The oncogene MYBL2 promotes the malignant phenotype and suppresses apoptosis through hedgehog signaling pathway in clear cell renal cell carcinoma.

Multiple cancers have been associated with MYB-related protein B (MYBL2), its involvement in clear cell renal cell carcinoma (ccRCC) has yet to be demonstrated. Our study revealed a significant upregulation of MYBL2 in ccRCC tissues, correlating with clinicopathological features and patient prognosis. Increased MYBL2 expression promoted cell proliferation and suppressed apoptosis. RNA-seq analysis unveiled a reduction in smoothened (SMO) expression upon MYBL2 silencing. However, luciferase and chromatin immunoprecipitation (ChIP) assays demonstrated MYBL2's positive regulation of SMO expression by directly targeting the SMO promoter. Reintroduction of SMO expression in MYBL2-knocked down cells partially restored cell proliferation and mitigated apoptosis inhibition. Overall, these results indicate that MYBL2 facilitates ccRCC progression by enhancing SMO expression, suggesting its potential as an intriguing drug target for ccRCC therapy.

SHOX2 promotes prostate cancer proliferation and metastasis through disruption of the Hippo-YAP pathway.

The transcription factor SHOX2 gene is critical in regulating gene expression and the development of tumors, but its biological role in prostate cancer (PCa) remains unclear. In this study, we found that SHOX2 expression was significantly raised in PCa tissues and was associated with clinicopathological features as well as disease-free survival (DFS) of PCa patients. Phenotypic tests showed that the absence of SHOX2 inhibited PCa growth and invasion, while SHOX2 overexpression promoted these effects. Mechanistically, SHOX2 was found to activate the transcription of nephronophthisis type 4 (NPHP4), a gene located downstream of SHOX2. Further analysis revealed that SHOX2 could potentially interfere with the Hippo-YAP signaling pathway through NPHP4 activation, facilitating the oncogenic behavior of PCa cells. These findings highlight SHOX2 as an oncogene in PCa and provide a basis for developing potential therapeutic approaches against this disease.

Reversible Change in Performances of Polymer Networks via Invertible Architecture-Transformation of Cross-Links.

A polymer nanoparticle network using single-chain nanoparticles (SCNPs) as cross-links is designed. The experimental and theoretical study shows that incorporating SCNPs in polymer networks leads to smaller mesh size, faster terminal relaxation time, and reduced fluctuation among cross-links, resulting in a significant increase in shear storage modulus, and enhancement in tensile stress. Notably, the reversible single-chain collapse of SCNPs under thermal stimulation enables the polymer network to undergo coherent changes between two topological states, thereby exhibiting reversible transformations between soft and stiff states. This approach and finding can effectively tailor the mechanical properties of polymer networks, potentially leading to the development of intelligent, responsive materials.

Mechanical properties and crack evolution characteristics of fractured rock with hidden fissures.

Natural defects, such as joints, structural surfaces and voids, significantly affect the mechanical properties and fracture modes of rock mass. Hidden fissures are widely distributed in magmatic rock, while their influences on the mechanical properties and the cracking mechanism are still unclear. Laboratory tests were conducted on prefabricating hidden-fissured rock-like specimens, as well as intact specimens and close-fissured specimens as a comparison. The real-time digital image correlation technology and acoustic emission monitoring technology were synchronously adopted to capture both the external and internal cracking process. The results show that the hidden fissures can weaken the uniaxial compression strength, while the deterioration effect of hidden fissures is weaker than closed fissures due to the internal cohesion among fissure internal particles. What's more, the initiation behavior of the α = 90° hidden-fissured specimen is different from that of ß = 90° closed-fissured specimen. Finally, the cracking mechanism of hidden-fissured specimens was revealed by analyzing the RA-AF relationship. The failure of the close-fissured specimens is mainly the tensile-shear mixed fracture mode, while the failure of the hidden-fissured specimens is mainly the tensile fracture mode and supplemented by the shear. The experimental results contribute to the understanding of cracking properties in hidden-fissured rock.

Anionic Hybrid Copolymerization of Sulfur with Acrylate: Strategy for Synthesis of High-Performance Sulfur-Based Polymers.

Copolymerization of elemental sulfur (S8) with vinyl monomers to develop new polymer materials is significant. Here, for the first time, we report the anionic hybrid copolymerization of S8 with acrylate at 25 °C, yielding a copolymer with short polysulfide segments; i.e., each of them consists of only one to four sulfur atoms. The formation of a longer polysulfide segment would be ceaselessly disrupted by carbon anions through the chain-transfer reaction. The copolymer of S8 with diacrylate was cross-linked and exhibited excellent mechanical properties, with an ultimate tensile strength as high as 10.7 MPa and a breaking strain of 22%. Furthermore, the introduction of tertiary amide groups to the copolymer enabled it not only to be reprocessed via press molding at room temperature but also to exhibit self-healing properties without external intervention. This study provides a facile strategy to synthesize high-performance sulfur-based copolymers under mild conditions.

Machine learning to improve prognosis prediction of metastatic clear-cell renal cell carcinoma treated with cytoreductive nephrectomy and systemic therapy.

Cytoreductive nephrectomy (CN) combined with systemic therapy is commonly used to treat metastatic clear-cell renal cell carcinoma (mccRCC). However, prognostic models for these patients are limited. In the present study, the clinical data of 782 mccRCC patients who received both CN and systemic therapy were obtained from the Surveillance, Epidemiology, and End Results (SEER) database (2010-2016), and patients were divided into training and internal test cohorts. A total of 144 patients who met the same criteria from our center (Peking Union Medical College Hospital) were placed in the external test cohort. The cancer-specific survival rate (CSS) at 1, 3, and 5 years was set as the research outcome. Then, four ML models, i.e., a gradient boosting machine (GBM), support vector machine (SVM), random forest (RF), and logistic regression (LR), were established. Fifteen potential independent features were included in this study.  Model performance was evaluated using the area under the receiver operating characteristic curves (AUC), calibration plots, and decision curve analysis (DCA). Seven clinical features, namely pathological grade, T stage, N stage, number of metastatic sites, brain or liver metastases, and metastasectomy were selected for subsequent analysis via the recursive feature elimination (RFE) algorithm. In conclusion, the GBM model performed best at 1-, 3- and 5-year CSS prediction (0.836, 0.819 and 0.808, respectively in the internal test cohort and 0.819, 0.805 and 0.786, respectively in the external cohort). Furthermore, we divided the patients into three strata (high-, intermediate- and low-risk) via X-tile analysis and concluded that clinically individualized treatment can be aided by these practical prognostic models.

Integrated Analysis Revealed an Inflammatory Cancer-Associated Fibroblast-Based Subtypes with Promising Implications in Predicting the Prognosis and Immunotherapeutic Response of Bladder Cancer Patients.

Inflammatory cancer-associated fibroblasts (iCAFs) are closely related to progression, anticancer therapeutic resistance, and poor prognosis of bladder cancer (BCa). However, the functional role of iCAFs in BCa has been poorly studied. In our study, two BCa scRNA-seq datasets (GSE130001 and GSE146137) were obtained and integrated by the Seurat pipeline. Based on reported markers (COL1A1 and PDGFRA), iCAFs were identified and the related signature of 278 markers was developed. Following unsupervised consensus clustering, two molecular subtypes of TCGA-BLCA were identified and characterized by distinct dysregulated cancer hallmarks, immunological tumor microenvironments, prognoses, responses to chemotherapy/immunotherapy, and stemness. Subsequently, the robustness of the signature-based clustering, in terms of prognosis and therapeutic response prediction, was validated in a GEO-meta cohort with seven independent GEO datasets of 519 BCa patients, and three immune checkpoint inhibitor (ICI)-treated cohorts. Considering the heterogeneity, re-clustering of iCAFs was performed and a subpopulation, named "LOXL2+ iCAFs", was identified. Co-culture CM derived from LOXL2 overexpression/silencing CAFs with T24 cells revealed that overexpression of LOXL2 in CAFs promoted while silencing LOXL2 inhibited the proliferation, migration, and invasion of T24 cells through IL32. Moreover, the positive correlation between LOXL2 and CD206, an M2 macrophage polarization marker, has been observed and validated. Collectively, integrated single-cell and bulk RNA sequencing analyses revealed an iCAF-related signature that can predict prognosis and response to immunotherapy for BCa. Additionally, the hub gene LOXL2 may serve as a promising target for BCa treatment.

A comprehensive analysis of the FOX family for predicting kidney renal clear cell carcinoma prognosis and the oncogenic role of FOXG1.

Previous studies have confirmed that the forkhead box (FOX) superfamily of transcription factors regulates tumor progression and metastasis in multiple cancer. The purpose of this study was to develop a model based on FOX family genes for predicting kidney renal clear cell carcinom (KIRC) prognosis. We downloaded the transcriptional profiles and clinical data of KIRC patients from the Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) datasets. To build a new prognosis model, we screened prognosis-related FOX family genes using Lasso regression and Multivariate Cox regression analyses. Receiver operating characteristic (ROC) curves were used to evaluate model performance. Additionally, a prognostic nomogram was developed using clinical information and selected genes to improve the accuracy of prognostic prediction. We also investigated whether prognosis-related FOX family genes are related to the immune response in KIRC. Finally, we validated the oncogenic role of FOXG1 in KIRC using an in vitro tumor function assay. Six prognosis-related FOX family genes were screened: FOXO1, FOXM1, FOXK2, FOXG1, FOXA1, and FOXD1. The ROC curves indicated that our model was capable of making accurate predictions for 1-, 3-, and 5-year overall survival (OS). The nomogram further improved the accuracy of prognostic predictions. In addition, compared to those in patients with low-risk scores, high-risk scores predicted a decreased level of immune cell infiltration and a lower immune response rate. Moreover, the results of in vitro studies confirmed that FOXG1 supports the proliferation and invasion of KIRC.

Neoadjuvant immunotherapy and chemoimmunotherapy for stage II-III muscle invasive bladder cancer.

Objective: Considering the striking evidence revealed by immunotherapy in advanced or metastatic bladder cancer, investigators have explored neoadjuvant immunotherapy and chemoimmunotherapy in muscle-invasive bladder cancer (MIBC). Currently, there have been a large number of studies reporting varied efficacy and safety of these approaches. Herein, we pooled the available evidence in terms of oncological outcomes (pathological complete response [pCR] and pathological partial response [pPR]) and safety outcomes (immune-related adverse events [irAEs], treatment-related adverse events [TRAEs]), through a systematic review and meta-analysis. Method: We searched PubMed, Embase, Cochrane Library, and American Society of Clinical Oncology meeting abstracts to identify relevant studies up to June 2022. Studies were included if they evaluated the neoadjuvant immunotherapy or chemoimmunotherapy in MIBC and reported at least the pCR. Results: A total of 22 records involving 843 patients were included. For pCR of immunotherapy, the pooled rate of immune checkpoint inhibitor (ICI) monotherapy and dual-ICIs therapy was 24% (95% confidence interval [CI]: 15.3% - 32.8%) and 32.1% (95%CI: 20.6% - 43.7%), respectively. For pCR of chemoimmunotherapy, the overall pooled rate was 42.6% (95% CI: 34.9% - 50.2%). Subgroup of gemcitabine/cisplatin (GC) plus ICI had a pCR rate of 41.7% (95%CI: 35.8% - 47.5%). In terms of safety, the pooled rate of Grade≥3 irAEs was 11.7% (95% CI: 6.5%-16.9%). In subgroup analysis, the Grade≥3 irAEs rate of ICI monotherapy, dual-ICIs therapy, and GC plus ICI therapy was 7.4% (95% CI: 4.3%-10.5%), 30.3% (95% CI: 15.3%-45.3%), and 14.5% (95% CI: 3.5% - 25.4%), respectively. Besides, the pooled Grade≥3 TRAEs rate for chemoimmunotherapy was 32.4% (95% CI: 13.1% - 51.6%). Conclusion: Neoadjuvant immunotherapy and chemoimmunotherapy were effective and safe in the treatment of MIBC. Compared to ICI monotherapy, dual-ICIs therapy or chemoimmunotherapy can improve the response rate, while increasing the morbidity of Grade≥ 3 irAEs or Grade≥ 3 TRAEs. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD4202233771.

Competitive Risk Model for Specific Mortality Prediction in Patients with Bladder Cancer: A Population-Based Cohort Study with Machine Learning.

Background: Noncancer death accounts for a high proportion of all patients with bladder cancer, while these patients are often excluded from the survival analysis, which increases the selection bias of the study subjects in the prediction model. Methods: Clinicopathological information of bladder cancer patients was retrieved from the Surveillance, Epidemiology, and End Results (SEER) database, and the patients were categorized at random into the training and validation cohorts. The random forest method was used to calculate the importance of clinical variables in the training cohort. Multivariate and univariate analyses were undertaken to assess the risk indicators, and the prediction nomogram based on the competitive risk model was constructed. The model's performance was evaluated utilizing the calibration curve, consistency index (C index), and the area under the receiver operator characteristic curve (AUC). Results: In total, we enrolled 39285 bladder cancer patients in the study (27500 patients were allotted to the training cohort, whereas 11785 were allotted to the validation cohort). A competitive risk model was constructed to predict bladder cancer-specific mortality. The overall C index of patients in the training cohort was 0.876, and the AUC values were 0.891, 0.871, and 0.853, correspondingly, for 1-, 3-, and 5-year cancer-specific mortality. On the other hand, the overall C index of patients in the validation cohort was 0.877, and the AUC values were 0.894, 0.870, and 0.847 for 1-, 3-, and 5-year correspondingly, suggesting a remarkable predictive performance of the model. Conclusions: The competitive risk model proved to be of great accuracy and reliability and could help clinical decision-makers improve their management and approaches for managing bladder cancer patients.

The reliability, functional quality, understandability, and actionability of fall prevention content in YouTube: an observational study.

BACKGROUND: Falls are common but dangerous in the elderly. More and more seniors are searching for healthcare information online. YouTube has become the world's most popular video streaming platform. Albeit thousands of fall prevention videos are available on YouTube, their reliability, functional quality, understandability, and actionability have not been verified. METHODS: The top 300 watched videos on YouTube related to fall prevention were retrieved. After exclusion, all qualified sample videos were evaluated by three validated assessment instruments (the PEMAT scale, the HONCode scale, and the DISCERN instrument) regarding their reliability, functional quality, understandability, and actionability. Each video's length, number of views/likes/comments, forms of expression, and the uploader's profile were collected as well. The Wilcoxon rank sum test was performed for further analysis from the perspective of expression forms and uploaders' identities. RESULTS: One hundred thirty-seven videos (45.67%) were qualified as sample videos, and individuals/organizations with medical backgrounds posted 54.01% of them. Most of the excluded videos (n = 163) were irrelevant (n = 91, 55.83%), and commercial (n = 52, 31.90%). The median video length for sample videos was 470 seconds. The DISCERN instrument indicated that 115 videos (83.94%) were of moderate to high overall quality. Medical practitioners and organizations gained the highest scores in functional quality and reliability (P < 0.05), while they also tended to use technical terms more often (mean = 3.15). The HONCode scale suggested a lack of traceability was common. The most popular and actionable form of expression was workout (n = 58, median score = 86.90, P < 0.05), while monolog and keynote presentations scored the highest in understandability (no significant difference between them). The PEMAT scale suggested videos uploaded by medical teams were the easiest to be understood (P = 0.011 and P < 0.001, respectively), whereas they were less actionable than those made by fitness trainers (P = 0.039 and P < 0.001, respectively). CONCLUSIONS: Cooperation between the medical team and fitness trainers is expected for better health promotion. Plain language is advised, and sources should be provided. As for expression form, monolog or keynote presentations, plus workout clips, might be the most effective.

Noncovalent Postmodification Guided Reversible Compartmentalization of Polymeric Micelles.

Compartmentalized micelles (CMs) are promising tailor-made soft matters that mimic natural designed structures and functions. Despite the structure of complex CMs, manipulating CM structures accessibly and reversibly remains elusive. Here, we report the fabrication of CMs via a generally valid noncovalent postmodification process. Starting from precursor micelles (PMs) based on one diblock copolymer, aromatic modification leads to the compartmentalization of PMs into well-defined spherical CMs. Control over compartment number, size and distribution in CMs, and segment distribution in their linear hierarchical assemblies is attained by simply tuning the postmodification degree and solvent composition. We also demonstrate the reversible transformation between PM and CMs during several heating-cooling cycles, which endows the micelles with potential in reversible functional transitions in situ close to nature's capability. Moreover, both hierarchically assembled or ill-structured micelles can rearrange into homogeneous CMs after one heating-cooling cycle, featuring the postmodification guided compartmentalization strategy with unprecedented micelle reproducibility.

Transanal endoscopic microsurgery: exploring its indications and novel applications. A narrative review.

Featuring some advantages of endoscopy and microsurgery, transanal endoscopic microsurgery (TEM) was first introduced in treating local early-stage rectal lesions in 1983. However, its applications to rectal surgery have remained virtually unchanged over the past 38 years. This review aims to describe some well-accepted indications for TEM and showcase other novel but successful applications. In this review, we conducted a thorough English literature review on the applications of transanal endoscopic microsurgery in the PubMed database. Published original articles, case reports, and letters from 1983 to 2020 were included. Retrieved articles were discussed and conclusions were made. The results showed that applications of TEM could be more flexible and extended, namely, TEM's niche applications in advanced rectal cancer after neoadjuvant chemoradiotherapy, neuroendocrine tumor, gastrointestinal stromal tumor, fistula, solitary rectal ulcer syndrome, benign stricture, and transanal total mesorectal excision are promising, while prospective studies are needed.

Enhanced recovery after surgery in patients undergoing laparoscopic partial nephrectomy. Results from a real-world randomized controlled trial.

INTRODUCTION: Enhanced recovery after surgery (ERAS) is a set of perioperative interventions to alleviate patients' stress response and complications, and to promote rehabilitation. Data on its implementation in renal cell carcinoma treated by laparoscopic partial nephrectomy are lacking. AIM: To evaluate the prospect of application of ERAS in laparoscopic partial nephrectomy based on real-world data. MATERIAL AND METHODS: Sixty patients with T1a staging renal cell carcinoma (RCC) were randomly classified as the ERAS group (31 patients) or traditional treatment group (29 patients). Relevant endpoints including postoperative length of stay, ambulation, fart, oral intake, pain at different movement and time points, postoperative nausea and vomiting, complications as well as hospitalization expenses in the two groups were analyzed and compared. RESULTS: The ERAS optimization group presented a shorter time of first-time ambulation (p = 0.008), less pain at rest and ankle movement (p < 0.05), and less feeling of nausea 2 and 4 h after surgery (p = 0.006 and 0.027, respectively). (Although the differences in hospitalization expenses, postoperative length of stay, and complications were not reached in our study (p > 0.05), they were significantly lower than those reported in other literature. CONCLUSIONS: The idea of ERAS has had an imperceptible influence on clinical strategy making for over 20 years. This study shows that it could alleviate postoperative pain both at rest and movement, enable earlier walking, and reduce postoperative nausea in patients who have undergone laparoscopic partial nephrectomy. However, its efficacy is sometimes over-extended when compared to extreme conserative. Also, specific ERAS protocols and large-sample clinical trials are needed.

Case report: laparoscopic radical cystectomy on a patient with Behçet's syndrome, our initial experience on perioperative safety.

Behçet's syndrome (BS) is a rare systemic vasculitis that involves multiple systems and organs. Owing to the long-term prescription of immunosuppressive drugs, patients with BS are prone to urothelial tumors. However, surgical treatment in these cases could be dangerous because of the potential BS-related vasculitis, bleeding, and anastomotic necrosis. Literature reported that only five radical cystectomy cases had been performed on patients with BS, whereas the perioperative mortality was 40%. Moreover, perioperative managements on these cases were less discussed due to their multidisciplinary nature and rarity. We herein report a 54-year-old patient with a 13-year history of BS, diagnosed with sarcomatoid urothelial carcinoma and successfully underwent laparoscopic radical cystectomy with bilateral ureterocutaneostomy. No evidence of tumor residual or ureterocutaneostomic necrosis was reported in the subsequent three months of follow-up. In this case, the advantages of minimally invasive surgery in dealing with the parailiac lymph nodes were demonstrated. This article presented our thoughts, strategies, and experience on ensuring the patient's perioperative safety, as well as the selection of urinary diversion. We reviewed the literature in both English and Mandarin Chinese. Currently, two published articles describe the adoption of cystectomy in treating bladder cancer patients complicated with BS, whereas not any had shared the experience of using minimally invasive surgery. Hopefully, it could offer updated and enlightening significance to all related medical practitioners.

TikTok as an Information Hodgepodge: Evaluation of the Quality and Reliability of Genitourinary Cancers Related Content.

BACKGROUND: TikTok is the world's fastest-growing video application, with 1.6 billion users in 2021. More and more patients are searching for information on genitourinary cancers via TikTok. We aim to evaluate the functional quality and reliability of genitourinary cancer-related videos on it and share our thoughts based on the results for better public health promotion. MATERIALS AND METHODS: We retrieved 167 videos on bladder, prostate, and kidney cancer from TikTok. Only 61 videos (36.53%) met the inclusion criteria and were eventually regarded as sample videos. Each video's length and descriptions, hashtags, number of views/likes/comments, forms of expression, and the uploader's profile were included. Three validated assessment instruments: the Hexagonal Radar Schema, the Health on the Net Code scale, and the DISCERN instrument, were used for evaluating the quality and reliability of the information. All misinformation was counted and categorized. Univariate analysis of variance was performed for analyzing the results. The Post-Hoc least significant difference test was conducted to explore further explanation. RESULTS: Amongst 61 sample videos, healthcare practitioners contributed the most content (n = 29, 47.54%). However, 22 posts (36.07%) were misinformative, and the most common type was using outdated data. More than half of the videos could provide good (> 1 point) content on the diseases' symptoms and examinations. However, the definition and outcomes were less addressed (tied at 21%). The HONcode scale and the DISCERN instrument revealed a consistent conclusion that most videos (n = 59, 96.72%) on TikTok were of poor to mediocre quality. Videos published by media agencies were statistically better in terms of reliability and overall score (P = 0.003 and 0.008, respectively). Fifty-three videos (86.89%) had at least two unexplained medical terms. Healthcare professionals tend to use professional terms most (mean = 5.28 words). CONCLUSIONS: Most videos on genitourinary cancers on TikTok are of poor to medium quality and reliability. However, videos posted by media agencies enjoyed great public attention and interaction. Medical practitioners could improve the video quality by cooperating with media agencies and avoiding unexplained terminologies.

Avatrombopag for chemotherapy-induced thrombocytopenia in patients with non-haematological malignancies: an international, randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: Chemotherapy-induced thrombocytopenia is common and causes chemotherapy dose reductions or treatment delays, bleeding, and suboptimal oncological outcomes. We aimed to evaluate avatrombopag, a thrombopoietin receptor agonist that increases platelet counts, in patients with non-haematological cancer and platelet counts lower than 50 ×109 cells per L. METHODS: In this randomised, double-blind, placebo-controlled, phase 3 study, patients aged 18 years or older at 71 hospitals or cancer treatment centres in China, Hungary, Poland, Russia, Serbia, Ukraine, and the USA and with ovarian, bladder, or lung cancer receiving chemotherapy who had severe thrombocytopenia were randomly assigned (2:1) to oral avatrombopag 60 mg or oral placebo once daily given 5 days before and after chemotherapy, with randomisation stratified by number of chemotherapy drugs used. Patients, investigators, and data collectors were masked to group allocation. Eligibility required two previous lines of chemotherapy or fewer, an ECOG performance status of 2 or less, and no previous history of chemotherapy-induced thrombocytopenia. The composite primary endpoint was the proportion of responders not requiring platelet transfusion or either a 15% or more chemotherapy dose reduction or a 4-day or more chemotherapy delay due to thrombocytopenia following study treatment until the start of the subsequent cycle. Analyses were done on the intention-to-treat and per protocol populations. Safety was analysed in all patients who received at least one dose of avatrombopag. The trial is registered with ClinicalTrials.gov, NCT03471078, and has been completed. FINDINGS: Between Oct 12, 2018, and June 28, 2020, 122 patients were enrolled and randomly assigned to receive avatrombopag (n=82) or placebo (n=40). Median follow-up was 31 days (IQR 22-61). Similar proportions of patients reached the primary endpoint in the avatrombopag and placebo groups (intention-to-treat: 57 [70%, 95% CI 58-79] of 82 vs 29 [73%, 95% CI 56-85] of 40; difference -3·0% (95% CI -21·6 to 15·6); p=0·72; per protocol: 51 [85%, 95% CI 73-93] of 60 vs 27 [84%, 95% CI 67-95] of 32; 0·6% (95% CI -20·8 to 22·1); p=0·96). 15 (18%) of 82 patients had serious adverse events in the avatrombopag group and eight (20%) of 40 in the placebo group, of which thrombocytopenia was most common (4 [5%] of 82 and 4 [10%] of 40 patients). Common grade 3-4 treatment-emergent adverse events were neutropenia (22 [27%] of 82 and 16 [40%] of 40 patients), leukopenia (19 [23%] of 82 and 5 [13%] of 40), anaemia (16 [20%] of 82 and 9 [23%] of 40), and thrombocytopenia (16 [20%] of 82 and 14 [35%] of 40). Most adverse events were considered unrelated to study drug. No treatment-related deaths were reported. INTERPRETATION: In this population of patients with non-haematological malignancies who are relatively chemotherapy naive, chemotherapy-induced thrombocytopenia treatment outcomes were similar between the avatrombopag and placebo groups. Given its safety and ability to augment platelet counts in patients with chemotherapy-induced thrombocytopenia, evaluation of avatrombopag in populations with more persistent chemotherapy-induced thrombocytopenia is warranted. FUNDING: Dova Pharmaceuticals, a Sobi company.

Pneumothorax during retroperitoneal laparoscopic partial nephrectomy in a lupus nephritis patient: A case report.

BACKGROUND: Downgrading target treatment and laparoscopic partial nephrectomy have become increasingly popular in patients with renal cell carcinomas. Rare as it is, pneumothorax is one of the most severe intraoperative complications which needs immediate recognition. On the other hand, as a rheumatological disease, lupus nephritis requires a long period of hormone therapy. Cases of pneumothorax in hormone-consuming renal cancer patients are even fewer. CASE SUMMARY: A 39-year-old woman was admitted to our department to take a laparoscopic partial nephrectomy. The patient had a medical history of lupus nephritis and renal clear cell carcinoma with hormone and target treatment. Her blood oxygen saturation dropped to 92% during the operation, and pneumothorax was detected by ultrasound. O2 inhalation and lung dilation were performed. Her vital signs were monitored closely throughout the operation. The operation was accomplished, and she regained consciousness smoothly. A postoperative bedside chest X-ray was conducted after she was transferred to the urosurgery ward, while no evidence of further pneumothorax or lib injury was observed. CONCLUSION: Pneumothorax is a severe complication in laparoscopic or robotic-assisted laparoscopic operations, especially in retroperitoneal ones. It is easily neglected unless the injury of the diaphragm is found. Low insufflation pressure and shorter operation time are necessary for patients with a history of long-term hormone consumption or chronic immune system disease.