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Introduction: Thymic carcinoma is a rare and aggressive malignancy with few treatment options. Preclinical studies suggested that targeting the angiogenic pathway may be beneficial in this disease., Methods: This randomized phase 2 trial enrolled patients with unresectable, locally advanced, recurrent, or metastatic thymic carcinoma. Patients were randomized to receive carboplatin-paclitaxel with or without ramucirumab. The primary end point was progression-free survival (PFS) and secondary end points included response by Response Evaluation Criteria in Solid Tumors, disease control, toxicity, and overall survival. The primary analysis was done using a one-sided 10%-level log-rank test. Target sample size was 66 patients., Results: Between 2018 and 2022, 21 patients enrolled to ramucirumab plus carboplatin-paclitaxel (RCP, n = 8) and to the control arm (carboplatin-paclitaxel [CP], n = 13) with one patient on CP not meeting eligibility criteria. Owing to slow accrual, the study was terminated early by the Data and Safety Monitoring Board. Of the 20 eligible patients, eight on RCP and nine on CP received protocol treatment. PFS was not statistically different (hazard ratio = 0.51, 80% confidence interval [CI]: 0.24-1.09, p  = 0.13). There were no grade 4 or higher treatment-related adverse events with RCP, although 50% experienced grade 3 adverse events, in which one patient had a grade 3 thromboembolic event. Among nine assessable patients for toxicity on CP, one patient (11%) encountered grade 4 neutropenia and one patient (11%) reported grade 3 thromboembolic events. Response rates favored the RCP arm, with an 88% (seven of eight, 80% CI: 59%-99%) response rate compared with 40% (four of 10, 80% CI: 19%-65%) on CP arm ( p  = 0.04). Disease control rate was higher in the RCP arm (100% versus 70%, p  = 0.09). At the time of analysis, as only one death has been reported, overall survival remains immature., Conclusions: Accrual to this population is challenging, and the study was closed early because of feasibility. Although PFS was not statistically better with RCP, the hazard ratio was 0.51 and the lack of significance was likely due to small sample sizes. Notably, addition of ramucirumab to CP led to higher response rates than CP alone. Future research should consider exploring larger multicenter trials and other combinations to improve outcomes. Challenges in enrollment emphasize the need for innovative strategies and larger collaborations in rare malignancies such as thymic carcinoma., Competing Interests: Dr. Tsao receives grant funding from Millennium, Polaris, Genentech, Merck, Boehringer Ingelheim, Bristol-Myers Squibb, Ariad, Epizyme, Seattle Genetics, and Novartis; receives consulting fees from Bristol-Myers Squibb, Eli Lilly, Genentech, Roche, Novartis, Ariad, EMD Serono, Merck, Seattle Genetics, AstraZeneca, Boehringer Ingelheim, Sellas Life Science, GlaxoSmithKline, Lilly, Summit, Novocure, and Gilead; and serves on the DSMB for XCovery. Dr. Riess receives grant funding from ArriVent, 10.13039/100004334Merck, 10.13039/100004336Novartis, Nuvalent, Revolution Medicines, Kinnate, AstraZeneca, IO Biotech, Summit, Seattle Genetics, and Novartis; receives consulting fees from Novartis, Janssen, Catalyst, Biodesix, Amgen, Seattle Genetics, Merck, Bristol-Myers Squibb, Beigene, Regeneron, Sanofi, Turning Point, Bayer, Merus NV, Daiichi Sankyo, and OncoHost; and receives travel support from IO Biotech and AstraZeneca. Dr. Edelman receives grant funding from the 10.13039/100000054National Cancer Institute and Stand Up to Cancer; receives consulting fees from Coherus, Regeneron, Novocure, Sanofi, Omega therapeutics, Intervenn, Harpoon, Seattle Genetics, Epic, and Great Debates; participates in DSMB for AstraZeneca, GlaxoSmithKline, Takeda, Duke, Bristol-Myers Squibb, Anheart, and Sana; and holds stock in Creatv Microtech and Biome. Dr. Gandara receives grants from 10.13039/100013870Astex, 10.13039/100002429Amgen, and 10.13039/100004328Genentech; receives consulting fees from AstraZeneca, Exact Sciences, Genentech, Guardant Health, IO Biotech, OncoHost, Adagene, Henlius USA, Foundation Medicine, Sanofi, AbbVie, Janssen, Merck, Mirati, Regeneron, and Revolution Medicine. Dr. Gray receives research grant support from 10.13039/100004325AstraZeneca, Boehringer Ingelheim, 10.13039/100002491Bristol-Myers Squibb, Genentech, G1 Therapeutics, Ludwig Institute of Cancer Research, Merck and Company, Novartis, and Pfizer; receives consulting fees for AbbVie, AstraZeneca, Blueprint Medicines, Daiichi Sankyo, EMD Serono - Merck, Gilead Sciences, IDEOlogy Health, Janssen Scientific Affairs, Jazz Pharmaceuticals, Loxo Oncology, Merck and Company, Novartis, OncoCyte Biotechnology, Spectrum ODAC, Takeda Pharmaceuticals, and Triptych Health Partners. Dr. Tsao and Dr. Kelly receive royalties from UptoDate. The remaining authors declare no conflict of interest., (© 2024 The Authors.)

Background: Liensinine and neferine are the main bisbenzylisoquinoline alkaloids obtained from the seeds of Nelumbo nucifera, which commonly used as edible food and traditional medicine in Asia. It was reported that liensinine and neferine could inhibit the activities of acetylcholinesterase and cross the blood-brain barriers, suggesting their therapeutic potential for the management of Alzheimer's disease., Methods: Here, we employed SH-SY5Y human neuroblastoma cells stably transfected with the human Swedish amyloid precursor protein (APP) mutation APP695 (APP695swe SH-SY5Y) as an in vitro model and transgenic Caenorhabditis elegans as an in vivo model to investigate the neuroprotective effects and underlying mechanism of liensinine and neferine., Results: We found that liensinine and neferine could significantly improve the viability and reduce ROS levels in APP695swe SH-SY5Y cells, inhibit β-amyloid and tau-induced toxicity, and enhance stress resistance in nematodes. Moreover, liensinine and neferine had obviously neuroprotective effects by assaying chemotaxis, 5-hydroxytryptamine sensitivity and the integrity of injured neurons in nematodes. Preliminary mechanism studies revealed that liensinine and neferine could upregulate the expression of autophagy related genes (lgg-1, unc-51, pha-4, atg-9 and ced-9) and reduce the accumulation of β-amyloid induced autophagosomes, which suggested autophagy pathway played a key role in neuroprotective effects of these two alkaloids., Conclusions: Altogether, our findings provided a certain working foundation for the use of liensinine and neferine to treat Alzheimer's disease based on neuroprotective effects., (© 2023. The Author(s).)

Objective: To investigate the effect of Ventriculoperitoneal shunt (VPS)in adult patients with idiopathic normal pressure hydrocephalus (iNPH). Methods: The patients with idiopathic normal pressure hydrocephalus were reviewed, who were admitted into the Peking union medical college hospital from October 2010 to October 2016.The patients treated via VPS were retrospectively analyzed by collecting the data including clinic features, iNPH score and imaging data. Results: 33 patients were included in the group.3 months after operation, the iNPH scores were significantly decreased (3.0±1.0 vs 6.0±2.5, P <0.01), and there were no difference among 3 month, 6 month and 12 month post operation.The Evans index and the width of the three ventricles were also significantly decreased.1 patient suffered from subdural hematoma and no other complications such as infection, obstruction or death occurred. Conclusions: VPS is an effective treatment approach of iNPH and multidisciplinary team is the key in diagnosis.

Background: Postoperative central nervous system infections (PCNSIs) represent a serious complication, and the timely use of antibiotics guided by the identification of the causative pathogens and their antibiotic sensitivities is essential for treatment. However, there are little data regarding the prevalence of PCNSI pathogens in China. The aim of this study is to investigate the features of pathogens in patients with PCNSIs, which could help clinicians to choose the appropriate empirical antibiotic therapy., Methods: We retrospectively examined the positive CSF cultures in patients who underwent craniotomy between January 2010 and December 2015. We collected data, including demographic characteristics, type of neurosurgery, laboratory data, causative organisms and antimicrobial susceptibility testing results., Results: A total of 62 patients with 90 isolates out of 818 patients with 2433 CSF culture samples were available for data analysis. The estimated incidence and culture-positive rate of PCNSIs were approximately 0.9 and 7.5%, respectively. The predominant organism was coagulase-negative staphylococci, of which most were methicillin-resistant coagulase-negative staphylococci (MRCoNS). All were susceptible to vancomycin, linezolid, rifampicin and amoxicillin-clavulanate. Acinetobacter baumannii was the most frequent causative Gram-negative agent and was resistant to 12 out of 18 antimicrobials tested. The sensitivity rates for tigecycline and minocycline were only 40 and 33%, respectively., Conclusion: PCNSIs could lead to high mortality. Although the MRCoNS were the predominant organism, the management of Acinetobacter baumannii was a major clinical challenge with few effective antimicrobials in PCNSIs., Competing Interests: This study was approved by the Ethics Committee of Peking Union Medical College Hospital (PUMCH) and written informed consents were obtained from all patients.All the authors approve and agree the article to this publication.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Objective: To investigate the pathogenesis and management of the hydrocephalus in patients with systemic lupus erythematosus (SLE). Methods: Eight cases of hospitalized lupus patients with hydrocephalus in Peking Union Medical College Hospital from Jan 1990 to Mar 2017 were analyzed retrospectively.We collected the patients' medical records including medical history, CT and/or MRI images and analysis of cerebrospinal fluid via lumbar puncture in order to investigate the pathogenesis of the hydrocephalus in patients with SLE and summarize treatment experience. Results: All the 8 patients with SLE complicated with hydrocephalus were treated with steroids or immunosuppressive agents, and 5 cases were diagnosed with the central nervous system infection. Three cases received ventriculoperitoneal shunt, 5 cases received treatment of medicine.They all were followed up for 2-12 months, of which 3 cases were markedly effective, 1 case effective and 4 cases dead. Conclusion: The pathogenesis of lupus combined with hydrocephalus may have a certain relationship with the central infection, should take effective anti-infection treatment.We recommend cerebrospinal fluid shunt surgery intervention.

Objective: To study the perioperative management and surgical treatment of patients with neurosurgical critical diseases and thrombocytopenia., Methods: Eleven patients with the diagnosis of neurosurgical critical diseases and thrombocytopenia who received surgical treatment in Department of Neurosurgery, Peking Union Medical College Hospital from 2010 to 2015 were reviewed retrospectively. All eleven patients received platelet transfusions preoperatively. The safety and efficacy of surgical treatment were analyzed by GOS score at 6 months after operations., Results: Platelet counts of six patients who received minimally invasive surgery reached 80×10(9) /L by platelet transfusions preoperatively. Platelet counts of five patients who received Craniotomy and ventriculoperitoneal shunt reached 100×10(9) /L by platelet transfusions preoperatively. Eight patients received platelet transfusions postoperatively according to a low platelet count 24 hours after operations. Two patients died after surgery and one died after discharge. All other eight survival patients got well recovery with an average GOS score of 4.5 at six months after operations., Conclusions: Patients with neurosurgical critical diseases and thrombocytopenia could receive surgical treatment in collaboration with relative departments.

Objective: To discuss the methods, timing and clinical outcomes of surgical treatment for open pilon fractures., Methods: From April 2003 to July 2008, 28 patients with open pilon fractures were treated. All had type C fractures according to the Arbeitsgemeinschaft für osteosynthesefragen-Association for the Study of Internal Fixation (AO/ASIF) classification. Three operative methods were applied, the methods being determined by the types of fracture, soft tissue damage and time interval after injury. Seven cases were treated by debridement and internal fixation with plate; 19 by limited internal fixation combined with external fixation; and 2 by delayed surgery. The clinical outcomes were evaluated by the Burwell-Charnley score., Results: All cases were followed up for from 6 to 48 months (average 24 months). The Burwell-Charnley score of clinical outcomes: anatomic reduction achieved in 12 cases, functional reduction in 15, and unsatisfactory reduction in 1. The healing time was from 2.5 to 11 months (average 4.7 months). Two cases had delayed union. According to the American Orthopaedic Foot and Ankle Society (AOFAS) scale for the ankle joint, there were excellent results in 8 cases, good in 14, fair in 5 and poor in 1. Complications included four cases of skin superficial sloughing, two of superficial infection, one of deep infection, two of delayed fracture union and ten of post-traumatic arthritis., Conclusion: It is important to perform appropriate surgeries for open pilon fracture according to fracture classification, different damage to skin and tissue and time interval after injury. Thorough debridement, proper use of anti-infective medication, appropriate bone grafting, and postoperative ankle function exercise can reduce the occurrence of complications., (© 2011 Tianjin Hospital and Blackwell Publishing Asia Pty Ltd.)