[Construction of a model based on multipoint full-layer puncture biopsy for predicting pathological complete response after neoadjuvant therapy for locally advanced rectal cancer].

Objective: To investigate the value of transanal multipoint full-layer puncture biopsy (TMFP) in predicting pathological complete response (pCR) after neoadjuvant radiotherapy and chemotherapy (nCRT) in patients with locally advanced rectal cancer (LARC) and to establish a predictive model for providing clinical guidance regarding the treatment of LARC. Methods: In this multicenter, prospective, cohort study, we collected data on 110 LARC patients from four hospitals between April 2020 and March 2023: Beijing Chaoyang Hospital of Capital Medical University (50 patients), Beijing Friendship Hospital of Capital Medical University (41 patients), Qilu Hospital of Shandong University (16 patients), and Zhongnan Hospital of Wuhan University (three patients). The patients had all received TMFP after completing standard nCRT. The variables studied included (1) clinicopathological characteristics; (2) clinical complete remission (cCR) and efficacy of TMFP in determining pCR after NCRT in LARC patients; and (3) hospital attended, sex, age, clinical T- and N-stages, distance between the lower margin of the tumor and the anal verge, baseline and post-radiotherapy serum carcinoembryonic antigen (CEA) and carbohydrate antigen (CA)19-9 concentrations, chemotherapy regimen, use of immunosuppressants with or without radiotherapy, radiation therapy dosage, interval between surgery and radiotherapy, surgical procedure, clinical T/N stage after radiotherapy, cCR, pathological results of TMFP, puncture method (endoscopic or percutaneous), and number and timing of punctures. Single-factor and multifactorial logistic regression analysis were used to determine the factors affecting pCR after NCRT in LARC patients. A prediction model was constructed based on the results of multivariat analysis and the performance of this model evaluated by analyzing subject work characteristics (ROC), calibration, and clinical decision-making (DCA) curves. pCR was defined as complete absence of tumor cells on microscopic examination of the surgical specimens of rectal cancer (including lymph node dissection) after NCRT, that is, ypT0+N0. cCR was defined according to the Chinese Neoadjuvant Rectal Cancer Waiting Watch Database Study Collaborative Group criteria after treatment, which specify an absence of ulceration and nodules on endoscopy; negative rectal palpation; no tumor signals on rectal MRI T2 and DWI sequences; normal serum CEA concentrations, and no evidence of recurrence on pelvic computed tomography/magnetic resonance imaging. Results: Of the 110 patients, 45 (40.9%) achieved pCR after nCRT, which was combined with immune checkpoint inhibitors in 34 (30.9%). cCR was diagnosed before puncture in 38 (34.5%) patients, 43 (39.1%) of the punctures being endoscopic. There were no complications of puncture such as enterocutaneous fistulae, vaginal injury, prostatic injury, or presacral bleeding . Only one (2.3%) patient had a small amount of blood in the stools, which was relieved by anal pressure. cCR had a sensitivity of 57.8% (26/45) for determining pCR, specificity of 81.5% (53/65), accuracy of 71.8% (79/110), positive predictive value 68.4% (26/38), and negative predictive value of 73.6% (53/72). In contrast, the sensitivity of TMFP pathology in determining pCR was 100% (45/45), specificity 66.2% (43/65), accuracy 80.0% (88/110), positive predictive value 67.2% (45/67), and negative predictive value 100.0% (43/43). In this study, the sensitivity of TMFP for pCR (100.0% vs. 57.8%, χ2=24.09, P<0.001) was significantly higher than that for cCR. However, the accuracy of pCR did not differ significantly (80.0% vs. 71.8%, χ2=2.01, P=0.156). Univariate and multivariate logistic regression analyses showed that a ≥4 cm distance between the lower edge of the tumor and the anal verge (OR=7.84, 95%CI: 1.48-41.45, P=0.015), non-cCR (OR=4.81, 95%CI: 1.39-16.69, P=0.013), and pathological diagnosis by TMFP (OR=114.29, the 95%CI: 11.07-1180.28, P<0.001) were risk factors for pCR after NCRT in LARC patients. Additionally, endoscopic puncture (OR=0.02, 95%CI: 0.05-0.77, P=0.020) was a protective factor for pCR after NCRT in LARC patients. The area under the ROC curve of the established prediction model was 0.934 (95%CI: 0.892-0.977), suggesting that the model has good discrimination. The calibration curve was relatively close to the ideal 45° reference line, indicating that the predicted values of the model were in good agreement with the actual values. A decision-making curve showed that the model had a good net clinical benefit. Conclusion: Our predictive model, which incorporates TMFP, has considerable accuracy in predicting pCR after nCRT in patients with locally advanced rectal cancer. This may provide a basis for more precisely selecting individualized therapy.

[Mechanisms and clinical management of small bowel obstruction caused by kinking of the jejunojejunal anastomosis after laparoscopic Roux-en-Y gastric bypass].

Currently, obesity and its complications have become increasingly serious health issues. Bariatric surgery is an effective method of treating obesity and related metabolic complications. Among them, Roux-en-Y gastric bypass (RYGB) is still considered the "gold standard" procedure for bariatric surgery. Small bowel obstruction is one of the possible complications after RYGB, and in addition to the formation of intra-abdominal hernias, kinking of the jejunojejunal anastomosis is an important cause of small bowel obstruction. The early clinical symptoms of kinking of the jejunojejunal anastomosis often lack clarity in the early stages. Therefore, early diagnosis, prevention, and effective treatment of kinking of the jejunojejunal anastomosis are challenging but crucial. The occurrence of kinking of the jejunojejunal anastomosis may be related to surgical techniques and the surgeon's experience. The use of anti-obstruction stitch, mesenteric division, and bidirectional jejunojejunal anastomosis may be beneficial in preventing kinking of the jejunojejunal anastomosis. If kinking of the jejunojejunal anastomosis occurs, timely abdominal CT scans and endoscopic examinations should be performed. Gastric and intestinal decompression should be initiated immediately, and exploratory surgery should be prepared.

Self-Supervised Learning Reveals Clinically Relevant Histomorphological Patterns for Therapeutic Strategies in Colon Cancer.

Self-supervised learning (SSL) automates the extraction and interpretation of histopathology features on unannotated hematoxylin-and-eosin-stained whole-slide images (WSIs). We trained an SSL Barlow Twins-encoder on 435 TCGA colon adenocarcinoma WSIs to extract features from small image patches. Leiden community detection then grouped tiles into histomorphological phenotype clusters (HPCs). HPC reproducibility and predictive ability for overall survival was confirmed in an independent clinical trial cohort (N=1213 WSIs). This unbiased atlas resulted in 47 HPCs displaying unique and sharing clinically significant histomorphological traits, highlighting tissue type, quantity, and architecture, especially in the context of tumor stroma. Through in-depth analysis of these HPCs, including immune landscape and gene set enrichment analysis, and association to clinical outcomes, we shed light on the factors influencing survival and responses to treatments like standard adjuvant chemotherapy and experimental therapies. Further exploration of HPCs may unveil new insights and aid decision-making and personalized treatments for colon cancer patients.

CLU (clusterin) and PPARGC1A/PGC1α coordinately control mitophagy and mitochondrial biogenesis for oral cancer cell survival.

Mitophagy involves the selective elimination of defective mitochondria during chemotherapeutic stress to maintain mitochondrial homeostasis and sustain cancer growth. Here, we showed that CLU (clusterin) is localized to mitochondria to induce mitophagy controlling mitochondrial damage in oral cancer cells. Moreover, overexpression and knockdown of CLU establish its mitophagy-specific role, where CLU acts as an adaptor protein that coordinately interacts with BAX and LC3 recruiting autophagic machinery around damaged mitochondria in response to cisplatin treatment. Interestingly, CLU triggers class III phosphatidylinositol 3-kinase (PtdIns3K) activity around damaged mitochondria, and inhibition of mitophagic flux causes the accumulation of excessive mitophagosomes resulting in reactive oxygen species (ROS)-dependent apoptosis during cisplatin treatment in oral cancer cells. In parallel, we determined that PPARGC1A/PGC1α (PPARG coactivator 1 alpha) activates mitochondrial biogenesis during CLU-induced mitophagy to maintain the mitochondrial pool. Intriguingly, PPARGC1A inhibition through small interfering RNA (siPPARGC1A) and pharmacological inhibitor (SR-18292) treatment counteracts CLU-dependent cytoprotection leading to mitophagy-associated cell death. Furthermore, co-treatment of SR-18292 with cisplatin synergistically suppresses tumor growth in oral cancer xenograft models. In conclusion, CLU and PPARGC1A are essential for sustained cancer cell growth by activating mitophagy and mitochondrial biogenesis, respectively, and their inhibition could provide better therapeutic benefits against oral cancer.

EPOS2020/EUFOREA expert opinion on defining disease states and therapeutic goals in CRSwNP.

Severe chronic rhinosinusitis with nasal polyps (CRSwNP), a form of diffuse bilateral (usually type 2) CRS, is a debilitating disease with a significant impact on quality of life (QoL). With novel knowledge and treatment options becoming available, there is a growing need to update or revise key definitions to enable communication across different specialties dealing with CRS, and to agree on novel goals of care in CRSwNP. The European Forum for Research and Education in Allergy and Airway diseases (EUFOREA) and EPOS expert members discussed how to measure treatment responses and set new treatment goals for CRSwNP. In this paper a consensus on a list of definitions related to CRSwNP is provided: control, remission, cure, recurrence/exacerbation, treatable traits, remodeling, progression, and disease modification. By providing these definitions, the involved experts hope to improve communication between all stakeholders involved in CRSwNP treatment for use in routine care, basic and clinical research and international guidelines aimed to harmonize and optimize standard of care of patients with CRSwNP in the future.

Two-year outcomes of radiofrequency device treatment of the nasal valve for nasal airway obstruction.

BACKGROUND: Temperature-controlled radiofrequency (TCRF) device treatment of nasal valve dysfunction (NVD) was superior to a sham procedure control in reducing the symptoms of nasal airway obstruction (NAO) in this randomised controlled trial (RCT). METHODOLOGY: Two-year outcomes for 108 patients actively treated in a prospective, multicenter, patient-blinded RCT were used to determine treatment effect durability and changes in medication/nasal dilator usage. A responder was defined as ≥20% reduction in NOSE score or ≥1 reduction in severity class. RESULTS: The mean (SD) age of patients was 48.5 (12.3) years; 66 (61.1%) women. Baseline NOSE score was 76.3. The 2-year responder rate was 90.4% and NOSE score treatment effect was -41.7; 54.7% improvement. Of 57 patients using medications/nasal dilators at baseline, 45 (78.9%) either stopped all use (33.3%) or stopped/decreased (45.6%) use in ≥1 class at 2 years. Concurrent septal deviation, septal swell body, or turbinate enlargement did not significantly affect the odds of exhibiting a NOSE score of ≤25 at 2 years. CONCLUSIONS: TCRF device treatment of NVD resulted in significant and sustained improvements in the symptoms of NAO at 2 years, accompanied by a substantial reduction in medication/nasal dilator use.

Mepolizumab improves sense of smell in severe chronic rhinosinusitis with nasal polyps: SYNAPSE.

BACKGROUND: Loss of smell is one of the most bothersome and difficult-to-treat symptoms in patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP). METHODOLOGY: SYNAPSE was a 52-week Phase III study of 4-weekly mepolizumab (100 mg subcutaneously) plus standard of care in adults with severe bilateral CRSwNP. This post hoc analysis assessed changes from baseline to study end in loss of smell visual analogue scale (VAS) symptom score, in patients stratified by several baseline clinical characteristics. SinoNasal Outcomes Test (SNOT)-22 sense of smell/taste item and University of Pennsylvania Smell Identification Test (UPSIT) scores were also assessed. RESULTS: SYNAPSE enrolled 407 patients (mepolizumab=206; placebo=201) with impaired sense of smell at baseline. Improvements from baseline to study end in loss of smell VAS score were greater with mepolizumab versus placebo (treatment difference: −0.37) and most notable in patients with fewer or more recent prior surgeries (treatment difference: 1 vs 2 vs more than 2 prior surgeries,−1.29 vs −0.23 vs −0.07; =3 years since last surgery, −0.89 vs 0.22). Approximately 25% of patients had baseline UPSIT scoresavailable; among those scoring =19 by study end. The SNOT-22 sense of smell/taste item score improved with mepolizumab versus placebo. CONCLUSIONS: Mepolizumab treatment improved patients' perceived sense of smell, as measured by loss of smell VAS score and SNOT-22 sense of smell/taste item score in patients with severe refractory CRSwNP.

Ethical Reflection on the "QR code Dilemma" Faced by Older People During COVID-19 in China.

The widespread application of QR code technology is best represented by the health codes used in China's pandemic prevention and control. This technology has enhanced the country's ability to manage the pandemic by achieving higher efficiency and accuracy. Unfortunately, a certain segment of the older population has encountered difficulties in adapting and maintaining their daily activities. This indicates the limitations of QR code technology in achieving social isolation. This article argues that for a more comprehensive pandemic prevention and control policy system to be established, managing the implementation of this very technology should be done in a more humane fashion, i.e. under the guidance of three moral principles: benevolence, justice, and non-maleficence. By doing so, implementation of QR code technology is done in a way that is not only conducive to COVID-19 prevention and control but also mitigate marginalization of the older people. In the post-pandemic era, the socialization of digital technology will accelerate. Therefore, in the field of public health, we should direct attention not only to the fair distribution of resources but also to the issue of identity that arises due to digital divide.

Comparison of nasal valve dysfunction treatment outcomes for temperature-controlled radiofrequency and functional rhinoplasty surgery: a systematic review and meta-analyses.

BACKGROUND: Nasal valve dysfunction (NVD) is a substantial contributor to nasal airway obstruction. Minimally-invasive temp-erature-controlled radiofrequency (TCRF) treatment of the nasal valve is available and comparison with surgical techniques is warranted. METHODOLOGY: Databases: Medline (PubMed), Embase, Cochrane Library. POPULATION: adults with preprocedural nasal obstruction symptom evaluation (NOSE) score ≥45. Treatment effects were derived from a random effects model and reported as weighted mean difference in NOSE score between baseline; 3, 6, and 12 months postprocedure. RESULTS: Of 2529 initial articles, 5 studies describing TCRF treatment and 63 studies describing functional rhinoplasty were included. Pooled effect sizes for TCRF treatment and functional rhinoplasty were comparable in all analyses. CONCLUSIONS: TCRF treatment of the internal nasal valve for NVD was associated with sustained effects comparable to functional rhinoplasty addressing the nasal valve only, rhinoplasty without concomitant turbinate treatment, and all rhinoplasty.

[Clinicopathological features of SMARCA4-deficient lung adenocarcinoma: a study of 42 cases].

Objective: To investigate the clinicopathological characteristics and genetic mutations of SMARCA4-deficient lung adenocarcinoma. Methods: From January 2021 to April 2023 in the First Affiliated Hospital of Zhengzhou University, 42 cases of SMARCA4-deficienct lung adenocarcinoma were diagnosed and now analyzed. All cases were retrospectively studied using hematoxylin-eosin staining and immunohistochemistry. The clinicopathological features were reviewed. Next-generation sequencing (NGS) was performed to investigate the mutations of related genes. Results: Among the 42 cases, there were 35 biopsy and 7 surgical specimens. There were 38 males and 4 females. The male to female ratio was 9.5∶1.0, with an age range from 42 to 78 years. Thirty-three patients were smokers. Overall, 4 cases (9.5%), 2 cases (4.7%), 18 cases (42.9%) and 18 cases (42.9%) were at stages Ⅰ, Ⅱ, Ⅲ, and Ⅳ, respectively. Microscopically, all the cases were non-mucinous adenocarcinoma, without lepidic pattern. The morphology was diverse. Rhabdomyoid cells, tumor giant cells and tumor necrosis were present. Most of the tumor cells had eosinophilic cytoplasm and occasionally clear cytoplasm. Defined cell borders and variable cytoplasmic hyaline secretory globules could be found. Inflammatory cells infiltrated the tumor stroma. Immunohistochemistry showed 29 cases (69.0%, 29/42) expressed TTF1, 10 cases (40.0%, 10/25) expressed Napsin A, and 20 cases (100.0%, 20/20) expressed INI1. Forty cases (95.2%, 40/42) showed BRG1 loss in all tumor cells, while 2 cases (4.8%, 2/42) had partial BRG1 loss. PD-L1 (22C3) was positive in 59.2% of the cases (16/27). NGS revealed mutations in EGFR, ROS1, MET, RET and KRAS. Six cases (6/8) showed SMARCA4 mutation, while some cases were accompanied by mutations of TP53 (7/15), STK11 (4/8), and KEAP1 (1/8). Driver gene mutations were more common in women (P<0.05). Patients were followed up for 1-25 months. Four patients died and 20 patients' diseases progressed. Conclusions: SMARCA4-deficient lung adenocarcinoma lacks characteristic morphology. Most of them express TTF1 and harbor driver gene mutations. It is necessary to identify this subset of lung adenocarcinoma by carrying out BRG1 stain routinely on lung adenocarcinoma. These patients can then be identified and benefit from targeted therapies.

Causal effects of diabetic retinopathy on depression, anxiety and bipolar disorder in the European population: a Mendelian randomization study.

PURPOSE: To verify the causal effects of diabetic retinopathy (DR) on depression, anxiety and bipolar disorder (BD). METHODS: Mendelian randomization (MR) analysis was performed to identify the causal relationships between DR and depression or anxiety or BD via using DR-related GWAS data (14,584 cases and 176,010 controls), depression-related GWAS data (59,851 cases and 113,154 controls), anxiety-related GWAS data (7016 cases and 14,745 controls) and BD-related GWAS data (41,917 cases and 371,549 controls). The inverse-variance weighted (IVW) model was adopted to estimate the causal relationship. The outcome was expressed as odds ratio (OR) with 95% confidence intervals (CI). RESULTS: The MR analysis results presented that DR was causally associated with a significantly increased risk of BD in the European population (IVW, OR = 1.06, 95%CI [1.03, 1.08], P = 2.44 × 10-6), while DR was unable to causally influence the risk of depression (IVW, OR = 1.01, 95%CI [0.99, 1.04], P = 0.32) and anxiety (IVW, OR = 0.97, 95%CI [0.89, 1.06], P = 0.48) in the European population. Subgroup analysis based on BD identified DR causally increased the risk of bipolar I disorder (BD I) but not bipolar II disorder (BD II). Sensitivity analysis results did not show any pleiotropy and heterogeneity in both groups of analyses, indicating that the results were stable and reliable. CONCLUSIONS: The results of the current MR analysis indicated a causal relationship between DR and BD in the European population, while there was no causal connection between DR and depression or anxiety. However, further research is needed to confirm these conclusions.

[New insights into the role of macrophages in tumor immunotherapy].

Macrophages are the main components of the innate immunity system, derived mainly from blood monocytes, and help the host to defend itself against many pathogens and cancers. Most established tumors can educate macrophages into tumor-associated macrophages (TAMs), which contribute to tumor growth, invasion and metastasis, as well as resistance to chemotherapeutic agents and immune checkpoint inhibitors. However, when appropriately activated, macrophages can also exert anti-tumor effects through enhanced phagocytosis and cytotoxicity against tumor cells. In addition, TAMs are associated with poor prognosis and drug resistance, including immunotherapies, suggesting that macrophages are attractive targets as part of combination therapy in cancer treatment. Herein, we review the recent findings on the role of macrophages in tumor development, metastasis and immunotherapy. We focus mainly on macrophage-centered therapy, including strategies to reduce and reshape TAMs, to represent potential targets for tumor immunotherapy.

[A randomized controlled trial on the effect of exercise prescription based on a progressive mode in treating elderly patients with lower limb dysfunction after deep burns].

Objective: To explore the effect of exercise prescription based on a progressive mode in treating elderly patients with lower limb dysfunction after deep burns. Methods: A randomized controlled trial was conducted. From January 2021 to January 2023, 60 elderly patients with lower limb dysfunction after deep burns who met the inclusion criteria were admitted to the First Affiliated Hospital of Air Force Medical University. The patients were divided into conventional rehabilitation group (30 cases, 17 males and 13 females, aged (65±3) years) and combined rehabilitation group (30 cases, 16 males and 14 females, aged (64±3) years) according to the random number table. For patients in both groups, the red-light treatment was started after the lower limb wounds healed or when the total area of scattered residual wounds was less than 1% of the total body surface area. After 2 weeks of red-light treatment, the patients in conventional rehabilitation group were given conventional rehabilitation treatments, including joint stretching, resistance, and balance training; in addition to conventional rehabilitation treatments, the patients in combined rehabilitation group were given exercise prescription training based on a progressive mode three times a week, mainly including dumbbell press, Bobath ball horizontal support, and high-level pulldown trainings. The training time for patients in both groups was 12 weeks. Before training (after 2 weeks of red-light treatment) and after 12 weeks of training, the upper limb and lower limb motor functions of the patients were evaluated using the simple Fugl-Meyer scale, the physical fitness of patients was evaluated using the simple physical fitness scale, and the patient's risk of falling was evaluated by the time consumed for the timed up and go test. The adverse events of patients that occurred during training were recorded. After 12 weeks of training, a self-designed satisfaction survey was conducted to investigate patients' satisfaction with the training effect. Data were statistically analyzed with independent sample t test, paired sample t test, Mann-Whitney U test, Wilcoxon signed rank test, and chi-square test. Results: Before training, the scores of upper limb and lower limb motor functions of patients between the two groups were similar (P>0.05). After 12 weeks of training, the scores of upper limb motor function of patients in conventional rehabilitation group and combined rehabilitation group were significantly higher than those before training (with t values of -11.42 and -13.67, respectively, P<0.05), but there was no statistically significant difference between the two groups (P>0.05). The score of lower limb motor function of patients in combined rehabilitation group was 28.9±2.6, which was significantly higher than 26.3±2.6 in conventional rehabilitation group (t=-3.90, P<0.05), and the scores of lower limb motor function of patients in conventional rehabilitation group and combined rehabilitation group were significantly higher than those before training (with t values of -4.14 and -6.94, respectively, P<0.05). Before training, the individual and total scores of physical fitness of patients between the two groups were similar (P>0.05). After 12 weeks of training, the balance ability score, walking speed score, chair sitting score, and total score of physical fitness of patients in conventional rehabilitation group and combined rehabilitation group were significantly increased compared with those before training (with Z values of -4.38, -3.55, -3.88, -4.65, -4.58, -4.68, -4.42, and -4.48, respectively, P<0.05), and the balance ability score, walking speed score, chair sitting score, and total score of physical fitness of patients in combined rehabilitation group were significantly increased compared with those in conventional rehabilitation group (with Z values of -3.93, -3.41, -3.19, and -5.33, P<0.05). Before training, the time consumed for the timed up and go test for patient's risk of falling in the two groups was close (P>0.05). After 12 weeks of training, the time consumed for the timed up and go test for patient's risk of falling in combined rehabilitation group was (28.0±2.1) s, which was significantly shorter than (30.5±1.8) s in conventional rehabilitation group (t=4.94, P<0.05). Moreover, the time consumed for the timed up and go test for patient's risk of falling in both conventional rehabilitation group and combined rehabilitation group was significantly shorter than that before training (with t values of 14.80 and 15.86, respectively, P<0.05). During the training period, no adverse events such as muscle tissue strain, edema, or falling occurred in any patient. After 12 weeks of training, the satisfaction score of patients with the training effect in combined rehabilitation group was 13.5±1.2, which was significantly higher than 8.5±1.4 in conventional rehabilitation group (t=21.78, P<0.05). Conclusions: The exercise prescription training based on a progressive mode can significantly promote the recovery of lower limb motor function and physical fitness of elderly patients with lower limb dysfunction after deep burns, and effectively reduce the patient's risk of falling without causing adverse events during the training period, resulting in patient's high satisfaction with the training effect.

[Research progress of bariatric and metabolic surgery in the prevention of gastroesophageal reflux disease].

Gastroesophageal reflux disease (GERD) is a common digestive tract disease. Obesity is an independent risk factor for GERD. Laparoscopic sleeve gastrectomy (laparoscopic sleeve gastrectomy, LSG) is becoming more popular in bariatric metabolic surgery and is simple to perform with fewer complications, but its efficacy in treating postoperative anti-reflux in obese patients remains controversial. LSG has been reported to disrupt anti-reflux barrier function, such as altered cardiac notch, disruption of diaphragmatic continuity, and increased hiatal hernia after surgery. The cardiac notch is one of the important anti-reflux barriers at the gastroesophageal junction, and its accentuation has been shown to be effective in alleviating the symptoms of GERD, and LSG combined with angle of cardiac notch accentuation is expected to be an effective measure to prevent GERD after obesity surgery. Therefore, this article mainly reviews the research on the prevention of GERD by bariatric surgery, aiming to explore the effective treatment of GERD in obese patients after surgery, so as to improve the symptoms and quality of life of patients with GERD, and provide reference for the surgical treatment of GERD.

Clonal Relationship and Mutation Analysis in Lymphoplasmacytic Lymphoma/Waldenström Macroglobulinemia Associated With Diffuse Large B-cell Lymphoma.

Patients with lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM) occasionally develop diffuse large B-cell lymphoma (DLBCL). This mostly results from LPL/WM transformation, although clonally unrelated DLBCL can also arise. LPL/WM is characterized by activating MYD88L265P (>95%) and CXCR4 mutations (~30%), but the genetic drivers of transformation remain to be identified. Here, in thirteen LPL/WM patients who developed DLBCL, the clonal relationship of LPL and DLBCL together with mutations contributing to transformation were investigated. In 2 LPL/WM patients (15%), high-throughput sequencing of immunoglobulin gene rearrangements showed evidence of >1 clonal B-cell population in LPL tissue biopsies. In the majority of LPL/WM patients, DLBCL presentations were clonally related to the dominant clone in LPL, providing evidence of transformation. However, in 3 patients (23%), DLBCL was clonally unrelated to the major malignant B-cell clone in LPL, of which 2 patients developed de novo DLBCL. In this study cohort, LPL displayed MYD88L265P mutation in 8 out of eleven patients analyzed (73%), while CXCR4 mutations were observed in 6 cases (55%). MYD88WT LPL biopsies present in 3 patients (27%) were characterized by CD79B and TNFAIP3 mutations. Upon transformation, DLBCL acquired novel mutations targeting BTG1, BTG2, CD79B, CARD11, TP53, and PIM1. Together, we demonstrate variable clonal B-cell dynamics in LPL/WM patients developing DLBCL, and the occurrence of clonally unrelated DLBCL in about one-quarter of LPL/WM patients. Moreover, we identified commonly mutated genes upon DLBCL transformation, which together with preserved mutations already present in LPL characterize the mutational landscape of DLBCL occurrences in LPL/WM patients.

[Efficacy of Barbed reposition pharyngoplasty combined with Han-Uvulopalatopharyngoplasty for the treatment of OSAHS patients].

Objective: To study the efficacy of Barbed reposition pharyngoplasty (BRP) combined with Han-Uvulopalatopharyngoplasty (H-UPPP) in surgical treatment of OSAHS patients. Methods: OSAHS patients admitted to our department from June 2021 to February 2022 who met the surgical enrollment criteria were divided into two groups by surgical procedure: H-UPPP operation group [Control group, 47 cases, including 42 males and 5 females, aged 18-64 (37.77±11.65)years, and H-UPPP+BRP group [Study group, 48 cases, including 45 males and 3 females, aged 23-60 (39.10±9.86) years]. The surgical efficacy 6 months after operation was retrospectively analyzed. Meanwhile, the relationship between the surgical efficacy and modified Friedman pharyngeal anatomical stages was analyzed. The postoperative pain VAS score at first 3 days and the incidence of foreign body sensation in pharynx after 6 months of operation were compared between the two groups. Statistical analysis was conducted by SPSS 23.0. Results: There were no significant differences in gender, age, BMI, Friedman pharyngeal anatomical stages, ESS score, AHI and LSpO2 between the two groups, preoperatively (P>0.05). There was significant difference between the two groups in ratio of cumulative time of oxygen saturation below 90% to total sleep time(CT90), preoperatively. Surgical efficacy of H-UPPP operation group was 48.9% (23/47), while H-UPPP+BRP operation group was 70.8% (34/48), which was statistically significant (χ2=4.74, P=0.029). H-UPPP+BRP group seemed to have a higher surgical efficacy than H-UPPP group in patients with Friedman Ⅱb (87% vs. 61.9%) and Ⅲ stage (44.4% vs. 15%), but there was no statistically significant difference (P>0.05). H-UPPP+BRP group had a higher pain VAS score in first three days (t=-3.10, P=0.003), also had higher incidence of pharyngeal foreign body sensation after 6 months of operation (χ2=4.727, P=0.030). Conclusions: In the surgical treatment of OSAHS patients, the overall efficacy of BRP combined H-UPPP surgery is higher than that of H-UPPP surgery alone. It may be more suitable for OSAHS patients with modified Friedman type Ⅱb and type Ⅲ stage.

[Effects of the anterolateral thigh chimeric perforator flaps in repairing complex wounds of foot and ankle].

Objective: To investigate the effects of anterolateral thigh chimeric perforator flap in repairing complex wounds of foot and ankle. Methods: A retrospective observational study was conducted. From May 2018 to June 2022, 23 patients who met the inclusion criteria were admitted to the First Affiliated Hospital of Air Force Medical University to repair complex wounds of foot and ankle with anterolateral thigh chimeric perforator flaps, including 15 males and 8 females, aged from 20 to 66 years. The wounds were all accompanied by bone exposure and defects, and were complicated with varying degrees of infection. All patients underwent debridement and continuous vacuum sealing drainage treatment for 1 week in stage Ⅰ, with the skin and soft tissue defect area after debridement being 10 cm×5 cm to 22 cm×7 cm. In stage Ⅱ, the anterolateral thigh chimeric perforator flap was used to cover the defective wound, of which the muscle flap was used to fill the deep invalid cavity of the ankle joint or cover bone and internal fixation exposures, and the skin flap was used to cover the superficial wound, with the area of the skin flap ranging from 11 cm×6 cm to 23 cm×8 cm, and the area of the muscle flap ranging from 4.0 cm×2.5 cm to 8.0 cm×5.0 cm. The survival of the flap was observed after operation. During follow-up, the color, texture, appearance, and complications of the flap were observed, the function of ankle joint and its range of dorsiflexion motion and plantar flexion motion were measured, and the scar hyperplasia and muscular hernia in donor area were observed. Results: Ecchymosis and epidermal necrosis occurred at the tip of the flap in 1 patient on 5 days after operation and healed after dressing change for 1 week; the other flaps of patients survived successfully. After 6 to 40 months of follow-up, the color, texture, and shape of flaps were good, but 1 patient was not satisfied with the shape of the flap because of flap swelling; the ankle joint movement was basically normal, the dorsiflexion motion was 15-30°, and the plantar flexion motion was 20-45°; the scar hyperplasia in the donor area of the flap was not obvious, and no muscular hernia occurred. Conclusions: The anterolateral thigh chimeric perforator flap can effectively fill the deep invalid cavity of ankle joint and cover the superficial wound at the same time, with minimal damage to the donor site. So it is an ideal flap for repairing the complex wounds of foot and ankle.

The International Consortium on Primary Graft Dysfunction: Redefining Clinical Risk Factors in the Contemporary Era of Heart Transplantation.

BACKGROUND: Primary graft dysfunction (PGD) is the leading cause of morbidity and mortality early after heart transplantation (HT). The International Consortium on PGD is a multicenter collaboration dedicated to identifying the clinical risk factors for PGD in the contemporary era of HT. The objectives of the current report were (1) to assess the incidence of severe PGD in an international cohort; (2) to evaluate the performance of the most strongly validated PGD risk tool, the RADIAL score, in a contemporary cohort; and (3) to redefine clinical risk factors for severe PGD in the current era of HT. METHODS: This is a retrospective, observational study of consecutive adult HT recipients between 2010 and 2020 in 10 centers in the United States, Canada and Europe. Patients with severe PGD were compared to those without severe PGD (comprising those with no, mild and moderate PGD). The RADIAL score was calculated for each transplant recipient. The discriminatory power of the RADIAL score was evaluated using receiver operating characteristic (ROC) analysis, and its calibration was assessed by plotting the percentage of PGD predicted vs that which was observed. To identify clinical risk factors associated with severe PGD, we performed multivariable mixed-effects logistic regression modeling to account for among-center variability. RESULTS: A total of 2746 patients have been enrolled in the registry to date, including 2015 (73.4%) from North America, and 731 (26.6%) from Europe; 215 participants (7.8%) met the criteria for severe PGD. There was an increase in the incidence of severe PGD over the study period (P value for trend by difference sign test = 0.004). The Kaplan-Meier estimate for 1-year survival was 75.7% (95% CI 69.4-80.9%) in patients with severe PGD as compared to 94.4% (95% CI 93.5-95.2%) in those without severe PGD (log-rank P value < 0.001). The RADIAL score performed poorly in our contemporary cohort and was not associated with severe PGD; it had an AUC of 0.53 (95% CI 0.48-0.58). In the multivariable regression model, acute preoperative dialysis (OR 2.41, 95% CI 1.31-4.43), durable left ventricular assist device support (OR 1.77, 95% CI 1.13-2.77), and total ischemic time (OR 1.20 for each additional hour, 95% CI 1.02-1.41) were associated with an increased risk of severe PGD. CONCLUSIONS: Our consortium has identified an increasing incidence of PGD in the modern transplant era. We identified contemporary risk factors for this early post-transplant complication, which confers a high mortality risk. These results may enable the identification of patients at high risk for developing severe PGD in order to inform peri-transplant donor and recipient management practices.