[Pre- and post-diagnosis body mass index in association with colorectal cancer death in a prospective cohort study].

Objective: To evaluate the association between pre-and post-diagnosis body mass index (BMI) and risk of colorectal cancer (CRC) death. Methods: The cohort consisted of 3, 057 CRC patients from Shanghai who were diagnosed from Jan. 1, 2009 to Dec. 31, 2011 and aged from 20 to 74 years. The pre- and post-diagnosis BMI and clinical and lifestyle factors were collected at baseline. Death information was collected using record linkage with the Shanghai Cancer Registry and telephone confirmation during follow-up by the end of 2019. The Cox proportional regression model was used to estimate HR with 95% CI. Results: Analysis by multivariable Cox model showed no association between pre-diagnosis BMI and death risk in both male and female patients. Male patients with a post-diagnosis underweight BMI had an elevated risk of death compared to those in normal weight (HR=1.69, 95% CI: 1.21-2.37), especially in early stage cases. Overweight patients (HR=0.74, 95% CI: 0.61-0.89) and patients with obesity class Ⅰ (HR=0.63, 95% CI: 0.45-0.89)had better survival with decreased risks of death, especially in advanced stage cases. The decreased death risk in patients with obesity class Ⅱ was not significant (HR=0.57, 95% CI: 0.24-1.39). The P(trend) value for decreased risk of death with increased BMI in female patients was statistically significant (P<0.001), and the overweight and obesity class Ⅰ categories had better survival in advanced stage(HR(overweight)=0.62, 95% CI: 0.42-0.93; HR(obesity class Ⅰ)=0.39, 95% CI: 0.16-0.98). Both male and female patients with post-diagnosis BMI loss >2.0 kg/m(2) had an increased death risk when compared with those with stable BMI (change≤1.0 kg/m(2)) between pre- and post-diagnosis. BMI gain after diagnosis did not change death risk. Conclusions: Post-diagnosis BMI in the overweight or obesity class Ⅰ groups might be conducive to prolonging male CRC patients' survival, while underweight might result in poor prognosis. Keeping weight and avoiding excessive weight loss should be suggested for all CRC patients after diagnosis.

[Repeated stellate ganglion blockade for the treatment of ventricular tachycardia storm in patients with nonischemic cardiomyopathy: a new therapeutic option for patients with malignant arrhythmias].

Objectives: This study sought to describe our institutional experience of repeated percutaneous stellate ganglion blockade (R-SGB) as a treatment option for drug-refractory electrical storm in patients with nonischemic cardiomyopathy (NICM). Methods: This prospective observational study included 8 consecutive NICM patients who had drug-refractory electrical storm and underwent R-SGB between June 1, 2021 and January 31, 2022. Lidocaine (5 ml, 1%) was injected in the vicinity of the left stellate ganglion under the guidance of ultrasound, once per day for 7 days. Data including clinical characteristics, immediate and long-term outcomes, and procedure related complications were collected. Results: The mean age was (51.5±13.6) years. All patients were male. 5 patients were diagnosed as dilated cardiomyopathy, 2 patients as arrhythmogenic right ventricular cardiomyopathy and 1 patient as hypertrophic cardiomyopathy. The left ventricular ejection fraction was 37.8%±6.6%. After the treatment of R-SGB, 6 (75%) patients were free of electrical storm. 24 hours Holter monitoring showed significant reduction in ventricular tachycardia (VT) episodes from 43.0 (13.3, 276.3) to 1.0 (0.3, 34.0) on the first day following R-SGB (P<0.05) and 0.5 (0.0, 19.3) after whole R-SGB process (P<0.05). There were no procedure-related major complications. The mean follow-up was (4.8±1.1) months, and the median time of recurrent VT was 2 months. Conclusion: Minimally invasive R-SGB is a safe and effective method to treat electrical storm in patients with NICM.

Factors influencing utilisation of assistive devices by the elderly in China: a community-based cross-sectional study.

OBJECTIVES: The study aimed to gain an insight into the utilisation, self-perceived needs, and attitudes towards and influencing factors of assistive device (AD) usage among community-dwelling older adults in China. STUDY DESIGN: This is a cross-sectional study. METHODS: A total of 5790 elderly people from eight communities within three provinces in China were recruited by convenience sampling. Utilisation, needs and attitudes towards ADs were assessed by a questionnaire designed by the authors. Barthel activities of daily living scale was used to determine disability, whereas cognitive function was assessed with the Mini-Mental State Examination. The impact of participant characteristics, enabling factors and demand factors on the utilisation of ADs were assessed by univariate and multifactor analyses. RESULTS: The prevalence of AD ownership among participants was 10.9% (n = 634), whereas the self-perceived need for ADs was 46.1% (n = 2670). Most participants had negative attitudes towards ADs, with only 37.6% (n = 2175) of participants believing that ADs were of significant help. Factors influencing the usage of ADs included participant characteristics (age, occupation, living area, education), enabling factors (economic situation, number of children) and demand factors (activities of daily living score, attitudes, self-perceived needs). CONCLUSIONS: Although ADs for the elderly in China have become more affordable and accessible after a series of reforms, there remains a gap in AD services resulting in low AD utilisation, high self-perceived needs and misconceptions of ADs. Certain factors influencing the use of ADs are more significant than others. The findings from this study will be informative for healthcare providers and decision-makers when designing strategies to achieve universal elderly AD usage.

[Clinical characteristics and long-term follow-up results of radiofrequency ablation for the treatment of ventricular tachycardia in patients with arrhythmogenic left ventricular cardiomyopathy].

Objective: To investigate the acute and long-term outcome of catheter ablation for the treatment of ventricular tachycardia (VT) in patients with arrhythmogenic left ventricular cardiomyopathy (ALVC). Methods: This retrospective, cross-sectional study enrolled ALVC patients undergoing radiofrequency ablation for the treatment of VT at the First Affiliated Hospital of Nanjing Medical University from January 2011 to December 2018 and collected their clinical characteristics and intraoperative electrophysiological examination. Patients were followed up every 6 months after radiofrequency ablation until August 2021. Echocardiographic results and VT recurrence post radiofrequency ablation were analysed. Results: Totally 12 patients were enrolled (mean age: (42±15) years, 11 males(11/12)). The mean of left ventricular end diastolic diameter (LVDd) and left ventricular ejection fraction (LVEF) were (51±5)mm and (65±5)%, respectively. Twelve VTs were induced in 10 patients during the electrophysiological study, and the mean tachycardia cycle length was (293±65) ms. Three-dimensional substrate mapping revealed the diseased area at endocardial site in one patient, at epicardial sites in the other 11 patients (involved endocardial sites in 2 cases) with the basal part near the mitral annulus being the predilection for the substrate (10/11). After the catheter ablation at the endocardial and epicardial sites respectively, the complete procedure endpoint was achieved in all patients (VT cannot be induced post ablation). The median follow-up time was 65 (25, 123) months. One patient was lost to follow-up, and the other 11 patients survived without VT. No significant cardiac function deterioration was detected by the echocardiographic examination ((51±5)mm vs. (52±5)mm, P>0.05 for LVDd, (65±5)% vs. (60±6)%, P>0.05 for LVEF) at the end of follow-up. Conclusion: After radiofrequency ablation, the complete procedure endpoint is achieved in ALVC patients, and the catheter ablation provides long-term ventricular tachycardia control during the long-term follow-up.

Progression of atypical femur stress fracture after discontinuation of bisphosphonate therapy.

Atypical femur fracture (AFF) is an uncommon complication of long-term bisphosphonate use, but the risk declines substantially after treatment cessation. We report a case of a 70-year-old woman with osteopenia treated with alendronate for 9 years who presented with right mid-thigh pain and radiographic findings of focal lateral cortical thickening in the right mid-femur and lateral cortex irregularity in the proximal-mid left femur. Alendronate was discontinued, but she remained on estrogen for menopausal symptoms. Four years later, a horizontal linear translucent defect was seen in the right mid-femur area of cortical hypertrophy, consistent with an incomplete AFF. The patient underwent prophylactic intramedullary rodding of the right femur and estrogen was discontinued. Three years later (7 years after initial presentation), the cortical irregularities in the left femur were more prominent and three small horizontal linear translucent defects were now evident, consistent with early incomplete atypical fracture development. The patient also suffered a wrist fracture. She was treated with teriparatide for 1.5 years with resolution of the translucent defects in the left but not the right femur, although abnormal thickening of the lateral cortex persisted in both femurs. Our case demonstrates incomplete atypical femur fracture progression in a patient with long-term bisphosphonate exposure, even after treatment cessation. These findings highlight the importance of follow-up for patients who develop diaphyseal femur stress fractures and the potential for early healing with anabolic therapy. This case also demonstrates the challenge in managing older patients with incomplete AFF at risk for progression to complete AFF and osteoporotic fracture.

Tea consumption and risk of fractures: an updated meta-analysis.

This meta-analysis included 16 studies, involving seven cohort studies and nine case-control studies, and the results indicated that tea consumption may be associated with a reduced the risk of fractures. INTRODUCTION: Regarding relationship of tea consumption with the risk of fractures remains controversial. We performed a meta-analysis to elucidate the association between tea consumption and the risk of fractures. METHODS: Relevant articles were identified up to March 2019 by searching PubMed, Web of Science, and Embase databases. The pooled relative risks (RRs) with 95% confidence intervals (CIs) were computed utilizing fixed or random effects model based on heterogeneity. RESULTS: Altogether 16 studies (seven cohort and nine case-control studies) were included in this meta-analysis, involving 772,707 participants with 37,166 fracture cases. The RRs (95% CIs) of fracture for the highest versus lowest category of tea consumption were 0.86 (0.78-0.94). Subgroup analysis indicated significant associations in cohort studies (0.90 (0.86-0.94)) and case-control studies (0.77 (0.69-0.85)). CONCLUSIONS: The current meta-analysis indicates that tea consumption may be associated with a reduced the risk of fractures.

Effects of lactic acid bacteria and smectite after aflatoxin B1 challenge on the growth performance, nutrient digestibility and blood parameters of broilers.

This study aimed to investigate the effect of lactic acid bacteria (LAB) and smectite on the growth performance, nutrient digestibility and blood parameters of broilers that were fed diets contaminated with aflatoxin B1 (AFB1 ). A total of 480 newly hatched male Arbor Acres broilers were randomly allocated into four groups with six replicates of 20 chicks each. The broilers were fed diets with the AFB1 (40 µg/kg) challenge or without (control) it and supplemented with smectite (3.0 g/kg) or LAB (4.0 × 1010  CFU/kg) based on the AFB1 diet. The trial lasted for 42 days. The results showed that during days 1-42 of AFB1 challenge, the feed intake (FI) and body weight gain (BWG) were depressed (p < .05). The inclusion of LAB and smectite increased (p < .05) the BWG by 71.58 and 41.89 g/bird, respectively, which reached the level of the control diet (p ≥ .05), but there were no differences (p ≥ .05) in performance between LAB and smectite. LAB and smectite also increased (p < .05) the apparent total tract digestibility of the crude protein. Regarding the blood parameters, AFB1 decreased (p < .05) the levels of red blood cell count, haematocrit, mean corpuscular volume, haemoglobin, albumin and total protein. In the meantime, the AFB1 increased (p < .05) leucocyte counts, urea nitrogen, cholesterol, total bilirubin, creatinine, glutamic-pyruvic transaminase, glutamic oxaloacetic transaminase and alkaline phosphatase. By contrast, LAB and smectite affected (p < .05) these parameters in the opposite direction. It can be concluded that after the AFB1 challenge, LAB and smectite have similar effects on the growth and health of the broilers, suggesting that LAB could be an alternative against AFB1 in commercial animal feeds.

The α-ß circular scanning with large range and low noise.

A circular-route scanning method called α-ß circular scanning is proposed and realized using sinusoidal signals with a constant phase difference of π/2. Experiments show that the circular scanning range of α-ß circular scanning is 57% greater than the rectangular scanning range of raster scanning within an effective optical field of view. Moreover, the scanning speed is improved by 7.8% over raster scanning because the whole sine signal is utilized in α-ß circular scanning whereas the flyback area of the saw-tooth signal needs to be discarded in raster scanning. The maximum scanning acceleration decreases by a factor of 44, drastically decreasing the high noise, which should considerably elongate the lifetime of the galvanometers while inhibiting internal vibration. The proposed α-ß circular scanning technique could be used in scanning imaging, optical tweezers and laser-beam fabrication.

[Analysis of the patterns of female breast cancer incidence in Shanghai, 2003-2012].

Objective: To analyze the patterns of female breast cancer and their incidence in Shanghai during 2003-2012, and to compare them with international data. Methods: The data of female breast cancer cases diagnosed between 2003 and 2012 were collected from the Shanghai Cancer Registry. The record of cancer cases included the patient's name, gender, date of birth, permanent and residential address, diagnosis site or name, histological type, date of first diagnosis, diagnostic basis and diagnostic stage, etc. Data source of cancer incidence of World, Developed Countries, Developing Countries, East Asia and China in 2012 sourced from GLOBOCAN 2012 database of the WHO International Agency for Research on Cancer (IARC); and the data of USA during 2008-2012 was collected from SEER 18 database from Surveillance, Epidemiology, and End Results Program of the National Cancer Institute (NCI). Incidence indicators of Shanghai female breast cancer were calculated, including the average cases, median age, average age, proportion, crude rate, age-specific rate and age-standardized rate. Results: During 2003-2012, 41 991 new cases of female breast cancer were diagnosed in Shanghai, with an average of 4 199 cases per year, accounting for 17.23% among total new female cancer cases, ranking first in female cancer incidence in Shanghai during 2003-2012, with a crude incidence rate of 60.90 per 100 000 and an age-standardized incidence rate of 33.90 per 100 000. During 2008-2012, an average 4 528 new cases of female breast cancer was diagnosed per year in Shanghai, with 16.97% among total female cancer cases. The median age was 56 years old and the mean age was 57.73 years old. The crude rate was 64.23 per 100 000 and the age-standardized rate was 35.00 per 100 0000, which was higher than those of China (22.1 per 100 000), Eastern Areas (27.0 per 100 000) and Developing Counties (31.3 per 100 000), and lower than that of World (43.1 per 100 000), and Yellow Race Population of USA (68.77 per 100 000). During 2003-2007, on average, 3 869 new cases of female breast cancer were diagnosed per year in Shanghai, accounting for 17.54% of total female cancer cases. The median age was 53 years old and the mean age was 56.44 years old. The crude rate was 57.42 per 100 000 and the age-standardized rate was 32.69 per 100 000. There was a continuing peak stage spanned 25 years old from 50 to 74 years old, during 2008-2012. Compared with those of 2003-2007, the beginning age group of the continuing peak stage was delayed for 5 years old and the ending age group was delayed for 10 years old. Conclusion: The age-standardized incidence rate in Shanghai was higher than those of China, Eastern Areas and Developing Counties, and lower than that of World, and that of Yellow Race Population of USA; Compared with 2003-2007, the crude rate and age-standardized rate increased, the median age, mean age and the beginning and ending age group of the continuing peak stage were delayed.

Breast cancer incidence and mortality: trends over 40 years among women in Shanghai, China.

BACKGROUND: Breast cancer incidence rates are increasing among Asian women, likely due to the changes in risk factors caused by globalization. Trends in breast cancer rates among Chinese women may differ from other Asian regions due to the implementation of a nationwide family planning program and resulting changes in women's reproductive practices. Appraisal of cancer trends can direct cancer control and public health planning, but relevant studies in China are scarce due to a lack of long-term data. We sought to evaluate secular time trends in breast cancer incidence and mortality using 40 years of cancer registry data for women in urban Shanghai. MATERIALS AND METHODS: Data on invasive breast cancer incidence and mortality were collected by the Shanghai Cancer Registry. Age-standardized rates (ASRs) for incidence and mortality were calculated using the Segi/Doll 1960 world standard population. Age, period, and birth cohort effects were evaluated using age-period-cohort (APC) Poisson regression models. Overall linear trends, interpreted as the estimated annual percentage change (EAPC), were derived from the net drift in age-drift models. RESULTS: A total of 53 885 breast cancer cases and 17 235 breast cancer-specific deaths were documented among women in urban Shanghai between 1 January 1973 and 31 December 2012. Breast cancer incidence and mortality ASRs increased by 141.2% and 26.6%, respectively. Significant age, cohort, and period effects were identified in both incidence and mortality APC models; cohort effects were pronounced. Overall, a substantial increase in breast cancer incidence (EAPC = 2.96%/year) and a moderate increase in breast cancer mortality (EAPC = 0.87%/year) was observed. A notable downward trend in mortality was identified among younger women born after 1960. CONCLUSIONS: Forty years of cancer registry data document a tremendous increase in incidence and a slight increase in mortality for breast cancer among women in Shanghai. Effective, appropriate, and affordable breast cancer prevention and control strategies are urgently needed in China.

Correlation of ERCC1 expression in peripheral blood lymphocytes with outcomes of patients with gastric cancer treated with oxaliplatin-based adjuvant chemotherapy.

Excision repair cross-complementing gene-1 (ERCC1) is a key regulatory enzyme whose expression patterns in tumor tissues are associated with survival in gastric cancer. The present study aimed to evaluate the effects of ERCC1 expression in peripheral blood lymphocytes (PBLs) on the outcome of patients with gastric cancer treated with oxaliplatin-based adjuvant chemotherapy. Tumor and PBL samples from 48 patients treated with adjuvant oxaliplatin-based chemotherapy for gastric cancer were analyzed. Immunohistochemistry was used to assess the expression of ERCC1. After a median follow-up of 18.5 months, the median disease-free survival (DFS) and overall survival (OS) were 12 and 20 months, respectively. Expression of ERCC1 was found in 72.9% (35/48), 56.3% (27/48), and 10.0% (2/20) of tumor tissues, PBLs from gastric cancer patients, and PBLs from controls, respectively. A significant positive correlation between ERCC1 expression in PBL and cancer tissue was found (χ(2) = 12.098, P = 0.001, Pearson contingency coefficient = 0.502). Patients with negative expression of ERCC1 in tumor tissues had a significantly longer median DFS and median OS compared to patients with positive expression of ERCC1 (median DFS, 18 vs 10 months, P = 0.006; median OS, 30 vs 17 months, P = 0.012). In PBLs, high expression of ERCC1 was associated with decreased DFS (9 vs 18 months, P = 0.032), but not OS (16 vs 24 months, P = 0.057). Patients with gastric cancer exhibiting negative expression of ERCC1 are more likely to benefit from oxaliplatin-based adjuvant chemotherapy.

Limited human-to-human transmission of avian influenza A(H7N9) virus, Shanghai, China, March to April 2013.

In April 2013, two members of one family were successively confirmed as cases of avian influenza A(H7N9) virus infection in Shanghai, China. Respiratory specimens from the two cases and their close contacts were tested using real-time reverse-transcription (RT)-PCR. Paired serum specimens from contacts were tested by haemagglutination inhibition assay and microneutralisation test. The index patient developed severe pneumonia. Her husband presented with pneumonia shortly thereafter. Both cases had highly similar clinical features and infection with A(H7N9) virus was confirmed in both cases by genetic analysis. Phylogenetic analysis revealed a high level of similarity between the sequences from the two patients and environmental samples collected from wet markets in Minhang and Changning districts. Six samples from the Changning wet market were confirmed as A(H7N9) positive. Of 27 close contacts, one developed mild respiratory symptoms and another tested positive for A(H7N9) antibodies, but both were negative by real-time RT-PCR. The other 25 close contacts of both cases were A(H7N9) negative. Limited human-to-human transmission of the virus most likely occurred in the family cluster. However, other close contacts did not test positive for the virus, suggesting limited potential for extensive human-to-human transmission of the virus.

Clinical retrospective analysis of cases with multiple primary malignant neoplasms.

The etiological factors, clinical characteristics, diagnosis, treatment strategies, and prognosis of multiple primary malignant neoplasms (MPMNs) were investigated in order to improve its diagnosis and therapy. Clinical data of 170 patients with MPMN who were admitted to the Oncology Department of the First Affiliated Hospital of Anhui Medical University from January 2004 to April 2010 were collected and analyzed retrospectively. The overall incidence of MPMNs was 2.25%. There were 167 cases with duplex primary cancers, 2 cases with triple primary cancers, 1 case with quadruple primary cancer, 46 synchronous MPMNs (SMPMNs), and 124 metachronous MPMNs (MMPMNs). There were 344 malignant neoplasms in the 170 MPMN patients, of which 161 were in the alimentary system, 48 in the respiratory system, 63 in mammary glands, 30 in the genital system, 7 in the urinary system, 23 in the head and neck, and the other 12 were in the brain, hematological system, and soft tissue. There were 22 cases of bilateral primary breast cancer and 41 cases of digestive MPMN. With a median survival time of 24 months, the 1-, 3-, and 5-year cumulative survival rates in the 170 patients were 68.8, 39.1, and 25.2%, respectively. The most common locations of MPMN were the alimentary system, mammary gland, and respiratory system. MPMN usually occurred in distinct organs of identical systems, conjugate organs, or identical organs. The survival rate of SMPMN was similar to that of MMPMN. There were differences in principles of treatment and diagnosis between MPMN and metastasis or recurrent cancers.

A new patient-specific helical maxillary distractor: a cadaver test.

The primary objective of this cadaver study was to assess the feasibility of a novel custom helical distraction system and a patient-specific antral maxillary distractor. The study involved two fresh cadaver heads and followed a systematic procedure. First, virtual planning was conducted for an asymmetric maxillomandibular advancement. Custom patient-specific hardware was then fabricated to enable sequential mandibular advancement and gradual maxillary distraction. The mandibular lengthening procedures were found to be highly accurate, with only minor deviations from the planned results. In terms of maxillary distraction, the patient-specific antral distractors demonstrated favorable outcomes, with two noteworthy exceptions. Ideal forward maxillary advancement was short by a modest 2-3 mm in both cadavers. Additionally, cadaver 2 exhibited an unplanned pitch malrotation. However, an excellent occlusion was achieved in cadaver 1 and an acceptable anterior occlusion in cadaver 2, albeit with bilateral posterior open bites that could be readily corrected with interdental elastics in a clinical setting. This cadaver model study provides compelling evidence for the feasibility of patient-specific antral helical distractors, highlighting their potential to yield positive outcomes. Importantly, the study results suggest that patient-specific antral distractors may offer superior results compared to the current standard of linear distractors.

A nanomaterial-based breath test for distinguishing gastric cancer from benign gastric conditions.

BACKGROUND: Upper digestive endoscopy with biopsy and histopathological evaluation of the biopsy material is the standard method for diagnosing gastric cancer (GC). However, this procedure may not be widely available for screening in the developing world, whereas in developed countries endoscopy is frequently used without major clinical gain. There is a high demand for a simple and non-invasive test for selecting the individuals at increased risk that should undergo the endoscopic examination. Here, we studied the feasibility of a nanomaterial-based breath test for identifying GC among patients with gastric complaints. METHODS: Alveolar exhaled breath samples from 130 patients with gastric complaints (37 GC/32 ulcers / 61 less severe conditions) that underwent endoscopy/biopsy were analyzed using nanomaterial-based sensors. Predictive models were built employing discriminant factor analysis (DFA) pattern recognition, and their stability against possible confounding factors (alcohol/tobacco consumption; Helicobacter pylori) was tested. Classification success was determined (i) using leave-one-out cross-validation and (ii) by randomly blinding 25% of the samples as a validation set. Complementary chemical analysis of the breath samples was performed using gas chromatography coupled with mass spectrometry. RESULTS: Three DFA models were developed that achieved excellent discrimination between the subpopulations: (i) GC vs benign gastric conditions, among all the patients (89% sensitivity; 90% specificity); (ii) early stage GC (I and II) vs late stage (III and IV), among GC patients (89% sensitivity; 94% specificity); and (iii) ulcer vs less severe, among benign conditions (84% sensitivity; 87% specificity). The models were insensitive against the tested confounding factors. Chemical analysis found that five volatile organic compounds (2-propenenitrile, 2-butoxy-ethanol, furfural, 6-methyl-5-hepten-2-one and isoprene) were significantly elevated in patients with GC and/or peptic ulcer, as compared with less severe gastric conditions. The concentrations both in the room air and in the breath samples were in the single p.p.b.v range, except in the case of isoprene. CONCLUSION: The preliminary results of this pilot study could open a new and promising avenue to diagnose GC and distinguish it from other gastric diseases. It should be noted that the applied methods are complementary and the potential marker compounds identified by gas-chromatography/mass spectrometry are not necessarily responsible for the differences in the sensor responses. Although this pilot study does not allow drawing far-reaching conclusions, the encouraging preliminary results presented here have initiated a large multicentre clinical trial to confirm the observed patterns for GC and benign gastric conditions.

Bevacizumab biosimilar candidate TAB008 compared to Avastin® in patients with locally advanced, metastatic EGFR wild-type non-squamous non-small cell lung cancer: a randomized, double-blind, multicenter study.

BACKGROUND: Bevacizumab (Avastin®) is a monoclonal antibody targeting the vascular endothelial growth factor (VEGF). Used alone or in combination with chemotherapy and/or immunotherapy, Avastin® has shown promising efficacy in many cancers. This study compared the efficacy and safety of TAB008 with Avastin® sourced from the EU (bevacizumab-EU), in patients with non-squamous non-small cell lung cancer (nsNSCLC). METHOD: In this randomized, double-blind, multicenter, phase III similarity study, treatment naïve for metastatic lung cancer., EGFR wild-type, locally advanced, metastatic, or recurrent non-squamous, non-small cell, lung cancer (nsNSCLC) patients were enrolled and randomized (1:1) into TAB008 or Avastin® groups. Patients received TAB008 or Avastin® 15 mg/kg intravenously plus paclitaxel/carboplatin for 4-6 cycles followed by TAB008 or Avastin® 7.5 mg/kg until disease progression, unacceptable toxicity or death. The primary endpoint compared the objective response rate (ORR) within 6 cycles as read by an independent radiological review committee (IRRC). Secondary endpoints compared disease control rate (DCR) Within 6 cycles, duration of response (DoR), progression-free survival (PFS), a year overall survival rate (OSR), overall survival (OS), safety, immunogenicity, and steady-state pharmacokinetics. RESULTS: A total of 549 nsNSCLC patients were enrolled (277 in TAB008 group and 272 in Avastin® group). In the full analysis set, ORRs were 55.957% for TAB008 and 55.720% for Avastin®, and the ORR ratio was 1 (90% CI 0.89-1.14), well within the predefined equivalence margin of 0.75-1.33. No significant differences were found in DCR within 6 cycles (95.703% vs 95.367%, p = 0.8536), DoR (8.17 vs 7.3 months, p = 0.3526), PFS (9.10 vs. 7.97 months, p = 0.9457), 1 year overall survival rate (66.2% vs 68%, p = 0.6793), or OS (20.4 vs 17.6 months, p = 0.6549). Serious adverse events (SAEs) occurred in 37.55% (104/277) of patients in the TAB008 group and 34.32% (93/271) in the Avastin® group. Anti-drug antibodies were reported in 3 of 277 (1.08%) TAB008 patients, and 5 of 271 (1.85%) Avastin® patients, neutralizing antibody (Nab) was positive in 1 patient on Avastin®, which became negative upon follow-up. The steady-state trough concentrations (Cssmin) were 106.13 µg/mL in TAB008 group and 96.03 µg/mL in Avastin® groups, with the treatment group ratio of LS geometric means fully contained within the bioequivalence limits of 80.00-125.00% (90% CI was 101.74-120.05%). CONCLUSIONS: TAB008 is similar to Avastin® in terms of efficacy, safety, and pharmacokinetic parameters, with comparable immunogenicity. TRIAL REGISTRATION: ClinicalTrials.gov number; NCT05427305.

Clinical feasibility of deep learning-based automatic head CBCT image segmentation and landmark detection in computer-aided surgical simulation for orthognathic surgery.

The purpose of this ambispective study was to investigate whether deep learning-based automatic segmentation and landmark detection, the SkullEngine, could be used for orthognathic surgical planning. Sixty-one sets of cone beam computed tomography (CBCT) images were automatically inferred for midface, mandible, upper and lower teeth, and 68 landmarks. The experimental group included automatic segmentation and landmarks, while the control group included manual ones that were previously used to plan orthognathic surgery. The qualitative analysis of segmentation showed that all of the automatic results could be used for computer-aided surgical simulation. Among these, 98.4% of midface, 70.5% of mandible, 98.4% of upper teeth, and 93.4% of lower teeth could be directly used without manual revision. The Dice similarity coefficient was 96% and the average symmetric surface distance was 0.1 mm for all four structures. With SkullEngine, it took 4 minutes to complete the automatic segmentation and an additional 10 minutes for a manual touchup. The results also showed the overall mean difference between the two groups was 2.3 mm for the midface and 2.4 mm for the mandible. In summary, the authors believe that automatic segmentation using SkullEngine is ready for daily practice. However, the accuracy of automatic landmark digitization needs to be improved.

Pembrolizumab versus chemotherapy for patients with esophageal squamous cell carcinoma enrolled in the randomized KEYNOTE-181 trial in Asia.

BACKGROUND: In the randomized phase III KEYNOTE-181 study, pembrolizumab prolonged overall survival (OS) compared with chemotherapy as second-line therapy in patients with advanced esophageal cancer and programmed death-ligand 1 (PD-L1) combined positive score (CPS) ≥10. We report a post hoc subgroup analysis of patients with esophageal squamous cell carcinoma (ESCC) enrolled in KEYNOTE-181 in Asia, including patients from the KEYNOTE-181 China extension study. PATIENTS AND METHODS: Three hundred and forty Asian patients with advanced/metastatic ESCC were enrolled in KEYNOTE-181, including the China cohort. Patients were randomly assigned 1 : 1 to receive pembrolizumab 200 mg every 3 weeks for ≤2 years or investigator's choice of paclitaxel, docetaxel, or irinotecan. OS, progression-free survival, response, and safety were analyzed without formal comparisons. OS was evaluated based on PD-L1 CPS expression level. RESULTS: In Asian patients with ESCC, median OS was 10.0 months with pembrolizumab and 6.5 months with chemotherapy [hazard ratio (HR), 0.63; 95% CI 0.50-0.80; nominal P < 0.0001]. Median progression-free survival was 2.3 months with pembrolizumab and 3.1 months with chemotherapy (HR, 0.79; 95% CI 0.63-0.99; nominal P = 0.020). Objective response rate was 17.1% with pembrolizumab and 7.1% with chemotherapy; median duration of response was 10.5 months and 7.7 months, respectively. In patients with PD-L1 CPS <1 tumors (pembrolizumab versus chemotherapy), the HR was 0.99 (95% CI 0.56-1.72); the HR (95% CI) for death was better for patients with PD-L1 CPS cut-offs >1 [CPS ≥1, 0.57 (0.44-0.75); CPS ≥5, 0.56 (0.41-0.76); CPS ≥10, 0.53 (0.37-0.75)]. Treatment-related adverse events were reported in 71.8% of patients in the pembrolizumab group and 89.8% in the chemotherapy group; grade 3-5 events were reported in 20.0% and 44.6%, respectively. CONCLUSIONS: Pembrolizumab monotherapy demonstrated promising efficacy in Asian patients with ESCC, with fewer treatment-related adverse events than chemotherapy. PD-L1 CPS ≥1 is an appropriate cut-off and a predictive marker of pembrolizumab efficacy in Asian patients with ESCC.

Reconsideration on the use of elastic models to predict the instantaneous load response of the knee joint.

Fluid pressurization in articular cartilages and menisci plays an important role in the mechanical function of the knee joint. However, fluid pressure has not been incorporated in previous finite element modelling of the knee, instead elastic models of the knee are widely used. It is believed that an elastic model can be used to predict the instantaneous load response of the knee as long as large effective moduli for the cartilaginous tissues are used. In the present study, the instantaneous response of the knee was obtained from a proposed model including fluid pressure and fibril reinforcement in the cartilaginous tissues. The results were then compared with those obtained from an elastic model using the effective modulus method. It was found that the deformations and contact pressures predicted by the two models were substantially different. An unconfined compression of a tissue disc was used to help understand the issue. It was clear that a full equivalence between the instantaneous and elastic responses could not be established even for this simple case. A partial equivalence in stress could be conditionally established for a given unconfined compression, but it was not valid for a different magnitude of compression. The instantaneous deformation of the intact tissues in the joint was even more difficult to determine using the effective modulus method. The results thus obtained were further compromised because of the uncertainty over the choice of effective modulus. The tissue non-linearity was one of the factors that made it difficult to establish the equivalence in stress. The pressurized tissue behaved differently from a solid material when non-linear fibril reinforcement was presented. The direct prediction of the instantaneous response using the proposed poromechanical model had the advantage of determining the fluid pressure and incompressible deformation.

Effect of oviposition by Bactrocera dorsalis on the antioxidant activity of orange juice.

Among fruits and fruit products, oranges and orange juice are the most widely consumed worldwide. However, the effects of pest infestation of oranges on the quality of orange juice are not yet known. To evaluate the effect of the oriental fruit fly Bactrocera dorsalis on the antioxidant activity of orange juice, we measured changes in the vitamin C (Vc) concentration, total phenol content, and antioxidant activity of orange juice after the introduction of fruit fly eggs. Ten days after the eggs were introduced (larvae removed), the concentration of Vc in orange juice was 18.65 µg/mL, which was 9.16 µg/mL lower than that measured in healthy orange juice. In addition, the total phenol content decreased by 46.519 mg Gallic Acid Equivalents (GAE)/g to 9.748 mg GAE/g. Furthermore, the free-radical scavenging activity decreased from 22.297% to 5.393%. Correlation analysis indicated significant correlations between Vc concentration, total phenol content, and antioxidant activity of orange juice after B. dorsalis infestation. The decrease in Vc concentration, total phenol content and free-radical scavenging activity indicated that B. dorsalis changed the quality of orange juice by affecting the antioxidant activity of the juice after the oranges were infested.