Time to lymphoma treatment within 24 months in 'watch and wait' follicular lymphoma is associated with inferior outcomes: A multicentre analysis.

Some 'watch and wait' (W&W) FL patients suffer from rapid progression in a short term. Herein, we sought to identify these patients and also develop a risk score to screen them at diagnosis. Between 2008 and 2022, a total of 411 FL patients managed by the W&W strategy from 16 cancer centres were retrospectively enrolled in this study, and their time to lymphoma treatment (TLT) and progression-free survival (PFS) were evaluated. Thirty-five percent of W&W FL patients experienced TLT within 24 months (TLT24) after diagnosis. Their 5-year PFS rate was significantly lower than those without treatment at 24 months (62.3% vs. 89.5%). In multivariable analysis, five factors were identified as independent predictors of TLT24: stages III-IV, ß2 microglobulin ≥3 mg/L, lymphocyte-to-monocyte ratio <3.8, bone marrow involvement and spleen enlargement (above umbilical line). Their AUCs for TLT24 were 0.76 (95% CI, 0.70-0.82) in the training cohort and 0.76 (95% CI, 0.67-0.85) in the validation cohort respectively. Risk groups were also associated with PFS (p < 0.001). In FL patients initially managed by W&W, TLT24 was associated with poor outcomes. This multivariable model helps screening for predicting TLT24, which may be useful to identify candidates for early interventional treatment.

Arsenical keratosis in China: A case report and review of the literature.

BACKGROUND: Arsenical keratosis is a precancerous dermatosis which could be induced by long-term exposure to arsenic poisoning. Arsenic is often added to traditional Chinese medicine in a non-compliant manner to increase the effectiveness of psoriasis treatment, which is often the main cause of arsenic poisoning in Chinese patients with psoriasis. OBJECTIVES: We performed a systemic review of arsenic keratosis during the past 32 years to better understand the sources, treatment, and prognosis of arsenic keratosis in China. METHODS: We searched Medline/PubMed, Embase, CNKI, and Wanfang databases for research studies published between 1992 and 2024. A total of 64 papers with 78 individual Chinese of arsenical keratosis were included in this analysis. RESULTS: Of the patients included in the analysis, 92.21% of arsenic poisoning was due to iatrogenic factors: Chinese traditional medicine. Seventy-six patients (98.70%) had skin manifestation of hyperkeratotic papules and plaques, 68 patients (88.31%) had hyperpigmentation, 43 cases (55.84%) had hypopigmentation, and only 4 had a clear indication of Mees' lines in nails. A total of 52.63% of patients presented with tumors, including squamous cell carcinoma, Bowen's disease, and basal cell carcinoma. For patients with tumors, 20 opted for surgery, 6 for radiotherapy, and 3 for PDT. All patients with only cutaneous tumors are currently well-controlled. Death occurred in one patient with metastatic squamous cell carcinoma. Keratinizing papules improved significantly in 70.59% of patients treated with Acitretin Capsules. CONCLUSIONS: In this study, arsenic sources in Chinese patients were mainly from traditional Chinese medicine, and there were no reports of exposure to water sources or occupational sources in the past 32 years. Most of the patients showed keratinizing papules and pigmentation, and more than 1/2 of the patients showed skin tumors, mainly squamous cell carcinoma. The treatments of tumors are mainly surgical treatment, PDT and radiotherapy can also be selected. The improvement in keratinizing rash was greater than 70% with acitretin capsules. Patients with this disease should be regularly followed up for early detection and timely treatment of potential malignant tumors.

CHRONOS-4: phase 3 study of copanlisib plus rituximab-based immunochemotherapy in relapsed indolent B-cell lymphoma.

ABSTRACT: Copanlisib, a pan-class I phosphatidylinositol 3-kinase inhibitor with predominant activity against the α and δ isoforms, previously demonstrated durable responses as monotherapy and improved progression-free survival (PFS) in combination with rituximab in patients with relapsed indolent non-Hodgkin lymphoma (iNHL). CHRONOS-4 was a phase 3, randomized, double-blind, placebo-controlled study to investigate the efficacy and safety of copanlisib in combination with standard immunochemotherapy in patients with relapsed iNHL. Patients (n = 524) were randomized (1:1) to copanlisib (60 mg IV) plus immunochemotherapy (rituximab and bendamustine [R-B] or placebo plus R-B). Copanlisib/placebo were administered with R-B (days 1, 8, and 15 of each 28-day cycle) for ≤6 cycles and as monotherapy from cycle 7 up to 12 months. The primary study end point was PFS. Median exposure was 8.5 months (0.2-12.9) for copanlisib plus R-B and 11.4 months (0.1-12.6) for placebo plus R-B. Median PFS was 32.9 months (95% confidence interval [CI], 24.4-38.6) for copanlisib plus R-B and 33.3 months (95% CI, 27.8-42.8) for placebo plus R-B (hazard ratio, 1.13; 95% CI, 0.88-1.44; P = .83). No differences between treatment arms were observed in overall survival (data not yet mature), objective response rate, and duration of response for the overall population or individual histology types. Overall, copanlisib plus R-B was associated with higher rates of serious treatment-emergent adverse events (TEAEs), grade 4 and 5 TEAEs, and treatment discontinuation. A number of serious TEAEs were infections. Overall, copanlisib plus R-B did not provide clinical benefit vs placebo plus R-B and was associated with worse tolerability in patients with relapsed iNHL. This trial was registered at www.ClinicalTrials.gov as #NCT02626455.

Preclinical evaluation and phase 1 study of the PI3Kα/δ inhibitor TQ-B3525 in Chinese patients with advanced cancers.

BACKGROUND: Phosphatidylinositol 3-kinase (PI3K) inhibitors transformed management of various malignancies. This study preclinically characterized TQ-B3525 (dual PI3Kα/δ inhibitor) and assessed the recommended phase 2 dose (RP2D), safety, efficacy, and pharmacokinetics in relapsed or refractory (R/R) lymphoma or advanced solid tumors (STs). METHODS: Oral TQ-B3525 was given at eight dose levels on a 28-day cycle. Primary end points were dose-limiting toxicity (DLT), maximum tolerated dose (MTD), and safety. RESULTS: TQ-B3525 showed high selectivity and suppressed tumor growth. Between June 12, 2018, and November 18, 2020, 80 patients were enrolled (63 in dose-escalation cohort; 17 in dose-expansion cohort). Two DLTs occurred in two (two of 63, 3.2%) DLT-evaluable patients; MTD was not identified. TQ-B3525 at 20 mg once daily was selected as RP2D. Grade 3 or worse treatment-related adverse events mainly included hyperglycemia (16.3%), neutrophil count decreased (15.0%), and diarrhea (10.0%). Two (2.5%) treatment-related deaths were reported. Sixty patients with R/R lymphoma and 11 advanced STs demonstrated objective response rates of 68.3% and 9.1%, disease control rates of 91.7% and 54.6%, median progression-free survivals of 12.1 and 1.1 months; median overall survivals were not reached. CONCLUSION: TQ-B3525 exhibited rapid absorption and a nearly proportional increase in exposure. Acceptable safety and promising efficacy support further investigation of TQ-B3525 (20 mg once daily) for R/R lymphoma.

Efficacy and Safety of a Self-Improved Continuous Bladder Irrigation Sensor Device in Patients after Transurethral Resection of the Prostate: A Prospective Study.

PURPOSE: To explore the efficacy and safety of a self-improved continuous bladder irrigation (CBI) sensor device after transurethral resection of the prostate (TURP). MATERIALS AND METHODS: A total of 160 patients with benign prostatic hyperplasia who received TURP from June 2021 to May 2022 were selected. According to the envelope randomization method, patients were divided into a control group (80 cases) and study group (80 cases). In the control group, the speed of bladder flushing fluid was adjusted according to the clinical experience of nurses. On the basis of the control group, the self-improved CBI sensor device was used in the study group to observe the postoperative comfort and complication rate in the two groups. RESULTS: The comfort of patients in the study group was significantly higher than that of patients in the control group (97.50% vs. 88.75%, P = .023), and the number of postoperative complications in the control group was significantly higher than that in the study group (8.75% vs. 1.25%, P = .021). Meanwhile, the average amount of irrigation fluid in the study group was obviously lower than that in the control group (26.4 L vs. 27.8 L, P = .011). In addition, patients in the study group had a significantly shorter hospital stay than the controls (3.3 days vs. 3.6 days, P = .005). CONCLUSION: Implementation of the new self-improved CBI sensor device for patients after TURP can improve their awareness regarding disease-related knowledge, alleviate their fear and anxiety, improve their compliance and comfort with treatment and nursing, and reduce the incidence of complications.

Incremental regression of localization context for automatic segmentation of ossified ligamentum flavum from CT data.

PURPOSE: Segmentation of ossified ligamentum flavum (OLF) plays a crucial role in developing computer-assisted, image-guided systems for decompressive thoracic laminectomy. Manual segmentation is time-consuming, tedious, and label-intensive. It also suffers from inter- and intra-observer variability. Automatic segmentation is highly desired. METHODS: A two-stage, localization context-aware framework is developed for automatic segmentation of ossified ligamentum flavum. In the first stage, localization heatmaps of OLFs are obtained via incremental regression. In the second stage, the obtained heatmaps are then treated as the localization context for a segmentation U-Net. Our framework can directly map a whole volumetic data to its volume-wise labels. RESULTS: We designed and conducted comprehensive experiments on datasets of 100 patients to evaluate the performance of the proposed method. Our method achieved an average Dice similarity coefficient of 61.2 ± 7.6%, an average surface distance of 1.1 ± 0.5 mm, and an average positive predictive value of 62.0 ± 12.8%. CONCLUSION: To the best knowledge of the authors, this is the first study aiming for automatic segmentation of ossified ligamentum flavum. Results from the comprehensive experiments demonstrate the superior performance of the proposed method over the state-of-the-art methods.

RIRS with FV-UAS vs. MPCNL for 2-3-cm upper urinary tract stones: a prospective study.

To observe the efficacy and safety of retrograde intrarenal surgery (RIRS) combined with flexible vacuum-assisted ureteral access sheath (FV-UAS) and minimally invasive percutaneous nephrolithotomy (MPCNL) in patients with 2-3 cm upper urinary tract stones. A total of 160 patients with 2-3 cm upper urinary tract stones were prospectively randomized into 2 groups-80 in the FV-UAS group and 80 cases as control in the MPCNL group. The stone-free rates (SFRs) at different times (postoperative 1st day and 4th week) were considered as the primary outcome of the study. The secondary end points were operative time, hemoglobin decrease, postoperative hospital stay, and operation-related complications. There was no obvious difference between the two groups in patient's demographics and preoperative clinical characteristics (all P > 0.05). Postoperative data showed that mean decrease in hemoglobin level was less in FV-UAS group than that in MPCNL group (5.3 vs. 10.8 g/L, P < 0.001). Postoperative hospital stay in FV-UAS group was more shorten than that in MPCNL group (2.7 vs. 4.9 days, P < 0.001). There was no statistical significance between the two groups in SFRs during postoperative 1st day and 4th week (both P > 0.05). However, in terms of the rates of bleeding and pain, MPCNL group were both significantly higher than FV-UAS group (6.2 vs. 0.0%, P = 0.023; 16.2 vs. 2.5%, P = 0.003; respectively). Our study showed that RIRS with FV-UAS, a new partnership to treat 2-3 cm upper urinary tract stones, was satisfying as it achieved a high SFR rate and a low rate of complications. This method was safe and reproducible in clinical practice.

Selinexor With Anti-PD-1 Antibody as a Potentially Effective Regimen for Patients With Natural Killer/T-Cell Lymphoma Failing Prior L-Asparaginase and PD-1 Blockade.

BACKGROUND: Natural killer/T-cell lymphoma (NKTCL) is a rare and heterogeneous tumor type of non-Hodgkin's lymphoma (NHL) with a poor clinical outcome. There is no standardized salvage treatment failing l-asparaginase-based regimens. Here we report our retrospective results of the combined use of selinexor and PD-1 blockade (tislelizumab) in 5 patients with NKTCL who had exhausted almost all available treatments. PATIENTS AND METHODS: A total of 5 patients with relapsed/refractory(R/R) NK/T-cell lymphomas failing prior l-asparaginase and anti-PD-1 antibody were retrospectively collected. They were treated with at least one cycle of XPO1 inhibitor plus the same anti-PD-1 antibody. Anti-PD-1 antibody (Tislelizumab) was administrated at 200 mg on day 1 every 3 weeks and selinexor doses and schedules ranged from 40 mg weekly for 2 weeks per 21-day cycle to 60 mg weekly per cycle. RESULTS: Five patients with relapsed NKTCL with extensive organ involvement including 4 central nervous system (CNS) infiltration patients were included. Four patients achieved objective responses including 3 complete responses (CR) and 1 partial response (PR). After a median follow-up time of 14.5 (range, 5-22) months, 1 patient was still in remission with CR, and the other 4 patients discontinued due to disease progression with a median progression-free survival (PFS) of 6 months and median overall survival (OS) of 12 months. Four patients with CNS involvement achieved a median OS of 8 months. Our data suggest that selinexor in combination with an anti-PD-1 antibody is a promising small molecule and immunotherapy combination regimen for patients with relapsed or refractory NKTCL.

Nonlinear regression of remaining surgery duration from videos via Bayesian LSTM-based deep negative correlation learning.

In this paper, we address the problem of estimating remaining surgery duration (RSD) from surgical video frames. We propose a Bayesian long short-term memory (LSTM) network-based Deep Negative Correlation Learning approach called BD-Net for accurate regression of RSD prediction as well as estimation of prediction uncertainty. Our method aims to extract discriminative visual features from surgical video frames and model the temporal dependencies among frames to improve the RSD prediction accuracy. To this end, we propose to train an ensemble of Bayesian LSTMs on top of a backbone network by the way of deep negative correlation learning (DNCL). More specifically, we deeply learn a pool of decorrelated Bayesian regressors with sound generalization capabilities through managing their intrinsic diversities. BD-Net is simple and efficient. After training, it can produce both RSD prediction and uncertainty estimation in a single inference run. We demonstrate the efficacy of BD-Net on publicly available datasets of two different types of surgeries: one containing 101 cataract microscopic surgeries with short durations and the other containing 80 cholecystectomy laparoscopic surgeries with relatively longer durations. Experimental results on both datasets demonstrate that the proposed BD-Net achieves better results than the state-of-the-art (SOTA) methods. A reference implementation of our method can be found at: https://github.com/jywu511/BD-Net.

Targeting Bcl-xL is a potential therapeutic strategy for extranodal NK/T cell lymphoma.

Extranodal natural killer/T cell lymphoma, nasal type (ENKTL) is an aggressive lymphoid malignancy with a poor prognosis and lacks standard treatment. Targeted therapies are urgently needed. Here we systematically investigated the druggable mechanisms through chemogenomic screening and identified that Bcl-xL-specific BH3 mimetics effectively induced ENKTL cell apoptosis. Notably, the specific accumulation of Bcl-xL, but not other Bcl-2 family members, was verified in ENKTL cell lines and patient tissues. Furthermore, Bcl-xL high expression was shown to be closely associated with worse patient survival. The critical role of Bcl-xL in ENKTL cell survival was demonstrated utilizing selective inhibitors, genetic silencing, and a specific degrader. Additionally, the IL2-JAK1/3-STAT5 signaling was implicated in Bcl-xL dysregulation. In vivo, Bcl-xL inhibition reduced tumor burden, increased apoptosis, and prolonged survival in ENKTL cell line xenograft and patient-derived xenograft models. Our study indicates Bcl-xL as a promising therapeutic target for ENKTL, warranting monitoring in ongoing clinical trials by targeting Bcl-xL.

cdh23 affects congenital hearing loss through regulating purine metabolism.

Introduction: The pathogenic gene CDH23 plays a pivotal role in tip links, which is indispensable for mechanoelectrical transduction in the hair cells. However, the underlying molecular mechanism and signal regulatory networks that influence deafness is still largely unknown. Methods: In this study, a congenital deafness family, whole exome sequencing revealed a new mutation in the pathogenic gene CDH23, subsequently; the mutation has been validated using Sanger sequencing method. Then CRISPR/Cas9 technology was employed to knockout zebrafish cdh23 gene. Startle response experiment was used to compare with wide-type, the response to sound stimulation between wide-type and cdh23-/-. To further illustrate the molecular mechanisms underlying congenital deafness, comparative transcriptomic profiling and multiple bioinformatics analyses were performed. Results: The YO-PRO-1 assay result showed that in cdh23 deficient embryos, the YO-PRO-1 signal in inner ear and lateral line neuromast hair cells were completely lost. Startle response experiment showed that compared with wide-type, the response to sound stimulation decreased significantly in cdh23 mutant larvae. Comparative transcriptomic showed that the candidate genes such as atp1b2b and myof could affect hearing by regulating ATP production and purine metabolism in a synergetic way with cdh23. RT-qPCR results further confirmed the transcriptomics results. Further compensatory experiment showed that ATP treated cdh23-/- embryos can partially recover the mutant phenotype. Conclusion: In conclusion, our study may shed light on deciphering the principal mechanism and provide a potential therapeutic method for congenital hearing loss under the condition of CDH23 mutation.

Interleukin-34-NF-κB signaling aggravates myocardial ischemic/reperfusion injury by facilitating macrophage recruitment and polarization.

BACKGROUND: Macrophage infiltration and polarization are integral to the progression of heart failure and cardiac fibrosis after ischemia/reperfusion (IR). Interleukin 34 (IL-34) is an inflammatory regulator related to a series of autoimmune diseases. Whether IL-34 mediates inflammatory responses and contributes to cardiac remodeling and heart failure post-IR remains unclear. METHODS: IL-34 knock-out mice were used to determine the role of IL-34 on cardiac remodeling after IR surgery. Then, immunofluorescence, flow cytometry assays, and RNA-seq analysis were performed to explore the underlying mechanisms of IL-34-induced macrophage recruitment and polarization, and further heart failure after IR. FINDINGS: By re-analyzing single-cell RNA-seq and single-nucleus RNA-seq data of murine and human ischemic hearts, we showed that IL-34 expression was upregulated after IR. IL-34 knockout mitigated cardiac remodeling, cardiac dysfunction, and fibrosis after IR and vice versa. RNA-seq analysis revealed that IL-34 deletion correlated negatively with immune responses and chemotaxis after IR injury. Consistently, immunofluorescence and flow cytometry assays demonstrated that IL-34 deletion attenuated macrophage recruitment and CCR2+ macrophage polarization. Mechanistically, IL-34 deficiency repressed both the canonical and noncanonical NF-κB signaling pathway, leading to marked reduction of P-IKKß and P-IκBα kinase levels; downregulation of NF-κB p65, RelB, and p52 expression, which drove the decline in chemokine CCL2 expression. Finally, IL-34 and CCL2 levels were increased in the serum of acute coronary syndrome patients, with a positive correlation between circulating IL-34 and CCL2 levels in clinical patients. INTERPRETATION: In conclusion, IL-34 sustains NF-κB pathway activation to elicit increased CCL2 expression, which contributes to macrophage recruitment and polarization, and subsequently exacerbates cardiac remodeling and heart failure post-IR. Strategies targeting IL-34-centered immunomodulation may provide new therapeutic approaches to prevent and reverse cardiac remodeling and heart failure in clinical MI patients after percutaneous coronary intervention. FUNDING: This study was supported by the National Nature Science Foundation of China (81670352 and 81970327 to R T, 82000368 to Q F).

Comparative efficacy between retrograde intrarenal surgery with vacuum-assisted ureteral access sheath and minimally invasive percutaneous nephrolithotomy for 1-2†cm infectious upper ureteral stones: a prospective, randomized controlled study.

Objective: To observe the efficacy and safety of retrograde intrarenal surgery combined with vacuum-assisted ureteral access sheath (V-UAS) and minimally invasive percutaneous nephrolithotomy (MPCNL) in patients with 1-2 cm infectious upper ureteral stone. Patients and methods: A total of 173 patients with 1-2 cm infectious upper ureteral stone were prospectively randomized into two groups. Eighty-six in the V-UAS group and 87 cases as control in the MPCNL group. The SFRs at different times (Postoperative 1 day, 2nd week and 4th week) was considered as the primary outcome of the study. The secondary end points were operative time, postoperative hospital stay and operative complications. Results: There was no obvious difference between two groups in patients' demographics and preoperative clinical characteristics (all P > 0.05). Postoperative data showed that the SFR at postoperative 1 day in the V-UAS group was significantly lower than that in the MPCNL group (73.2% vs. 86.2%, P = 0.034). However, there was no statistical significance between two groups in SFRs during postoperative 2 weeks and 4 weeks (All P > 0.05). The levels of WBC, CRP and PCT were all significant lower in the V-UAS group than those in the MPCNL group at the postoperative 24 h and 48 h (all P < 0.05). Postoperative complications included fever (≥38.5°C), bleeding, pain and urosepsis. In terms of the rates of fever, pain and urosepsis, MPCNL group were all significantly higher than those in the V-UAS group (10.3 vs. 2.4%, P = 0.031; 14.9 vs. 2.4%, P = 0.003; 4.6 vs. 0.0%, P = 0.044; respectively). No significant difference was found between two groups in bleeding. Meanwhile, postoperative hospital stay in the V-UAS group was more shorten than that in the MPCNL group (3.7 vs. 5.9 days, P < 0.001). Conclusions: Our study showed that RIRS with V-UAS, a new partnership to treat 1-2 cm infectious upper ureteral stones, was satisfying as it achieved a high SFR rate and a low rate of infectious complications. This method was safe and reproducible in clinical practice.

The regulatory role and mechanism of lncTUG1 on cartilage apoptosis and inflammation in osteoarthritis.

BACKGROUND: Long-stranded non-coding RNA TUG1 is lowly expressed in osteoarthritic chondrocytes. This study aimed to elucidate the role of TUG1 in osteoarthritic cartilage damage and the underlying mechanisms. METHODS: Combined database analysis, using primary chondrocytes as well as the C28/I2 cell line, was performed by qRT-PCR, Western blotting, and immunofluorescence to determine the expression of TUG1, miR-144-3p, DUSP1, and other target proteins. Dual luciferase reporter gene and RIP to verify direct interaction of TUG1 with miR-144-3-p and miR-144-3-p with DUSP1, Annexin V-FITC/PI double staining to detect apoptosis. CCK-8 to detect cell proliferation. The biological significance of TUG1, miR-144-3p, and DUSP1 was assessed in vitro experiments using siRNA for TUG1, mimic and repressor for miR-144-3p, and overexpression plasmid for DUSP1. In this study, all data were subjected to a t-test or one-way analysis of variance with a p-value < 0.05 as the cutoff. RESULTS: TUG1 expression was closely associated with osteoarthritic chondrocyte damage, and knockdown of TUG1 significantly promoted chondrocyte apoptosis and inflammation. In the present study, we found that TUG1 inhibited chondrocyte apoptosis and inflammation by competitively binding miR-144-3p, deregulating the negative regulatory effect of miR-144-3p on DUSP1, promoting DUSP1 expression, and inhibiting the p38 MAPK signaling pathway. CONCLUSIONS: In conclusion, our study clarifies the role of the ceRNA regulatory network of TUG1/miR-144-3p/DUSP1/P38 MAPK in OA cartilage injury and provides an experimental and theoretical basis for genetic engineering tools to promote articular cartilage repair.

LAST: LAtent Space-Constrained Transformers for Automatic Surgical Phase Recognition and Tool Presence Detection.

When developing context-aware systems, automatic surgical phase recognition and tool presence detection are two essential tasks. There exist previous attempts to develop methods for both tasks but majority of the existing methods utilize a frame-level loss function (e.g., cross-entropy) which does not fully leverage the underlying semantic structure of a surgery, leading to sub-optimal results. In this paper, we propose multi-task learning-based, LAtent Space-constrained Transformers, referred as LAST, for automatic surgical phase recognition and tool presence detection. Our design features a two-branch transformer architecture with a novel and generic way to leverage video-level semantic information during network training. This is done by learning a non-linear compact presentation of the underlying semantic structure information of surgical videos through a transformer variational autoencoder (VAE) and by encouraging models to follow the learned statistical distributions. In other words, LAST is of structure-aware and favors predictions that lie on the extracted low dimensional data manifold. Validated on two public datasets of the cholecystectomy surgery, i.e., the Cholec80 dataset and the M2cai16 dataset, our method achieves better results than other state-of-the-art methods. Specifically, on the Cholec80 dataset, our method achieves an average accuracy of 93.12±4.71%, an average precision of 89.25±5.49%, an average recall of 90.10±5.45% and an average Jaccard of 81.11 ±7.62% for phase recognition, and an average mAP of 95.15±3.87% for tool presence detection. Similar superior performance is also observed when LAST is applied to the M2cai16 dataset.

CholecTriplet2021: A benchmark challenge for surgical action triplet recognition.

Context-aware decision support in the operating room can foster surgical safety and efficiency by leveraging real-time feedback from surgical workflow analysis. Most existing works recognize surgical activities at a coarse-grained level, such as phases, steps or events, leaving out fine-grained interaction details about the surgical activity; yet those are needed for more helpful AI assistance in the operating room. Recognizing surgical actions as triplets of combination delivers more comprehensive details about the activities taking place in surgical videos. This paper presents CholecTriplet2021: an endoscopic vision challenge organized at MICCAI 2021 for the recognition of surgical action triplets in laparoscopic videos. The challenge granted private access to the large-scale CholecT50 dataset, which is annotated with action triplet information. In this paper, we present the challenge setup and the assessment of the state-of-the-art deep learning methods proposed by the participants during the challenge. A total of 4 baseline methods from the challenge organizers and 19 new deep learning algorithms from the competing teams are presented to recognize surgical action triplets directly from surgical videos, achieving mean average precision (mAP) ranging from 4.2% to 38.1%. This study also analyzes the significance of the results obtained by the presented approaches, performs a thorough methodological comparison between them, in-depth result analysis, and proposes a novel ensemble method for enhanced recognition. Our analysis shows that surgical workflow analysis is not yet solved, and also highlights interesting directions for future research on fine-grained surgical activity recognition which is of utmost importance for the development of AI in surgery.

Sugemalimab Monotherapy for Patients With Relapsed or Refractory Extranodal Natural Killer/T-Cell Lymphoma (GEMSTONE-201): Results From a Single-Arm, Multicenter, Phase II Study.

PURPOSE: Relapsed or refractory extranodal natural killer/T-cell lymphoma (R/R ENKTL) is a rare and aggressive type of non-Hodgkin lymphoma with limited treatment options. This phase II study evaluated the efficacy and safety of sugemalimab, an anti-PD-L1 monoclonal antibody, in R/R ENKTL. METHODS: Eligible patients received sugemalimab 1,200 mg intravenously once every 3 weeks for up to 24 months or until progression, death, or study withdrawal. The primary end point was objective response rate (ORR) assessed by an independent radiologic review committee. Key secondary end points included ORR assessed by the investigators, complete response rate, duration of response, and safety. RESULTS: At the data cutoff (February 23, 2022), 80 patients were enrolled and followed for a median of 18.7 months. At baseline, 54 (67.5%) had stage IV disease and 39 (48.8%) had received ≥2 lines of prior systemic therapy. Independent radiologic review committee-assessed ORR was 44.9% (95% CI, 33.6 to 56.6); 28 (35.9%) patients achieved a complete response and seven (9.0%) achieved a partial response, with a 12-month duration of response rate of 82.5% (95% CI, 62.0 to 92.6). Investigator-assessed ORR was 45.6% (95% CI, 34.3 to 57.2), and 24 (30.4%) patients achieved a complete response. Most treatment-emergent adverse events were grade 1-2 in severity, and grade ≥ 3 events were reported in 32 (40.0%) patients. CONCLUSION: Sugemalimab showed robust and durable antitumor activity in R/R ENKTL. Treatment was well tolerated with expected safety profile for this drug class.

Diagnostic performance and prognostic value of circulating tumor DNA methylation marker in extranodal natural killer/T cell lymphoma.

Circulating tumor DNA (ctDNA) carries tumor-specific genetic and epigenetic variations. To identify extranodal natural killer/T cell lymphoma (ENKTL)-specific methylation markers and establish a diagnostic and prognosis prediction model for ENKTL, we describe the ENKTL-specific ctDNA methylation patterns by analyzing the methylation profiles of ENKTL plasma samples. We construct a diagnostic prediction model based on ctDNA methylation markers with both high specificity and sensitivity and close relevance to tumor staging and therapeutic response. Subsequently, we built a prognostic prediction model showing excellent performance, and its predictive accuracy is significantly better than the Ann Arbor staging and prognostic index of natural killer lymphoma (PINK) risk system. Notably, we further establish a PINK-C risk grading system to select individualized treatment for patients with different prognostic risks. In conclusion, these results suggest that ctDNA methylation markers are of great value in diagnosis, monitoring, and prognosis, which might have implications for clinical decision-making of patients with ENKTL.

Meniere's Disease Patients with Distinct Sac Pathoanatomic Findings React Differently to Endolymphatic Duct Blockage.

OBJECTIVES: To explore the possible difference in response to endolymphatic duct blockage (EDB) treatment in patients with Meniere's disease (MD) with distinct pathoanatomic characteristics of the sac. METHODS: In a total of 24 patients with MD receiving EDB treatment, the dynamics of the vertigo attack, hearing, vestibular function, and endolymph hydrops (EH) before surgery and 40 months following surgery in patients with normoplastic extraosseous portion of endolymphatic sac (eES) were compared with that in patients with atrophic eES. RESULTS: A higher prevalence of complete vertigo control, better cochlear and vestibular function, and lower endolymph to vestibule-volume ratio were found in patients with normoplastic eES than in those with atrophic eES. Moreover, the reversal of EH was found in a total of six patients in normoplastic eES group, but no reversal of EH was detected in the atrophic eES group after surgery. CONCLUSIONS: A difference in response to EDB treatment was shown in the MD patients with normoplastic eES and those with atrophic eES; the reversal of EH was found in the normoplastic eES group, but not in the atrophic eES group after surgery, suggesting two distinct pathologies in the eESs may underlie the pathogenesis of EH in two subgroups of MD patients. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:2761-2769, 2023.