Hasil untuk "Surgery"

K. Varadhan, K. Neal, C. Dejong et al.

D. Jayne, H. Thorpe, J. Copeland et al.

K. Lassen, M. Soop, J. Nygren et al.

D. Shahian, Sean M. O'Brien, G. Filardo et al.

P. Quirke, R. Steele, J. Monson et al.

Summary Background Local recurrence rates in operable rectal cancer are improved by radiotherapy (with or without chemotherapy) and surgical techniques such as total mesorectal excision. However, the contributions of surgery and radiotherapy to outcomes are unclear. We assessed the effect of the involvement of the circumferential resection margin and the plane of surgery achieved. Methods In this prospective study, the plane of surgery achieved and the involvement of the circumferential resection margin were assessed by local pathologists, using a standard pathological protocol in 1156 patients with operable rectal cancer from the CR07 and NCIC-CTG CO16 trial, which compared short-course (5 days) preoperative radiotherapy and selective postoperative chemoradiotherapy, between March, 1998, and August, 2005. All analyses were by intention to treat. This trial is registered, number ISRCTN 28785842. Findings 128 patients (11%) had involvement of the circumferential resection margin, and the plane of surgery achieved was classified as good (mesorectal) in 604 (52%), intermediate (intramesorectal) in 398 (34%), and poor (muscularis propria plane) in 154 (13%). We found that both a negative circumferential resection margin and a superior plane of surgery achieved were associated with low local recurrence rates. Hazard ratio (HR) was 0·32 (95% CI 0·16–0·63, p=0·0011) with 3-year local recurrence rates of 6% (5–8%) and 17% (10–26%) for patients who were negative and positive for circumferential resection margin, respectively. For plane of surgery achieved, HRs for mesorectal and intramesorectal groups compared with the muscularis propria group were 0·32 (0·16–0·64) and 0·48 (0·25–0·93), respectively. At 3 years, the estimated local recurrence rates were 4% (3–6%) for mesorectal, 7% (5–11%) for intramesorectal, and 13% (8–21%) for muscularis propria groups. The benefit of short-course preoperative radiotherapy did not differ in the three plane of surgery groups (p=0·30 for trend). Patients in the short-course preoperative radiotherapy group who had a resection in the mesorectal plane had a 3-year local recurrence rate of only 1%. Interpretation In rectal cancer, the plane of surgery achieved is an important prognostic factor for local recurrence. Short-course preoperative radiotherapy reduced the rate of local recurrence for all three plane of surgery groups, almost abolishing local recurrence in short-course preoperative radiotherapy patients who had a resection in the mesorectal plane. The plane of surgery achieved should therefore be assessed and reported routinely. Funding Medical Research Council (UK) and the National Cancer Institute of Canada.

Sung-Bum Kang, J. Park, Seung-Yong Jeong et al.

James V Lewis

U. Gustafsson, J. Hausel, A. Thorell et al.

Glenn M. Chertow, Glenn M. Chertow, E. Levy et al.

E. McFalls, H. Ward, Thomas E. Moritz et al.

P. Serruys, Felix Unger, J. Sousa et al.

D. Mangano, I. C. Tudor, Cynthia Dietzel

R. Milroy, Fergus R Macbeth, R. Rosell et al.

Martin D. Fried, V. Yumuk, Jean-Michel Oppert et al.

H. Uramoto, F. Tanaka

Xindong Wei, Anfeng Si, Shuai Zhao et al.

Abstract Background Circular (circ)RNAs have emerged as crucial contributors to cancer progression. Nonetheless, the expression regulation, biological functions, and underlying mechanisms of circRNAs in mediating hepatocellular carcinoma (HCC) progression remain insufficiently elucidated. Methods We identified circUCK2(2,3) through circRNA sequencing, RT–PCR, and Sanger sequencing. CircUCK2(2,3) levels were measured in two independent HCC cohorts using quantitative real-time PCR (qRT–PCR). We explored the functions of circUCK2(2,3) using gain- and loss-of-function assays. Techniques such as RNA-sequencing, RNA immunoprecipitation (RIP), polysome fractionation, RNA pulldown, dual luciferase reporter assay, inhibitors of EGFR downstream signaling, CRISPR–Cas9, and medium transfer assays were employed to investigate the regulatory mechanisms and the protumoral activities of circUCK2(2,3). Additionally, in vitro cytotoxic assays and patient-derived xenograft (PDX) models assessed the effects of circUCK2(2,3) on the cytotoxic synergy of lenvatinib and EGFR inhibitors. Results CircUCK2(2,3) is upregulated in HCC tissues and serves as an independent risk factor for poor recurrence-free survival. The expression of circUCK2(2,3) is independent on its host gene, UCK2, but is regulated by its upstream promoter and flanking inverted complementary sequences. Functionally, circUCK2(2,3) enhances HCC proliferation, migration, and invasion, both in vitro and in vivo. Mechanistically, by sponging miR-149-5p, circUCK2(2,3) increases CNIH4 levels, which in turn amplifies TGFα secretion, resulting in the activation of EGFR and downstream pAKT and pERK signaling pathways. Moreover, circUCK2(2,3) overexpression sensitizes HCC cells to EGFR inhibitors, and increases the synergistic cytotoxicity of combined lenvatinib and EGFR inhibitor treatment. Conclusions CircUCK2(2,3) regulates a novel oncogenic pathway, miR-149-5p–CNIH4–TGFα–EGFR, in HCC, presenting a viable therapeutic target and biomarker for the precision treatment of HCC. Graphical Abstract

Kaixuan Chen, Longjun Chen, Yizhong Ma et al.

The skeletal system is an important support structure in the human body, and its homeostatic state is highly relevant to the development of a wide range of orthopaedic diseases. The search for key regulatory factors associated with skeletal development is essential for exploring potential therapeutic targets for bone diseases. Nerve Growth Factor (NGF), the first neurotrophic factor to be discovered, plays an important role in regulating immune cell function, influencing angiogenesis and participating in the physiological and pathological processes of bone homeostasis. Here, we mainly review the biological functions of NGF in the skeletal system and its molecular mechanisms, analyse the pathophysiological roles of the NGF signaling pathway in skeletal diseases such as osteoporosis, osteoarthritis, and fracture healing, and summarize the progress and challenges of the current clinical research on therapeutic strategies targeting NGF. In addition, we provide an overview of NGF and highlight the role of NGF in the regulation of bone formation and bone resorption. Therefore, by reviewing the literature related to NGF and bone diseases, this paper summarises the specific regulatory mechanisms of NGF in various bone diseases, which provides new perspectives and intervention targets for the treatment of skeletal diseases, especially in the field of diseases in which the effects of traditional treatments are limited. The therapeutic strategies targeting neurotrophic factors show broad prospects for clinical application.

S.B. Jelsma, M. Zijlmans, I.B. Heijink et al.

Epilepsy surgery is usually based on the removal of a local epileptogenic zone. If epilepsy is considered a network disease, a network approach might be more suitable. Insight into patient-specific epileptic brain networks is necessary to establish network-based surgical strategies.We included epilepsy surgery candidates who underwent diffusion-weighted imaging and intracranial EEG implantation with single pulse electrical stimulation (SPES, 0.2 Hz, 1–8 mA, 1 ms, monophasic stimuli) during presurgical evaluation. We reconstructed structural connectivity using fiber tractography taking intracranial electrodes as nodes. We reconstructed effective connectivity with SPES cortico-cortical evoked responses. We determined the inter-modal similarity between structural and effective connectivity with the Jaccard index, and compared network topologies using degree and betweenness centrality. We constructed a linear multilevel model to evaluate the relation between structural and effective connectivity at subject group level. The seizure onset zone nodes (SOZ), node proximity, and the volume of the electrode contact areas (VEA) were added to the model as possible predictors to accommodate for epilepsy and irregular spatial sampling.We included 13 patients (five with electrocorticography, eight with stereo-EEG). The median Jaccard index was 0.25 (IQR: 0.20–0.29), which means there is a higher overlap than expected by chance (median expected Jaccard index = 0.1 (IQR: 0.07–0.17)) with a considerable amount of connections that did not overlap. The structural connectivity degree showed a significant positive correlation with the effective connectivity degree in 9/13 patients and at group level after accommodating for node proximity (β = 0.13, 95 %-CI = [0.04, 0.21], t(852) = 2.79, p = 0.0054). SOZ and VEA were no significant predictors for the correlation between structural and effective connectivity.We showed a moderate overlap between non-invasive structural (measured with DWI) and invasive effective (measured with SPES) connectivity in epileptic brain networks. This overlap supports using non-invasively determined connectivity along with intracranial EEG to understand the epileptic brain. Future research needs to translate these findings towards network-based surgical strategies.

Piroozeh Taheri, Mohammad Taghi Beig Mohammadi, Mostafa Mohammadi et al.

Background: Exploring risk factors for the development of COVID-19 in vital organs of the body is necessary to improve patient survival and reduce disability and morbidity due to disease progression. By identifying these underlying risk factors and controlling them, it is possible to prevent extra-pulmonary involvement and even alleviate pulmonary involvement in patients, resulting in a significant reduction in mortality and morbidity rates. This study aimed to identify the underlying risk factors associated with pulmonary and extrapulmonary organ complications of COVID-19. Methods: This study was a cross-sectional descriptive-analytical study. Patients with a definitive diagnosis of COVID-19 who were admitted to the intensive care unit of Imam Khomeini Hospital in Tehran due to respiratory distress and poor clinical condition were included in the study population and were clinically followed up on. Patients' information was collected by reviewing patients' records and the hospital information system. Results: A total of 123 patients were included in the study (63.4% were male, mean age = 58.87 ± 12.37). Using ROC curve analysis, the calculated risk score is considered statistically significant for diagnostic accuracy (AUC = 0.862 [0.797–0.927], P value < value<0.001). A risk score cutoff greater than 1.5 (sensitivity 89.9%, specificity 38.9%) favors an increased likelihood of in-hospital mortality. According to multiple linear regression (F (9,93).369, P value=0.001), chronic obstructive pulmonary disease, asthma, diabetes, SOFA score on days 2 & 3, and ventilation support were predictors of ICU length of stay. Conclusion: A history of chronic heart failure with renal impairment, liver cirrhosis with liver complication, and any underlying disease are associated with pulmonary complications in COVID-19 patients.

J. Meara, S. Greenberg