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Si-Min Ruan,1,* Mei-Qing Cheng,1,* Hui Huang,1 Hang-Tong Hu,1 Wei Li,1 Xiao-Yan Xie,1 Ming-De Lu,1,2 Ming Kuang,1,2 Man-Xia Lin,1 Wei Wang1 1Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China; 2Department of Hepatobiliary Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Man-Xia Lin; Wei Wang, Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, 58 Zhongshan Road 2, Guangzhou, 510080, People’s Republic of China, Tel/Fax +86-20-87765183, Email linmxia@mail.sysu.edu.cn; wangw73@mail.sysu.edu.cnPurpose: The contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS) treatment response algorithm (TRA) is still in development. The aim of this study was to explore whether the CT/MRI LI-RADS TRA features were applicable to CEUS in evaluating the liver locoregional therapy (LRT) response.Patients and Methods: This study was a retrospective review of a prospectively maintained database of patients with hepatocellular carcinoma undergoing ablation between July 2017 and December 2018. The standard criteria for a viable lesion were a histopathologically confirmed or typical viable appearance in the follow-up CT/MRI. Performance of the LI-RADS TRA assessing tumor viability was then compared between CEUS and CT/MRI. Inter-reader association was calculated.Results: A total of 244 patients with 389 treated observations (118 viable) were evaluated. The sensitivity and specificity of the CEUS TRA and CT/MRI LI-RADS TRA viable categories for predicting viable lesions were 55.0% (65/118) versus 56.8% (67/118) (P = 0.480) and 99.3% (269/271) versus 96.3% (261/271) (P = 0.013), respectively. The PPV of CEUS was higher than that of CT/MRI (97.0% vs 87.0%). Subgroup analysis showed that the sensitivity was low in the 1-month assessment for both CEUS (38.1%, 16/42) and CT/MR (47.6%, 20/42) and higher in the 2– 6-month assessment for both CEUS (65.7%, 23/35) and CT/MR (62.9%, 22/35). Interobserver agreements were substantial for both CEUS TRA and CT/MRI LI-RADS TRA (κ, 0.74 for both).Conclusion: The CT/MRI LI-RADS TRA features were applicable to CEUS TRA for liver locoregional therapy. The CEUS TRA for liver locoregional therapy has sufficiently high specificity and PPV to diagnose the viability of lesions after ablation.Keywords: contrast-enhanced ultrasound, Liver Imaging Reporting and Data System, treatment response, hepatocellular carcinoma, locoregional therapy

Ting Li, Ruochuan Sun, Mingdian Lu, Jiacong Chang, Xiangling Meng,* Huo Wu* Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, He Fei, 230222, China *These authors contributed equally to this work Background: NDRG3 is an N-myc downregulated gene (NDRG). The aim of this article was to identify the role of NDRG3 in colorectal cancer (CRC) and to determine the mechanism underlying its function. Methods: Using immunohistochemical staining, expression and clinicopathological variables of NDRG3 were analyzed in 170 CRC samples. Overexpression of NDRG3 was employed in SW1116 cells, downregulation of NDRG3 was achieved in RKO cells, then migration and invasion assays were performed in vitro, and a mouse model was constructed in vivo. Results: Increased expression of NDRG3 was observed in primary CRC tissues, and this expression was correlated with distant metastasis. Consistently, ectopic expression of NDRG3 in SW1116 cells enhanced cell migration and invasion, while knockdown of NDRG3 in RKO cells significantly suppressed CRC cell metastasis. The portal vein injection models suggested that NDRG3 overexpression facilitates liver metastasis. These events were associated with the phosphorylation of Src (c-Src) at Tyr 419 site. Conclusion: Our results showed that NDRG3 facilitates CRC migration and invasion by activating Src phosphorylation, suggesting the role of NDRG3 as a candidate oncogene. Keywords: NDRG3, colorectal cancer, metastasis, Src

Qiusha Tang,1 Mudan Lu,2 Daozhen Chen,2 Peidang Liu1 1School of Medicine, Southeast University, Nanjing, 2Genetic Laboratory, Wuxi Hospital for Maternal and Child Health Care, the Affiliated Hospital of Nanjing Medical University, Wuxi, People’s Republic of China Background: To explore a new combination of thermal treatment and gene therapy for hepatoma, a heat-inducible herpes simplex virus thymidine kinase/ganciclovir (HSV-TK/GCV) gene therapy system was developed in which thermal energy generated by Mn0.5Zn0.5Fe2O4 nanoparticles (MZF-NPs) under an alternating magnetic field was used to activate gene expression.Methods: First, a recombinant eukaryotic plasmid, pHsp 70-HSV-TK, was constructed as a target gene for therapy. This recombinant plasmid was used to transfect SMMC-7721 hepatoma cells and the gene expression was evaluated. Magnet-induced heating was then applied to cells to assess the antihepatoma effects of the polyethylenimine (PEI)-MZF-NPs/pHsp 70-HSV-TK/GCV complex, in vitro and in vivo.Results: The results showed that cells were successfully transfected with pHsp 70-HSV-TK and that expression levels of HSV-TK remained stable. Both in vitro and in vivo results indicated that the combination of gene therapy and heat treatment resulted in better therapeutic effects than heating-alone group. The rates of apoptosis and necrosis in the combined treatment group were 49.0% and 7.21%, respectively. The rate of inhibition of cell proliferation in the combined treatment group was significantly higher (87.5%) than that in the heating-alone group (65.8%; P

Background Takotsubo syndrome has been reported in patients with COVID-19, although minimal data are available. This investigation assessed the incidence and impact of takotsubo syndrome on patients hospitalized with COVID-19. Methods A retrospective cohort study was conducted using International Statistical Classification of Diseases, Tenth Revision, codes to identify patients with a primary diagnosis of COVID-19 with or without takotsubo syndrome in the National Inpatient Sample 2020 database. Outcomes between groups were compared after propensity score matching for patient and hospital demographics and comorbidities. Results A total of 211,448 patients with a primary diagnosis of COVID-19 were identified. Of these, 171 (0.08%) had a secondary diagnosis of takotsubo syndrome. Before matching, patients with COVID-19 and takotsubo syndrome, compared with patients without takotsubo syndrome, were older (68.95 vs 64.26 years; P < .001); more likely to be female (64.3% vs 47.2%; P < .001); and more likely to have anxiety (24.6% vs 12.8%; P < .001), depression (17.5% vs 11.4%; P = .02), and chronic obstructive pulmonary disease (24.6% vs 14.7%; P < .001). The takotsubo syndrome group had worse outcomes than the non–takotsubo syndrome group for death (30.4% vs 11.1%), cardiac arrest (7.6% vs 2.1%), cardiogenic shock (12.9% vs 0.4%), length of hospital stay (10.7 vs 7.5 days), and total charges ($152,685 vs $78,468) (all P < .001). After matching and compared with the non–takotsubo syndrome group (n = 508), the takotsubo syndrome group (n = 170) had a higher incidence of inpatient mortality (30% vs 14%; P < .001), cardiac arrest (7.6% vs 2.8%; P = .009), and cardiogenic shock (12.4% vs 0.4%; P < .001); a longer hospital stay (10.7 vs 7.6 days; P < .001); and higher total charges ($152,943 vs $79,523; P < .001). Conclusion Takotsubo syndrome is a rare but severe in-hospital complication in patients with COVID-19.

We present a case of a 94-year-old female who was shown to have an incidental subclavian venous aneurysm on CT during stroke workup. Subclavian venous aneurysms are a rare finding with only 13 reported in our literature search. Patients can present clinically with pain or supraclavicular swelling, or not unusually with no symptoms at all. These aneurysms can be detected on multiple imaging modalities, with ultrasound providing information on presence of a thrombus. Recent advances in minimally invasive procedures provide a new avenue of management for these aneurysms, with multiple cases involving an endovascular approach.

Background: Coronary plaque is common among people with HIV (PWH) with low-to-moderate traditional atherosclerotic cardiovascular disease (ASCVD) risk. Objectives: The purpose of this study was to determine the association of high-sensitivity cardiac troponin T (hs-cTnT) levels with coronary plaque characteristics and evaluate if hs-cTnT improves identification of these features beyond traditional ASCVD risk factors among PWH. Methods: Among PWH receiving stable antiretroviral therapy with low-to-moderate ASCVD risk and no known history of ASCVD, hs-cTnT levels and measures of plaque by coronary computed tomography angiography were assessed. Primary outcomes included the association of hs-cTnT level with the presence of any plaque, vulnerable plaque, coronary artery calcium (CAC) score, and Leaman score. Assessment of model discrimination of hs-cTnT for plaque characteristics was also performed. Results: The cohort included 708 U.S. participants with a mean age of 51 ± 6 years, 119 (17%) females, a median ASCVD risk score of 4.4% (Q1-Q3: 2.5%-6.6%), and a median hs-cTnT level of 6.7 ng/L (detectable level ≥6 ng/L in 61%). Any plaque was present in 341 (48%), vulnerable plaque in 155 (22%), CAC>100 in 68 (10%), and a Leaman score >5 in 105 (15%). After adjustment for ASCVD risk score, participants with hs-cTnT >9.6 ng/L (highest category) versus an undetectable level (100 (2.58, 95% CI: 1.37-4.83), and Leaman score >5 (2.13, 95% CI: 1.32-3.46). The addition of hs-cTnT level modestly improved the discrimination of ASCVD risk score to identify critical plaque features. Conclusions: In PWH without known ASCVD, hs-cTnT levels were strongly associated with and improved prediction of subclinical coronary plaque. (Evaluating the Use of Pitavastatin to Reduce the Risk of Cardiovascular Disease in HIV-Infected Adults [REPRIEVE]; NCT02344290)

Background:. Apert syndrome is a relatively rare genetic disorder with a constellation of distinct craniofacial deformities and bilateral syndactyly of the hands and feet. Although the literature contains ample evidence for the need to treat cranial, midfacial, and hand abnormalities, there are severe shortcomings in the literature when attempting to describe the pathology and management of the entire upper limb in patients with Apert syndrome. Methods:. A thorough literature search was performed using PubMed, Scopus, Web of Science, and Google Scholar, on the management of the upper extremity in Apert syndrome, including the shoulder, elbow, and hand. Results:. Our findings of the literature discuss the clinical presentation and management trends of the upper extremity in patients with Apert syndrome. Through multicenter collaboration, discussion among experts in the field, and evidence gathered from the literature, we propose treatment algorithms to treat deformities of the hand, shoulder, and elbow in patients with Apert syndrome. Conclusions:. This review identifies that even if hand pathologies have been correctly treated, shoulder and elbow abnormalities in patients with Apert syndrome are largely ignored. To optimize outcomes, added cognizance of additional upper limb congenital differences and their management should be highly advocated in this patient population.

Background:. Surgical innovation has provided new options for the management of complex peripheral nerve injuries, generating renewed interest in this field. Historic literature may be misinterpreted or misquoted, or create dogma, which is perpetuated in teaching, research publications, and clinical practice. The management of peripheral nerve injuries is based on complex decision-making, with potential lifelong ramifications for patients incorrectly receiving an expectant or surgical management plan. Methods:. This article includes opinion from expert leaders in the field of peripheral nerve surgery and questions some of the current assumptions and preconceptions around nerve surgery based on clinical evidence. There was extensive debate regarding the contents of the final article, and the different opinions expressed represent the uncertainty in this field and the differing levels of confidence in available published evidence. Results:. Individual practices vary and, therefore, absolute consensus is impossible to achieve. The work is presented as 10 myths which are assessed using both historical and emerging evidence, and areas of uncertainty are discussed. Conclusions:. It is important to learn lessons from the past, and scholars of history bear the task of ensuring references are accurately quoted. Expunging myths will enhance care for patients, focus research efforts, and expand on the surgical possibilities within this specialty.

Background: Integrating immune checkpoint inhibitors with multi-target tyrosine kinase inhibitors presents an innovative and hopeful strategy in liver cancer treatment. Nonetheless, a degree of resistance to this treatment is noticeable in certain patients. Alternative splicing (AS) represents a common biological process that controls the variety of life functions via isoforms. Purpose: Investigating how gene AS affects the effectiveness of combined immunotherapy in treating hepatocellular carcinoma (HCC). Methods: Our retrospective examination focused on AS's effect on immune therapy effectiveness, utilizing accessible tissue sequencing and clinical records for HCC. For corroborating our results, we gathered samples of drug-resistant HCC tissue, nearby tissues, HCC tissue with high drug responsiveness, and healthy liver tissue from clinical studies. Results: The study revealed a link between the frequency of AS occurrences, the expression levels of programmed cell death 1 ligand 1, and the resistance to tumor medications. Our study detailed the AS occurrences in HCC, leading to the creation of a risk-assessment function and a predictive model using AS data. The results of our study revealed that the risk score effectively distinguished between various immune subtypes and the effectiveness of immune therapy. Additional examination of the chosen AS occurrences uncovered their effects on both the immune microenvironment and cellular immunity. Our investigation also delved into the regulatory framework of AS, uncovering the role of stringently controlled splicing factors in the emergence of tumors and the modulation of the body's immune response. Conclusions: Increased AS in HCC diminishes the efficacy of immunotherapy; conversely, more AS in peritumoral tissue elevates the likelihood of tumor immune evasion.

Head and neck malignancies are a significant global health concern, with head and neck squamous cell carcinoma (HNSCC) being the sixth most common cancer worldwide accounting for > 90% of cases. In recent years, there has been growing recognition of the potential role of alternative splicing (AS) in the etiology of cancer. Increasing evidence suggests that AS is associated with various aspects of cancer progression, including tumor occurrence, invasion, metastasis, and drug resistance. Additionally, AS is involved in shaping the tumor microenvironment, which plays a crucial role in tumor development and response to therapy. AS can influence the expression of factors involved in angiogenesis, immune response, and extracellular matrix remodeling, all of which contribute to the formation of a supportive microenvironment for tumor growth. Exploring the mechanism of AS events in HNSCC could provide insights into the development and progression of this cancer, as well as its interaction with the tumor microenvironment. Understanding how AS contributes to the molecular changes in HNSCC cells and influences the tumor microenvironment could lead to the identification of new therapeutic targets. Targeted chemotherapy and immunotherapy strategies tailored to the specific AS patterns in HNSCC could potentially improve treatment outcomes and reduce side effects. This review explores the concept, types, processes, and technological advancements of AS, focusing on its role in the initiation, progression, treatment, and prognosis of HNSCC.

Right-sided subclavian artery aneurysms (SAAs) are exceedingly rare. The most common cause of intrathoracic SAAs is atherosclerosis; however, causes can also include infection, trauma, cystic medial degeneration, Marfan syndrome, and Takayasu arteritis. Symptoms present most commonly with compression of surrounding structures, although adverse events, including rupture, thrombosis, and embolization, can also occur. We present a case of a 30-year-old woman with an asymptomatic, 15-mm, right-sided SAA, which was successfully resected with subsequent end-to-end primary anastomosis.

Purpose: To assess the clinical benefits of surface-guided radiation therapy (SGRT) in terms of setup error, positioning time, and clinical target volume-to-planning target volume (CTV-PTV) margin in extremity soft tissue sarcoma (STS). Methods and Materials: Fifty consecutive patients treated with radiation therapy were selected retrospectively. Treatment setup was performed with either laser-based imaging only (control group), or with laser-based and daily optical surface-based imaging (SGRT group). Pretreatment cone beam computed tomography images were acquired daily for the first 3 to 5 fractions and weekly thereafter, with the frequency adjusted as necessary. Translational and rotational errors were collected. CTV-PTV margin was calculated using the formula, 2.5Σ + 0.7σ. Results: Each group consisted of 10 and 15 upper and lower limb STSs, respectively. For patients with upper limb sarcomas, the translation errors were 1.64 ± 1.34 mm, 1.10 ± 1.50 mm, and 1.24 ± 1.45 mm in the SGRT group, and 1.48 ± 3.16 mm, 2.84 ± 2.85 mm, and 3.14 ± 3.29 mm in control group in the left-right, supero-inferior, and antero-posterior directions, respectively. Correspondingly, for patients with lower limb sarcomas, the translation errors were 1.21 ± 1.65 mm, 1.39 ± 1.71 mm, and 1.48 ± 2.10 mm in the SGRT group, and 1.81 ± 2.60 mm, 2.93 ± 3.28 mm, and 3.53 ± 3.75 mm in control group, respectively. The calculated CTV-PTV margins of the SGRT group and control group were 5.0, 3.8, 4.1 versus 5.9, 9.1, 10.1 mm for upper limb sarcomas; and 4.2, 4.7, 5.2 mm versus 6.3, 9.6, and 11.4 mm for lower limb sarcomas in the left-right, supero-inferior, and antero-posterior directions, respectively. Conclusions: Daily optical surface guidance can effectively improve the setup accuracy of extremity STS patients, and safely reduce the required CTV-PTV margins.

Background Acute venous thromboembolism (VTE) in children presents unique challenges due to the limitations of standard anticoagulation therapies. Herein, we aimed to systematically review randomized controlled trials (RCTs) evaluating the efficacy and safety of direct oral anticoagulants (DOACs) in pediatric patients with acute VTE. Methods PubMed and Embase databases were searched for RCTs comparing DOACs to standard anticoagulation in pediatric VTE patients. Efficacy outcomes included VTE recurrence and all-cause mortality, while safety outcomes comprised major bleeding and other adverse events. Results Three RCTs with 790 participants were included. When compared with standard anticoagulation, DOACs demonstrated a reduced risk of VTE recurrence (risk difference[RD] = −3%, 95% confidence interval[CI]: −6% to 0%, P = 0.04) and an increased risk of any adverse event (RD = 8%, 95% CI: 1% to 14%, P = 0.02). No significant differences were found in all-cause mortality, major bleeding, clinically relevant non-major bleeding, or total bleeding between the DOAC and control groups. Conclusion DOACs, primarily dabigatran and rivaroxaban, are non-inferior to standard anticoagulants in reducing VTE recurrence in pediatric patients, with comparable safety profiles. Further research is essential to confirm these findings.

Background: Compliance to sublingual immunotherapy (SLIT) is generally low, resulting in reduced short- and long-term clinical efficacy. Compliance is a critical factor determining the success of allergic rhinitis (AR) treatment. Objective: To analyze the compliance of patients with house dust mite (HDM)-induced AR to SLIT and the impact of coronavirus disease 2019 (COVID-19) on compliance. Methods: The clinical data of 3117 patients with HDM-induced AR who started SLIT between July 2018 and April 2022 were retrospectively reviewed. We assessed the reasons for non-compliance and the changes in non-compliance during the COVID-19 pandemic compared to the pre-pandemic period. Results: Of 3117 patients, 507 (16.27%) patients (ages, 5–67 years) were identified as non-compliant. The most common reason for non-compliance was poor efficacy (27.22%). The non-compliance rate was highest during 24–36 months of SLIT (28.13%, 153/544), followed by 12–24 months (7.02%, 91/1296). Non-compliance was significantly higher in adolescents/adults than in children (P = 0.000). Although the generalized linear model analysis indicated that compliance was affected by the COVID-19 pandemic during 3–6 months of SLIT, the overall compliance to SLIT was not significantly affected by the pandemic, according to the Kaplan-Meier survival analysis. Conclusions: The non-compliance rate of SLIT in this study was low, and poor efficacy was the most common reason for non-compliance. The compliance of adolescents/adults was lower than that of children. The COVID-19 pandemic did not significantly impact compliance to SLIT, which is an appropriate strategy for the home treatment of AR patients during major public health events.

Purpose: Genome-wide association studies have recently uncovered many loci associated with variation in intraocular pressure (IOP). Artificial intelligence (AI) can be used to interrogate the effect of specific genetic knockouts on the morphology of trabecular meshwork cells (TMCs) and thus, IOP regulation. Design: Experimental study. Subjects: Primary TMCs collected from human donors. Methods: Sixty-two genes at 55 loci associated with IOP variation were knocked out in primary TMC lines. All cells underwent high-throughput microscopy imaging after being stained with a 5-channel fluorescent cell staining protocol. A convolutional neural network was trained to distinguish between gene knockout and normal control cell images. The area under the receiver operator curve (AUC) metric was used to quantify morphological variation in gene knockouts to identify potential pathological perturbations. Main Outcome Measures: Degree of morphological variation as measured by deep learning algorithm accuracy of differentiation from normal controls. Results: Cells where LTBP2 or BCAS3 had been perturbed demonstrated the greatest morphological variation from normal TMCs (AUC 0.851, standard deviation [SD] 0.030; and AUC 0.845, SD 0.020, respectively). Of 7 multigene loci, 5 had statistically significant differences in AUC (P

Background: Open reduction and internal fixation with plate is one of the most widely used treatments for distal third humeral shaft fractures. The purpose of this study was to report the outcomes of the treatment of distal third humeral shaft fractures with posterior minimally invasive plate osteosynthesis (MIPO) with segmental isolation of the radial nerve. Methods: We performed an observational, retrospective, consecutive, monocentric, continuous multioperator study. We reviewed 22 distal third humeral shaft fractures treated with posterior MIPO in our institution with an extra-articular distal humerus plate from 2018 to 2021. Inclusion was limited to functionally independent patients with displaced fractures involving the junction of the middle and distal thirds of the humerus and minimum 12-month follow-up for implant removal. We assessed clinical outcomes including range of motion; QuickDASH score; Mayo Elbow Performance Score; and Constant-Murley score. Results: The average follow-up period of the sample was 31.7 ± 11.6 months (range, 15.7-51.3 months). The average elbow flexion and extension were 146.4° ± 7.3° (range, 120°-150°) and −0.7° ± 3.3° (range, −15° to 0°), respectively. The average shoulder anterior flexion, elevation, and abduction were 178.6° ± 3.6° (range, 170°-180°), 179.1° ± 2.9° (range, 170°-180°), and 140.9° ± 14.8° (range, 110°-160°), respectively. The average external rotation was 88.6° ± 6.4 (range, 65°-90°). The mean visual analog scale score for pain was 1.0 ± 1.6 (range, 0-5) and the mean Mayo Elbow Performance Score was 90.5 ± 9.9 (range, 70-100). The mean QuickDASH and Constant–Murley scores were 4.7 ± 6.8 (range, 0-20.5) and 95.5 ± 5.1 (range, 81-100), respectively. Two patients presented with relevant compromise of radial nerve motor function postoperatively (M3 and M2; the more compromised was preoperative injury). All patients recovered radial nerve neuropraxia within six weeks postoperatively. All fractures achieved union. The average anteroposterior and lateral axis were 175.0 ± 3.6 (168.0°-180.0°) and 177.5 ± 2.0 (173.0°-180.0°), respectively. No superficial or deep infection was reported. No cases of re-displacement of fracture, implant failure, or any other implant-related complication in follow-up were reported. No patient required plate withdrawal. Conclusion: The results of this study demonstrate that the posterior MIPO technique is a reliable option for treating distal third shaft humeral fractures. The radial nerve must be identified and protected in all cases to prevent palsy.

Purpose: The role of preoperative stereotactic body radiation therapy (SBRT) in pancreatic cancer is controversial, and questions regarding the optimal dose and radiation treatment field remain. To better inform future investigations of SBRT dose and radiation fields, we evaluated the patterns of failure in patients with borderline resectable/locally advanced pancreatic cancer (BR/LAPC) after preoperative chemotherapy and SBRT in patients who underwent surgical resection. Methods and Materials: We performed a single-institution retrospective review of consecutive patients treated from September 2017 to January 2022 with BR/LAPC. Patients who underwent preoperative chemotherapy and SBRT followed by surgical resection were reviewed. SBRT was delivered to a dose of 33 Gy in 5 fractions. Kaplan–Meier overall survival and progression-free survival estimates were calculated. Results: In total, 18 patients (12 BRPC, 6 LAPC) were included. Median age was 69 years (range 41-84 years). Median follow-up was 30 months (range 13-59 months). Seventeen patients (94%) had a R0 resection and 13 (72%) underwent vascular reconstruction. Median overall survival and progression-free survival was 42 months (range 13-59 months) and 23 months (range 1-45 months), respectively. In total, 61% (11/18) patients experienced progression at any point during follow-up. Of the patients who experienced recurrence, 27% (3/11) experienced local progression as component of their first recurrence, whereas 100% (11/11) experienced distant progression as a component of their first recurrence. When examining all recurrences that occurred at any point in follow-up, 28% (5/18) of patients experienced local or locoregional recurrence and 61% (11/18) experienced distant progression. Conclusions: Local control and margin negative resection rates were excellent with preoperative chemotherapy and nondose-escalated SBRT in surgically resected patients with BR/LAPC. Distant recurrence was the predominant site of failure with lower incidences of isolated locoregional recurrences. Additional research is needed to determine the ideal treatment volume and patients who may benefit from dose escalation.

Objective:. To determine the magnitude of the perioperative costs associated with robotic gastrectomy (RG). Background:. A robotic surgery platform has a high implementation cost and requires maintenance costs; however, whether the overall cost of RG, including all perioperative costs, is higher than conventional open gastrectomy (OG) remains unknown. Methods:. Patients who underwent a major gastrectomy during February 2018 through December 2021 were retrospectively identified. We calculated the perioperative costs of RG and OG and compared them overall as well as in different phases, including intraoperative costs and 30-day postsurgery inpatient and outpatient costs. We investigated factors potentially associated with high cost and estimated the likelihood of RG to reduce overall cost under a Bayesian framework. All cost data were converted to ratios to the average cost of all operations performed at our center in year FY2021. Results:. We identified 119 patients who underwent gastrectomy. The incidence of postoperative complications (Clavien-Dindo >IIIa; RG, 10% vs OG, 13%) did not significantly differ between approaches. The median length of stay was 3 days shorter for RG versus OG (4 vs 7 days, P < 0.001). Intraoperative cost ratios were significantly higher for RG (RG, 2.6 vs OG, 1.7; P < 0.001). However, postoperative hospitalization cost ratios were significantly lower for RG (RG, 2.8 vs OG, 3.9; P < 0.001). Total perioperative cost ratios were similar between groups (RG, 6.1 vs OG, 6.4; P = 0.534). The multiple Bayesian generalized linear analysis showed RG had 76.5% posterior probability of overall perioperative cost reduction (adjusted risk ratio of 0.95; 95% credible interval, 0.85–1.07). Conclusions:. Despite increased intraoperative costs, total perioperative costs in the RG group were similar to those in the OG group because of reduced postoperative hospitalization costs.

Introduction: In Chinese patients with NSCLC, prevalence of EGFR-mutated (EGFRm) disease is high. In the global phase 3 ADAURA study (NCT02511106), adjuvant osimertinib was found to have a statistically significant and clinically meaningful improvement in disease-free survival (DFS) versus placebo in resected stage IB to IIIA EGFRm NSCLC. We present efficacy and safety data from a subgroup analysis of 159 Chinese patients enrolled in the People’s Republic of China from ADAURA. Methods: In ADAURA, patients with completely resected stage IB to IIIA EGFRm (exon 19 deletion/exon 21 L858R) NSCLC were randomized 1:1 to receive osimertinib (80 mg once daily) or placebo for 3 years or until disease recurrence/discontinuation. Adjuvant chemotherapy was permitted before randomization, per physician/patient choice. Primary end point was investigator-assessed DFS in stage II to IIIA disease; secondary end points included DFS in stage IB to IIIA (overall population), overall survival, health-related quality of life (HRQoL), and safety. Results: Of 682 patients enrolled globally, 159 patients in the People’s Republic of China were included in this subgroup analysis (osimertinib n = 77; placebo n = 82). Baseline characteristics were balanced across the treatment arms. At data cutoff, stage II to IIIA DFS hazard ratio (HR) was 0.23 (95% confidence interval [CI]: 0.13–0.42; maturity 59%); stage IB to IIIA DFS HR was 0.29 (95% CI: 0.17–0.48; maturity 42%). At 13% maturity (21 deaths), HR for overall survival in the stage IB to IIIA population was 0.51 (95% CI: 0.21–1.20). HRQoL was maintained from baseline, and safety was consistent with the global population. Conclusions: In this population of Chinese patients from ADAURA, adjuvant osimertinib was found to have a clinically meaningful improvement in DFS versus placebo, with maintained HRQoL and a safety profile consistent with the global study population.

We report a case of aortoduodenal fistula formed after an abdominal aortic aneurysm ruptured into the duodenum. There is also an aortic dissection involving the celiac trunk, superior mesenteric artery and renal arteries. Successful treatment was achieved through endovascular aortic repair, followed by anti-infective and supportive therapy over 3 months.

Background:. Letibotulinum toxin A has an established efficacy and safety profile for aesthetic treatment of glabellar wrinkles. This study was conducted to demonstrate the noninferiority of letibotulinum toxin A versus onabotulinum toxin A in improving the appearance of moderate-to-severe glabellar wrinkles in Chinese patients. Methods:. This phase-III multicenter, randomized, parallel positive control, double-blinded study compared the efficacy and safety of letibotulinum toxin A and onabotulinum toxin A. Eligible participants were randomized 3:1 to receive 20 U of letibotulinum toxin A or onabotulinum toxin A and were observed for 16 weeks postinjection. The primary endpoint was noninferiority in the proportion of study participants receiving a score of 0 or 1 for glabellar wrinkles on a four-point photographic evaluation scale, as assessed by an institution evaluator at maximum frown at week 4. Secondary endpoints included assessments at rest, photographic assessment of efficacy, and subjective self-assessment of the study participants. Results:. The proportion of participants (N = 500) receiving a score of 0 or 1 at maximum frown by the institution evaluator at week 4 was 88.49% for letibotulinum toxin A and 87.39% for onabotulinum toxin A (difference, 1.10%; 95% confidence interval, −5.02 to 8.82; P = 0.7469). No significant differences were observed between the treatments for secondary efficacy or safety endpoints. Participants’ self-assessment and satisfaction tended to be higher for letibotulinum toxin A than onabotulinum toxin A. Conclusion:. Letibotulinum toxin A is noninferior to onabotulinum toxin A in improving the appearance of moderate-to-severe glabellar wrinkles in Chinese patients.

Background: In China, traditional Chinese medicines (TCMs), as a complementary therapy combined with chemotherapy, is widely used in the treatment of gastric cancer (GC). In order to systematically evaluate and synthesize existing evidence to provide a scientific basis for the efficacy and safety of this complementary therapy, we present an overview of systematic reviews (SRs) and meta-analyses (MAs) on the topic of TCMs as a complementary therapy in combination with chemotherapy for the treatment of GC. Methods: SRs/MAs on TCMs combined with chemotherapy for GC were comprehensively searched in 8 databases. Methodological quality, risk of bias, reporting quality, and quality of evidence were assessed using the Assessment of Multiple Systematic Reviews 2 (AMSTAR-2), the Risk of Bias in Systematic (ROBIS) scale, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 (PRISMA 2020), as well as the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Results: Thirteen published SRs/MAs were included in our study. In terms of methodology, all SRs/MAs were considered to be of very low quality. Only 3 SRs/MAs has been assessed as low risk of bias. None of the SRs/MAs has been fully reported on the checklist. A total of 97 outcome indicators extracted from the included SRs/MAs were evaluated, and only 1 item was assessed as high quality. Conclusions: TCMs may be an effective and safe complementary therapy in combination with chemotherapy for the treatment of GC. However, this conclusion must be treated with caution as the quality of the evidence provided by SRs/MAs is generally low.

Purpose: Thyroid eye disease (TED) is an autoimmune condition with an array of clinical manifestations, which can be complicated by compressive optic neuropathy. It is important to identify patients with TED early to ensure close monitoring and treatment to prevent potential permanent disability or vision loss. Deep learning artificial intelligence (AI) algorithms have been utilized in ophthalmology and in other fields of medicine to detect disease. This study aims to introduce a deep learning model to evaluate orbital computed tomography (CT) images for the presence of TED and potential compressive optic neuropathy. Design: Retrospective review and deep learning algorithm modeling. Subjects: Patients with TED with dedicated orbital CT scans and with an examination by an oculoplastic surgeon over a 10-year period at a single academic institution. Patients with no TED and normal CTs were used as normal controls. Those with other diagnoses, such as tumors or other inflammatory processes, were excluded. Methods: Orbital CTs were preprocessed and adopted for the Visual Geometry Group-16 network to distinguish patients with no TED, mild TED, and severe TED with compressive optic neuropathy. The primary model included training and testing of all 3 conditions. Binary model performance was also evaluated. An oculoplastic surgeon was also similarly tested with single and serial images for comparison. Main Outcome Measures: Accuracy of deep learning model discernment of region of interest for CT scans to distinguish TED versus normal control, as well as TED with clinical signs of optic neuropathy. Results: A total of 1187 photos from 141 patients were used to develop the AI model. The primary model trained on patients with no TED, mild TED, and severe TED had 89.5% accuracy (area under the curve: range, 0.96–0.99) in distinguishing patients with these clinical categories. In comparison, testing of an oculoplastic surgeon in these 3 categories showed decreased accuracy (70.0% accuracy in serial image testing). Conclusions: The deep learning model developed in the study can accurately detect TED and further detect TED with clinical signs of optic neuropathy based on orbital CT. The model proved superior compared with human expert grading. With further optimization and validation, this TED deep learning model could help guide frontline health care providers in the detection of TED and help stratify the urgency of a referral to an oculoplastic surgeon and endocrinologist. Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article.

Multiple system atrophy (MSA) is a rare form of adult-onset α-synucleinopathy. Meige syndrome, identified as bilateral blepharospasm and oromandibular dystonia, is a type of focal dystonic movement disorder. This case report aims to highlight the clinical features of multiple system atrophy associated with Meige syndrome in a patient. Additionally, we aim to provide the treatment experience in a patient with Meige syndrome as this is an extremely rare clinical case.

Pheochromocytoma (PHEO) is a rare and complex molecularly driven endocrine disease that can present with a variety of clinical manifestations, including paroxysmal hypertension, episodic anxiety, tremors, devastating acute heart failure and acute pulmonary edema. The variety of PHEO-related symptoms increase the difficulty of identifying and diagnosing PHEO. We reported a case of a 27-year-old Chinese male was diagnosed PHEO by CT scan because of upper abdominal pain. The patient complicated with hypertensive crisis and headache following his admission, and he was underwent adrenal tumor surgical resection by carrying out appropriate clinical, laboratory and radiological imaging. Thus, the patient's PHEO-related symptoms were relieved and the blood pressure returned to normal, and discharged from the hospital with a follow-up plan. Although the PEHO-related symptoms are varied and difficult to diagnose, CT examination can be used for the preliminary detection and diagnosis. This case report emphasizes the importance of considering PHEO by CT scan and atypical symptoms, which help others better understand PHEO for early detection and timely surgical treatment to reduce catecholamine-related complications.

OBJECTIVES:. To evaluate the study design and feasibility of drug administration and safety in a randomized clinical trial of recombinant human annexin A5 (SY-005), a constitutively expressed protein with anti-inflammatory, antiapoptotic, and anticoagulant properties, in patients with severe coronavirus disease 2019 (COVID-19). DESIGN:. Double-blind, randomized clinical trial. SETTING:. Two ICUs at an academic medical center. PATIENTS/SUBJECTS:. Adults admitted to the ICU with a confirmed diagnosis of COVID-19 and requiring ventilatory or vasopressor support. INTERVENTIONS:. SY-005, a recombinant human annexin A5, at 50 or 100 µg/kg IV every 12 hours for 7 days. MEASUREMENTS AND MAIN RESULTS:. We enrolled 18 of the 55 eligible patients (33%) between April 21, 2021, and February 3, 2022. We administered 82% (196/238) of the anticipated doses of study medication and 86% (169/196) were given within 1 hour of the scheduled time. There were no drug-related serious adverse events. We captured 100% of the data that would be required for measuring clinical outcomes in a phase 2 or 3 trial. LIMITATIONS:. The small sample size was a result of decreasing admissions of patients with COVID-19, which triggered a stopping rule for the trial. CONCLUSIONS:. Although enrollment was low, administration of SY-005 to critically ill patients with COVID-19 every 12 hours for up to 7 days was feasible and safe. Further clinical trials of annexin A5 for the treatment of COVID-19 are warranted. Given reduction of severe COVID-19 disease, future studies should explore the safety and effectiveness of SY-005 use in non-COVID-related sepsis.

Background: The artery involvement explains the majority of primary unresectability of non-metastatic pancreatic cancer patients and both arterial resection and artery-sparing dissection techniques are utilized in curative-intent pancreatectomies for artery-involving pancreatic cancer (ai-PC) patients. Methods: This narrative review summarized the history of resectability evaluation for ai-PC and attempted to interpret its current pitfalls that led to the divergence of resectability prediction and surgical exploration, with a focus on the rationale and the surgical outcomes of the sub-adventitial divestment technique. Results: The circumferential involvement of artery by tumor currently defined the resectability of ai-PC but insufficient to preclude laparotomy with curative intent. The reasons behind could be: 1. The radiographic involvement of tumor to arterial circumference was not necessarily resulted in histopathological artery wall invasion; 2. the developed surgical techniques facilitated radical resection, better perioperative safety as well as oncological benefit. The feasibility of periadventitial dissection, sub-adventitial divestment and other artery-sparing techniques for ai-PC depended on the tumor invasion depth to the artery, i.e., whether the external elastic lamina (EEL) was invaded demonstrating a hallmark plane for sub-adventitial dissections. These techniques were reported to be complicated with preferable surgical outcomes comparing to arterial resection combined pancreatectomies, while the arterial resection combined pancreatectomies were considered performed in patients with more advanced disease. Conclusions: Adequate preoperative imaging modalities with which to evaluate the tumor invasion depth to the artery are to be developed. Survival benefits after these techniques remain to be proven, with more and higher-level clinical evidence needed. Key message: The current resectability evaluation criteria, which were based on radiographic circumferential involvement of the artery by tumor, was insufficient to preclude curative-intent pancreatectomies for artery-involving pancreatic cancer patients. With oncological benefit to be further proven, periarterial dissection and arterial resection have different but overlapping indications, and predicting the tumor invasion depth in major arteries was critical for surgical planning.

Background:. Removal of the eschar has gradually become a consensus on treatments of deep dermal necrosis after skin trauma in recent years, whereas exaggerated scar contracture and tissue proliferation developed during healing have received little attention. Here, the authors investigated the effects of eschar on excessive wound healing of small dermal damage and focused on the role M2 macrophages played, hoping to offer a theoretical basis to improve patients’ cosmetic satisfaction. Methods:. A mouse dorsal wound model (n = 12) was established by electric heating pads heating for 20 seconds on each side of the spine, and the left side was the preserved group. Macrophage numbers, expression of wound-healing-associated proteins, and inflammatory cytokine levels were assessed at different time points by immunohistochemistry and quantitative real-time polymerase chain reaction. A co-culture system of M2 macrophages and myofibroblasts was created in vitro. Immunohistochemistry, real-time polymerase chain reaction, and Western blot were performed to evaluate the proliferation, migration, and protein expression of myofibroblasts. Results:. Preserving eschar inhibited contraction-associated proteins (α-smooth muscle actin and vimentin) and collagen expression, inflammatory cytokine (IL-1β, IL-10, TFN-α, and IL-4) expression, and M2 macrophage infiltration. Mechanistically, M2 macrophages potentially contributed to excessive wound healing by promoting myofibroblasts proliferation, migration, and production of contraction-associated proteins. Conclusion:. Eschar preservation in wounds could reduce inflammation and negatively modulate myofibroblasts by inhibiting M2 macrophage polarization and infiltration, preventing excessive wound contraction and collagen deposition.

Summary: Background: Mediastinal neoplasms are typical thoracic diseases with increasing incidence in the general global population and can lead to poor prognosis. In clinical practice, the mediastinum's complex anatomic structures and intertype confusion among different mediastinal neoplasm pathologies severely hinder accurate diagnosis. To solve these difficulties, we organised a multicentre national collaboration on the basis of privacy-secured federated learning and developed CAIMEN, an efficient chest CT-based artificial intelligence (AI) mediastinal neoplasm diagnosis system. Methods: In this multicentre cohort study, 7825 mediastinal neoplasm cases and 796 normal controls were collected from 24 centres in China to develop CAIMEN. We further enhanced CAIMEN with several novel algorithms in a multiview, knowledge-transferred, multilevel decision-making pattern. CAIMEN was tested by internal (929 cases at 15 centres), external (1216 cases at five centres and a real-world cohort of 11 162 cases), and human–AI (60 positive cases from four centres and radiologists from 15 institutions) test sets to evaluate its detection, segmentation, and classification performance. Findings: In the external test experiments, the area under the receiver operating characteristic curve for detecting mediastinal neoplasms of CAIMEN was 0·973 (95% CI 0·969–0·977). In the real-world cohort, CAIMEN detected 13 false-negative cases confirmed by radiologists. The dice score for segmenting mediastinal neoplasms of CAIMEN was 0·765 (0·738–0·792). The mediastinal neoplasm classification top-1 and top-3 accuracy of CAIMEN were 0·523 (0·497–0·554) and 0·799 (0·778–0·822), respectively. In the human–AI test experiments, CAIMEN outperformed clinicians with top-1 and top-3 accuracy of 0·500 (0·383–0·633) and 0·800 (0·700–0·900), respectively. Meanwhile, with assistance from the computer aided diagnosis software based on CAIMEN, the 46 clinicians improved their average top-1 accuracy by 19·1% (0·345–0·411) and top-3 accuracy by 13·0% (0·545–0·616). Interpretation: For mediastinal neoplasms, CAIMEN can produce high diagnostic accuracy and assist the diagnosis of human experts, showing its potential for clinical practice. Funding: National Key R&D Program of China, National Natural Science Foundation of China, and Beijing Natural Science Foundation.

Background: Type 2 CRSwNP is characterized by severe symptoms, multiple comorbidities, longer recovery course and high recurrence rate. A simple and cost-effective diagnostic model for CRSwNP endotype integrating clinical characteristics and histopathological features is urgently needed. Objective: To establish a clinical diagnostic model of inflammatory endotype in CRSwNP based on the clinical characteristics, pathological characteristics, and cytokines profile in the polyp tissue of patients. Methods: A total of 244 participants with CRSwNP were enrolled at 2 different centers in China and Belgium from 2018 to 2020. IL-5 level of nasal polyp tissue was used as gold standard. Clinical characteristics were used to establish diagnostic models. The area under the receiver operating curve (AUC) was used to evaluate the diagnostic performance. The study was approved by the ethics board of the First Affiliated Hospital of Sun Yat-sen University ([2020] 302), and written informed consent was obtained from all subjects before inclusion. Results: In total, 134 patients from China (training set) and 110 patients from Belgium (validation set) were included. The logistic regression (LR) model in predicting inflammatory endotype of CRSwNP showed the AUC of 83%, which was better than the diagnostic performance of machine learning models (AUC of 61.14%–82.42%), and single clinical variables. We developed a simplified scoring system based on LR model which shows similar diagnostic performance to the LR model (P = 0.6633). Conclusion: The LR model in this diagnostic study provided greater accuracy in prediction of inflammatory endotype of CRSwNP than those obtained from the machine learning model and single clinical variable. This indicates great potential for the use of diagnostic model to facilitate inflammatory endotype evaluation when tissue cytokines are unable to be measured.

Objective To evaluate the clinical value of diabetes mellitus for diagnosis and postoperative prognosis in patients with cervical spondylotic myelopathy undergoing anterior decompression and fusion. Methods A total of 84 Patients (50 males and 34 females) who underwent anterior decompression and fusion were reviewed in this single‐center retrospective study. The patients were divided into two groups (44 patients in the diabetes mellitus group and 40 in the non‐diabetic group). Clinical manifestations were evaluated, including characteristics baseline, clinical tests, MRI information, clinical scores, and complications. The predictive effect of diabetes mellitus on clinical scores were assessed via the receiver operating characteristic curve. The correlation between the severity of diabetes mellitus and neurological function recovery was estimated using the Pearson correlation coefficient. Results Patients with diabetes mellitus exhibited a higher ratio of hyperintensity of the spinal cord (P 0.05). Conclusion This present study revealed that the neurological impairment caused by diabetes mellitus in patients undergoing anterior decompression and fusion does not only affect postoperative functional recovery but also interferes with the preoperative clinical manifestations, especially the sensory function in the upper and lower limbs.

Objective In the present study, we aimed to evaluate the diagnostic performance of superb microvascular imaging (SMI) for breast masses through a meta-analysis. Methods PubMed, EMBASE, Cochrane Library, and Web of Science Core Collection databases, as well as the most comprehensive Chinese academic databases in medicine, such as China Biology Medicine Disc, China National Knowledge Infrastructure, and Wanfang Database, were systematically searched. All included studies used histopathological results as the reference standard. To assess the diagnostic performance, we calculated the pooled sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR-), diagnostic odds ratio (DOR), and the area under the curve (AUC). In addition, a subgroup meta-regression analysis was performed to investigate the heterogeneity. Results Fourteen of 1,075 identified articles were included in the current review. The pooled sensitivity, specificity, LR+, LR-, and DOR for SMI were 0.85 (95% CI: 0.79-0.89), 0.80 (95% CI: 0.71-0.87), 4.3 (95% CI: 2.9-6.2), 0.19 (95% CI 0.14-0.26), and 22 (95% CI: 14-36), respectively. The AUC was 0.90 (0.87 - 0.92). Meta-regression showed that there were heterogeneities for sensitivity, but not for specificity. Conclusions SMI had good sensitivity, specificity, and excellent diagnostic value in distinguishing benign breast masses from malignant masses and could potentially help select suspicious breast masses for surgery.

Purpose: To explore the diagnostic value and the prognostic significance of cerebrospinal fluid (CSF) examination by flow cytometry (FC) in children with central nervous system leukemia (CNSL). Method: This is a retrospective observational study. We select 986 pediatric patients with newly diagnosed acute lymphoblastic leukemia from January 2012 to December 2018 as the research objects and analyze the sensitivity and specificity of different methods for diagnosing CNSL. The recurrence rate and survival rate of CNSL in different groups were compared. Results: Among the 986 cases, 31 cases (positive rate of 3.14%) were positive by FC, and the cytospin-based cytomorphology (CC) test was positive in 6 cases (positive rate of 0.61%). CC combined with FC might improve the diagnostic sensitivity (from 30% to 65%, 𝑥 2 value was 5.143, P = .016). The 2-year event-free survival (EFS) of 31 FC + children was 59.5% ± 9.2%, and that of 955 FC − children was 74.1% ± 1.8% ( P = .004). The 2-year overall survival (OS) of the 2 groups were 63.6% ± 9.7% and 80.2% ± 1.5%, respectively ( P = .004). In order to exclude the influence of CNSL, we divided the patients into 3 groups: CNSL group and non-CNSL group with CSF FC + , FC − group. There was no significant difference in EFS between FC − group and non-CNSL group with FC + (2-year EFS were 74.1% ± 1.8% and 68.7% ± 9.8%, respectively, P = .142), and there was a significant difference in OS (2-year OS were 80.2% ± 1.5% and 67.5% ± 10.3%, respectively, P = .029). Conclusion: The test of FC combined with CC may improve the diagnostic sensitivity of CNSL. The EFS and OS of children with FC + are worse than those of children with FC −. However, for those patients with non-CNSL, but only FC + at the initial diagnosis, the EFS is not significantly affected by strengthening systemic chemotherapy and increasing the number of intrathecal injections.

Background:. Complete brachial plexus injuries are devastating injuries. A viable C5 spinal nerve can offer additional sources of axons and alter surgical treatment. We aimed to determine factors that portend C5 nerve root avulsion. Methods:. A retrospective study of 200 consecutive patients with complete brachial plexus injuries at two international centers (Mayo Clinic in the United States and Chang Gung Memorial Hospital in Taiwan) was performed. Demographic information, concomitant injuries, mechanism, and details of the injury were determined, and kinetic energy (KE) and Injury Severity Score were calculated. C5 nerve root was evaluated by preoperative imaging, intraoperative exploration, and/or intraoperative neuromonitoring. A spinal nerve was considered viable if it was grafted during surgery. Results:. Complete five-nerve root avulsions of the brachial plexus were present in 62% of US and 43% of Taiwanese patients, which was significantly different. Increasing age, the time from injury to surgery, weight, body mass index of patient, motor vehicle accident, KE, Injury Severity Score, and presence of vascular injury significantly increased the risk of C5 avulsion. Motorcycle (≤150cc) or bicycle accident decreased the risk of avulsion. Significant differences were found between demographic variables between the two institutions: age of injury, body mass index, time to surgery, vehicle type, speed of injury, KE, Injury Severity Score, and presence of vascular injury. Conclusions:. The rate of complete avulsion injury was high in both centers. Although there are a number of demographic differences between the United States and Taiwan, overall the KE of the accident increased the risk of C5 avulsion.

Introduction Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with a poor response to chemotherapy and an extremely poor prognosis. Recent studies have revealed that phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) can inhibit the growth of various cancers. Therefore, the current study was conducted to investigate the antitumor effects of LHPP in PDAC and to explore its mechanism using proteomics analysis. Methods and Results Immunohistochemical analysis of clinical samples demonstrated that LHPP expression levels were lower in tumor tissues compared to adjacent nontumor tissues. Moreover, multivariate COX regression analysis showed that LHPP expression level was an independent prognostic factor for the patients with PDAC. Patients with high LHPP expression had a better prognosis. The lentiviral vectors for normal control (NC), LHPP knockdown (KD), and LHPP overexpression (OE) were infected with BxPC-3 and PANC-1 cell lines. Cell counting kit-8 assay, Transwell assay, and flow cytometry analyses showed that LHPP overexpression significantly inhibited the cell viability, migration, and proliferation of BxPC-3 and PANC-1 cells. Moreover, xenograft tumor model demonstrated that LHPP overexpression inhibited xenograft tumor growth in vivo. Subsequently, proteins with significantly altered expression in BxPC-3 cells after lentivirus infection were detected using proteomics analyses. Interestingly, compared to the NC group, the expression of Syndecan 1 (SDC1) was significantly upregulated in the KD group, while that of S100P was significantly downregulated in the OE group. Conclusion LHPP might emerge as an important target for delaying the advancement of PDAC, thereby providing a novel therapeutic approach for the treatment of PDAC.

Objectives: To investigate the dosimetric advantages of the voluntary deep inspiration breath-hold technique assisted by optical surface monitoring system for whole breast irradiation in left breast cancer after breast-conserving surgery and verify the reproducibility and acceptability of this technique. Methods: Twenty patients with left breast cancer receiving whole breast irradiation after breast-conserving surgery were enrolled in this prospective phase II study. Computed tomography simulation was performed during both free breathing and voluntary deep inspiration breath-hold for all patients. Whole breast irradiation plans were designed, and the volumes and doses of the heart, left anterior descending coronary artery, and lung were compared between free breathing and voluntary deep inspiration breath-hold. Cone beam computed tomography was performed for the first 3 treatments, then weekly during voluntary deep inspiration breath-hold treatment to evaluate the accuracy of the optical surface monitoring system technique. The acceptance of this technique was evaluated with in-house questionnaires completed by patients and radiotherapists. Results: The median age was 45 (27-63) years. All patients received hypofractionated whole breast irradiation using intensity-modulated radiation therapy up to a total dose of 43.5 Gy/2.9 Gy/15f. Seventeen of the 20 patients received concomitant tumor bed boost to a total dose of 49.5 Gy/3.3 Gy/15f. Voluntary deep inspiration breath-hold showed a significant decrease in the heart mean dose (262 ± 163 cGy vs 515 ± 216 cGy, P