Robotic-assisted differential total knee arthroplasty with patient-specific implants: surgical techniques and preliminary results.

OBJECTIVE: In total knee arthroplasty (TKA), achieving soft-tissue balance while retaining acceptable lower limb alignment is sometimes difficult and may lead to patient dissatisfaction. Theoretically, patient-specific implants can bring great benefits, while the lack of precise surgical tools may hinder the improvement of outcomes. The objective of this study was to illustrate surgical techniques and evaluate kinematics and early clinical outcomes of robotic-assisted TKA using patient-specific implants. METHODS: Based on preoperative CT scan, femoral and tibial components were 3D printed. Medial and lateral tibial liners were separate with different thicknesses, posterior slopes and conformity. TiRobot Recon Robot was used for surgery, and was armed with smart tools that quantify gap, force and femoral-tibial track. We collected data on demographics, intraoperative gap balance and femoral-tibial motion. In the follow-up, we evaluated the range of motion, Visual Analogue Scale (VAS), forgotten joint score (FJS), Knee injury and Osteoarthritis Outcome Score, Joint Replacement (KOOS, JR) score. Radiological data were also harvested. RESULTS: Fifteen patients (17 knees) were enrolled with a mean age of 64.6 ± 6.4 (53-76) years. In 5 knees, we used symmetric tibial liners, the rest were asymmetric. After surgery, the average alignment was 1.6 ± 2.0 (-3-5) degrees varus. The average follow-up lasted 6.7 ± 4.2 (1-14) months. The mean visual analogue scale was 0.8 ± 0.7 (0-2), FJS was 62.4 ± 25.3 (0-87), KOOS was 86.5 ± 9.4 (57-97). 11 patients were "very satisfied", 3 were "satisfied" with the result, and one patient was neutral due to restricted extension and unsatisfactory rehabilitation at five months' follow-up. CONCLUSIONS: With patient-specific implants and robotics, TKA could be performed by a mathematical way, which was dubbed a "differential" TKA. Intraoperative kinematics was excellent in terms of gap-force balancing and femoral-tibial relative motion. Preliminary clinical outcomes were overall satisfactory.

The application of deep learning in abdominal trauma diagnosis by CT imaging.

BACKGROUND: Abdominal computed tomography (CT) scan is a crucial imaging modality for creating cross-sectional images of the abdominal area, particularly in cases of abdominal trauma, which is commonly encountered in traumatic injuries. However, interpreting CT images is a challenge, especially in emergency. Therefore, we developed a novel deep learning algorithm-based detection method for the initial screening of abdominal internal organ injuries. METHODS: We utilized a dataset provided by the Kaggle competition, comprising 3,147 patients, of which 855 were diagnosed with abdominal trauma, accounting for 27.16% of the total patient population. Following image data pre-processing, we employed a 2D semantic segmentation model to segment the images and constructed a 2.5D classification model to assess the probability of injury for each organ. Subsequently, we evaluated the algorithm's performance using 5k-fold cross-validation. RESULTS: With particularly noteworthy performance in detecting renal injury on abdominal CT scans, we achieved an acceptable accuracy of 0.932 (with a positive predictive value (PPV) of 0.888, negative predictive value (NPV) of 0.943, sensitivity of 0.887, and specificity of 0.944). Furthermore, the accuracy for liver injury detection was 0.873 (with PPV of 0.789, NPV of 0.895, sensitivity of 0.789, and specificity of 0.895), while for spleen injury, it was 0.771 (with PPV of 0.630, NPV of 0.814, sensitivity of 0.626, and specificity of 0.816). CONCLUSIONS: The deep learning model demonstrated the capability to identify multiple organ injuries simultaneously on CT scans and holds potential for application in preliminary screening and adjunctive diagnosis of trauma cases beyond abdominal injuries.

Protocol to identify DNA-binding proteins recognizing nucleotide repeat dsDNAs.

DNA-binding proteins perform diverse functions, including regulating cellular growth and orchestrating chromatin architecture. Here, we present a protocol to discover proteins specifically interacting with a hexanucleotide repeat DNA, the expansion of which is known as the most frequent genetic cause of familial C9orf72 amyotrophic lateral sclerosis and frontotemporal dementia. We describe steps to fish out DNA-binding proteins recognizing double-stranded repeat DNAs using a SILAC (stable isotope labelling by amino acids in cell culture)-based approach and validate the results using electrophoretic mobility shift assay. For complete details on the use and execution of this protocol, please refer to Liu et al.1.

Development of dynamic nomogram for predicting cancer-specific survival in hepatoid adenocarcinoma: A comprehensive SEER-based population analysis.

Hepatoid adenocarcinoma (HAC) is a poorly differentiated extrahepatic tumor that can produce alpha-fetoprotein (AFP). The literature does not provide a comprehensive understanding of the prognostic factors for HAC. Therefore, we present a novel nomogram to predict the cancer-specific survival (CSS) of patients with HAC. We analyzed 265 cases of HAC from the Surveillance, Epidemiology, and End Results (SEER) database spanning from 2004 to 2015. Using a Cox proportional hazard regression model, we identified several risk factors and incorporated them into our predictive nomogram. The nomogram's predictive ability was assessed by utilizing the concordance index (C-index), calibration curve, and receiver operating characteristic (ROC). Results from a multivariate Cox regression showed that CSS was independently correlated with liver metastasis, surgery, and chemotherapy. Our nomogram had a C-index of 0.71 (95% CI 0.71-0.96). Furthermore, calibration curves demonstrated concordance between the predicted survival probability from the nomogram and the observed survival probability. The areas under the curve (AUC) for 6-month, 1-, and 3-year survival were 0.80, 0.82, and 0.88, respectively. Our study successfully formulated a prognostic nomogram that offers promising predictions for the 6-month, 1-, and 3-year CSS of patients with HAC. This nomogram holds potential for practical use in guiding treatment decisions and designing clinical trials.

Neoadjuvant-Adjuvant vs Neoadjuvant-Only PD-1 and PD-L1 Inhibitors for Patients With Resectable NSCLC: An Indirect Meta-Analysis.

Importance: Neoadjuvant therapy combining programmed cell death 1 (PD-1) and programmed death ligand 1 (PD-L1) inhibitors with platinum-based chemotherapy has demonstrated significant improvement in pathologic response and survival rates among patients with resectable non-small cell lung cancer (NSCLC). However, it remains controversial whether PD-1 blockade therapy given before and after surgery (neoadjuvant-adjuvant treatment) is associated with better outcomes than when given only before surgery (neoadjuvant-only treatment). Objective: To compare the efficacy and safety associated with neoadjuvant-adjuvant anti-PD-1 and anti-PD-L1 therapy with neoadjuvant-only anti-PD-1 and anti-PD-L1 therapy for patients with resectable NSCLC. Data Sources: A systematic search was conducted across databases including PubMed, Embase, and the Cochrane Library, as well as major oncology conferences, through July 31, 2023. Study Selection: Randomized clinical trials comparing neoadjuvant-adjuvant or neoadjuvant-only PD-1 and PD-L1 inhibitor therapy vs chemotherapy alone for patients with resectable NSCLC were selected. Data Extraction and Synthesis: Following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline, 2 authors independently extracted data. Hazard ratios (HRs) and 95% CIs for event-free survival (EFS) and overall survival (OS) were extracted and then pooled through the generic inverse-variance methods. Relative risks (RRs) for treatment-related adverse events (TRAEs) were derived via the Mantel-Haenszel method. Using chemotherapy as a common comparator, indirect comparisons between neoadjuvant-adjuvant immunotherapy and neoadjuvant-only immunotherapy were conducted using frequentist methods. A random or fixed model was used based on intertrial heterogeneity identified through the Cochran Q test. Main Outcomes and Measures: The primary outcome was EFS, with secondary outcomes including OS and TRAEs. Results: The study encompassed 4 trials of neoadjuvant-adjuvant immunotherapy and 1 trial of neoadjuvant-only immunotherapy, involving 2385 patients. Direct meta-analysis revealed significant improvements in EFS for both neoadjuvant-adjuvant and neoadjuvant-only immunotherapy compared with chemotherapy alone. In indirect meta-analysis, the addition of adjuvant immunotherapy to neoadjuvant immunotherapy was not associated with improved EFS (HR, 0.90; 95% CI, 0.63-1.30; P = .59) or OS (HR, 1.18; 95% CI, 0.73-1.90; P = .51) compared with neoadjuvant-only immunotherapy. Moreover, the incidence of any grade of TRAEs significantly increased with the addition of adjuvant immunotherapy (RR, 1.08; 95% CI, 1.00-1.17; P = .04). Conclusions and Relevance: This meta-analysis suggests that adding PD-1 or PD-L1 inhibitors in the adjuvant phase to neoadjuvant treatment with PD-1 or PD-L1 inhibitors and chemotherapy may not improve survival outcomes for patients with resectable NSCLC and may be associated with increased adverse events. Future validation of these findings is warranted through head-to-head randomized clinical trials.

Computational screening of biomarkers and potential drugs for arthrofibrosis based on combination of sequencing and large nature language model.

Background: Arthrofibrosis (AF) is a fibrotic joint disease resulting from excessive collagen production and fibrous scar formation after total knee arthroplasty (TKA). This devastating complication may cause consistent pain and dramatically reduction of functionality. Unfortunately, the conservative treatments to prevent the AF in the early stage are largely unknown due to the lack of specific biomarkers and reliable therapeutic targets. Methods: In this study, we extracted1782 fibrosis related genes (FRGs) from 373,461published literature based on the large natural language processing models (ChatGPT) and intersected with the 2750 differential expressed genes (DEGs) from mRNA microarray (GSE135854). A total of 311 potential AF biomarker genes (PABGs) were obtained and functional analysis were performed including gene ontology (GO) annotation and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Subsequently, we accomplished validation in AF animal models with immobilization of the unilateral knee joints of 16 rabbits for 1-week, 2-weeks, 3-weeks and 4-weeks. Finally, we tested the biomarkers in a retrospective cohort enrolled 35 AF patients and 35 control group patients. Results: We identified G-protein-coupled receptor 17 (GPR17) as a reliable therapeutic biomarker for AF diagnosis with higher AUC (0.819) in the ROC curve. A total of 21 potential drugs targeted to GPR17 were screened. Among them, pranlukast and montelukast have achieved therapeutic effect in animal models. In addition, we established an online AF database for data integration (https://chenxi2023.shinyapps.io/afdbv1). Conclusions: These results unveiling therapeutic biomarkers for AF diagnosis, and provide potential drugs for clinical treatment. The translational potential of this article: Our study demonstrated that GPR17 holds significant promise as a potential biomarker and therapeutic target for arthrofibrosis. Moreover, pranlukast and montelukast targeted to GPR17 that could be instrumental in the treatment of AF.

Variety of femoral anteversion and its measurement in cementless total hip arthroplasty: Does robotic technology improve accuracy?

BACKGROUND: High-performance total hip arthroplasty (THA) depends on the accurate position of components. However, femoral anteversion is variable, and current studies only used traditional instruments to evaluate it, such as protractor and spirit level with limited cases. This study aimed to identify the variability in the measured femoral native anteversion and intraoperative stem anteversion under different measurement methods, including intraoperative robotic method. We hypothesized that robotic technology was more accurate than traditional instruments for femoral anteversion evaluation. METHODS: This study included 117 hips of patients who underwent robotic-assisted THA between November 2019 and March 2021. Preoperative native femoral anteversion was measured using a robotic system. Intraoperative femoral stem anteversion was evaluated visually, and then measured with a goniometer and a robotic system, respectively. Variability in the measured femoral native anteversion and intraoperative femoral stem anteversion was calculated and compared. Intraclass correlation coefficient (ICC) and Pearson correlation analysis were used to assess the consistency and correlation of anteversion of different measurements and postoperative CT-measured stem anteversion, respectively. RESULTS: The result of measurement for preoperative native femoral anteversion was more variable than the intraoperative robotic-measured stem anteversion. Intraoperative robotic-measured stem version showed the highest correlation with postoperative CT measurement of stem version (r = 0.806, P < 0.001), while intraoperative surgeon estimation had the lowest correlation coefficient (r = 0.281, P = 0.025). As for the consistency with postoperative CT measurement of femoral stem anteversion, the intraoperative robotic-measured femoral stem version also had the highest value (ICC = 0.892, P < 0.001). CONCLUSION: Native femoral anteversion was variable preoperatively. Using cementless stems, anteversion was also highly variable. Robotic assessment for stem anteversion during surgery was more consistent with the final position than the preoperative assessment and conventional intraoperative estimation.

Dynamic evolution of antibiotic resistance genes in plastisphere in the vertical profile of urban rivers.

Microplastics (MPs) can vertically transport in the aquatic environment due to their aging and biofouling, forming distinct plastisphere in different water layers. However, even though MPs have been regarded as hotspots for antibiotic resistance genes (ARGs), little is known about the propagation and transfer of ARGs in plastisphere in waters, especially in the vertical profile. Therefore, this study investigated the dynamic responses and evolution of ARGs in different plastisphere distributed vertically in an urbanized river. The biofilm biomass in the polylactic acid (PLA) plastisphere was relatively higher than that in the polyethylene terephthalate (PET), showing depth-decay variations. The ARGs abundance in plastisphere were much higher than that in the surrounding waters, especially for the PLA. In the vertical profiles, the ARGs abundance in the PET plastisphere increased with water depths, while the highest abundance of ARGs in the PLA mostly appeared at intermediate waters. In the temporal dynamic, the ARGs abundance in plastisphere increased and then decreased, which may be dominated by the MP types at the initial periods. After long-term exposure, the influences of water depths seemed to be strengthened, especially in the PET plastisphere. Compared with surface waters, the microbiota attached in plastisphere in deep waters showed high species richness, strong diversity, and complex interactions, which was basically consistent with the changes of nutrient contents in different water layers. These vertical variations in microbiota and nutrients (e.g., nitrogen) may be responsible for the propagation of ARGs in plastisphere in deep waters. The host bacteria for ARGs in plastisphere was also developed as water depth increased, leading to an enrichment of ARGs in deep waters. In addition, the abundance of ARGs in plastisphere in bottom waters was positively correlated with the mobile genetic elements (MGEs) of intI1 and tnpA05, indicative of a frequent horizontal gene transfer of ARGs. Overall, water depth played a critical role in the propagation of ARGs in plastisphere, which should not be ignored in a long time series. This study provides new insights into the dynamic evolution of ARGs propagation in plastisphere under increasing global MPs pollution, especially in the vertical profile.

Association of radiological severity of hip involvement with clinical characteristics and sagittal spinopelvic balance in patients with ankylosing spondylitis.

INTRODUCTION: This is the first study to analyze the associations between the radiological severity of hip involvement with clinical characteristics and sagittal spinopelvic balance in patients with ankylosing spondylitis (AS). METHOD: We evaluated 182 patients with AS who were referred to outpatient clinics. Patient demographic data and clinical and radiographic parameters were collected. Patients were divided into three groups based on the Bath Ankylosing Spondylitis Radiology Hip Index. Clinical characteristics and spinopelvic parameters acquired by a low-dose biplanar imaging system were evaluated among these groups. RESULTS: Patients with more severe hip involvement were older and had longer disease duration and diagnostic delay, with lower Harris Hip Score (p < 0.001) and 12-item Short Form Health Survey Physical Component Score (p < 0.001) and higher Bath Ankylosing Spondylitis Disease Activity Index (p = 0.030) and Functional Index (p < 0.001). Patients with more severe hip involvement had significantly higher sacroiliac grade (p < 0.001) and higher modified Stoke Ankylosing Spondylitis Spinal Score (p < 0.001). Patients with moderate and severe hip involvement had similar lumbar lordosis and spino-sacral angle, whereas patients with severe hip involvement had lower pelvic tilt, pelvic femoral angle, higher sacral slope, and sagittal vertical axis. CONCLUSIONS: The severity of hip involvement is associated with physical function and is not consistent with the severity of spinal involvement. Severe hip involvement impairs the ability to retrovert the pelvis to accommodate the sagittal deformity, and spinopelvic parameters should be concretely evaluated in preoperative counseling of patients with AS waiting for total hip arthroplasty. Key Points • The severity of hip involvement in patients with AS is associated with physical function. • Severe hip involvement impairs the ability to retrovert the pelvis to accommodate the sagittal deformity.

A patient-specific algorithm for predicting the standing sagittal pelvic tilt one year after total hip arthroplasty.

Aims: The aim of this study was to evaluate the reliability and validity of a patient-specific algorithm which we developed for predicting changes in sagittal pelvic tilt after total hip arthroplasty (THA). Methods: This retrospective study included 143 patients who underwent 171 THAs between April 2019 and October 2020 and had full-body lateral radiographs preoperatively and at one year postoperatively. We measured the pelvic incidence (PI), the sagittal vertical axis (SVA), pelvic tilt, sacral slope (SS), lumbar lordosis (LL), and thoracic kyphosis to classify patients into types A, B1, B2, B3, and C. The change of pelvic tilt was predicted according to the normal range of SVA (0 mm to 50 mm) for types A, B1, B2, and B3, and based on the absolute value of one-third of the PI-LL mismatch for type C patients. The reliability of the classification of the patients and the prediction of the change of pelvic tilt were assessed using kappa values and intraclass correlation coefficients (ICCs), respectively. Validity was assessed using the overall mean error and mean absolute error (MAE) for the prediction of the change of pelvic tilt. Results: The kappa values were 0.927 (95% confidence interval (CI) 0.861 to 0.992) and 0.945 (95% CI 0.903 to 0.988) for the inter- and intraobserver reliabilities, respectively, and the ICCs ranged from 0.919 to 0.997. The overall mean error and MAE for the prediction of the change of pelvic tilt were -0.3° (SD 3.6°) and 2.8° (SD 2.4°), respectively. The overall absolute change of pelvic tilt was 5.0° (SD 4.1°). Pre- and postoperative values and changes in pelvic tilt, SVA, SS, and LL varied significantly among the five types of patient. Conclusion: We found that the proposed algorithm was reliable and valid for predicting the standing pelvic tilt after THA.

Efficacy and safety analysis of a HER2-targeting antibody-drug conjugate combined with immune checkpoint inhibitors in solid tumors: a real-world study.

BACKGROUND: Disitamab Vedotin is a novel antibody-drug conjugate (ADC) drug targeting HER2, which has shown a potential synergistic effect between Disitamab Vedotin and immune checkpoint inhibitors (ICIs). Therefore, we plan to conduct a retrospective real-world study to evaluate the efficacy and safety of Disitamab Vedotin monotherapy or combined with ICIs in the treatment of advanced or metastatic solid tumors. METHODS: This retrospective study involved patients with locally advanced or metastatic solid tumors who were treated with Disitamab Vedotin monotherapy or combined with ICIs at West China Hospital of Sichuan University from July 2019 to June 2023. The observation items included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events (TRAEs). RESULTS: This study included 49 patients, out of which 34 patients were treated with Disitamab Vedotin plus ICIs and 15 patients received Disitamab Vedotin alone. In all patients, the median PFS was 10 months. The 6-month and 1-year OS rates were 91.1% and 82.3%, respectively. Eighteen (36.7%) patients achieved a partial response, and sixteen (32.7%) patients had stable disease. The combination therapy of Disitamab Vedotin plus ICIs showed a higher ORR (44.1% vs. 20.0%) and a longer median PFS (14 vs. 8 months) compared to Disitamab Vedotin alone. The median PFS for patients expressed with HER2 2+/3+ was 10 months and was not reached for patients expressed with HER2 0/1+. Grade 3-4 TRAEs occurred in 14.7% of patients who received the combination treatment and in 26.7% of patients who received Disitamab Vedotin alone. CONCLUSIONS: Our study showed that Disitamab-Vedotin-based treatment, alone or in combination with ICIs, exerted considerable prognosis and good tolerance in patients with locally advanced or metastatic solid tumors, regardless of the HER2 expression levels. Whether combination therapy with ICIs provides greater therapeutic benefits compared to monotherapy needs to be further explored through randomized controlled trials.

Using sequential bone cutting to titrate soft tissue balance in total knee arthroplasty effectively minimizes soft tissue release.

BACKGROUND: Achieving soft tissue balance while maintaining limb alignment within acceptable boundaries is crucial for successful total knee arthroplasty (TKA). We proposed a sequential bone cutting (SBC) technique to titrate the soft tissue balance in robot-assisted TKA to achieve the desired balance with minimum soft tissue release. METHODS: In total, 106 robot-assisted TKAs using the SBC technique were included. The preoperative hip-knee-ankle angle (HKA) was < 10° in 76 and ≥ 10° in 30 knees. The gaps were initially balanced with the help of the pre-resection balancing provided by the robotic system. Soft tissue balance and alignment were quantitatively measured after the initial bone cutting and final bone cutting. Additional adjustments (bone recuts and soft tissue releases) required to address soft tissue imbalance after initial bone cutting were recorded. The frequencies of soft tissue releases, soft tissue balance, and resultant alignment ≤ 3° were compared between non-severe (HKA < 10°) and severe deformity (HKA ≥ 10°) groups. RESULTS: Soft tissue balance was achieved in 45 knees (42.5%) after initial bone cutting and in 93 knees (87.7%) after final balancing. The postoperative alignment was within 3° from neutral in 87 knees (82.1%) and 3-5° in 17 knees (16.0%). For unbalanced knees (n = 61) after initial bone cutting, soft tissue release was avoided by SBC in 37 knees (60.7%) and was deemed necessary in 24 knees (39.3%). Soft tissue release was more likely to be avoided in the non-severe deformity cohort (86.8% [33 of 38]) than in the severe deformity cohort (17.4% [4 of 23]; p < 0.001). The non-severe deformity cohort showed a significantly higher rate of resultant alignment ≤ 3° from neutral than the severe deformity cohort (90.8% vs. 60.0%; p < 0.001). CONCLUSION: Pre-resection balancing is inappropriate to ensure soft tissue balance. The SBC technique is effective in minimizing soft tissue release while maintaining overall alignment within acceptable boundaries.

Personalised neoantigen-based therapy in colorectal cancer.

Colorectal cancer (CRC) has become one of the most common tumours with high morbidity, mortality and distinctive evolution mechanism. The neoantigens arising from the somatic mutations have become considerable treatment targets in the management of CRC. As cancer-specific aberrant peptides, neoantigens can trigger the robust host immune response and exert anti-tumour effects while minimising the emergence of adverse events commonly associated with alternative therapeutic regimens. In this review, we summarised the mechanism, generation, identification and prognostic significance of neoantigens, as well as therapeutic strategies challenges of neoantigen-based therapy in CRC. The evidence suggests that the establishment of personalised neoantigen-based therapy holds great promise as an effective treatment approach for patients with CRC.

Impact of prophylactic dexamethasone on the efficacy of immune checkpoint inhibitors plus platinum-based chemotherapy in patients with advanced Non-Squamous Non-Small-Cell lung cancer.

BACKGROUND: Baseline corticosteroids exposure is associated with inferior clinical outcomes in patients with non-small-cell lung cancer (NSCLC) treated with programmed cell death-1 (PD-1) axis blockade. Dexamethasone is a potent corticosteroid used in the prevention of chemotherapy-associated adverse events (CAAEs). OBJECTIVE: Since dexamethasone has immunosuppressive properties, this study attempted to elucidate its effects on the efficacy of immunotherapy plus chemotherapy in patients with non-squamous NSCLC. METHODS: The study retrospectively analyzed the medical records of 254 advanced non-squamous NSCLC patients who received front-line treatment with a PD-1 pathway inhibitor and platinum-based chemotherapy at three academic institutions. The average dosage of prophylactic dexamethasone per chemotherapy cycle was calculated. Patients were divided into three groups based on the dose of dexamethasone: High-d (≥24 mg), Moderate-d (12-24 mg), and Low-d (<12 mg). Spearman's rank correlation was used to assess the correlation between the dosage of dexamethasone and progression-free survival (PFS). Logistic regression was used to assess the correlation between dexamethasone dosage and the occurrence of immune related adverse effects (irAE). Univariate and multivariate Cox proportional hazards regression models were used to analyze the differences in survival among the different dexamethasone dosage groups. RESULT: The dosage of prophylactic dexamethasone was not significantly correlated with PFS (Spearman's rho = -0.103, P = 0.098). Results from the univariate [hazard ratio (HR)Low-d/High-d, 1.00; P = 0.997; HRModerate-d/High-d, 0.85; P = 0.438] and multivariate (HRLow-d/High-d, 0.71; P = 0.174; HRModerate-d/High-d, 0.87; P = 0.512) analyses showed no significant association between dexamethasone and PFS. Dexamethasone did not have significant effect on the objective response rate, disease control rate or overall survival. The toxicity profiles of irAE were similar across all three groups. CONCLUSION: The results of this study suggest that the use of prophylactic dexamethasone does not have an adverse effect on the clinical outcomes of non-squamous NSCLC patients treated with PD-1 blockade therapy and chemotherapy. Routine use of dexamethasone for preventing CAAEs should be recommended for patients undergoing combined immunotherapy and chemotherapy.

Tumor response assessment by measuring the single largest lesion per organ in advanced non-small cell lung cancer patients treated with PD-1/PD-L1 inhibitor.

Background: For Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST1.1), measuring up to two target lesions per organ is an arbitrary criterion. Objectives: We sought to compare response assessment using RECIST1.1 and modified RECIST1.1 (mRECIST1.1, measuring the single largest lesion per organ) in advanced non-small cell lung cancer (aNSCLC) patients undergoing anti-PD-1/PD-L1 monotherapy. Methods: Concordance of radiologic response categorization between RECIST1.1 and mRECIST1.1 was compared using the Kappa statistics. C-index was calculated to evaluate prognostic accuracy of radiologic response by the two criteria. The Kaplan-Meier method and Cox regression analysis were conducted for progression-free survival (PFS) and overall survival (OS). Results: Eighty-seven patients who had at least two target lesions in any organ per the RECIST1.1 were eligible for comparison analysis. Tumor response showed excellent concordance when measured using the RECIST1.1 and mRECIST1.1 (Kappa = 0.961). C-index by these two criteria was similar for PFS (0.784 versus 0.785) and OS (0.649 versus 0.652). Responders had significantly longer PFS and OS versus non-responders (p < 0.05), whichever criterion adopted. Radiologic response remained a significant predictor of PFS and OS in multivariate analysis (p < 0.05). Conclusion: The mRECIST1.1 was comparable to RECIST1.1 in response assessment among aNSCLC patients who received single-agent PD-1/PD-L1 inhibitor. The mRECIST1.1, with reduced number of lesions to be measured, may be sufficient and more convenient to assess antitumor activity in clinical practice.

High tibial lateral closing wedge and opening wedge valgus osteotomy produce different effects on posterior tibial slope and patellar height.

Objective: To compare the clinical outcomes of performing a closed tibial high osteotomy with an open osteotomy and the changes in posterior tibia slope and patellar height. Methods: Methods were collected from three hundred and forty patients (440 knees) with high tibial osteotomy performed from January 2019 to January 2020. Forty patients (50 knees) had a lateral closed wedge tibial osteotomy (LCWHTO), and 300 patients (390 knees) had a medial open wedge tibial osteotomy (MOWHTO). The follow-up periods were 20.5 months and 19.9 months, respectively. At the final follow-up visit, both groups evaluated the Lysholm score and joint range of motion (ROM). Changes in preoperative and postoperative mechanical axis deviation (MAD), proximal medial tibial angle (MPTA), posterior tibial slope (PTS), and M-K index were compared between the two groups of patients. Results: Lysholm scores were 79.6 ± 15.6 preoperatively and 96.0 ± 5.0 postoperatively in the LCWHTO group (p < 0.01); 83.7 ± 16.0 preoperatively and 94.3 ± 9.1 postoperatively in the MOWHTO group (p < 0.01). ROM was 136.0° ± 8.4° preoperatively and 133.2° ± 10.1° postoperatively in the LCWHTO group (p > 0.05); 136.5° ± 8.4° preoperatively and 135.7° ± 9.3° postoperatively in the MOWHTO group (p > 0.05). the MAD was (26.5 ± 4.1) mm preoperatively and 0.3 ± 2.9 mm postoperatively in the LCWHTO group (p < 0.01); 21.8 ± 6.5 mm preoperatively and -0.3 ± 2.6 mm postoperatively in the MOWHTO group (p < 0.01). The MPTA in the LCWHTO group was 75.3° ± 3.2° preoperatively and 89.5° ± 2.4° postoperatively (p < 0.01). 77.1° ± 3.0° preoperatively and 90.6° ± 2.7° postoperatively in the MOWHTO group (p < 0.01). M-K index was 0.78 ± 0.08 preoperatively and 0.79 ± 0.07 postoperatively in the LCWHTO group (p > 0.05). 0.78 ± 0.05 before and 0.75 ± 0.05 after surgery in the MOWHTO. 10.8° ± 3.0° PTS before and 8.1° ± 3.4° after surgery in the LCWHTO group (p < 0.05); 10.2° ± 3.1° preoperatively and 10.9° ± 4.0° postoperatively (p > 0.05). Conclusions: LCWHTO decreases the PTS and has no effect on patellar height; MOWHTO does not affect the PTS but decreases patellar height. The patient should individualize the choice of the osteotomy.

Management of soft tissues in patients with periprosthetic joint infection.

BACKGROUND: Appropriate soft tissue management represents a critical step in treating periprosthetic joint infection (PJI). This review discusses relevant guidelines that surgeons should follow in the management of soft tissues in PJI treatment. BODY: It is imperative for arthroplasty surgeons to thoroughly debride and rebuild soft tissue with a good blood supply. Relevant guidelines that surgeons should follow rigorously include preoperative evaluation of soft tissue status and plan-making, adequate surgical area exposure, intraoperative removal of all necrotic and infected soft tissues, adequate coverage of soft tissue defects, timely postoperative assessment and management of soft tissues, wound management and proper rehabilitation. CONCLUSION: Soft tissue management plays a critical role in the treatment of PJI. To improve the infection control rate and postoperative joint function, surgeons should be familiar with these general principles and rigorously practice them in PJI management.

Using novel porous metal pillars for tibial bone defects in primary total knee arthroplasty.

BACKGROUND: The optimal method to treat tibial bone defects during primary total knee arthroplasty (TKA) is still unclear. A novel technique of porous metal pillar augmentation has been applied recently. This study aimed to assess the short-term outcomes of primary TKA with the use of novel porous metal pillars for tibial bone defects. METHODS: A total of 24 cases (22 patients) of primary TKA between January 2019 and December 2020 using porous metal pillars for tibial bone defects were reviewed. Clinical results were evaluated using the Knee Society knee score (KSKS) and function score (KSFS), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and range of motion (ROM). Hip-knee-ankle angle (HKAA), femorotibial angle (FTA), and radiolucent lines were assessed radiologically. RESULTS: The median follow-up period was 36.0 months (interquartile range: 31-37 months). The KSKS, KSFS, WOMAC score, and ROM improved significantly at the final follow-up assessment compared with the preoperative evaluation. Both of the HKAA and FTA were corrected after surgery. Only one knee had a nonprogressive radiolucent line at the bone-cement interface. No radiolucent lines were detected around the pillar in any of the cases. There were no cases of prosthesis loosening and revision. CONCLUSIONS: The use of novel porous metal pillars yielded satisfactory clinical outcomes and reliable radiological evidence of fixation in this study with a minimum 2-year follow-up. Porous metal pillar augmentation can be considered as a valuable and easy-to-use method for the management of tibial bone defects in primary TKA.

Adjuvant therapy in completely resected, EGFR-mutant non-small cell lung cancer: a comparative analysis of treatment efficacy between EGFR-TKI and anti-PD-1/PD-L1 immunotherapy.

The IMpower010 and KEYNOTE-091 trials have demonstrated the benefit of adjuvant immunotherapy (IO) after chemotherapy (C+IO) in resected non-small cell lung cancer (NSCLC), including those with epidermal growth factor receptor gene (EGFR) mutation. Meanwhile, several studies have reported that EGFR-tyrosine kinase inhibitor (EGFR-TKI) may prolong disease-free survival (DFS) in these patients. However, there is currently a lack of head-to-head comparison between these two adjuvant therapy strategies. Therefore, we designed a comparative analysis of their efficacy to inform clinical decision-making by assessing DFS as the primary outcome. The results of direct meta-analysis indicated that EGFR-TKI reduced the risk of recurrence and/or death in completely resected NSCLC (HREGFR-TKI/chemo = 0.41, 95% CI: 0.23 to 0.74, p=0.003), while C+IO did not significantly improve DFS compared with chemotherapy alone (HRC+IO/chemo=0.68, 95% CI: 0.31 to 1.50, p=0.338). Indirect comparison suggested that EGFR-TKI has a trend to prolong DFS compared with C+IO (HR EGFR-TKI/C+IO = 0.60, 95% CI: 0.23 to 1.61, p=0.312), while the third-generation TKI (3rd-TKI) osimertinib significantly outperformed C+IO (HR3rd-TKI/C+IO = 0.29, 95% CI: 0.12 to 0.70, p=0.006). In conclusion, osimertinib rather than immunotherapy should be regarded as the preferred adjuvant therapy in completely resected, EGFR-mutant NSCLC.