Amivantamab plus lazertinib versus osimertinib in first-line EGFR-mutant advanced non-small-cell lung cancer with biomarkers of high-risk disease: a secondary analysis from MARIPOSA.

BACKGROUND: Amivantamab-lazertinib significantly prolonged progression-free survival (PFS) versus osimertinib in patients with epidermal growth factor receptor (EGFR)-mutant advanced non-small-cell lung cancer [NSCLC; hazard ratio (HR) 0.70; P < 0.001], including those with a history of brain metastases (HR 0.69). Patients with TP53 co-mutations, detectable circulating tumor DNA (ctDNA), baseline liver metastases, and those without ctDNA clearance on treatment have poor prognoses. We evaluated outcomes in these high-risk subgroups. PATIENTS AND METHODS: This analysis included patients with treatment-naive, EGFR-mutant advanced NSCLC randomized to amivantamab-lazertinib (n = 429) or osimertinib (n = 429) in MARIPOSA. Pathogenic alterations were identified by next-generation sequencing (NGS) of baseline blood ctDNA with Guardant360 CDx. Ex19del and L858R ctDNA in blood was analyzed at baseline and cycle 3 day 1 (C3D1) with Biodesix droplet digital polymerase chain reaction (ddPCR). RESULTS: Baseline ctDNA for NGS of pathogenic alterations was available for 636 patients (amivantamab-lazertinib, n = 320; osimertinib, n = 316). Amivantamab-lazertinib improved median PFS (mPFS) versus osimertinib for patients with TP53 co-mutations {18.2 versus 12.9 months; HR 0.65 [95% confidence interval (CI) 0.48-0.87]; P = 0.003} and for patients with wild-type TP53 [22.1 versus 19.9 months; HR 0.75 (95% CI 0.52-1.07)]. In patients with EGFR-mutant, ddPCR-detectable baseline ctDNA, amivantamab-lazertinib significantly prolonged mPFS versus osimertinib [20.3 versus 14.8 months; HR 0.68 (95% CI 0.53-0.86); P = 0.002]. Amivantamab-lazertinib significantly improved mPFS versus osimertinib in patients without ctDNA clearance at C3D1 [16.5 versus 9.1 months; HR 0.49 (95% CI 0.27-0.87); P = 0.015] and with clearance [24.0 versus 16.5 months; HR 0.64 (95% CI 0.48-0.87); P = 0.004]. Amivantamab-lazertinib significantly prolonged mPFS versus osimertinib among randomized patients with [18.2 versus 11.0 months; HR 0.58 (95% CI 0.37-0.91); P = 0.017] and without baseline liver metastases [24.0 versus 18.3 months; HR 0.74 (95% CI 0.60-0.91); P = 0.004]. CONCLUSIONS: Amivantamab-lazertinib effectively overcomes the effect of high-risk features and represents a promising new standard of care for patients with EGFR-mutant advanced NSCLC.

T2-FLAIR mismatch sign and machine learning-based multiparametric MRI radiomics in predicting IDH mutant 1p/19q non-co-deleted diffuse lower-grade gliomas.

AIM: To investigate the application of the T2-weighted (T2)-fluid-attenuated inversion recovery (FLAIR) mismatch sign and machine learning-based multiparametric magnetic resonance imaging (MRI) radiomics in predicting 1p/19q non-co-deletion of lower-grade gliomas (LGGs). MATERIALS AND METHODS: One hundred and forty-six patients, who had pathologically confirmed isocitrate dehydrogenase (IDH) mutant LGGs were assigned randomly to the training cohort (n=102) and the testing cohort (n=44) at a ratio of 7:3. The T2-FLAIR mismatch sign and conventional MRI features were evaluated. Radiomics features extracted from T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), FLAIR, apparent diffusion coefficient (ADC), and contrast-enhanced T1WI images (CE-T1WI). The models that displayed the best performance of each sequence were selected, and their predicted values as well as the T2-FLAIR mismatch sign data were collected to establish a final stacking model. Receiver operating characteristic curve (ROC) analyses and area under the curve (AUC) values were applied to evaluate and compare the performance of the models. RESULTS: The T2-FLAIR mismatch sign was more common in the IDH mutant 1p/19q non-co-deleted group (p<0.05) and the area under the curve (AUC) value was 0.692 with sensitivity 0.397, specificity 0.987, and accuracy 0.712, respectively. The stacking model showed a favourable performance with an AUC of 0.925 and accuracy of 0.882 in the training cohort and an AUC of 0.886 and accuracy of 0.864 in the testing cohort. CONCLUSION: The stacking model based on multiparametric MRI can serve as a supplementary tool for pathological diagnosis, offering valuable guidance for clinical practice.

[Preoperative prediction of HER-2 expression status in breast cancer based on MRI radiomics model].

Objective: This study aims to explore the predictive value of T2-weighted imaging (T2WI), apparent diffusion coefficient (ADC), and early-delayed phases enhanced magnetic resonance imaging (DCE-MRI) radiomics prediction model in determining human epidermal growth factor receptor 2 status in breast cancer. Methods: A retrospective study was conducted, involving 187 patients with confirmed breast cancer by postsurgical pathology at Zhenjiang First People's Hospital during January 2021 and May 2023. Immunohistochemistry or fluorescence in situ hybridization was used to determine the HER-2 status of these patients, with 48 cases classified as HER-2 positive and 139 cases as HER-2 negative. The training set was used to construct the prediction models and the validation set was used to verify the prediction models. Layers of T2WI, ADC, and early-delayed phase DCE-MRI images were used to delineate the volumeof interest and 960 radiomic features were extracted from each case using Pyradiomic. After screening and dimensionality reduction by intraclass correlation coefficient, Pearson correlation analysis, least absolute shrinkage, and selection operator, the radiomics labels were established. Logistic regression analysis was used to construct the T2WI radiomics model, ADC radiomics model, DCE-2 radiomics model, DCE-6 radiomics model, and the joint sequence radiomics model to predict the HER-2 expression status of breast cancer, respectively. Based on the clinical, pathological, and MRI image characteristics of patients, univariate and multivariate logistic regression analysis wasused to construct a clinicopathological MRI feature model. The radscore of every patient and the clinicopathological MRI features which were statistically significant after screening were used to construct a nomogram model. The receiver operating characteristic (ROC) curve was used to evaluate the predictive performance of each model and the decision curve analysis wasused to evaluate the clinical usefulness. Results: The T2WI, ADC, DCE-2, DCE-6, and joint sequence radiomics models, the clinicopathological MRI feature model, and the nomogram model were successfully constructed to predict the expression status of HER-2 in breast cancer. ROC analysis showed that in the training set and validation set, the areas under the curve (AUC) of the T2WI radiomics model were 0.797 and 0.760, of the ADC radiomics model were 0.776 and 0.634, of the DCE-2 radiomics model were 0.804 and 0.759, of the DCE-6 radiomics model were 0.869 and 0.798, of the combined sequence radiomics model were 0.908 and 0.847, of the clinicopathological MRI feature model were 0.703 and 0.693, and of the nomogram model were 0.938 and 0.859, respectively. In the training set, the combined sequence radiomics model outperformed the clinicopathological features model (P＜0.001). In the training and validation sets, the nomogram outperformed the clinicopathological features model (P＜0.05). In addition, the diagnostic performance of the nomogram was better than that of the four single-modality radiomics models in the training cohort (P＜0.05) and was better than that of DCE-2 and ADC models in the validation cohort (P＜0.05). Decision curve analysis indicated that the value of individualized prediction models was higher than clinical and pathological prediction models in clinical practice. The calibration curve showed that the multimodal radiomics model had a high consistency with the actual results in predicting HER-2 expression. Conclusions: T2WI, ADC and early-delayed phase DCE-MRI imaging histology models for HER-2 expression status in breast cancer are expected to provide a non-invasive virtual pathological basis for decision-making on preoperative neoadjuvant regimens in breast cancer.

[A retrospective study of postoperative adjuvant therapy following immunotherapy combined with targeted therapy and sequential curative surgical procedures for initially unresectable hepatocellular carcinoma].

Objective: To report the clinical efficacy of adjuvant therapy based on pathological results following immunotherapy combined with targeted therapy and sequential curative surgical procedures in patients with initially unresectable hepatocellular carcinoma. Methods: This is a retrospective case series study. Data from 100 patients who underwent adjuvant therapy based on pathological results following immunotherapy combined with targeted therapy and sequential curative surgical procedures with long-term survival were collected from December 2018 to December 2022 at the Faculty of Hepato-Pancreato-Biliary Surgery, First Medical Center, Chinese People's Liberation Army General Hospital. According to inclusion and exclusion criteria, 47 cases were included, among which patients who met the discontinuation criteria and maintained a drug-free tumor-free status. Thirty-nine male and eight female patients were included, with an age of (54.2±18.8)years(range:38 to 73 years) at initial diagnosis. At the time of initial diagnosis, 43 cases (91.5%) were classified as Barcelona Clinic Liver Cancer stage C. Survival curves were made using Kaplan Meier method. Results: Forty-seven patients underwent R0 resection, all achieved a drug-free tumor-free state through postoperative adjuvant therapy based on pathological examination results. Thirty-six patients(76.6%) maintained a drug-free tumor-free survival status for more than 6 months,28 patients(59.6%) for more than 12 months,and 8 patients(17.0%) for more than 24 months. The longest drug-free tumor-free survival in this cohort reached 48 months. The median follow-up time in this study was 32 months. After diagnosis, the overall survival rates at 1- and 3- years were 97.7%(95%CI:93.4% to 100%) and 90.7%(95%CI:82.5% to 99.8%). The postoperative recurrence-free survival rates at 1- and 3- years were 91.0%(95%CI:83.0% to 99.8%) and 71.3%(95%CI:58.7% to 86.5%). Conclusions: The adjuvant therapy based on pathological results following immunotherapy combined with targeted therapy and sequential curative surgical approach provides long-term survival benefits for patients with initially unresectable hepatocellular carcinoma. Standardized adjuvant therapy maybe sustain long-term tumor-free status,and achieve drug-free tumor-free survival.

[Long-term outcomes of intravascular ultrasound-guided drug-eluting stents implantation in patients with acute coronary syndrome: ULTIMATE ACS subgroup].

Objective: To explore the long-term effects of intravascular ultrasound (IVUS) guidance on patients with acute coronary syndrome (ACS) undergoing drug-eluting stents (DES) implantation. Methods: Data used in this study derived from ULTIMATE trial, which was a prospective, multicenter, randomized study. A total of 1 448 all-comer patients were enrolled between 2014 August and 2017 May. Primary endpoint of this study was target vessel failure (TVF) at 3 years, including cardiac death, target-vessel-related myocardial infarction, and clinically-driven target vessel revascularization. Results: ACS was present in 1 136 (78.5%) patients, and 3-year clinical follow-up was available in 1 423 patients (98.3%). TVF in the ACS group was 9.6% (109/1 136), which was significantly higher than 4.5% (14/312) in the non-ACS group (log-rank P=0.005). There were 109 TVFs in the ACS patients, with 7.6% (43/569) TVFs in the IVUS group and 11.6% (66/567) TVFs in the angiography group (log-rank P=0.019). Moreover, patients with optimal IVUS guidance were associated with a lower risk of 3-year TVF compared to those with suboptimal IVUS results (5.4% (16/296) vs. 9.9% (27/273),log-rank P=0.041). Conclusions: This ULTIMATE-ACS subgroup analysis showed that ACS patients undergoing DES implantation were associated with a higher risk of 3-year TVF. More importantly, the risk of TVF could be significantly decreased through IVUS guidance in patients with ACS, especially in those who had an IVUS-defined optimal procedure.

Prediction of knee pain improvement over two years for knee osteoarthritis using a dynamic nomogram based on MRI-derived radiomics: a proof-of-concept study.

OBJECTIVES: To develop and validate a nomogram to detect improved knee pain in osteoarthritis (OA) by integrating magnetic resonance imaging (MRI) radiomics signature of subchondral bone and clinical characteristics. METHODS: Participants were selected from the Vitamin D Effects on Osteoarthritis (VIDEO) study. The primary outcome was 20% improvement of knee pain score over 2 years in participants administrated either vitamin D or placebo. Radiomics features of subchondral bone and clinical characteristics from 216 participants were extracted and analyzed. The participants were randomly split into the training and validation cohorts at a ratio of 8:2. Least absolute shrinkage and selection operator (LASSO) regression was used to select features and generate radiomics signatures. The optimal radiomics signature and clinical indicators were fitted into a nomogram using multivariable logistic regression model. RESULTS: The nomogram showed favorable discrimination performance [AUCtraining, 0.79 (95% CI: 0.72-0.79), AUCvalidation, 0.83 (95% CI: 0.70-0.96)] as well as a good calibration. Additional contributing value of fusion radiomics signature to the nomogram was statistically significant (NRI, 0.23; IDI, 0.14, P < 0.001 in training cohort and NRI, 0.29; IDI, 0.18, P < 0.05 in validating cohort). Decision curve analysis confirmed the clinical usefulness of nomogram. CONCLUSION: The radiomics-based nomogram comprising the MR radiomics signature and clinical variables achieves a favorable predictive efficacy and accuracy in differentiating improvement in knee pain among OA patients. This proof-of-concept study provides a promising way to predict clinically meaningful outcomes.

Prognostic value of multiphase CT angiography: estimated infarct core volume in the patients with acute ischaemic stroke after mechanical thrombectomy.

BACKGROUND AND PURPOSE: Recent studies reported the feasibility of quantifying a reliable infarct core (IC) volume using multiphase computed tomography (mCTA) based on deep learning, however its prognostic value was not fully clarified. Therefore, we aimed to evaluate the prognostic value of mCTA-estimated IC volume in patients with acute ischemic stroke (AIS) after mechanical thrombectomy (MT). MATERIALS AND METHODS: We retrospectively reviewed patients who underwent mCTA and MT for large vessel occlusion in middle cerebral artery and (or) internal carotid artery within 6 hours after symptom onset between January 2018 and November 2019. Patients were dichotomized into good (modified Rankin Scale [mRS] score, 0-2) and poor (mRS, 3-6) outcome groups. mCTA-estimated IC volume were generated based on a multi-scale three-dimensional convolutional neural network. Univariate, multivariate logistic regression and receiver operating characteristic (ROC) curve analyses were used to identify the independent variables, and evaluate their performances in predicting the clinical outcome. RESULTS: Of 44 included patients, 27 (61.4%) patients achieved good outcome. National Institutes of Health Stroke Scale scores at admission [NIHSSpre] (odds ratio [OR], 1.191; 95%confidence interval [CI], 1.028-1.379; P=0.020) and mCTA-estimated IC volume (OR, 1.076; 95%CI, 1.016-1.140; P=0.013) were found to be independently associated with functional outcome in patients with AIS after MT. After integrating NIHSSpre and mCTA-estimated IC volume, optimal performance (area under the ROC curve, 0.874; 95%CI, 0.739-0.954) could be obtained in predicting the clinical outcome. CONCLUSIONS: mCTA-estimated IC volume might be promising for predicting the prognosis, and assisting in making individualized treatment decision in patients with AIS.

How do forms and characteristics of Asian public housing neighbourhoods affect dementia risk among senior population? A cross-sectional study in Hong Kong.

BACKGROUND: Public housing estate is a key determinant of community health risk in American/European cities. However, how forms/characteristics of compact/hilly public housing's neighbourhoods affect dementia among Asian seniors was underestimated. DESIGN: This was a cross-sectional study. METHODS: A total of 2,077 seniors living in Hong Kong's public housing estates were included. Dementia was measured by a Cantonese version of Montreal - Cognitive Assessment. Built environment was measured based on three dimensions (greenery, walkability, accessibility), including 11 metrics. Circular buffers (without walking paths) and service areas (considering walking paths) with two-dimensional/three-dimensional (terrain) adjustment were applied to quantify forms/characteristics of neighbourhoods. Two spatial buffers were applied: immediate distance (200 m) and walkable distance (500 m). Exposure-by-exposure regressions were applied to evaluate the associations between form/characteristics of neighbourhood and dementia. RESULTS: Forms/characteristics without considering walking paths may overestimate health benefits from built environment. For circular buffers, higher percentage of building coverage, higher land use mix and more community/transportation/leisure facilities were negatively associated with dementia. All measures of greenery were positively associated with dementia. For service areas, measures of walkability and accessibility became insignificant except more community facilities at the immediate distance. Furthermore, terrain effect was insignificant when it was compared with the impacts of walking paths. CONCLUSION: Dementia among seniors in hilly public housing estates was negatively associated with neighbourhood's walkability and accessibility and was influenced by walking paths. For healthy ageing, improved forms/characteristics of public housing neighbourhoods should include more accessible spaces and community facilities along walking paths for physical activities and basic daily needs.

[Chinese multidisciplinary expert consensus on the management of adverse drug reactions associated with savolitinib].

MET gene is a proto-oncogene, which encodes MET protein with tyrosine kinase activity. After binding to its ligand, hepatocyte growth factor, MET protein can induce MET dimerization and activate downstream signaling pathways, which plays a crucial role in tumor formation and metastasis. Savolitinib, as a specific tyrosine kinase inhibitor (TKI) targeting MET, selectively inhibits the phosphorylation of MET kinase with a significant inhibitory effect on tumors with MET abnormalities. Based on its significant efficacy shown in the registration studies, savolitinib was approved for marketing in China on June 22, 2021 for the treatment of advanced non-small cell lung cancer with MET 14 exon skipping mutations. In addition, many studies have shown that MET TKIs are equally effective in patients with advanced solid tumors with MET gene amplification or MET protein overexpression, and relevant registration clinical studies are ongoing. The most common adverse reactions during treatment with savolitinib include nausea, vomiting, peripheral edema, pyrexia, and hepatotoxicity. Based on two rounds of extensive nationwide investigations to guide clinicians, the consensus is compiled to use savolitinib rationally, prevent and treat various adverse reactions scientifically, and improve the clinical benefits and quality of life of patients. This consensus was prepared under the guidance of multidisciplinary experts, especially including the whole-process participation and valuable suggestions of experts in Traditional Chinese Medicine, thus reflecting the clinical treatment concept of integrated Chinese and western medicines.

[Response characteristics of tislelizumab combined with chemotherapy in first-line treatment of locally advanced or metastatic non-squamous non-small cell lung cancer].

Objective: To investigate the response characteristics of patients with locally advanced/metastatic non-squamous non-small cell lung cancer (nsq-NSCLC) treated with tislelizumab in combination with chemotherapy in the first line. Methods: Patients with nsq-NSCLC who achieved complete or partial remission after treatment with tislelizumab in combination with chemotherapy or chemotherapy alone in the RATIONALE 304 study, as assessed by an independent review board, were selected to analyze the response characteristics and safety profile of the responders. Time to response (TTR) was defined as the time from randomization to the achievement of first objective response. Depth of response (DpR) was defined as the maximum percentage of tumor shrinkage compared with the sum of the baseline target lesion length diameters. Results: As of January 23, 2020, 128 patients treated with tislelizumab in combination with chemotherapy achieved objective tumor response (responders), representing 57.4%(128/223) of the intention-to-treat population, with a TTR of 5.1 to 33.3 weeks and a median TTR of 7.9 weeks. Of the responders (128), 50.8%(65) achieved first remission at the first efficacy assessment (week 6), 31.3%(40) at the second efficacy assessment (week 12), and 18.0%(23) at the third and subsequent tumor assessments. The percentages of responders who achieved a depth of tumor response of 30% to <50%, 50% to <70% and 70% to 100% were 45.3%(58/128), 28.1%(36/128) and 26.6%(34/128), respectively, with median progression-free survival (PFS) of 9.0 months (95% CI: 7.7 to 9.9 months), 11.5 months (95% CI: 7.7 months to not reached) and not reached (95% CI: 11.8 months to not estimable), respectively. Tislelizumab plus chemotherapy were generally well tolerated in responders with similar safety profile to the overall safety population. Conclusion: Among responders to tislelizumab in combination with chemotherapy for nsq-NSCLC, 82.0%(105/128) achieves response within the first two tumor assessments (12 weeks) and 18.0%(23/128) achieves response at later (18 to 33 weeks) assessments, and there is a trend toward prolonged PFS in responders with deeper tumor response.

[Establishment and validation of a risk predictive model of preoperative drug-induced limitation of pupil dilation in type 2 diabetes mellitus patients with concomitant cataract].

Objective: To establish and validate a risk predictive model of preoperative drug-induced limitation of pupil dilation (PD) in type 2 diabetes mellitus (T2DM) patients with concomitant cataract. Methods: A cross-sectional study was performed, in which 376 T2DM patients with concomitant cataract who received cataract operation in the Second Affiliated Hospital of Zhejiang University School of Medicine from October 2022 to March 2023 were randomly selected as the study subjects. Of the 376 patients, 268 who were admitted to the hospital from October to December 2022 served as the modeling group, and were divided into PD limited group (n=187) and PD unlimited group (n=81) based on whether they had drug-induced limitation of PD. Logistic regression was used to establish a risk predictive model, R software was used to draw the nomogram, Hosmer-Lemeshow test was utilized to judge the model's goodness of fit, and receiver operating characteristic (ROC) curve was adopted to validate the predicting efficacy of the model. Another 108 T2DM patients who received cataract operation in the same hospital from January to March 2023 served as the validation group, and Hosmer-Lemeshow test and ROC curve were used for the external validation of the model. Results: In the modeling group (n=268), there were 124 males and 144 females, with the mean age of (66.6±6.8) years, while in the validation group (n=108), there were 51 males and 57 females, with the mean age of (64.9±9.1) years. The incidence of preoperative drug-induced limitation of PD was 69.8% (187/268) in T2DM patients with concomitant cataract. T2DM disease course (OR=1.134, 95%CI: 1.074-1.198, P<0.001), body mass index (BMI) (OR=0.863, 95%CI: 0.767-0.972, P=0.015), glycohemoglobin (HbA1c) level (OR=1.397, 95%CI: 1.055-1.849, P=0.019) and baseline pupil dimeter (OR=0.089, 95%CI: 0.045-0.179, P<0.001) were the risk factors of drug-induced limitation of PD. Hosmer-Lemeshow test showed χ2=6.231 and P=0.621, the area under curve (AUC) of ROC curve was 0.897 (95%CI: 0.857-0.937, P<0.001), and when the Youden index was the maximum (0.655), the model's sensitivity and specificity was 0.877 and 0.778, respectively. The external validation results demonstrated that the AUC of ROC curve was 0.928 (95%CI: 0.875-0.981, P<0.001), the maximum Youden index was 0.761, the sensitivity was 0.932, the specificity was 0.829, and the overall accuracy was 89.8%. Conclusion: The risk predictive model established in the current study can provide reference for the clinical assessment of the risk of preoperative drug-induced limitation of PD in T2DM patients with concomitant cataract.

[Clinical application of a classification based on crucial curvature of coronal imbalance in degenerative lumbar scoliosis].

Objective: To present efficacy of clinical application of a classification based on crucial curvature of coronal imbalance in degenerative lumbar scoliosis (DLS). Methods: A case series study. Clinical data of 61 cases (8 males, 53 females) who underwent posterior correction surgery for DLS from January 2019 to January 2021 were retrospectively analyzed. The mean age was (71.7±6.2) years (ranged 60-82 years). According to the direction of C7 plumb line (C7PL) deviated from central sacral vertical line (CSVL) and orientation of L4 coronal tilt, the author determined which one was the crucial curve. If C7PL deviated from CSVL in the same direction as concave side of the thoracolumbar curve and L4 coronally tilts opposite direction of C7PL deviates from CSVL, then the crucial curve was thoracolumbar curve (type 1). On the contrary, if C7PL deviated from CSVL in the same direction as concave side of the lumbosacral curve and L4 coronally tilts consist with direction of C7PL deviates from CSVL, then the crucial curve was lumbosacral curve (type 2). According to absolute value of coronal balance distance (|CBD|), each type of patients was divided into two groups, respectively, namely coronal balance (CB) (|CBD|≤3 cm) and coronal imbalance (CIB) (|CBD|>3 cm). Changes of Cobb angles of thoracolumbar curve and lumbosacral curve and CBD were recorded and analyzed. Results: The rate of preoperative CIB was 55.7% (34/61) in all the patients. Of the patients, 23 cases were classified as type 1 and 38 cases as type 2. The rate of preoperative CIB was 34.8% (8/23) in type 1 patients and 68.4% (26/38) in type 2. The rate of postoperative CIB was 27.9% (17/61) in all the patients, with 13.0% (3/23) in type 1 and 36.8% (14/38) in type 2. The |CBD| of CB group in type 1 patients decreased from (2.6±1.4) cm before the operation to (1.5±1.0) cm after (P=0.015); and the correction rate of thoracolumbar curve (68.8%±18.4%) was significantly higher than that of lumbosacral curve (34.5%±23.9%) (P=0.005). The |CBD| of CB group in type 2 patients decreased from (2.6±3.0) cm before the operation to (1.6±1.2) cm after (P=0.027); the correction rate of lumbosacral curve (71.3%±18.6%) was higher than that of thoracolumbar curve (57.3%±21.1%), but the difference was not statistically significant (P=0.546). There was no significant difference in |CBD| of CIB group in type 2 patients before and after the operation (P=0.222); the correction rate of lumbosacral curve (38.3%±14.8%) was significantly lower than that of thoracolumbar curve (53.6%±16.0%) (P=0.001). There was a correlation between the change of CBD (3.8±1.5) cm and the difference in correction rate between thoracolumbar and lumbosacral curve (32.3%±19.6%) in CB group in type 1 patients after surgery (r=0.904, P<0.001). There was a correlation between the change of CBD (1.9±2.2) cm and the difference in correction rate between lumbosacral and thoracolumbar curve (14.0%±26.2%) in CB group in type 2 patients after surgery (r=0.960, P<0.001). Conclusion: Clinical application of a classification based on crucial curvature of coronal imbalance in DLS is satisfactory, and its combination with matching correction can effectively prevent the occurrence of coronal imbalance after spinal correction surgery.

[Nodal T-follicular helper cell lymphoma, angioimmunoblastic-type associated with diffuse large B-cell lymphoma: a clinicopathological study].

Objective: To investigate the clinicopathological features and molecular genetics of diffuse large B-cell lymphomas (DLBCL) with concurrent or secondary to nodal T-follicular helper cell lymphoma, angioimmunoblastic-type (nTFHL-AI). Methods: The clinicopathological features and molecular genetics of DLBCL associated with nTFHL-AI diagnosed between January 2015 and October 2022 at the First Affiliated Hospital of Zhengzhou University were analyzed using histology, immunohistochemistry, PCR, EBV-encoded RNA in situ hybridization and fluorescence in situ hybridization (FISH). Clinical information was collected and analyzed. Results: A total of 6 cases including 3 nTFHL-AI with secondary DLBCL and 3 composite lymphomas were reviewed. There were 4 male and 2 female patients, whose ages ranged from 40 to 74 years (median 57 years). All patients presented with nodal lesions at an advanced Ann Arbor stage Ⅲ/Ⅳ (6/6). Bone marrow involvement was detected in 4 patients. All cases showed typical histologic and immunophenotypic characteristics of nTFHL-AI. Among them, 5 cases of DLBCL with concurrent nTFHL-AI exhibited numerous large atypical lymphoid cells and the tumor cells were CD20 and CD79α positive. The only case of DLBCL secondary to nTFHL-AI showed plasma cell differentiation and reduced expression of CD20. All of cases were activated B-cell (ABC)/non-germinal center B-cell (non-GCB) subtype. Three of the 6 cases were EBV positive with>100 positive cells/high power field, meeting the diagnostic criteria of EBV+DLBCL. The expression of MYC and CD30 protein in the DLBCL region was higher than that in the nTFHL-AI region (n=5). C-MYC, bcl-6 and bcl-2 translocations were not detected in the 4 cases that were subject to FISH. Four of the 6 patients received chemotherapy after diagnosis. For the DLBCL cases of nTFHL-AI with secondary DLBCL, the interval was between 2-20 months. During the follow-up period ranging from 3-29 months, 3 of the 6 patients died of the disease. Conclusions: DLBCL associated with nTFHL-AI is very rare. The expansion of EBV-infected B cells in nTFHL-AI may progress to secondary EBV+DLBCL. However, EBV-negative cases have also been reported, suggesting possible other mechanisms. The up-regulation of MYC expression in these cases suggests a possible role in B-cell lymphomagenesis. Clinicians should be aware that another biopsy is still necessary to rule out concurrent or secondary DLBCL when nodal and extranodal lesions are noted after nTFHL-AI treatment.

[Research progress in stent associated respiratory tract infection].

Airway stents are commonly used to treat patients with central airway obstruction, but several complications have been identified, including mucus plugging, granulation tissue, stent migration, and infection. Stent associated respiratory tract infection (SARTI) has often been neglected by the practicing clinicians. Therefore, we reviewed the available current literatures on the diagnosis and management of stent associated respiratory tract infection.

[Definition of severe pulmonary tuberculosis: a scoping review].

Objective: To clarify the definition of severe pulmonary tuberculosis and its inclusion criteria by summarizing and analyzing the studies of severe pulmonary tuberculosis (TB). Methods: A systematic search of Medline (via PubMed), Cochrane Library, Web of Science, Web of Science, Epistemonikos, Embase, CNKI, WanFang database, and CBM database was conducted to collect studies published between 2017 and 2022 on patients with severe pulmonary TB. Searches were performed using a combination of subject terms and free words. The search terms included: tuberculosis, severe, serious, intensive care, critical care, respiratory failure, mechanical ventilation, hospitalization, respiratory distress syndrome, multiple organ failure, pulmonary heart disease, and pneumothorax. The definitions and inclusion criteria for severe pulmonary TB in the included studies were extracted. Results: A total of 19 981 studies were identified and 100 studies were finally included, involving 8 309 patients with severe pulmonary TB. A total of 8 (8.00%) studies explicitly mentioned the definition of severe pulmonary TB, and 53 (53.00%) studies clearly defined the inclusion criteria for patients with severe pulmonary TB. A total of 5 definitions and 30 inclusion criteria were extracted. A total of 132 dichotomous variables and 113 continuous variables were included in the outcome indicators related to patients with severe pulmonary TB of concern in the studies. Conclusions: The definition and diagnostic criteria for severe TB are unclear, and there is an urgent need to develop a clear definition and diagnostic criteria to guide clinical practice.

Use of MRI signal intensity ratio to differentiate between autoimmune pancreatitis and pancreatic ductal adenocarcinoma.

AIM: To evaluate the accuracy of the lesion-to-erector spinae signal intensity ratio (SIR) on magnetic resonance imaging (MRI) for distinguishing autoimmune pancreatitis (AIP) from pancreatic ductal adenocarcinoma (PDA). MATERIALS AND METHODS: The MRI data of 21 patients with AIP and 27 patients with PDA were analysed retrospectively, and the signal intensity in pancreatic lesions and erector spinae muscles at the same level on T2-weighted imaging (T2WI), arterial phase (AP) imaging, and delayed phase (DP) imaging was measured for calculation of SIRs. RESULTS: The mean SIRs of the pancreatic lesions and erector spinae from T2WI, AP, and DP images of AIP patients were 0.96, 1.27, and 1.42, respectively, while those of PDA patients were 1.35, 0.80, and 0.91, respectively. The differences in the SIRs between the AIP and PDA groups were statistically significant (p<0.001), with corresponding area under curve (AUC) values of 0.925, 0.906, and 0.961, respectively. The optimal cut-off values for the SIRs on T2WI, AP and DP images were 1.21, 1.01, and 1.08, respectively. SIR values < 1.21 on T2WI, >1.01 on AP imaging, and >1.08 on DP imaging identified AIP with sensitivities of 85.7%, 90.5%, and 90.5%, respectively, and specificities of 81.5%, 74.6%, and 81.5%, respectively. The AUC values for SIRs did not differ significantly between T2WI and DP imaging or AP and DP imaging (Z = 0.778, p=0.436; Z = 1.279, p=0.201). CONCLUSION: The SIRs of pancreatic lesions and erector spinae on T2WI, AP, and DP images can be used to differentiate AIP from PDA.

Hypoperfusion intensity ratio correlates with clinical outcome of endovascular thrombectomy in acute ischaemic stroke patients with late therapeutic window.

AIM: To evaluate the prognostic value of the hypoperfusion intensity ratio (HIR) on 90-day clinical outcome in acute ischaemic stroke (AIS) patients with late therapeutic window. MATERIALS AND METHODS: One hundred and sixty-eight consecutive AIS patients with anterior-circulation large-vessel occlusion who underwent endovascular thrombectomy during the late window were enrolled retrospectively. Clinical data, Alberta Stroke Program Early Computed Tomography Score (ASPECTS) based on unenhanced computed tomography (CT), and perfusion parameters included ischaemic core, hypoperfusion volume, mismatch volume between core and penumbra, and the HIR were assessed and compared between patients with or without favourable outcomes (defined as modified Rankin Scale score of 0-2). Statistical analysis included binary logistic regression and receiver operating characteristic (ROC) analyses. RESULTS: A favourable outcome was achieved in 76 (45.2%) patients. In univariable analysis, age, National Institutes of Health Stroke Scale (NIHSS) score at admission, ASPECTS score, HIR, ischaemic core, and hypoperfusion volume were significantly associated with functional outcome (p<0.05). In multivariate analyses, age (OR 0.95; 95% CI 0.92-0.99), NIHSS score at admission (OR 0.89, 95% CI 0.84-0.96) and HIR (OR 0.018, 95% CI 0.003-0.113) remained as independent outcome predictors (p<0.01). The optimal threshold of HIR was 0.36 (sensitivity 70.7%, specificity 61.8%). The combination of age, NIHSS score at admission, and HIR yield good performance for outcome prediction with an area under the ROC curve of 0.815 (sensitivity 88.2%, specificity 64.1%), significantly higher than individual variable (p<0.05). CONCLUSION: Low HIR was a predictor for favourable outcome in AIS patients with late therapeutic window. Integrating HIR with clinical variables improved the ability for outcome classification.

A single-arm pilot of a web-based intervention to improve itch-related quality of life.

BACKGROUND: Many patients with chronic itch and atopic dermatitis (AD) or psoriasis do not receive/use available medical and psychosocial treatments properly due to system, provider and/or patient factors. OBJECTIVE: An educational website (ITCH-RELIEF) to improve itch-related quality of life (QoL) for adults with AD or psoriasis and chronic itch was developed and assessed. ITCH RELIEF stands for Interactive Toolbox of Comprehensive Health Resources to Enhance Living with Itch - Educational Facilitation (for Adults). METHODS: Single-arm pre- and post-test design with 1-month follow-up (N = 137 at baseline). RESULTS: There was statistically and clinically significant improvement in the primary outcome of itch-related QoL impairment as assessed by the ItchyQoL from baseline [M = 78.9, 95% confidence interval (CI) = 75.9, 81.9] to follow up (M = 75.4, CI = 72.4, 78.5), P = 0.007, as well as statistically significant improvement in several itch-related secondary outcomes (all Ps < 0.05). CONCLUSIONS: This study demonstrated initial effectiveness of an online intervention to improve itch-related QoL among individuals with AD or psoriasis and chronic itch. Future studies should address limitations by randomizing more heterogeneous participants, utilizing a longer follow-up and assessing medication use.

Pregnancy of cryopreserved ovine embryos at different developmental stages.

BACKGROUND: Developmental stage and cryopreservation method have significant impact on the pregnancy rate after transfer of embryos produced in vivo. OBJECTIVE: To determine the pregnancy outcomes from ovine embryos cryopreserved at different developmental stages. MATERIALS AND METHODS: Embryos at different developmental stages were obtained from donor ewes through simultaneous estrus treatment and laparoscopic artificial insemination. Embryos, either cryopreserved via vitrification or slow freezing method, were implanted into recipient ewes. The pregnancy rate was determined 35 days after transfer. RESULTS: The pregnancy rate of developing embryos increases after transfer from the morula stage, early blastocyst to expanded blastocyst stages (64.9%, 73.9% and 81.3%, respectively). However, cryopreservation significantly decreases the pregnancy rate of embryos at all three developmental stages, and there is no significant difference among developmental stages (43.9%, 43.7%, 52.9%, respectively). There is also no significant difference in the pregnancy rate between slowly-frozen embryos and vitrified embryos. CONCLUSION: The pregnancy outcomes of embryo transfer is better at the expanded blastocyst stage than at earlier stages. However, no difference is observed in the pregnancy rate of embryos at different developmental stage after cryopreservation, either by slow freezing and vitrification. Cryopreservation methods for ovine embryos, both slow freezing and vitrification, need further improvement. doi.org/10.54680/fr22510110512.

Sequence analyses of mitochondrial gene may support the existence of cryptic species within Ascaridia galli.

Ascaridia galli (Nematoda: Ascaridiidae) is the most common intestinal roundworm of chickens and other birds with a worldwide distribution. Although A. galli has been extensively studied, knowledge of the genetic variation of this parasite in detail is still insufficient. The present study examined genetic variation in the mitochondrial cytochrome c oxidase subunit 1 (cox1) gene among A. galli isolates (n = 26) from domestic chickens in Hunan Province, China. A portion of the cox1 (pcox1) gene was amplified by polymerase chain reaction separately from adult A. galli individuals and the amplicons were subjected to sequencing from both directions. The length of the sequences of pcox1 is 441 bp. Although the intra-specific sequence variation within A. galli is 0-7.7%, the inter-specific sequence differences among other members of the infraorder Ascaridomorpha were 11.4-18.9%. Phylogenetic analyses based on the maximum likelihood method using the sequences of pcox1 confirmed that all of the Ascaridia isolates were A. galli, and also resolved three distinct clades. Taken together, the findings suggest that A. galli may represent a complex of cryptic species. Our results provide an additional genetic marker for the management of A. galli in chickens and other birds.