Effects of lower limb length discrepancy on spinopelvic compensation following total hip arthroplasty in patients with developmental dysplasia of the hip.

BACKGROUND: Limited research has examined the impact of lower limb length discrepancy (LLLD) alteration on spinopelvic compensation in individuals with developmental dysplasia of the hip (DDH). This study aimed to investigate the effects of LLLD on spinopelvic compensation following total hip arthroplasty (THA) and elucidate the complex biomechanical adaptations in the spinopelvic structures. METHODS: A retrospective review of DDH patients undergoing THA from January 2014 to December 2021 categorized individuals with Crowe type I and II into the low dislocation group (LDG, n = 94) and those with Crowe type III and IV into the high dislocation group (HDG, n = 43). Demographic data, as well as preoperative, postoperative, and last follow-up imaging data, including lower limb length (LLL), sacral obliquity (SO), iliac obliquity (IO), hip obliquity (HO), Cobb angle, apical vertebral translation (AVT), and coronal decompensation (CD), were collected for analysis. RESULTS: Patients in the LDG had a significantly higher surgical age and shorter disease duration (P<0.05). In LDG, patients exhibited substantial postoperative reductions in LLLD, SO, IO, and HO (P<0.05), while Cobb Angle, AVT, and CD showed no statistically significant changes (P>0.05). The variation in LLLD correlated significantly with the variations in SO, IO, and HO (P<0.05). Postoperative outcomes in the HDG demonstrated marked decreases in LLLD, SO, IO, HO, and CD (P<0.05), with no significant change in Cobb angle and AVT (P>0.05). The variation in LLLD correlated significantly with the variations in SO, IO, HO, and CD (P<0.05). CONCLUSIONS: THA effectively reduces LLLD in patients with DDH, and the variation in LLLD correlates meaningfully with the recovery of spinopelvic compensatory mechanisms.

Effects of Physical Exercise Interventions for Individuals With Gynecologic Cancer: A Systematic Review and Meta-Analysis.

PROBLEM IDENTIFICATION: Data on the efficacy of physical exercise interventions for individuals with gynecologic cancer are limited and discordant. The purpose of this review was to determine the benefits of exercise interventions in this population. LITERATURE SEARCH: The PubMed®, Web of Science, Embase® (Ovid), and Cochrane Central Register of Controlled Trials databases were searched for studies published from January 1, 2010, to November 9, 2022. DATA EVALUATION: 12 randomized controlled trials were included. A quantitative synthesis method was used to investigate the effects of exercise interventions on individuals with gynecologic cancer. SYNTHESIS: The findings indicate that physical exercise interventions may have beneficial effects on the fatigue, depression, and health-related quality of life of this patient population. However, because of the small group of studies available, the evidence must be regarded as preliminary. IMPLICATIONS FOR PRACTICE: Clinicians and oncology nurses should recommend and refer individuals with gynecologic cancer to clinic- or community-based physical exercise programs.

Combined Aerobic and Resistance Exercise Interventions for Children and Adolescents With Cancer: A Systematic Review and Meta-Analysis.

PROBLEM IDENTIFICATION: Systematic reviews in adults with cancer have shown the benefits of combined aerobic and resistance exercise (CE) interventions on physical and psychological fitness. However, data on the efficacy of CE interventions for children and adolescents are limited and discordant. LITERATURE SEARCH: The PubMed®, Embase®, Cochrane Central Register of Controlled Trials, Web of Science, and China National Knowledge Infrastructure electronic databases were searched from inception to April 19, 2022. DATA EVALUATION: Nine randomized controlled trials met the inclusion criteria. A quantitative synthesis method was used to investigate the effects of CE interventions on fatigue, cardiorespiratory fitness, physical activity levels, and health-related quality of life. SYNTHESIS: This systematic review and meta-analysis indicates that CE interventions have beneficial effects on the fatigue, cardiorespiratory fitness, and physical activity levels of this population. IMPLICATIONS FOR PRACTICE: Healthcare providers should implement CE interventions during hospital care and recommend home-based CE interventions to patients who have barriers to performing hospital-based sessions.

Effects of Preoperative High-Intensity Interval Training Combined With Team Empowerment Education in Lung Cancer Patients With Surgery: A Quasi-experimental Trial.

BACKGROUND: Cancer itself and surgery put a heavy burden on lung cancer patients, physiologically and psychologically. Enhancing self-efficacy during high-intensity interval training is essential for achieving the full benefit of pulmonary rehabilitation in lung cancer patients. OBJECTIVE: This study aimed to explore the effects of high-intensity interval training combined with team empowerment education on patients with lung resection. METHODS: This is a quasi-experimental trial with a pretest-posttest design. Participants were assigned to one of the 3 groups according to the order of admission: (1) combined intervention group, (2) intervention group, or (3) routine care group. The outcome measures included dyspnea, exercise capacity, exercise self-efficacy, anxiety, depression, postoperative indwelling time of thoracic drainage tube, and total in-hospital stay. RESULTS: Per-protocol results showed that dyspnea, exercise capacity, exercise self-efficacy, anxiety, and depression of the patients in the combined intervention group were significantly improved. However, no significant difference was observed in postoperative indwelling time of thoracic drainage tube or total in-hospital stay among the 3 groups. CONCLUSION: This hospital-based short-term high-intensity interval training combined with team empowerment education for lung cancer patients undergoing surgery was safe and feasible, indicating this program can be a promising strategy to manage perioperative symptoms. IMPLICATIONS FOR PRACTICE: This study provides evidence supporting preoperative high-intensity interval training as a promising method to make the best use of preoperative time, thus improving adverse symptoms in lung cancer patients undergoing surgery, and also provides a new strategy to raise exercise self-efficacy and promote patients' rehabilitation.

Comparison of risk of complication between neuraxial anaesthesia and general anaesthesia for hip fracture surgery: a systematic review and meta-analysis.

BACKGROUND: Controversy remains over the choice of anaesthetic technique for patients undergoing surgery for hip fracture. AIM: The aim was to compare the risk of complication of neuraxial anaesthesia with that of general anaesthesia in patients undergoing hip fracture surgery. METHODS: This systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines and was registered at PROSPERO (CRD42022337384). The study included eligible randomised controlled trials published before February 2022. Data synthesis was performed to compare the differences between general and neuraxial anaesthesia. Meta-regression analysis was performed to investigate the influence of the publication year. A subgroup analysis was performed based on patient age and the anaesthetic technique used. A grading of recommendations, assessment, development and evaluations assessment was performed to assess the quality of each outcome. RESULTS: Twenty randomised controlled trials and 4802 patients were included. Data synthesis revealed significant higher risk of acute kidney injury in the general anaesthesia group ( P =0.01). There were no significant differences between the two techniques in postoperative short-term mortality ( P =0.34), delirium ( P =0.40), postoperative nausea and vomiting ( P =0.40), cardiac infarction ( P =0.31), acute heart failure ( P =0.34), pulmonary embolism ( P =0.24) and pneumonia ( P =0.15). Subgroup analysis based on patient age and use of sedative medication did not reveal any significant differences. Meta-regression analysis of the publication year versus each adverse event revealed no statistically significant differences. CONCLUSION: A significantly higher risk of postoperative acute kidney injury was found in patients receiving general anaesthesia. This study revealed no significant differences in terms of postoperative mortality and other complications between general and neuraxial anaesthesia. The results were consistent across the age groups.

Acetabular Diameter Assessment and Three-Dimensional Simulation for Acetabular Reconstruction in Dysplastic Hips.

BACKGROUND: This study aimed to investigate the relationship between acetabular width, three-dimensional (3D) simulation, and surgical results in total hip arthroplasty patients who have developmental dysplasia of the hip (DDH). METHODS: This retrospective study included 216 DDH cases. Inner and outer acetabular width (OAW) was measured at the plane passing through the center of acetabular fossa. 3D simulation and 2D standard templating were performed. The actual cup size and the use of augments during surgery were recorded. Association among the indices and their distribution in different types of DDH were analyzed. RESULTS: A difference of 13 to 14 millimeters (mm) was found between the inner acetabular width and actual cup size used in type II, III, and IV cases, while the difference was 0.2 to 3.6 mm for OAW. The accuracy of 2D templating and 3D simulation in predicting cup size was comparable in Crowe type I (86.5 versus 76%, P = .075), type II (72.7 versus 51.5%, P = .127), and type III (93.3 versus 66.7%, P = .169). The 3D simulation was significantly more accurate in Crowe type IV (89.1% versus 60.9%, P = .001). Augments and bone grafts were significantly more commonly used in type II (25%) than in the other types (0 to 6.5%). CONCLUSION: OAW more accurately predicted actual cup size than inner acetabular width. The supero-lateral acetabular bone defects in type II cases require additional attention. Compared with 2D templating, 3D simulation is more accurate in predicting actual cup size in dysplastic hips with severe deformity and may be recommended in these selected cases, especially for Crowe IV patients.

Clinical Indicators of Effects of Yoga Breathing Exercises on Patients With Lung Cancer After Surgical Resection: A Randomized Controlled Trial.

BACKGROUND: Cancer itself and surgery pose a heavy burden on adults with lung cancer. Yoga breathing exercises have been proposed as a form of pulmonary rehabilitation exercises to improve these patients' perioperative outcomes. OBJECTIVE: To investigate the impact of yoga breathing exercises based on a problem-solving model on dyspnea, exercise capacity, anxiety, depression, and postoperative indwelling time of thoracic drainage tube and compliance in adults with lung cancer undergoing surgery. METHODS: One hundred eight lung cancer patients were randomly assigned to receive problem-solving model-based yoga breathing exercises, yoga breathing exercises, or usual care. Outcomes were collected at admission, the day before surgery, and at discharge. RESULTS: Patients in the combined intervention group showed a significantly greater improvement in dyspnea, exercise capacity, and anxiety compared with the control group. Yoga breathing training can significantly improve patients' dyspnea and anxiety. Significant difference favoring the combined group was observed in exercise capability and compliance between the 2 intervention groups. However, there was no significant difference in depression or indwelling time of thoracic drainage tube among the 3 groups at any time point. CONCLUSION: Findings indicate that yoga breathing exercises are effective in alleviating perioperative symptoms of lung resection patients. Compared with yoga breathing exercises, applying additional problem-solving model may achieve a better effect. IMPLICATIONS FOR PRACTICE: Yoga breathing exercises can be considered as a promising pulmonary rehabilitation strategy for lung cancer patients with surgery. The problem-solving model could be integrated into yoga breathing exercises in clinical practice to enhance the rehabilitation effect.

Computer Navigation Assisted Restricted Kinematic Alignment Improves Short-Term Outcomes in Total Knee Arthroplasty: An Ambispective Cohort Study.

OBJECTIVES: Mechanical alignment (MA)-total knee arthroplasty (TKA) has been challenged due to the excessive soft tissue release and the evidence of the clinical outcomes of computer assisted navigation is still limited. The aim of this ambispective cohort study was to: (i) investigate whether computer assisted navigation is capable to achieve restricted kinematic alignment (rKA)-TKA; and (ii) compare the short-term outcomes between rKA-TKA and MA-TKA. METHODS: We retrospectively included 41 patients diagnosed with osteoarthritis who received MA-TKA between April 2019 and January 2021 and 43 patients diagnosed with osteoarthritis who received rKA-TKA were included in the prospective cohort from January 2021 to September 2021. Demographical, peri-operative, and radiological data were collected and compared. Unpaired two-sample t-test for continuous variables and χ2 test for categorical variables were used to compare various measurements in two groups. The patient-reported outcome measures at baseline, 10 days (T1), and 6 months (T6) after surgery were statistically analyzed by generalized estimating equation (GEE) models. RESULTS: Fourty-one patients (45 knees) and 43 patients (48 knees) were included in the MA and the rKA group respectively. Three constitutional knee phenotypes (II, I, IV) were the commonest in our population. Navigation improved the surgical accuracy (1.5° vs 3.5°, p < 0.001) and precision (interquartile range 4.0 vs 2.0, p < 0.001) in the rKA group than the MA group. The changes in Knee Injury and Osteoarthritis Outcome Score 12 (KOOS12), EuroQol five-dimension questionnaire (EQ5D) from baseline to T1 and T6 for patients with on-target rKA were larger than on-target MA counterparts (26.053 vs 18.607, P < 0.001(KOOS12, T1) , 0.457 vs 0.367 p < 0.001(EQ5D, T1) ; 51.017 vs 46.896, P = 0.023(KOOS12, T6) , 0.606 vs 0.565, P = 0.01(EQ5D, T6) ). Patients with on-target rKA had better Forgotten Joint Score (FJS) at T1 (54.126 vs 40.965, P = 0.002) compared with on-target MA counterparts. CONCLUSIONS: Computer assisted navigation achieved the level of accuracy required by rKA-TKA. rKA-TKA offered significantly better short-term outcomes than MA-TKA.

Patient-Derived Spheroid Culture Models Are Better Than Monolayer Models in Chondrosarcoma Research.

Purpose: Chondrosarcoma (CSA) are mesenchymal tissue-derived bone tumors. CSA mainly occurs in older people. CSA has demonstrated resistance to chemotherapy and radiation; complete surgical removal with negative margins is the only treatment option. In the case of metastatic CSA, the chance of survival is meager. Since the conventional two-dimensional cell culture models failed to retain tumor characteristics, developing preclinical models mimicking the disease with the highest fidelity is paramount for personalized treatments. Methods: In this study, we established spherical cultured cells as new models for CSA. First, we demonstrated that CSA cells could form spheroids when cultured in ultra-low attachment plates. Next, tissue samples from CSA patients were collected and processed into primary cells, which were subsequently cultured as primary spheroids. The growth rate of primary spheroids was monitored and the histology of mature spheroids were characterized. These primary spheroids were used in drug susceptibility studies where traditional doxorubicin therapy and our novel disulfiram-copper therapy were tested. Results: Compared with conventional monolayer cultures, spheroids better recapitulated the features of the in vivo tumor in the aspect of the formation of extracellular matrix. In the drug susceptibility study, spheroids demonstrated high resistance to the classic therapies, suggesting that monolayer cultures may give false positive results. Therefore, using spheroids for drug research and development in the CSA field should provide more accurate results. Conclusion: In summary, our study of primary CSA spheroids brought new insight into their chemoresistance and demonstrated its potential for personalized treatment of CSA in clinical medicine.

Total Knee Arthroplasty in Patients with Primary Sjögren's Syndrome: A Retrospective Case-Control Study Matched Patients without Rheumatic Diseases.

Background: The number of patients with primary Sjögren's syndrome (pSS) who require total knee arthroplasty (TKA) is expected to increase, and there are few studies describing their outcomes. This research was focused on the evaluation of a TKA cohort in pSS patients and to compare outcomes with those of matched individuals from the general population. Methods: From 2004 to 2020, we found 36 TKAs in 30 patients with pSS from the single-institution arthroplasty registry, and they were matched for age, gender, bilateral or unilateral surgery, American Society of Anesthesiologists (ASA) score, and year of surgery with 72 TKAs in 60 osteoarthritis patients without rheumatic diseases (1:2 ratio). Perioperative outcomes were obtained, and clinical evaluations were performed at the last follow-up. Results: After a mean six-year follow-up, both cohorts had similar knee function and health-related quality of life outcomes. The pSS group had more patients with post-operative anemia and hypoalbuminemia and more patients needing platelet transfusion. There were no significant differences in other complications, the rates of 90-day readmission, or overall revision. By multivariate analysis, the influencing factor for anemia in pSS patients was lower preoperative hemoglobin (OR = 0.334, 95% CI (0.125−0.889), p < 0.05). Conclusions: Our study demonstrated that pSS patients who received TKA could achieve comparable clinical outcomes to the general population. However, more attention should be paid to the perioperative hematological management of pSS patients who underwent TKA.

Serine Protease Inhibitor Kazal Type 1, A Potential Biomarker for the Early Detection, Targeting, and Prediction of Response to Immune Checkpoint Blockade Therapies in Hepatocellular Carcinoma.

Background: We aimed to characterize serine protease inhibitor Kazal type 1 (SPINK1) as a gene signature for the early diagnosis, molecular targeting, and prediction of immune checkpoint blockade (ICB) treatment response of hepatocellular carcinoma (HCC). Methods: The transcriptomics, proteomics, and phenotypic analyses were performed separately or in combination. Results: We obtained the following findings on SPINK1. Firstly, in the transcriptomic training dataset, which included 279 stage I and II tumor samples (out of 1,884 stage I-IV HCC specimens) and 259 normal samples, significantly higher area under curve (AUC) values and increased integrated discrimination improvement (IDI) and net reclassification improvement (NRI) were demonstrated for HCC discrimination in SPINK1-associated models compared with those of alpha-fetoprotein (AFP). The calibration of both SPINK1-related curves fitted significantly better than that of AFP. In the two independent transcriptomic validation datasets, which included 201, 103 stage I-II tumor and 192, 169 paired non-tumor specimens, respectively, the obtained results were consistent with the above-described findings. In the proteomic training dataset, which included 98 stage I and II tumor and 165 normal tissue samples, the analyses also revealed better AUCs and increased IDI and NRI in the aforementioned SPINK1-associated settings. A moderate calibration was shown for both SPINK1-associated models relative to the poor results of AFP. Secondly, in the in vitro and/or in vivo murine models, the wet-lab experiments demonstrated that SPINK1 promoted the proliferation, clonal formation, migration, chemoresistance, anti-apoptosis, tumorigenesis, and metastasis of HCC cells, while the anti-SPINK1 antibody inhibited the growth of the cells, suggesting that SPINK1 has "tumor marker" and "targetable" characteristics in the management of HCC. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that SPINK1 was engaged in immunity-related pathways, including T-cell activation. Thirdly, in the transcriptomic analyses of the 368 HCC specimens from The Cancer Genome Atlas (TCGA) cohort, the high abundance of SPINK1 was positively correlated with the high levels of activated tumor-infiltrating CD4+ and CD8+ T lymphocytes and dendritic and natural killer cells, while there were also positive correlations between SPINK1 and immune checkpoints, including PD-1, LAG-3, TIM-3, TIGIT, HAVCR2, and CTLA-4. The ESTIMATE algorithm calculated positive correlations between SPINK1 and the immune and ESTIMATE scores, suggesting a close correlation between SPINK1 and the immunogenic microenvironment within HCC tissues, which may possibly help in predicting the response of patients to ICB therapy. Conclusions: SPINK1 could be a potential biomarker for the early detection, targeted therapy, and prediction of ICB treatment response in the management of HCC.

Auricular Acupressure for Improving Sleep Quality in Patients With Lung Cancer: A Systematic Review and Meta-analysis.

This meta-analysis was conducted to systematically evaluate the efficacy and safety of auricular acupressure on sleep quality in patients with lung cancer. Nine articles with a total of 802 patients were retrieved after searching on 11 electronic databases. Results of the meta-analysis showed that auricular acupressure improved sleep score (standard mean difference: -0.80, 95% confidence intervals: -1.30 to -0.30, P = .002) and reduced sleep disturbance rate (risk ratio: 0.65, 95% confidence intervals: 0.51-0.84, P = .001) and sleep medicine usage (risk ratio: 0.26, 95% confidence intervals: 0.11-0.65, P = .004) significantly. Our review suggests that auricular acupressure is effective and relatively safe in improving sleep quality among patients with lung cancer.

Validation of CT-Based Three-Dimensional Preoperative Planning in Comparison with Acetate Templating for Primary Total Hip Arthroplasty.

OBJECTIVE: This study aims to compare the accuracy of CT-based preoperative planning with that of acetate templating in predicting implant size, neck length, and neck cut length, and to evaluate the reproducibility of the two methods. METHODS: This prospective study was conducted between August 2020 and March 2021. Patients who underwent elective primary total hip arthroplasty by a single surgeon were assessed for eligibility. The included patients underwent both acetate templating and CT-based planning by two observers after the operation. Each observer conducted both acetate templating and CT-based planning twice for each case. The outcome measures included the following: (1) the accuracy of surgical planning in predicting implant size, calcar length, and neck length, which was defined as the difference between the planned size and length and the actual size and length; (2) reproducibility of the two planning techniques, which were assessed by inter-observer and intra-observer reliability analysis; (3) the influence of potential confounding factors on planning accuracy, which was evaluated using generalized estimating equations. RESULTS: A total of 57 cases were included in the study. CT-based planning was more accurate than acetate templating for predicting cup size (93% vs 79%, p < 0.001) and stem size (93% vs 75%, p < 0.001). When assessed by mean absolute difference, the comparison between acetate templating and CT-based planning was 4.28 mm vs 3.74 mm (p = 0.122) in predicting neck length and 3.05 mm vs 2.93 mm (p = 0.731) in predicting neck cut length. In the inter-observer reliability analysis, an intraclass correlation coefficient (ICC) of 0.790 was achieved for predicting cup size, and an ICC of 0.966 was achieved for predicting stem size using CT-based planning. In terms of intra-observer reliability, Observer 1 achieved an ICC of 0.803 for predicting cup size and 0.965 for predicting stem size in CT-based planning. Observer 2 achieved ICC values of 0.727 and 0.959 for predicting cup and stem sizes, respectively. The average planning time was 6.48 ± 1.55 min for CT-based planning and 6.12 ± 1.40 min for acetate templating (p = 0.015). CONCLUSION: The CT-based planning system is more accurate than acetate templating for predicting implant size and has good reproducibility in total hip arthroplasty.

Active Cycle of Breathing Technique: A Respiratory Modality to Improve Perioperative Outcomes in Patients With Lung Cancer.

BACKGROUND: Cancer and surgery put a physiologic and psychological burden on patients with lung cancer. The active cycle of breathing technique (ACBT) has been considered as an effective airway clearance method for patients with lung diseases. Its effectiveness on perioperative outcomes in patients with lung cancer warrants study. OBJECTIVES: This prospective study explored the effects of the ACBT on patients with lung cancer undergoing surgical resection. METHODS: Patients were randomly allocated to the intervention (N = 34) or control group (N = 34). The intervention group received the ACBT, and the control group received usual pre-/postoperative breathing exercises. Outcomes included dyspnea, exercise capacity, anxiety, depression, and postoperative pulmonary complications. Intention-to-treat analysis was also performed. FINDINGS: Dyspnea, anxiety, depression, and postoperative pulmonary complications were significantly improved at discharge for patients in the intervention group.

Multimodal Exercise Program: A Pilot Randomized Trial for Patients With Lung Cancer Receiving Surgical Treatment.

BACKGROUND: Curative lung resection is the best option for patients with stage I-III lung cancer, and the best exercise intervention in these patients has not been determined. OBJECTIVES: This pilot study explored whether a short-term pre- and postsurgery multimodal exercise program affected dyspnea, exercise capacity, inspiratory capacity, anxiety, and depression. METHODS: A total of 101 patients were randomly allocated into the combined intervention group (n = 34), the breathing exercise group (n = 32), or the control group (n = 35). During hospitalization, patients in the two intervention groups received one or more kinds of exercise intervention, and patients in the control group only received usual care. Outcomes were assessed at admission, on the day before surgery, and at discharge. FINDINGS: Both intervention groups achieved significant improvements in dyspnea, exercise capacity, and inspiratory capacity, and patients in the combined intervention group exhibited greater improvements in outcomes as compared to those randomized to the breathing exercise group.

Outcomes of local thoracic surgery in patients with stage IV non-small-cell lung cancer: A SEER-based analysis.

BACKGROUND: The outcomes of thoracic surgery for patients with stage IV non-small-cell lung cancer (NSCLC) are controversial and uncertain. PATIENTS AND METHODS: The National Cancer Institute's Surveillance, Epidemiology, and End Results was queried for patients with stage IV NSCLC, including those treated with surgery-participated therapy modalities. Overall survival (OS) was evaluated using a variety of statistical analyses. RESULTS: The analysis was carried out for 90,982 patients from 1975 to 2016 who had been diagnosed as stage IV NSCLC. Propensity score-matched (PSM) analyses that were well-balanced with all the important confounding covariates revealed improved OS (median survival time [MST]) with patients receiving surgery versus non-surgery (MST: 15 versus 8 months, P < 0.001); undergoing surgery plus chemotherapy versus chemotherapy (MST: 19 versus 11 months, P < 0.001); and having surgery plus chemoradiation versus chemoradiation (MST: 18 versus 11 months, P < 0.001). Sequential landmark analyses for long-term survivors of ≥1 and ≥3 years all indicated improved OS (P < 0.001) on univariate and multivariate analyses for the patients receiving the three surgery-related treatment patterns listed earlier, relative to the corresponding surgery-absent treatment modalities. For synchronous presentations of varied treatment paradigms, surgical intervention significantly led to increased OS (MST, months) benefits following treatment paradigms: surgery plus chemotherapy (22), surgery plus chemoradiation (18), chemotherapy (10), surgery only (9), chemoradiation (9), surgery plus radiation (6) and radiation alone (2). The subgroup analysis demonstrated that the elevated OS associated with local thoracic surgery in addition to chemotherapy (versus chemotherapy) or chemoradiation (versus chemoradiation) fell in the subcategories of T0-3, N0-2 and 0-1 (metastatic sites) tumours. The comparison of the aforementioned two types of treatment patterns indicated that the optimal patients for the surgery were those with any combination of T1-4, N0-3, Msite0-1 and adeno- or squamous carcinoma. CONCLUSIONS: The patients with T1-4, N0-3, Msite0-1 and adeno- or squamous carcinoma of stage IV NSCLC had a longer OS with local thoracic surgery in combination with chemotherapy or chemoradiation.

Systematic Review and Meta-analysis of Nonpharmacological Interventions for Lung Cancer Fatigue.

Fatigue is one of the most common adverse effects of lung cancer, and the efficacy of nonpharmacological interventions on fatigue in lung cancer patients is still unclear. We aimed to assess the effectiveness of nonpharmacological interventions on lung cancer-induced fatigue. A systematic review and meta-analysis were performed on studies retrieved from the PubMed, Embase Ovid, Cochrane Central Register of Controlled Trials, and Web of Science databases from inception to June 2020. A total of 18 of randomized controlled trials with three intervention categories were identified, comprising 1,446 patients. We observed that fatigue was significantly affected by physical therapies (standard mean difference [SMD] = -1.26, 95% confidence intervals [CI]: -2.05 to -0.47, p = .002), but not by exercise interventions (SMD = -0.52, 95% CI: -1.46 to 0.43, p = .29) or education and psychological interventions (SMD = -0.39, 95% CI: -0.92 to 0.14, p = .15). More research with robust methodology is needed to justify these findings.

Do Patient-derived Spheroid Culture Models Have Relevance in Chondrosarcoma Research?

BACKGROUND: In high-grade chondrosarcoma, 5-year survival is lower than 50%. Therefore, it is important that preclinical models that mimic the disease with the greatest possible fidelity are used to potentially develop new treatments. Accumulating evidence suggests that two-dimensional (2-D) cell culture may not accurately represent the tumor's biology. It has been demonstrated in other cancers that three-dimensional (3-D) cancer cell spheroids may recapitulate tumor biology and response to treatment with greater fidelity than traditional 2-D techniques. To our knowledge, the formation of patient-derived chondrosarcoma spheroids has not been described. QUESTIONS/PURPOSES: (1) Can patient-derived chondrosarcoma spheroids be produced? (2) Do spheroids recapitulate human chondrosarcoma better than 2-D cultures, both morphologically and molecularly? (3) Can chondrosarcoma spheroids provide an accurate model to test novel treatments? METHODS: Experiments to test the feasibility of spheroid formation of chondrosarcoma cells were performed using HT-1080, an established chondrosarcoma cell line, and two patient-derived populations, TP19-S26 and TP19-S115. Cells were cultured in flasks, trypsinized, and seeded into 96-well ultra-low attachment plates with culture media. After spheroids formed, they were monitored daily by bright-field microscopy. Spheroids were fixed using paraformaldehyde and embedded in agarose. After dehydration with isopropanol, paraffin-embedded spheroids were sectioned, and slides were stained with hematoxylin and eosin. To compare differences and similarities in gene expression between 2-D and 3-D chondrosarcoma cultures and primary tumors, and to determine whether these spheroids recapitulated the biology of chondrosarcoma, RNA was extracted from 2-D cultures, spheroids, and tumors. Quantitative polymerase chain reaction was performed to detect chondrosarcoma markers of interest, including vascular endothelial growth factor alpha, hypoxia-inducible factor 1α, COL2A1, and COL10A1. To determine whether 2-D and 3-D cultures responded differently to novel chondrosarcoma treatments, we compared their sensitivities to disulfiram and copper chloride treatment. To test their sensitivity to disulfiram and copper chloride treatment, 10,000 cells were seeded into 96-well plates for 2-D culturing and 3000 cells in each well for 3-D culturing. After treating the cells with disulfiram and copper for 48 hours, we detected cell viability using quantitative presto-blue staining and measured via plate reader. RESULTS: Cell-line and patient-derived spheroids were cultured and monitored over 12 days. Qualitatively, we observed that HT-1080 demonstrated unlimited growth, while TP19-S26 and TP19-S115 contracted during culturing relative to their initial size. Hematoxylin and eosin staining of HT-1080 spheroids revealed that cell-cell attachments were more pronounced at the periphery of the spheroid structure than at the core, while the core was less dense. Spheroids derived from the intermediate-grade chondrosarcoma TP19-S26 were abundant in extracellular matrix, and spheroids derived from the dedifferentiated chondrosarcoma TP19-S115 had a higher cellularity and heterogeneity with spindle cells at the periphery. In the HT-1080 cells, differences in gene expression were appreciated with spheroids demonstrating greater expressions of VEGF-α (1.01 ± 0.16 versus 6.48 ± 0.55; p = 0.003), COL2A1 (1.00 ± 0.10 versus 7.46 ± 2.52; p < 0.001), and COL10A1 (1.01 ± 0.19 versus 22.53 ± 4.91; p < 0.001). Differences in gene expressions were also noted between primary tumors, spheroids, and 2-D cultures in the patient-derived samples TP19-S26 and TP19-S115. TP19-S26 is an intermediate-grade chondrosarcoma. With the numbers we had, we could not detect a difference in VEGF-α and HIF1α gene expression compared with the primary tumor. COL2A1 (1.00 ± 0.14 versus 1.76 ± 0.10 versus 335.66 ± 31.13) and COL10A1 (1.06 ± 0.378 versus 5.98 ± 0.45 versus 138.82 ± 23.4) expressions were both greater in the tumor (p (COL2A1) < 0.001; p (COL10A1) < 0.0001) and 3-D cultures (p (COL2A1) = 0.004; p (COL10A1) < 0.0001) compared with 2-D cultures. We could not demonstrate a difference in VEGF-α and HIF1α expressions in TP19-S115, a dedifferentiated chondrosarcoma, in the tumor compared with 2-D and 3-D cultures. COL2A1 (1.00 ± 0.02 versus 1.86 ± 0.18 versus 2.95 ± 0.56) and COL10A1 (1.00 ± 0.03 versus 5.52 ± 0.66 versus 3.79 ± 0.36) expressions were both greater in spheroids (p (COL2A1) = 0.003; p (COL10A1) < 0.0001) and tumors (p (COL2A1) < 0.001; p (COL10A1) < 0.0001) compared with 2-D cultures. Disulfiram-copper chloride treatment demonstrated high cytotoxicity in HT-1080 and SW-1353 chondrosarcoma cells grown in the 2-D monolayer, but 3-D spheroids were highly resistant to this treatment. CONCLUSION: We provide preliminary findings that it is possible to generate 3-D spheroids from chondrosarcoma cell lines and two human chondrosarcomas (one dedifferentiated chondrosarcoma and one intermediate-grade chondrosarcoma). Chondrosarcoma spheroids derived from human tumors demonstrated morphology more reminiscent of primary tumors than cells grown in 2-D culture. Spheroids displayed similar expressions of cartilage markers as the primary tumor, and we observed a higher expression of collagen markers in the spheroids compared with cells grown in monolayer. Spheroids also demonstrated greater chemotherapy resistance than monolayer cells, but more patient-derived spheroids are needed to further conclude that 3-D cultures may mimic the chemoresistance that chondrosarcomas demonstrate clinically. Additional studies on patient-derived chondrosarcoma spheroids are warranted. CLINICAL RELEVANCE: Chondrosarcomas demonstrate resistance to chemotherapy and radiation, and we believe that if they can be replicated, models such as 3-D spheroids may provide a method to test novel treatments for human chondrosarcoma. Additional comprehensive genomic studies are required to compare 2-D and 3-D models with the primary tumor to determine the most effective way to study this disease in vitro.

Effect of Exercise Interventions on Quality of Life in Patients With Lung Cancer: A Systematic Review of Randomized Controlled Trials.

PROBLEM IDENTIFICATION: Improving quality of life (QOL) is a key issue for patients with lung cancer. Exercise interventions could positively affect patients' QOL; however, there is no clear-cut understanding of the role of exercise in improving QOL in patients with lung cancer. LITERATURE SEARCH: The PubMed®, Embase®, Cochrane Library, and Web of Science electronic databases were searched from inception to September 6, 2019. DATA EVALUATION: 16 randomized controlled trials met the inclusion criteria. A qualitative synthesis method was used to identify the effect of exercise interventions on QOL in patients with lung cancer. SYNTHESIS: This review indicates that exercise interventions may have beneficial effects on the QOL of patients with lung cancer. The effectiveness seems to be affected by the duration of the intervention, as well as exercise frequency, intensity, and adherence. IMPLICATIONS FOR PRACTICE: Exercise interventions can be integrated into management plans for patients with lung cancer to improve their QOL. Healthcare providers should consider developing optimal exercise prescriptions to maximize the results for this population.

Comparison of cachectic and non-cachectic sarcoma patients reveals an important role of Notch signaling in metastasis and myogenesis.

Cancer-associated cachexia is a wasting syndrome that affects up to 50% of cancer patients. It is defined as unintentional weight loss ≥5% over 6 months and characterized by muscle atrophy, fatigue, and anorexia that are refractory to nutritional support. Sarcoma describes a diverse group of malignancies arising from the connective tissues. Sarcoma patients are uniquely susceptible to cancer-associated cachexia given its origins in the musculoskeletal system. Our previous research suggests that sarcoma cells may contribute to sarcoma-associated cachexia (SAC) via establishment of TNF-α-mediated inflammation and dysregulation of muscle homeostasis by abnormal Notch signaling. Here, we examine the role of the Notch pathway and pro-inflammatory cytokines in cells derived from cachectic and non-cachectic human sarcoma patients. We observed increased expression of Notch pathway genes in the cachexia group while no differences in pro-inflammatory cytokines were observed. Co-culture of muscle-derived stem cells (MDSCs) and sarcoma cells demonstrated the inhibition of MDSC maturation with both cachectic and non-cachectic patient cells, corresponding to elevated Pax7 and Notch pathway expression in MDSCs. Our findings suggest that there is no difference in inflammatory profile between cachexia and non-cachexia sarcoma samples. However, Cachectic sarcoma samples express increased Notch that mediates muscle wasting possibly through inhibition of myogenesis.