tbuckley/cabot-search huggingface dataset:
Ultra-short-period perioperative pulmonary rehabilitation on short-term outcomes after surgery in smoking patients with lung cancer: A randomized clinical trial
Authors: Dingpei Han, Xinyi Wang, Xin Sun, Yuqin Cao, Chengqiang Li, Wei Guo, Yanxia Hu, Junbiao Hang, Jian Li, Qing Xie, Hecheng Li
Journal: International Journal of Surgery (2024)

Background: Pulmonary rehabilitation is essential for airway management after thoracic surgery. Most current pulmonary rehabilitations are composed of 2-4-week exercises, which require significant consumption of medical resources and concerns about disease progression. Materials and Methods: This single-center, prospective, randomized controlled trial enrolled smoking patients with pulmonary masses or nodules suitable for lobectomy, aged 18-80, with smoking history (≥20 pack-years). Eligible patients were randomized in a 1:1 ratio into two groups. Patients in the intervention group underwent perioperative breathing exercises based on positive pressure vibration expectoration and three-day preoperative lower limb endurance training. Patients in the control group received routine perioperative care. The primary outcome was in-hospital incidence of postoperative pulmonary complications. Secondary outcomes included postoperative hospital stay, total hospitalization cost, postoperative drainage time, drainage volume, semiquantitative cough strength score, pain score, Borg scale‐assessed fatigue, and walking distance on postoperative days 1 and 2. Results: A total of 194 patients were included in the study with 94 in the intervention group and 100 in the control group. Our ultrashort pulmonary rehabilitation program potentially reduced pulmonary complications incidence (24.5% vs. 33.0%), but without statistical significance ( P =0.190). No significant differences were found in other perioperative outcomes, except for postoperative semiquantitative cough strength score (3 [interquartile range, 3-3.75] vs. 3 [interquartile range, 2-3], P &lt;0.001) and change in walking distance from postoperative days 1 to 2 (60 [interquartile range, 40-82.5] vs. 30 [interquartile range, 10-60], P =0.003). Conclusion: There were no significant differences in postoperative complications and other hospitalizations, but our ultrashort rehabilitation program improved patients’ semiquantitative cough strength score and walking distance, indicating potential for better outcomes. This treatment is a safe and effective means of airway management for thoracic surgery in the era of enhanced recovery. (ClinicalTrials.gov Identifier: XXX).
Innovations in 3D printed individualized bone prosthesis materials: revolutionizing orthopedic surgery: a review
Authors: Zhigang Qu, Jiaji Yue, Ning Song, Shenglong Li
Journal: International Journal of Surgery (2024)

The advent of personalized bone prosthesis materials and their integration into orthopedic surgery has made a profound impact, primarily as a result of the incorporation of three-dimensional (3D) printing technology. By leveraging digital models and additive manufacturing techniques, 3D printing enables the creation of customized, high-precision bone implants tailored to address complex anatomical variabilities and challenging bone defects. In this review, we highlight the significant progress in utilizing 3D printed prostheses across a wide range of orthopedic procedures, including pelvis, hip, knee, foot, ankle, spine surgeries, and bone tumor resections. The integration of 3D printing in preoperative planning, surgical navigation, and postoperative rehabilitation not only enhances treatment outcomes but also reduces surgical risks, accelerates recovery, and optimizes cost-effectiveness. Emphasizing the potential for personalized care and improved patient outcomes, this review underscores the pivotal role of 3D printed bone prosthesis materials in advancing orthopedic practice towards precision, efficiency, and patient-centric solutions. The evolving landscape of 3D printing in orthopedic surgery holds promise for revolutionizing treatment approaches, enhancing surgical outcomes, and ultimately improving the quality of care for orthopedic patients.
Efficacy of a smartphone application assisting home-based rehabilitation and symptom management for patients with lung cancer undergoing video-assisted thoracoscopic lobectomy: a prospective, single-blinded, randomised control trial (POPPER study)
Authors: Chao Lv, Fangliang Lu, Xiugeng Zhou, Xiang Li, Wenhua Yu, Chune Zhang, Kaishen Chen, Songtao Du, Chao Han, Jia Wang, Yuzhao Wang, Shaolei Li, Liang Wang, Yinan Liu, Shanyuan Zhang, Miao Huang, Dongdong Song, Dachuan Zhao, Bing Liu, Yaqi Wang, Xinrun Cui, Zhiwei Zhou, Shi Yan, Nan Wu
Journal: International Journal of Surgery (2024)

Background: Video-assisted thoracoscopic (VATS) lobectomy can affect patients’ pulmonary function and quality of life significantly. No optimal protocol combining patient-reported outcome-based symptom management and post-discharge rehabilitation programme has yet been established. This study aimed to assess the efficacy of a novel smartphone app designed for home-based symptom management and rehabilitation. Methods: The app was developed based on three modules: a symptom reporting system with alerts, aerobic and respiratory training exercises, and educational material. Four core symptoms were selected based on a questionnaire survey of 201 patients and three rounds of Delphi voting by 30 experts. We screened 265 patients and randomly assigned 136 equally to the app group and usual care group. The primary outcome was pulmonary function recovery at 30 days postoperatively. Secondary outcomes included symptom burden and interference with daily living (both rated using the MD Anderson Symptom Inventory for Lung Cancer), aerobic exercise intensity, emergency department visits, app-related safety, and satisfaction with the app. Findings: Of the 136 participants, 56.6% were women and their mean age was 61 years. The pulmonary function recovery ratio 1 month after surgery in the app group was significantly higher than that in the usual care group (79.32% vs. 75.73%; P =0.040). The app group also recorded significantly lower symptom burden and interference with daily living scores and higher aerobic exercise intensity after surgery than the usual care group. Thirty-two alerts were triggered in the app group. The highest pulmonary function recovery ratio and aerobic exercise intensity were recorded in those patients who triggered alerts in both groups. Interpretation: Using a smartphone app is an effective approach to accelerate home-based rehabilitation after VATS lobectomy. The symptom alert mechanism of this app could optimise recovery outcomes, possibly driven by patients’ increased self-awareness.
Comparison of learning curves and related postoperative indicators between endoscopic and robotic thyroidectomy: a systematic review and meta-analysis
Authors: Jian-Peng Wang, Da-Peng Li, Yu-Chen Liu, Lei Zhang, Zi-Yue Fu, Bing-Yu Liang, Si-Yue Yin, Yi-Pin Yang, Min Fan, Zhao Ding, Shan-Wen Chen, Liang Zhang, Kai-Le Wu, Ye-Hai Liu, Fan Cao, Hai-Feng Pan, Yan-Xun Han
Journal: International Journal of Surgery (2024)

Endoscopic thyroidectomy (ET) and robotic thyroidectomy (RT) yield similar perioperative outcomes. This study investigated how the learning curve (LC) affects perioperative outcomes between ET and RT, identifying factors that influence the LC.
T cell receptor and immune gene expression pharmacodynamics for durvalumab monotherapy and in combination with tremelimumab or bevacizumab in unresectable hepatocellular carcinoma (uHCC).
Authors: Robin Kate Kelley, Young S Lee, James Conway, John F Kurland, Alejandra Negro, Patricia McCoon
Journal: Journal of Clinical Oncology (2024)

4022 Background: Study 22 (NCT02519348), a Phase 2 trial of immune checkpoint inhibitor (ICI) monotherapy and combination regimens in uHCC, showed higher rates of objective response (ORR) with STRIDE (Single Tremelimumab [T] Regular Interval Durvalumab [D]) or D plus bevacizumab (B) than with D (1,2). Pharmacodynamic analyses showed that improved efficacy with STRIDE versus D was associated with increased expansion of T cell clones at the end of cycle 1 (C1) versus D (3). We performed further T cell clone analyses to include D+B and compared gene expression signatures (GES) associated with each treatment arm to explore commonalities and differences in mechanistic biomarkers underpinning the efficacies associated with STRIDE and D+B. Methods: Participants (pts) with uHCC and no prior ICI therapy received STRIDE (T 300 mg + D 1500 mg [1 dose during C1] then D 1500 mg once every 4 weeks [Q4W]), T75+D (T 75 mg + D 1500 mg Q4W [4 doses] then D 1500 mg Q4W, D (1500 mg Q4W), T (750 mg Q4W [7 doses] then Q12W), or D+B (D 1120 mg + B 15 mg/kg Q3W). DNA and RNA were isolated from PAXgene-preserved whole blood collected at baseline and at the end of C1. CDR3 sequencing of T cell receptor β using the immunoSEQ Assay (Adaptive Biotechnologies, Seattle, WA) and RNA sequencing (Q Squared Solutions, Morrisville, NC) were performed. ImmunoSeq results and immunologic gene expression changes were reported with ORR across treatment arms. Results: ImmunoSeq did not show significant differences in baseline T cell clonality across treatment arms. In contrast to STRIDE versus D, the number of expanded T cell clones at the end of C1 for D+B versus D was unchanged, and no association between expanded T cell clones and ORR was observed (Table). While increases in Type I and II interferon and mitotic GES were seen for both STRIDE and D+B, more changes in immune-related peripheral GES, with greater magnitude of change, were associated with STRIDE. Significant changes in CD8 T cell, M1 macrophage, and Treg GES were only observed for STRIDE. Conclusions: While STRIDE and D+B both had higher ORRs than D monotherapy in uHCC, only STRIDE was associated with an increased expansion of T cell clones versus D. This, in addition to the differences in magnitude and type of GES changes, suggest that STRIDE and D+B have distinct and potentially complementary mechanisms of action. 1. Kelley, et al. J Clin Oncol 2021. 2. Lim, et al. J Clin Oncol2022, A436. 3. McCoon, et al. J Clin Oncol2021, A4087. Clinical trial information: NCT02519348 . [Table: see text]
Left ventricular posterior wall hypertrophy leads to poor prognosis of hypertrophic obstructive cardiomyopathy in children - a cohort study
Authors: Shun Liu, Xiumeng Hua, Yiqi Zhao, Han Mo, Xiao Chen, Weiteng Wang, Yijing Li, Qian Zhao, Jun Yan, Jiangping Song
Journal: International Journal of Surgery (2024)

Objective: The modified Morrow operation for hypertrophic obstructive cardiomyopathy (HOCM) in children has a favorable outcome, but some children still have a poor prognosis after the procedure. In this study, we aimed to investigate the application of cardiac computed tomography (CCT) to construct a three-dimensional(3D) model of the left ventricle (LV) and analyze the association between hypertrophy in different parts of the LV and poor prognosis. Methods: We retrospectively analyzed 57 children with HOCM from April 2015 to October 2022, among whom 16 underwent preoperative CCT examination. All children underwent the modified Morrow surgery in our center. We defined heart failure (HF), malignant ventricular arrhythmia, and recurrent left ventricular outflow tract obstruction (LVOTO) as adverse events. We performed a retrospective Cox analysis and conducted genetic testing. A 3D model of the LV was built through the standard 17-segment method and analyzing the high-risk factors. Results: 17 (29.8%) had adverse events during follow-up. Multivariate Cox analysis revealed that genetic mutation ( HR: 5.634, 95%CI: 1.663-19.086, P =0.005), Noonan syndrome ( HR: 3.770, 95%CI: 1.245-11.419, P =0.019), preoperational systolic anterior motion (SAM)( HR: 4.596, 95%CI: 1.532-13.792, P =0.007)and mid-ventricular obstruction ( HR: 4.763, 95%CI: 1.538-14.754, P =0.007) were high-risk factors, suggesting that the degree of hypertrophy in the left ventricle is associated with poor prognosis. By analyzing the CCT with 3D model, children with poor prognosis have more hypertrophy in basal-inferior ( P =0.014), mid-inferoseptal( P =0.044), mid-inferior( P =0.017). It suggests that a more hypertrophied posterior left ventricular wall portends a worse prognosis. Conclusion: Even after modified Morrow surgery, the prognostic impact of genetic mutation remains significant. Moreover, the degree of hypertrophy of the posterior wall in the LV was also related to the postoperative prognosis through CCT combined with 3D technology. It provides surgeons guiding to evaluate the overall prognosis and the treatment plan before surgery.
Microbiome signature, immune landscape and global methylation in early onset colorectal cancer.
Authors: Ning Jin, Rebecca Hoyd, Ayse Selen Yilmaz, Shiqi Zhang, YunZhou Liu, Dennis Grencewicz, Malvenderjit Jagjit Singh, Jiangjiang Zhu, Bei Liu, Xiaokui Mo, Daniel Spakowicz
Journal: Journal of Clinical Oncology (2024)

3580 Background: The incidence of colorectal cancer (CRC) in young adults (age at diagnosis &lt; 50 years old) has been rapidly increasing. Approximately 20% of early-onset (EO) CRC cases are due to germline gene mutations. However, the etiology of sporadic EO CRC remains poorly understood. Research suggests that environmental factors such as Western diet may be associated with increased incidence of sporadic EO CRC. The gut microbiota decomposes and ferments dietary fibers to produce microbial metabolites, which play important roles in maintaining the intestinal epithelium integrity. A high-fat, low-fiber diet has been associated with intestinal dysbiosis, which disrupts intestinal bacterial homeostasis. An increased inflammation state characterizes dysbiosis and may promote an immunosuppressive tumor microenvironment (TME) and suppress antitumor immune surveillance. In addition, epigenetic modifications are influenced by environmental changes and therefore epigenetics may bridge the knowledge gap in understanding the development of sporadic EOCRC. Methods: We obtained RNA sequencing data from the Cancer Genome Atlas (TCGA) and the Oncology Research Information Exchange Network (ORIEN) from the Ohio State University biospecimen services to characterize intra-tumor microbiota composition, tumor-infiltrating lymphocytes (TILs) and differential pathways in EO CRC. We used Infinium HM450 methylation array in The Cancer Genome Atlas (TCGA) and performed genome-wide analyses using reduced representation bisulfite sequencing (RRBS) method to identify differentially methylated regions (DMRs) in EO CRC. Results: Gene expression analysis is consistent with Fusobacterium promoting inflammation in EO CRC. Intra-tumor microbes are positively correlated with M2 macrophages. Compared to late onset (LO) CRC, EO CRC patients have unique gene signatures of phagosome formation, S100 family signaling pathway and CREB signaling in neurons by using ingenuity pathway analysis (IPA). In addition, we found that methylation ages predicted by epigenetic clocks in EO CRC patients were 15 years older on average than their chronological ages, whereas methylation ages in late onset (LO) CRC patients were comparable with chronological ages. The enriched pathways based on DMRs associated with EO CRC have significant overlap with canonical pathways based on differentially expressed genes (DEGs), including CREB signaling in neurons and S100 family signaling pathways. Conclusions: These data suggest that pathogenic microbes may induce inflammation, which leads to accelerated aging in EO CRC.
Genomic alterations in early-onset versus average-onset stage IV colorectal cancer.
Authors: Eric Michael Lander, Samuel Rivero-Hinojosa, Vasily N. Aushev, Adham A Jurdi, Minetta C. Liu, Cathy Eng
Journal: Journal of Clinical Oncology (2024)

3586 Background: The etiology of the rising incidence of early-onset colorectal cancer (EOCRC), defined as in patients aged &lt;50, remains unknown. EOCRC is diagnosed at advanced pathologic stages compared to average-onset colorectal cancer (AOCRC; age &gt;60). We previously reported data for Stages I-III disease. In this analysis, we evaluated tumor genomic differences in stage IV EOCRC versus AOCRC. Methods: The cohort included 3212 patients diagnosed with stage IV colon or rectal cancer who had whole exome sequencing (WES) as part of clinical tumor-informed ctDNA testing (Signatera, bespoke mPCR NGS assay, Natera, Inc.). Tumor mutational burden (TMB) and microsatellite instability (MSI) status were derived from tumor WES analysis. The prevalence of somatic variants, gene mutations and mutational signatures were compared between EOCRC and AOCRC groups, stratified by TMB and MSI status. Fisher’s exact test was used to test significance between age groups and p-values were adjusted using the FDR method for multiple test correction. Results: A total of 1070 patients with EOCRC (75.8% colon, 22.2% rectal, 2% unknown) and 2141 patients with AOCRC (80.2% colon, 18.3% rectal, 1.5% unknown) were included. No significant differences were found in the frequency of MSI and TMB status between age groups. In the TMB-Low/MSS group (EOCRC N=982; AOCRC N=1930), TP53 mutations were more common in EOCRC (62% vs. 54.5%, p=0.0036), but APC gene mutations were less common in EOCRC (59% vs. 65%, p=0.02). In the TMB-High/MSI-H group (EOCRC N=64; AOCRC N=182), BRAFand BEND4 mutations were less common in EOCRC (6.2% vs. 59.3%, p&lt;0.001 and 6.2% vs 31.9%, p=0.036), but KRASgene mutations were more common in EOCRC (54.7% vs. 17%, p&lt;0.001). BRAF V600E was the only significant single variant (0% vs 59.3% p&lt;0.001). No significant differences were found in the TMB-High/MSS group (EOCRC N=24; AOCRC N=29). In the mutational signature analysis for the TMB-Low/MSS group, the clock-like signature was less frequent in EOCRC (76.9% vs. 85.4%, p&lt; 0.001). In the TMB-High/MSI-H group, MMR deficiency signature was the most frequent signature, however no significant differences were found between EOCRC and AOCRC (81.25% vs. 85.71, p=0.42). In the TMB-High/MSS group, POLE exonuclease domain mutations signature was 2.2 times more frequent in EOCRC (62.5% vs. 27.6%, p&lt;0.024). MMR deficiency signature was also less common in EOCRC vs. AOCRC (33.33% vs. 55.17%; p&lt;0.10). Conclusions: Tumors in EOCRC harbored unique genomic alterations that varied between the TMB-Low/MSS, TMB-High/MSI-H, and TMB-High/MSS subpopulations. In TMB-Low/MSS tumors, similar gene mutations and genomic signatures were observed. However, the TMB-High/MSI-H and TMB-High/MSS subgroups harbored gene mutations and signatures that differed between age groups, suggesting that EOCRC may arise from uniquely different mutagenic processes in these subgroups.
Artemin and immune checkpoint inhibitor (ICI) efficacy in metastatic colorectal cancer (mCRC): A correlative analysis of the Canadian Cancer Trials Group (CCTG) CO.26 trial.
Authors: Lucy Xiaolu Ma, Emma Titmuss, Derek J. Jonker, Hagen Fritz Kennecke, Scott R. Berry, Felix Couture, Chaudhary E. Ahmad, John R. Goffin, Petr Kavan, Mohammed Harb, Bruce Colwell, Setareh Samimi, Benoit Samson, Tahir Abbas, Francine Aubin, Sheryl L. Koski, Dongsheng Tu, Christopher J. O'Callaghan, Jonathan M. Loree, Eric Xueyu Chen
Journal: Journal of Clinical Oncology (2024)

3587 Background: ICIs have limited efficacy in microsatellite stable (MSS) mCRC. The mechanisms of resistance to ICI remain incompletely understood. Recent findings suggest that erythyroid progenitor cells (EPCs) in the tumour microenvironment can exert immunosuppressive properties and promote tumour progression through the secretion of artemin, a neurotrophic factor. We conducted this post-hoc analysis of the Phase II CCTG CO.26 trial (NCT02870920) to investigate the relationship between artemin and ICI treatment outcomes in MSS mCRC. Methods: The CO.26 trial randomized patients (pts) with refractory mCRC to durvalumab plus tremelimumab (D+T) and best supportive care (BSC) compared to BSC alone in a 2:1 fashion. Serum artemin concentrations were determined from pre-treatment and serial on-treatment blood samples. The median artemin value (1.051ng/ml) was used to stratify pts into high versus low artemin groups. Progression-free (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method and compared between groups using the log-rank test. Cox proportional hazard models were used to analyze prognostic and predictive impacts of artemin on PFS and OS. Results: Of 180 pts enrolled in CO.26, blood samples were available for 161 pts (N= 114 D+T, 47 BSC) at baseline, 94 at week 8 and 69 at progression. In the BSC arm, OS was lower for pts with high artemin at baseline compared to low pts (mOS 3.17 vs. 5.65 months, HR 1.74 [0.94-3.25], p=0.080). In artemin high pts, D+T improved OS compared to BSC (mOS 6.44 vs. 3.17 months, HR 0.54 [0.33-0.91] p=0.020). There was no difference in OS between D+T and BSC arms in artemin low pts (mOS 6.64 vs. 5.65 months, HR 0.87 [0.53-1.43], p=0.58, multivariable p-interaction=0.061). In the D+T arm, pts with progressive disease had significant increases in artemin levels at week 8 compared to baseline (p=0.026), while there was no significant change in week 8 artemin levels in pts with stable disease (p=0.14). Conclusions: High baseline artemin may be a poor prognostic marker in MSS mCRC and increase in artemin level during treatment can be indicative of progressive disease. High baseline artemin may predict benefit from ICI treatment. Studies are warranted to better understand and explore targeting the EPC-artemin axis to enhance efficacy of ICI in MSS mCRC.