Systemic bevacizumab for pediatric patients with aggressive recurrent respiratory papillomatosis: One single-center experience of eight patients.

Recurrent respiratory papillomatosis (RRP) is a human papilloma virus (HPV)-driven benign neoplasm, affecting larynx, trachea, and even lung, leading to voice disorders, airway obstruction, and postobstructive pneumonia. Several case reports have documented the promising efficacy of intravenous bevacizumab in reducing the need for surgical intervention among RRP patients. Herein, we present our experience on systemic bevacizumab for pediatric patients with aggressive RRP. Methods: We retrospectively analyzed clinical, laboratory, radiological, and bronchoscopy findings of pediatric patients with aggressive RRP treated with systemic bevacizumab from July 26, 2021 to March 1, 2022. Results: Eight consecutive patients were included. Median age at treatment initiation was 5.5 (range 2.5-8) years old. Twenty-five percentage (2/8) of patients experienced tracheotomy. Pulmonary papilloma was present in 62.5% (5/8) patients. Patients received median 10 cycles of bevacizumab (range 5-12). Patients received initial dosing of 4-7.5 mg/kg every 2-10 weeks of bevacizumab and subsequently extended after achieving the maximum response. None of the patients required surgical intervention during a median 10 (range 8.2-15.4) months follow-up after initiating bevacizumab treatment. Both patients with evaluable lung lesions showed objective response. Only Grade 1 abdominal pain and Grade 1 hyperuricemia were recorded. Conclusion: Systemic bevacizumab seems to be a well-tolerated and effective treatment option for pediatric patients with aggressive RRP.

Efficacy and safety of angiogenesis inhibitors plus immune checkpoint inhibitors in advanced soft tissue sarcoma: a real-world, single-center study.

Angiogenesis inhibitors (AIs) and immune checkpoint inhibitors (ICIs) are new treatment options for advanced soft tissue sarcoma (STS) patients. This study evaluated the efficacy and safety of AIs plus ICIs in patients with advanced STS. A retrospective cohort study was performed on STS patients treated with AIs and ICIs at Shandong Cancer Hospital and Institute between August 2020 and December 2021. The primary endpoint was objective response rate (ORR); secondary endpoints included progression-free survival (PFS), disease control rate (DCR), overall survival (OS), and adverse events. Thirty-three patients were enrolled; 27 were evaluable for objective response. The ORR and DCR were 48.1% (95% CI 30.7-66.0%) and 85.2% (95% CI 67.5-94.1%). With a median follow-up of 7.6 months (range, 0.8-25.5), the median PFS for all 33 patients was 8.90 months (95% CI 5.98-11.82). The median OS was not reached. The most common treatment-related adverse events (TRAEs) of any grade were hypertension (50.0%), ECG T-wave abnormality (30.0%), hypothyroidism (26.7%), elevated alanine aminotransferase or aspartate aminotransferase (23.3%), elevated thyroid-stimulating hormone (23.3%), and fatigue (16.7%). The most common grade 3-4 TRAE was hypertension (27.3%). Three serious TRAEs (two myocarditis and one rapid atrial fibrillation) were recorded. This study suggests that adding AIs to ICIs is beneficial in STS.

Efficacy and safety of sintilimab plus docetaxel in patients with previously treated advanced non-small cell lung cancer: a prospective, single-arm, phase II study in China.

PURPOSE: Although immune checkpoint inhibitor monotherapy has been used as a second-line treatment in advanced non-small cell lung cancer (NSCLC), the improvement in progression-free survival (PFS) remains unsatisfactory. We investigated the feasibility of sintilimab plus chemotherapy as a second-line treatment in advanced NSCLC. METHODS: This was a phase II, single-arm, prospective study in advanced NSCLC patients who had failed standard platinum-based chemotherapy (ChiCTR1900027634, Registered 22 November 2019). Eligible patients received docetaxel 75 mg/m2 (day 1) plus sintilimab 200 mg (day 3) Q3W. Those did not progress after 4-6 cycles received sintilimab 200 mg Q3W as maintenance treatment. The primary endpoint was PFS. RESULTS: Forty patients were enrolled between October 2019 and October 2020. With a median follow-up of 12.2 months, the median PFS was 5.8 months, and the PFS rates at 6 and 12 months were 48% and 30%, respectively. The median overall survival (OS) was 12.6 months, with a 12-month OS rate of 62.0%. The overall response rate was 32.4%, and the disease control rate was 89.2%. The incidence of all and ≥ grade 3 treatment-related adverse events (TRAEs) were 65% (26/40) and 17.5% (7/40), respectively. No TRAEs-related permanent treatment discontinuation or death occurred. bTMB reduction at 6 weeks was associated with a longer PFS (NR vs 3.0 months, P < 0.0001). CONCLUSION: This prospective phase II study in China suggested that sintilimab plus docetaxel might improve PFS and tumor response with good tolerability for Chinese patients with previously treated advanced NSCLC. bTMB reduction at 6 weeks could serve as a potential predictive biomarker for this regimen.

Effect of Ginkgo biloba leaves on the removal efficiency of Cr(VI) in soil and its underlying mechanism.

Cr(VI) is a toxic, teratogenic, and carcinogenic heavy metal element in soil that poses major ecological and human health risks. In this study, microcosm tests combined with X-ray absorption near-edge spectra (XANES) and 16Sr DNA amplification techniques were used to explore the effect of Ginkgo biloba leaves on the removal efficiency of Cr(VI) in soil and its underlying mechanism. Ginkgo biloba leaves had a favorable remediation effect on soil varying in Cr(VI) contamination levels, and the optimal effect was observed when 5% Ginkgo biloba leaves were added. The occurrence state of Cr(VI) in soil before and after the addition of Ginkgo biloba leaves was analyzed by XANES, which revealed that Cr(VI) was fully converted to the more biologically innocuous Cr(III), and the hydroxyl-containing quercetin in Ginkgo biloba leaves was one of the primary components mediating this reduction reaction. The Cr(VI) content was significantly lower in non-sterilized soil than in sterilized soil, suggesting that soil microorganisms play a key role in the remediation process. The addition of Ginkgo biloba leaves decreased the α-diversity and altered the ß-diversity of the soil bacterial community. Actinobacteria was the dominant phylum in the soil remediated by Ginkgo biloba leaves; four genera of Cr(VI)-reducing bacteria were also enriched, including Agrococcus, Klebsiella, Streptomyces, and Microbacterium. Functional gene abundances predicted by PICRUST indicated that the expression of glutathione synthesis genes was substantially up-regulated, which might be the main metabolic pathway underlying the mitigation of Cr(VI) toxicity in soil by Cr(VI)-reducing bacteria. In sum, Ginkgo biloba leaves can effectively remove soil Cr(VI) and reduce Cr(VI) to Cr(III) via quercetin in soil, which also functions as a carbon source to drive the production of glutathione via Cr(VI)-reducing bacteria and mitigate Cr(VI) toxicity. The findings of this study elucidate the chemical and microbial mechanisms of Cr(VI) removal in soil by Ginkgo biloba leaves and provide insights that could be used to enhance the remediation of Cr(VI)-contaminated soil.

Case Report: Primary Pleural Angiosarcoma in a Patient With Klippel-Trenaunay Syndrome.

Klippel-Trenaunay syndrome (KTS) was demonstrated as a mosaic activating PIK3CA mutations related overgrowth syndrome. We present the first case of primary pleural angiosarcoma in a 17-year-old woman with a history of KTS. The combined targeted DNA and RNA sequencing revealed an activating mutation in PIK3CA in the tumor tissue. Our case suggested an association and perhaps a causal link between the two different PIK3CA-related genetic diseases.

Short-term dynamics of circulating tumor DNA predicting efficacy of sintilimab plus docetaxel in second-line treatment of advanced NSCLC: biomarker analysis from a single-arm, phase 2 trial.

OBJECTIVE: Robust biomarker predicting efficacy of immunotherapy is limited. Circulating tumor DNA (ctDNA) sought to effectively monitor therapeutic response as well as disease progression. This study aims to investigate predictive role of ctDNA short-term dynamic change (6 weeks postimmunotherapy) in a single-arm, phase 2 trial of sintilimab plus docetaxel for previously treated advanced non-small cell lung cancer (NSCLC) patients. METHODS: A total of 33 patients with advanced NSCLC with disease progression during or after any first-line treatment were prospectively enrolled between 2019 and 2020. Patients received sintilimab (200 mg, day 1, every 3 weeks) plus docetaxel (75 mg/m2, day 3, every 3 weeks) for 4-6 cycles, followed by maintenance therapy with sintilimab (200 mg, day 1, every 3 weeks) until disease progression or unacceptable toxic effects. Blood samples were prospectively collected at baseline, and after 2 cycles of treatment (6 weeks post-treatment). All samples were subjected to targeted next-generation sequencing with a panel of 448 cancer-related genes. The landscape of high-frequency genomic profile of baseline and 6th week was described. Major molecular characteristics in preselected genes of interest associated with response to second-line chemoimmunotherapy were analyzed. The curative effects and prognosis of patients were evaluated. RESULTS: Patients with ctDNA clearance at 6th week had decreased tumor volume, while most patients with positive ctDNA at 6th-week experienced an increase in tumor volume. Positive 6th-week ctDNA was associated with significantly shorter progression-free survival (PFS) (91 vs NR days; p<0.0001) and overall survival (47 vs 467 days; p =0.0039). Clearance of clonal mutations and none new clonal formation at 6th week were associated with longer PFS (mPFS 89 vs 266 days, p =0.003). ctDNA clearance at 6th week was an independent risk factor for progression or death (HR=100 (95% CI 4.10 to 2503.00), p=0.005). CONCLUSION: ctDNA status and ctDNA mutation clearance putatively serve as predictive biomarkers for sintilimab combined with docetaxel chemotherapy in pretreated advanced NSCLC patients.

Therapeutic Response of Soft Tissue Sarcoma With Novel SS18-POU5F1 Fusion: A Case Report.

A novel SS18-POU5F1 fusion gene was recently reported in soft tissue sarcoma occurring in three adolescent and young adult patients. Herein, we firstly reported the treatment response of SS18-POU5F1 sarcoma to immune checkpoint inhibitor, angiogenesis inhibitor, chemotherapy and radiotherapy. Our patient demonstrated no response to various systemic therapies including immune checkpoint inhibitor, angiogenesis inhibitor and chemotherapy. However, we noted that the SS18-POU5F1 sarcoma had a quick, robust but transient clinical response to radiotherapy. Further studies are needed to elucidate the mechanism underlying the different tumor response to radiotherapy and systemic therapy in this kind of tumor.

Iodine-125 radioactive particles antagonize hyperprogressive disease following immunotherapy: A case report.

RATIONALE: Increasing evidence has shown that immune checkpoint inhibitors are associated with hyperprogressive disease (HPD). HPD usually resulted in dramatically reduced survival duration, which limited the opportunity to administer other therapies. PATIENT CONCERNS: A heavily pretreated lung adenocarcinoma patient experienced rapid progression of rib metastasis soon after immune checkpoint inhibitor -based combination therapy. DIAGNOSES: On the basis of radiographic and pathological findings, the patient was diagnosed with HPD. INTERVENTIONS: We treated the patient with iodine-125 radioactive particle implantation to the metastatic lesions in the chest wall. OUTCOMES: The metastatic lesions shrank significantly 1 month later. LESSONS: Early detection and adequate treatment are essential for prolonged survival when HPD occurs.

Self-calibration method for temperature errors in multi-axis rotational inertial navigation system.

Rotation modulation technology of inertial navigation system brings navigation performance increasement without any new requirement on inertial sensors. However, device errors still make significant influence on navigation precision. Traditional temperature model identification methods cost plenty of time which reduce production efficiency. Therefore, it is necessary to study an effective solution decreasing temperature resulted errors for engineering application. The paper proposes a fast-self-calibration method for temperature errors. A continuous rotation scheme is designed to excite 21 errors inside of 10 minutes. Kalman Filter algorithm is applied to estimate 21 errors taking velocity errors and position errors as measurements. In order to identify temperature model, the rotation scheme is repeated ten times to estimate error parameters under different temperature. Due to the fast rotation scheme, temperature rising rate can be higher than traditional methods and calibration time is shortened. Finally, the method is verified by simulations and experiments.

A Calibration Method for the Errors of Ring Laser Gyro in Rate-Biased Mode.

Ring laser gyro (RLG) can work in mechanically dithered mode or rate-biased mode according to the working state of the inertial navigation system (INS). It can change from one mode to the other by receiving outer instructions. To evaluate the performance of RLG in rate-biased mode, an inertial measurement unit (IMU) based on RLG is installed on a dual-axis turntable, the turntable offers a constant angular velocity to the RLGs, in that way RLG can work in the rate-biased mode. A calibration method is proposed to calibrate the scale factor error, misalignments and constant bias of RLG in rate-biased mode, experiment results show that the differences of scale factor of the three gyros in two modes are 9 ppm, 7 ppm and 3.5 ppm, the constant biases of the three RLGs in rate-biased mode are also different from that in mechanically dithered mode with the difference of 0.017°/h, 0.011°/h and 0.020°/h, the input axis misalignment angle of RLGs in different modes also changed. What is more, a calculation method of angle random walk (ARW) of RLG in rate-biased mode is also presented. Experimental results show that the ARW of the RLG in rate-biased mode is about one third of that in mechanically dithered.

Esophago-tracheobronchial fistula following treatment of anlotinib in advanced squamous cell lung cancer: Two case reports.

RATIONALE: Anlotinib, a novel orally administered multitargeted tyrosine kinase inhibitor, inhibiting tumor angiogenesis and growth, significantly prolonged overall survival, and progression-free survival with a manageable safety profile as a third-line therapy among refractory advanced nonsmall cell lung cancer (NSCLC) patients in ALTER 0303 trail (NCT02388919). PATIENT CONCERNS: Two squamous cell lung cancer patients with mediastinal metastasis undergoing the treatment of anlotinib developed clinical symptom of cough, which was worse upon ingestion. DIAGNOSES: On the basis of patients' clinical symptoms and radiographic findings, they were diagnosed with acquired esophago-tracheobronchial fistula. INTERVENTIONS: We treated them with fully covered self-expandable metallic stents. OUTCOMES: The clinical symptom of cough was immediately relieved after palliative treatment. Both patients elected to discontinue anlotinib treatment. LESSONS: These 2 cases imply that a close follow-up schedule for esophago-tracheobronchial fistula should be established when squamous cell lung cancer patients with mediastinal metastasis are undergoing anlotinib therapy. Early detection and adequate treatment are essential for patient symptom relief and survival.

Innovative self-calibration method for accelerometer scale factor of the missile-borne RINS with fiber optic gyro.

The calibration of an inertial measurement unit (IMU) is a key technique to improve the preciseness of the inertial navigation system (INS) for missile, especially for the calibration of accelerometer scale factor. Traditional calibration method is generally based on the high accuracy turntable, however, it leads to expensive costs and the calibration results are not suitable to the actual operating environment. In the wake of developments in multi-axis rotational INS (RINS) with optical inertial sensors, self-calibration is utilized as an effective way to calibrate IMU on missile and the calibration results are more accurate in practical application. However, the introduction of multi-axis RINS causes additional calibration errors, including non-orthogonality errors of mechanical processing and non-horizontal errors of operating environment, it means that the multi-axis gimbals could not be regarded as a high accuracy turntable. As for its application on missiles, in this paper, after analyzing the relationship between the calibration error of accelerometer scale factor and non-orthogonality and non-horizontal angles, an innovative calibration procedure using the signals of fiber optic gyro and photoelectric encoder is proposed. The laboratory and vehicle experiment results validate the theory and prove that the proposed method relaxes the orthogonality requirement of rotation axes and eliminates the strict application condition of the system.

MRI-guided celiac plexus neurolysis for pancreatic cancer pain: Efficacy and safety.

PURPOSE: To prospectively determine the efficacy and safety of magnetic resonance imaging (MRI)-guided celiac plexus neurolysis (CPN) for pancreatic cancer pain. MATERIALS AND METHODS: In all, 39 patients with pancreatic cancer underwent 0.23T MRI-guided CPN with ethanol via the posterior approach. The pain relief, the opioid intake, and pain interference with appetite, sleep, and communication in patients were assessed after CPN during a 4-month follow-up period. The complications were also evaluated during or after CPN. RESULTS: CPN procedures were successfully completed for all patients. Minor complications included diarrhea (9 of 39; 23.1%), orthostatic hypotension (14 of 39; 35.9%), and local backache (20 of 39; 51.3%). No major complication occurred. Pain relief was observed in 36 (92.3%), in 15 (40.5%), and in 11 (35.5%) patients at 1-, 2-, and 3-month visits, respectively. The median duration of pain relief was 2.9 months (95% confidence interval [CI], 2.4-3.4). The opioid intake significantly decreased at the 1-, 2-, and 3-month visits (P < 0.001, < 0.001, = 0.001 respectively), and there was significant improvement in sleep at the 1-, 2-, and 3-month visits (P < 0.001, < 0.001, = 0.001 respectively), and appetite and communication were significantly improved at the 1- and 2-month visits (all P < 0.001); all compared with baseline. CONCLUSION: MRI-guided CPN appears to be an effective and minimally invasive procedure for palliative pain management of pancreatic cancer. J. MAGN. RESON. IMAGING 2016;44:923-928.

Rapid detection of index for encoder in rotary inertial navigation system.

This paper presents an approach to detect the index of incremental photoelectric encoder with shorter time for rotary inertial navigation system. The order of index detection and coarse alignment is exchanged in this approach and information from coarse alignment is used to calculate the direction of index. Then two cases of azimuth axis and four cases of horizontal axes are analyzed and corresponding solutions are designed. The paper examines the solutions through two experiments in a tri-axis rotary inertial navigation system, and the results demonstrate that the system can capture index pulse in the application of the presupposes schemes with shorter time.

An Accurate Calibration Method Based on Velocity in a Rotational Inertial Navigation System.

Rotation modulation is an effective method to enhance the accuracy of an inertial navigation system (INS) by modulating the gyroscope drifts and accelerometer bias errors into periodically varying components. The typical RINS drives the inertial measurement unit (IMU) rotation along the vertical axis and the horizontal sensors' errors are modulated, however, the azimuth angle error is closely related to vertical gyro drift, and the vertical gyro drift also should be modulated effectively. In this paper, a new rotation strategy in a dual-axis rotational INS (RINS) is proposed and the drifts of three gyros could be modulated, respectively. Experimental results from a real dual-axis RINS demonstrate that the maximum azimuth angle error is decreased from 0.04° to less than 0.01° during 1 h. Most importantly, the changing of rotation strategy leads to some additional errors in the velocity which is unacceptable in a high-precision INS. Then the paper studies the basic reason underlying horizontal velocity errors in detail and a relevant new calibration method is designed. Experimental results show that after calibration and compensation, the fluctuation and stages in the velocity curve disappear and velocity precision is improved.

Risk patterns of subsequent primary cancers following esophagectomy in early-stage thoracic esophageal squamous cell cancer patients.

AIMS AND BACKGROUND: Subsequent primary cancers (SPCs) have been demonstrated to be the major causes of death among patients with thoracic esophageal squamous cell cancer (ESCC) negative for lymph node involvement. We designed this study to investigate clinical characteristics and risk patterns of SPCs following esophagectomy in patients with early-stage thoracic ESCC. METHODS: We retrospectively analyzed clinical factors in 512 patients with early-stage thoracic ESCC collected from 3 independent hospitals over a 10-year interval. RESULTS: The overall standard incidence rate (SIR) of SPCs was 3.84 (95% confidence interval 2.98-4.95). The most common SPCs were head and neck cancers, lung cancer, and stomach cancer. The risk patterns of SPCs varied across organs. A 3-phase risk pattern with a U-shaped curve between 2 rising phases was seen for head and neck cancers, while for the other cancers, the risk patterns all displayed as an approximately linear upward trend. It was further noted that sex, smoking habits, and cancer histories among first-degree relatives were 3 significant independent risk factors in the development of SPCs. CONCLUSIONS: We observed significant associations between early-stage ESCC and SPCs arising from anatomically adjacent sites. The different risk patterns of SPCs indicated that follow-up strategies should be established accordingly in different organs at different times, with particularly close follow-up for head and neck cancers in the first 5 years and beyond 15 years after diagnosis of ESCC.

Use of a whole-cell bioreporter, Acinetobacter baylyi, to estimate the genotoxicity and bioavailability of chromium(VI)-contaminated soils.

A whole-cell bioreporter, Acinetobacter baylyi ADPWH_recA, was used to estimate the genotoxicity and bioavailability of chromium (VI) [Cr(VI)] in contaminated soils. Upon direct exposure to pre-sonicated soil samples, ADPWH_recA gave the highest response to the genotoxicity of Cr(VI) within 5 h with a detection limit of 2 µM Cr(VI). Investigations on sites contaminated with Cr(VI) revealed that soil-associated Cr(VI) was bioavailable to the bioreporter although it could not be extracted into the aqueous phase. The physical and chemical properties of soil might influence the bioavailability of Cr(VI), and higher genotoxicity was found in soils with a lower pH. This whole cell bioreporter approach makes it feasible to evaluate the bioavailability and genotoxicity of Cr(VI)-contaminated soils to uncover their potential impact on human health.

[Correlations between MRI apparent diffusion coefficient and histological grade and molecular biology of breast invasive ductal carcinoma].

OBJECTIVE: To study the correlation between the MRI apparent diffusion coefficient (ADC) value and histological grade and molecular biology of breast invasive ductal carcinoma (IDC). METHODS: This retrospective study included 125 patients with IDC verified by pathology from February 2010 to February 2013. Conventional MRI and diffusion-weighted imaging (DWI) examination were performed using a 3.0T scanner with diffusion factor of 0 and 800 s/mm(2). The region of interest (ROI) was drawn on the largest lesion and/or its two adjacent slices. The ADC value of the whole tumor was calculated as the mean ADC value. The correlation between mean ADCs and histological grade and biological factors was analyzed. RESULTS: The mean ADC of pathological grade I, II and III IDC was (1.152 ± 0.072)×10(-3) mm(2)/s, (1.102 ± 0.101)×10(-3) mm(2)/s, and (1.035 ± 0.107)×10(-3) mm(2)/s, respectively. There was a statistically significant difference among them (P = 0.003). Statistically a significant difference was observed between grade III and I (P = 0.034), grade III and II (P = 0.006), but not between grade I and II (P = 0.741). A significant correlation was observed between ADC value and pathological grade (r = -0.342, P < 0.001). The median ADC values were significantly higher in the ER-negative than in the ER-positive cases [(1.130 ± 0.115)×10(-3) mm(2)/s vs. (1.060 ± 0.089) ×10(-3) mm(2)/s, P < 0.001)], in PR-negative than in PR-positive cases [(1.121 ± 0.106)×10(-3) mm(2)/s vs. (1.055 ± 0.096) ×10(-3) mm(2)/s, P < 0.001)], and in Ki-67-negative than in Ki-67-positive cases [(1.153 ± 0.090)×10(-3) mm(2)/s vs. (1.063 ± 0.101) ×10(-3) mm(2)/s, P < 0.001]. A statistically significant correlation was observed between ADC value and expressions of ER, PR, and Ki-67 (r = -0.311, r = -0.317, r = -0.414, P < 0.001). CONCLUSION: ADC value of breast invasive ductal carcinoma is correlated with histological grade, and expression of ER, PR and Ki-67.