled across 15 institutions. A total of 185 endovenous stents were placed, with 91.81% of subjects receiving one stent and 8.19% receiving 2 stents. Within 30 days, only two major adverse events occurred (1.17%; 95% confidence interval [CI], 0.14-4.16%), below the literature-defined performance goal of 11% (P < .001). The 12-month primary patency rate (91.36%; 95% CI, 85.93-95.19%; P < .001) exceeded the literature-defined performance goal. VCSS changes from baseline demonstrated clinical improvement at 6 months (- 4.30 ± 3.66) and 12 months (- 4.98 ± 3.67) (P < .001). Significant reduction in symptoms, as measured by CEAP C classification and CIVIQ-14, was observed from pre-procedure to 12 months (P < .001). CONCLUSIONS: The 12-month outcomes confirm the safety and effectiveness of the V-Mixtent Venous Stent in managing symptomatic iliofemoral venous outflow obstruction, including clinical symptom improvement compared to before treatment.

Treatment Trends and Epidemiologic Changes in Acetabular Fracture Management over the Course of 10 Years: An Analysis Based on 2853 Patients as Treated by the German Pelvic Multicenter Study Group.

Background/Objectives: Acetabular fractures, traditionally linked to high-impact trauma in younger adults, are increasingly observed in the elderly due to falls and poor bone quality. This demographic shift necessitates updated treatment approaches. This study analyzes demographic trends and treatment evolution over a decade using the German pelvic fracture registry. Methods: Data on acetabular fractures were analyzed from the German pelvic fracture registry of the German Trauma Society. Parameters included classification, demographics, treatment methods, and surgical details. Trends were assessed by grouping patients based on treatment intervals and age, comparing treatment methods, surgical approaches, and reduction quality across these groups, considering fracture types and treatment volume. Results: The study included 2853 unilateral acetabular fractures with a mean patient age of 61.5 years, showing an increasing age trend. A shift from simple to complex fractures involving the anterior acetabular column was observed. Operative treatment was performed in 62.5% of cases, more common in non-geriatric patients and those with posterior column involvement. The use of anterior intrapelvic approaches increased over time, replacing the Ilioinguinal extrapelvic approach. Anatomical reduction was achieved in 47.4% of cases, with 31.7% having imperfect reductions and 20.9% poor reductions. High-volume centers had significantly better reduction outcomes, particularly for simple fractures. Geriatric patients exhibited worse reduction quality compared to younger patients. In-hospital mortality was stable at 3.3%. Conclusions: The study highlights a demographic shift towards an older patient population, leading to more complex fracture patterns. Despite advancements in surgical techniques and new implant technologies, these demographic changes have resulted in lower reduction quality for complex fractures. Emphasis is placed on careful patient selection for reconstructive surgery or endoprosthetic replacement to ensure high-quality outcomes.