Purpose: Adjuvant pembrolizumab improved disease-free survival (DFS) and overall survival (OS) versus placebo in participants with renal cell carcinoma (RCC) at increased risk of recurrence after nephrectomy in the global phase 3 KEYNOTE-564 study. This post hoc subgroup analysis evaluated the efficacy and safety of adjuvant pembrolizumab in East Asian (Japan, South Korea, and Taiwan) participants enrolled in KEYNOTE-564. Materials and Methods: Eligible participants were randomly assigned 1:1 to receive adjuvant pembrolizumab 200 mg or placebo intravenously every 3 weeks for ≤ 17 cycles. The primary endpoint was DFS by investigator assessment. OS was a key secondary endpoint. Safety was a secondary endpoint. Results: The East Asian subgroup included 126 participants (pembrolizumab, n=58; placebo, n=68). Median follow-up was 62.1 months (range, 49.6 to 73.0 months). Hazard ratio for DFS with pembrolizumab versus placebo was 0.70 (95% confidence interval 0.41 to 1.20). Median DFS was not reached with pembrolizumab versus 58.8 months with placebo; estimated 48-month rate was 61.3% versus 51.2%. Hazard ratio for OS was 0.47 (95% confidence interval, 0.15 to 1.49). Median OS was not reached with pembrolizumab and placebo; estimated 48-month rate was 94.8% versus 91.2%. Treatment-related adverse events occurred in 70.7% of participants (29.3% grade 3 or 4) receiving pembrolizumab and 36.8% of participants (0.0% grade 3 or 4) receiving placebo. No pembrolizumab-related deaths occurred. Conclusion In the KEYNOTE-564 East Asian subgroup, adjuvant pembrolizumab provided DFS and OS benefits versus placebo and had a safety profile consistent with the global results. These results further support pembrolizumab as adjuvant treatment for East Asian patients with RCC at increased risk of recurrence after nephrectomy.

Objective:To describe the current status and trends in the outcomes and care practices of extremely preterm infants at 22-25 weeks′ gestation age from the Chinese Neonatal Network (CHNN) from 2019 to 2021.Methods:This cross-sectional study used data from the CHNN cohort of very preterm infants. All 963 extremely preterm infants with gestational age between 22-25 weeks who were admitted to neonatal intensive care units (NICU) of the CHNN from 2019 to 2021 were included. Infants admitted after 24 hours of life or transferred to non-CHNN hospitals were excluded. Perinatal care practices, survival rates, incidences of major morbidities, and NICU treatments were described according to different gestational age groups and admission years. Comparison among gestational age groups was conducted using χ2 and Kruskal-Wallis tests. Trends by year were evaluated by Cochran-Armitage and Jonckheere-Terpstra tests for trend. Results:Of the 963 extremely preterm infants enrolled, 588 extremely preterm infants (61.1%) were male. The gestational age was 25.0 (24.4, 25.6) weeks, with 29 extremely preterm infants (3.0%), 88 extremely preterm infants (9.1%), 264 extremely preterm infants (27.4%), and 582 extremely preterm infants (60.4%) at 22, 23, 24, and 25 weeks of gestation age, respectively. The birth weight was 770 (680, 840) g. From 2019 to 2021, the number of extremely preterm infants increased each year (285, 312, and 366 extremely preterm infants, respectively). Antenatal steroids and magnesium sulfate were administered to 67.7% (615/908) and 51.1% (453/886) mothers of extremely preterm infants. In the delivery room, 20.8% (200/963) and 69.5% (669/963) extremely preterm infants received noninvasive positive end-expiratory pressure support and endotracheal intubation. Delayed cord clamping and cord milking were performed in 19.0% (149/784) and 30.4% (241/794) extremely preterm infants. From 2019 to 2021, there were significant increases in the usage of antenatal steroids, antenatal magnesium sulfate, and delivery room noninvasive positive-end expiratory pressure support (all P<0.05). Overall, 349 extremely preterm infants (36.2%) did not receive complete care, 392 extremely preterm infants (40.7%) received complete care and survived to discharge, and 222 extremely preterm infants (23.1%) received complete care but died in hospital. The survival rates for extremely preterm infants at 22, 23, 24 and 25 weeks of gestation age were 10.3% (3/29), 23.9% (21/88), 33.0% (87/264) and 48.3% (281/582), respectively. From 2019 to 2021, there were no statistically significant trends in complete care, survival, and mortality rates (all P>0.05). Only 11.5% (45/392) extremely preterm infants survived without major morbidities. Moderate to severe bronchopulmonary dysplasia (67.3% (264/392)) and severe retinopathy of prematurity (61.5% (241/392)) were the most common morbidities among survivors. The incidences of severe intraventricular hemorrhage or periventricular leukomalacia, necrotizing enterocolitis, and sepsis were 15.3% (60/392), 5.9% (23/392) and 19.1% (75/392), respectively. Overall, 83.7% (328/392) survivors received invasive ventilation during hospitalization, with a duration of 22 (10, 42) days. The hospital stay for survivors was 97 (86, 116) days. Conclusions:With the increasing number of extremely preterm infants at 22-25 weeks′ gestation admitted to CHNN NICU, the survival rate remained low, especially the rate of survival without major morbidities. Further quality improvement initiatives are needed to facilitate the implementation of evidence-based care practices.

Humans ; Lung Transplantation/adverse effects* ; Risk Factors

Objective:To investigate the current status, trends, and differences among institutions in the application of delivery room continuous positive airway pressure (DRCPAP) for very preterm infants treated in the institutions in the Chinese Neonatal Network (CHNN). Also, to explore the impact of DRCPAP on the outcomes of very preterm infants in China.Methods:A retrospective cohort study was conducted. Based on the CHNN very preterm infant cohort, very preterm infants (gestational ages ranging from 25 weeks +0 to 31 weeks +6) born in-hospital and treated in 79 tertiary neonatal intensive care units (NICUs) participating in the CHNN from 2019 to 2021 were included. The usage rates of DRCPAP in different hospitals, as well as gestational ages and years, were described. Data were analyzed using the Chi-square test (or Fisher's exact test) or t-test. A multivariate logistic regression model was established to explore the correlation between DRCPAP and clinical outcomes. Results:(1) A total of 18 048 very preterm infants were included. Among them, 3 666 (20.3%) received DRCPAP, and 14 382 (79.7%) did not. (2) The usage rate of DRCPAP for very preterm infants among different institutions is from 0.0% to 94.5%. Fourteen institutions did not use DRCPAP, and 55 institutions had a usage rate below 30%. The usage rate of DRCPAP in very preterm infants increased annually, from 13.8% (818/5 916) in 2019 to 26.0% (1 583/6 097) in 2021 ( χ2trend=122.00, P<0.001). (3) The DRCPAP group had higher rates of maternal assisted reproductive technology pregnancy, chorioamnionitis, a full course of antenatal corticosteroids, gestational diabetes, fetal distress, antenatal magnesium sulfate use, and cesarean delivery compared to the non-DRCPAP group [20.3% (744/3 665) vs. 17.6% (2 529/14 369), χ2=14.45; 23.0% (695/3 021) vs. 16.4% (1 956/11 926), χ2=72.57; 57.1% (2 090/3 660) vs. 54.3% (7 766/14 302), χ2=9.55; 23.0% (844/3 669) vs. 20.7% (2 969/14 342), χ2=9.77; 8.7% (319/3 666) vs. 7.0% (1 006/14 371), χ2=12.51; 87.1% (3 186/3 657) vs. 82.0% (11 736/14 312), χ2=81.38; 63.5% (2 327/3 664) vs. 60.7% (8 722/14 369), χ2=9.59; all P<0.05]. While the incidence of hypertensive disorders of pregnancy and the proportion of infants not using antenatal corticosteroids were lower in the non-DRCPAP group [17.1% (626/3 660) vs. 22.6% (3 183/14 084), χ2=44.70; 14.2% (520/3 661) vs. 19.7% (2 814/14 284), χ2=57.34; all P<0.05]. The DRCPAP group had lower birth weight and gestational age, higher 1 min and 5 min Apgar scores, and lower neonatal transport stabilization index scores [(1 308±314) g vs. (1 325±315) g, t=2.90; (29.5±1.7) weeks vs. (29.7±1.6) weeks, t=3.96; (7.9±1.8) scores vs. (7.6±1.9) scores, t=－9.80; (9.0±1.1) scores vs. (8.7±1.3) scores, t=－13.01; (11.0±9.4) scores vs. (13.1±9.8) scores, t=11.31; all P<0.05]. The incidence of early-onset sepsis was higher in the DRCPAP group than in the non-DRCPAP group [1.8% (68/3 578) vs. 1.3% (193/14 296), adjusted OR (95% CI): 1.417 (1.028-1.955)], while the rates of tracheal intubation within 72 hours, PS use, invasive mechanical ventilation, mortality, admission hypothermia, grade Ⅲ-Ⅳ intracranial hemorrhage, and stage≥3 ROP were all lower in the DRCPAP group compared to the non-DRCPAP group [22.6% (830/3 666) vs. 36.9% (5 310/14 374), adjusted OR (95% CI): 0.499 (0.448-0.555); 53.1% (1 947/3 666) vs. 58.3% (8 388/14 377), adjusted OR (95% CI): 0.764 (0.697-0.836); 30.1% (1 104/3 662) vs. 43.9% (6 307/14 366), adjusted OR (95% CI): 0.539 (0.487-0.595); 7.4% (274/3 666) vs. 10.6% (1 526/14 342), adjusted OR (95% CI): 0.709 (0.601-0.836); 57.5% (2 103/3 657) vs. 66.5% (9 501/14 287), adjusted OR (95% CI): 0.722 (0.661-0.788); 3.0% (101/3 366) vs. 5.9% (763/12 932)], adjusted OR (95% CI): 0.525 (0.412-0.669); 2.2% (65/2 954) vs. 3.3% (367/11 121), adjusted OR (95% CI): 0.692 (0.505-0.947); all P<0.05]. There were no statistically significant differences between the two groups in the incidence rates of BPD at a corrected gestational age of 36 weeks, patent ductus arteriosus ligation, spontaneous intestinal perforation, and pneumothorax. Conclusions:Domestically, the application of DRCPAP might be related to a decrease in the demand for invasive ventilation, the use of surfactants, and mortality, but it might not reduce the occurrence of bronchopulmonary dysplasia, at a corrected gestational age of 36 weeks. In recent years, the use of DRCPAP in very premature infants in China has increased, but the overall usage rate is still low, and there are significant differences between units, requiring continuous quality improvement.

Objective:To investigate the current status, trends, and differences among institutions in the application of delivery room continuous positive airway pressure (DRCPAP) for very preterm infants treated in the institutions in the Chinese Neonatal Network (CHNN). Also, to explore the impact of DRCPAP on the outcomes of very preterm infants in China.Methods:A retrospective cohort study was conducted. Based on the CHNN very preterm infant cohort, very preterm infants (gestational ages ranging from 25 weeks +0 to 31 weeks +6) born in-hospital and treated in 79 tertiary neonatal intensive care units (NICUs) participating in the CHNN from 2019 to 2021 were included. The usage rates of DRCPAP in different hospitals, as well as gestational ages and years, were described. Data were analyzed using the Chi-square test (or Fisher's exact test) or t-test. A multivariate logistic regression model was established to explore the correlation between DRCPAP and clinical outcomes. Results:(1) A total of 18 048 very preterm infants were included. Among them, 3 666 (20.3%) received DRCPAP, and 14 382 (79.7%) did not. (2) The usage rate of DRCPAP for very preterm infants among different institutions is from 0.0% to 94.5%. Fourteen institutions did not use DRCPAP, and 55 institutions had a usage rate below 30%. The usage rate of DRCPAP in very preterm infants increased annually, from 13.8% (818/5 916) in 2019 to 26.0% (1 583/6 097) in 2021 ( χ2trend=122.00, P<0.001). (3) The DRCPAP group had higher rates of maternal assisted reproductive technology pregnancy, chorioamnionitis, a full course of antenatal corticosteroids, gestational diabetes, fetal distress, antenatal magnesium sulfate use, and cesarean delivery compared to the non-DRCPAP group [20.3% (744/3 665) vs. 17.6% (2 529/14 369), χ2=14.45; 23.0% (695/3 021) vs. 16.4% (1 956/11 926), χ2=72.57; 57.1% (2 090/3 660) vs. 54.3% (7 766/14 302), χ2=9.55; 23.0% (844/3 669) vs. 20.7% (2 969/14 342), χ2=9.77; 8.7% (319/3 666) vs. 7.0% (1 006/14 371), χ2=12.51; 87.1% (3 186/3 657) vs. 82.0% (11 736/14 312), χ2=81.38; 63.5% (2 327/3 664) vs. 60.7% (8 722/14 369), χ2=9.59; all P<0.05]. While the incidence of hypertensive disorders of pregnancy and the proportion of infants not using antenatal corticosteroids were lower in the non-DRCPAP group [17.1% (626/3 660) vs. 22.6% (3 183/14 084), χ2=44.70; 14.2% (520/3 661) vs. 19.7% (2 814/14 284), χ2=57.34; all P<0.05]. The DRCPAP group had lower birth weight and gestational age, higher 1 min and 5 min Apgar scores, and lower neonatal transport stabilization index scores [(1 308±314) g vs. (1 325±315) g, t=2.90; (29.5±1.7) weeks vs. (29.7±1.6) weeks, t=3.96; (7.9±1.8) scores vs. (7.6±1.9) scores, t=－9.80; (9.0±1.1) scores vs. (8.7±1.3) scores, t=－13.01; (11.0±9.4) scores vs. (13.1±9.8) scores, t=11.31; all P<0.05]. The incidence of early-onset sepsis was higher in the DRCPAP group than in the non-DRCPAP group [1.8% (68/3 578) vs. 1.3% (193/14 296), adjusted OR (95% CI): 1.417 (1.028-1.955)], while the rates of tracheal intubation within 72 hours, PS use, invasive mechanical ventilation, mortality, admission hypothermia, grade Ⅲ-Ⅳ intracranial hemorrhage, and stage≥3 ROP were all lower in the DRCPAP group compared to the non-DRCPAP group [22.6% (830/3 666) vs. 36.9% (5 310/14 374), adjusted OR (95% CI): 0.499 (0.448-0.555); 53.1% (1 947/3 666) vs. 58.3% (8 388/14 377), adjusted OR (95% CI): 0.764 (0.697-0.836); 30.1% (1 104/3 662) vs. 43.9% (6 307/14 366), adjusted OR (95% CI): 0.539 (0.487-0.595); 7.4% (274/3 666) vs. 10.6% (1 526/14 342), adjusted OR (95% CI): 0.709 (0.601-0.836); 57.5% (2 103/3 657) vs. 66.5% (9 501/14 287), adjusted OR (95% CI): 0.722 (0.661-0.788); 3.0% (101/3 366) vs. 5.9% (763/12 932)], adjusted OR (95% CI): 0.525 (0.412-0.669); 2.2% (65/2 954) vs. 3.3% (367/11 121), adjusted OR (95% CI): 0.692 (0.505-0.947); all P<0.05]. There were no statistically significant differences between the two groups in the incidence rates of BPD at a corrected gestational age of 36 weeks, patent ductus arteriosus ligation, spontaneous intestinal perforation, and pneumothorax. Conclusions:Domestically, the application of DRCPAP might be related to a decrease in the demand for invasive ventilation, the use of surfactants, and mortality, but it might not reduce the occurrence of bronchopulmonary dysplasia, at a corrected gestational age of 36 weeks. In recent years, the use of DRCPAP in very premature infants in China has increased, but the overall usage rate is still low, and there are significant differences between units, requiring continuous quality improvement.

Postoperative dysesthesia following lumbar spine surgery is a highly bothersome symptom in the follow-up period. Although many factors contribute to this condition, the most important one is the use of radiofrequency in endoscopic spine surgery. Nonetheless, there is widespread acceptance regarding the use of radiofrequency in endoscopic spine surgery, and the literature contains few reports related to thermal damage to nerves. We describe 3 cases of nondermatomal dysesthesia syndrome in patients who had undergone lumbar unilateral biportal endoscopic surgery for lumbar spinal stenosis. All diagnostic modalities were equivocal, and no pathological lesion was identified. Therefore, we interpreted the dysesthesia as secondary to thermal damage to neural structures, resulting from the radiofrequency.

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. Although previous studies have demonstrated that exercise independently reduces hepatic steatosis measured by imaging modalities in NAFLD, the effect of exercise on histological endpoints remains unclear. We aimed to conduct a systematic review of the independent effect of exercise on hepatic steatosis, steatohepatitis, and liver fibrosis as measured by histological assessment or non-invasive tests (NITs) in biopsy-proven NAFLD. A systematic literature search of PubMed, Embase, and Web of Science databases was performed using keywords related to exercise, NAFLD, and biopsy. Articles were selected based on the following inclusion criteria: (1) involved human subjects with biopsy-proven NAFLD, (2) analyzed the independent effect of exercise, (3) assessed changes in hepatic steatosis, steatohepatitis, or liver fibrosis via either histological evaluation or NITs, and (4) were original research studies. We identified a total of six studies that analyzed the independent effect of exercise on histological endpoints in biopsy-proven NAFLD. Two randomized controlled trials (RCTs) did not detect significant histological improvement following exercise interventions, while other non-randomized interventional studies showed that exercise reduces hepatocyte ballooning and liver fibrosis. In addition, five studies assessed NIT outcomes, collectively demonstrating that exercise improves hepatic steatosis measured by magnetic resonance imaging-based techniques but not serum biomarkers for steatohepatitis and liver fibrosis. Additional large RCTs and meta-analyses are warranted to investigate the independent effect of exercise on histological and clinical outcome endpoints in NAFLD.

Objective: To investigate the safety and efficacy of laparoscopic surgery in locally advanced gastric cancer patients with neoadjuvant SOX chemotherapy combined with PD-1 inhibitor immunotherapy. Methods: Between November 2020 and April 2021, patients with locally advanced gastric cancer who were admitted to the Union Hospital of Tongji Medical College of Huazhong University of Science and Technology were prospectively enrolled in this study. Inclusion criteria were: (1) patients who signed the informed consent form voluntarily before participating in the study; (2) age ranging from 18 to 75 years; (3) patients staged preoperatively as cT3-4N+M0 by the TNM staging system; (4) Eastern Collaborative Oncology Group score of 0-1; (5) estimated survival of more than 6 months, with the possibility of performing R0 resection for curative purposes; (6) sufficient organ and bone marrow function within 7 days before enrollment; and (7) complete gastric D2 radical surgery. Exclusion criteria were: (1) history of anti-PD-1 or PD-L1 antibody therapy and chemotherapy; (2) treatment with corticosteroids or other immunosuppre- ssants within 14 days before enrollment; (3) active period of autoimmune disease or interstitial pneumonia; (4) history of other malignant tumors; (5) surgery performed within 28 days before enrollment; and (6) allergy to the drug ingredients of the study. Follow-up was conducted by outpatient and telephone methods. During preoperative SOX chemotherapy combined with PD-1 inhibitor immunotherapy, follow-up was conducted every 3 weeks to understand the occurrence of adverse reactions of the patients; follow-up was conducted once after 1 month of surgical treatment to understand the adverse reactions and survival of patients. Observation indicators were: (1) condition of enrolled patients; (2) reassessment after preoperative therapy and operation received (3) postoperative conditions and pathological results. Evaluation criteria were: (1) tumor staged according to the 8th edition of the American Joint Committee on Cancer (AJCC) TNM staging system; (2) tumor regression grading (TRG) of pathological results were evaluated with reference to AJCC standards; (3) treatment-related adverse reactions were evaluated according to version 5.0 of the Common Terminology Criteria for Adverse Events; (4) tumor response was evaluated by CT before and after treatment with RECIST V1.1 criteria; and (5) Clavien-Dindo complication grading system was used for postoperative complications assessment. Results: A total of 30 eligible patients were included. There were 25 males and 5 females with a median age of 60.5 (35-74) years. The primary tumor was located in the gastroesophageal junction in 12 cases, in the upper stomach in 8, in the middle stomach in 7, and in the lower stomach in 3. The preoperative clinical stage of 30 cases was III. Twenty-one patients experienced adverse reactions during neoadjuvant chemotherapy combined with immunotherapy, including four cases of CTCAE grade 3-4 adverse reactions resulting in bone marrow suppression and thoracic aortic thrombosis. All cases of adverse reactions were alleviated or disappeared after active symptomatic treatment. Among the 30 patients who underwent surgery, the time from chemotherapy combined with immunotherapy to surgery was 28 (23-49) days. All 30 patients underwent laparoscopic radical gastrectomy, of which 20 patients underwent laparoscopic-assisted radical gastric cancer resection; 10 patients underwent total gastrectomy for gastric cancer, combined with splenectomy in 1 case and cholecystectomy in 1 case. The surgery time was (239.9±67.0) min, intraoperative blood loss was 84 (10-400) ml, and the length of the incision was 7 (3-12) cm. The degree of adenocarcinoma was poorly differentiated in 18 cases, moderately differentiated in 12 cases, nerve invasion in 11 cases, and vascular invasion in 6 cases. The number lymph nodes that underwent dissection was 30 (17-58). The first of gas passage, the first postoperative defecation time, the postoperative liquid diet time, and the postoperative hospitalization time of 30 patients was 3 (2-6) d, 3 (2-13) d, 5 (3-12) d, and 10 (7-27) d, respectively. Postoperative complications occurred in 23 of 30 patients, including 7 cases of complications of Clavien-Dindo grade IIIa or above. Six patients improved after treatment and were discharged from hospital, while 1 patient died 27 days after surgery due to granulocyte deficiency, anemia, bilateral lung infection, and respiratory distress syndrome. The remaining 29 patients had no surgery-related morbidity or mortality within 30 days of discharge. Postoperative pathological examination showed TRG grades 0, 1, 2, and 3 in 8, 9, 4, and 9 cases, respectively, and the number of postoperative pathological TNM stages 0, I, II, and III was 8, 7, 8, and 7 cases, respectively. The pCR rate was 25.0% (8/32). Conclusion: Laparoscopic surgery after neoadjuvant SOX chemotherapy combined with PD-1 inhibitor immunotherapy for locally advanced gastric cancer is safe and feasible, with satisfactory short-term efficacy. Early detection and timely treatment of related complications are important.
Male ; Female ; Humans ; Middle Aged ; Aged ; Adolescent ; Young Adult ; Adult ; Stomach Neoplasms/pathology* ; Neoadjuvant Therapy ; Immune Checkpoint Inhibitors ; Gastrectomy/methods* ; Esophagogastric Junction/pathology* ; Laparoscopy ; Immunotherapy ; Postoperative Complications ; Retrospective Studies ; Treatment Outcome

Surgical resection plays pivotal role in the treatment of gastric cancer. Adequate preoperative evaluation, precise intraoperative maneuver and delicate postoperative management lay the foundation for successful gastrectomy. The aim of preoperative evaluation is to stage tumor and identify potential risk factors (including preoperative factors like age, ASA status, body mass index, comorbidity, hypoalbuminemia, and intraoperative factors like blood loss and combined resection) which could lead to postoperative complication. With the management of prehabilitation, adequate medical decision could be made and patient's fast recovery could be ensured. With the rapid adoption of ERAS concept, there is increasing attention to prehabilitation which focus on optimization of cardio-pulmonary capacity and muscular-skeletal capacity. Despite of the efficacy of prehabilitation demonstrated by randomized controlled trials, consensus has yet to be reached on the following items: specific intervention, optimal measurement, candidate population and optimal timing for intervention. Balancing the efficiency and safety, preoperative evaluation could be put into clinical practice smoothly.
Humans ; Stomach Neoplasms/complications* ; Preoperative Care/adverse effects* ; Postoperative Complications/etiology* ; Gastrectomy/adverse effects* ; Risk Factors