Immune checkpoint inhibitors in head and neck squamous cell carcinoma: A systematic review of phase-3 clinical trials

BACKGROUNDThe outcomes of patients diagnosed with head and neck squamous cell carcinoma (HNSCC) who are not candidates for local salvage therapy and of those diagnosed with recurrent or metastatic disease are dismal. A relatively new systemic therapy option that emerged in recent years in the treatment of advanced HNSCC is immunotherapy using immune checkpoint inhibitors (ICIs). The safety profile and anti-tumor activity of these agents demonstrated in early phase clinical trials paved the way to the initiation of several promising phase-3 trials in the field.AIMTo evaluate the evidence on the effectiveness of ICIs in HNSCC, based on published phase-3 clinical trials.METHODSWe searched PubMed, Cochrane Library, Embase, and Scopus to identify published literature evaluating immunotherapy using ICIs in recurrent or metastatic HNSCC (R/M HNSCC) and locally advanced head and neck squamous cell carcinoma (LAHNSCC). We used a combination of standardized search terms and keywords including head and neck squamous cell carcinoma, recurrent, metastatic, locally advanced, immunotherapy, immune checkpoint inhibitors, monoclonal antibodies, programmed cell death protein-1 (PD-1), programmed death-ligand 1 (PD-L1), cytotoxic T- lymphocyte associated protein-4 (CTLA-4), and phase-3 clinical trial. A sensitive search filter was used to limit our results to randomized controlled trials.RESULTSFive phase-3 clinical trials have reported the data on the effectiveness of immunotherapy in HNSCC so far: Four in R/M HNSCC and one in LAHNSCC. In patients with R/M HNSCC, anti-PD-1 agents nivolumab and pembrolizumab demonstrated improved survival benefits in the second-line treatment setting compared to the standard of care (standard single-agent systemic therapy). While the net gain in overall survival (OS) with nivolumab was 2.4 mo [hazard ratio (HR) = 0.69, P = 0.01], that with pembrolizumab was 1.5 mo (HR = 0.80 nominal P = 0.0161). The anti-PD-L1 agent durvalumab with or without the anti-cytotoxic T- lymphocyte associated protein-4 agent tremelimumab did not result in any beneficial outcomes. In the first-line setting, in R/M HNSCC, pembrolizumab plus platinum-based chemotherapy resulted in significant improvement in survival with a net gain in OS of 2.3 mo (HR = 0.77, P = 0.0034) in the overall population and a net gain in OS of 4.2 mo in the PD-L1 positive (combined positive score > 20) population compared to standard of care (EXTREME regime). In patients with PD-L1 positive R/M HNSCC, monotherapy with pembrolizumab also demonstrated statistically significant improvement in survival compared to EXTREME. In LAHNSCC, immunotherapy using avelumab (an anti-PD-L1 agent) along with standard chemoradiation therapy did not result in improved outcomes compared to placebo plus chemoradiation therapy.CONCLUSIONAnti-PD-1 agents provide survival benefits in R/M HNSCC in the first and second-line settings, with acceptable toxicity profiles compared to standard therapy. There is no proven efficacy in the curative setting to date.     

甲状旁腺激素相关蛋白及转化生长因子β与乳腺癌的相关性研究

目的 观察乳腺癌原发肿瘤组织中甲状旁腺激素相关蛋白（PTHrP）和转化生长因子β（TGF-β）的表达情况,并探讨其与乳腺癌肿瘤生物病理学特征的相关性.方法 以免疫组化染色（Envision法）对乳腺癌及乳腺良性肿瘤标本进行检测.分析研究PTHrP及TGF-β与乳腺癌肿瘤生物病理学特征的相关性;Kaplan-Meier 方法分析患者无病生存情况;Log-Rank （Mantel-Cox）时序检验比较无病生存分布.结果 ①约60%的乳腺癌组织中存在TGF-β的阳性表达,PTHrP在90%以上的乳腺癌中表达阳性,而乳腺良性肿瘤组织PTHrP表达的阳性率很低;②TGF-β表达阳性的患者具有较高的淋巴结转移率,且组织学分级较差;③乳腺癌组织中PTHrP高表达与较大的肿瘤直径、较多的腋淋巴结转移、累及皮肤、较差的组织学分级相关;④PTHrP与乳腺癌患者术后无病生存无明显相关性;⑤TGF-β阳性表达与乳腺癌患者术后复发转移率有明显的相关性;⑥TGF-β阳性且PTHrP高表达的患者无病生存率最差,而TGF-β阴性且PTHrP高表达组的预后最好.结论 乳腺癌肿瘤组织中PTHrP和TGF-β的表达均与乳腺癌进展呈正相关.PTHrP联合TGF-β检测可能成为乳腺癌预后有意义的预测指标.     

Intradural extramedullary capillary hemangioma with intramedullary component: A case series

Rationale:Capillary hemangioma in the spinal cord is an exceedingly rare entity that is liable to be misdiagnosed. To summarize the clinical presentation, radiological characteristics, and pathological features of capillary hemangioma in the spinal cord and to share our experience for the diagnosis and treatment of intradural extramedullary capillary hemangioma.Patient concerns:Three patients underwent surgical treatment at our hospital between January 2020 and August 2020. All patients were male[median age at presentation: 57 years (range: 56–60)]. Two patients were experiencing pain and numbness in the lower back, and 1 patient was experiencing numbness and weakness in the left lower limb. The duration of symptoms ranged from 1 to 5 months.Diagnosis:All patients were diagnosed with spinal cord capillary hemangioma after treatment. All lesions were in an intradural extramedullary location and involved spinal cord components. Two patients had lesions in thoracic segments (T8, Th9-10), and 1 patient had a lesion in lumbar segment (L1).Interventions:All patients underwent microscopic laminectomy and complete resection of the extramedullary and intramedullary components of the spinal cord capillary hemangiomas.Outcomes:Postoperatively, all patients experienced transient numbness and pain in the lower limbs, which gradually decreased over time. None of the patients experienced bleeding, severe numbness or pain, or recurrence of symptoms at 3-month follow-up.Conclusion:Intradural extramedullary capillary hemangioma has unique morphological characteristics. Gross-total resection of the extramedullary and intramedullary components of spinal cord capillary hemangioma is recommended for patients with symptoms of spinal cord compression. Careful preoperative imaging and intraoperative decision-making may help avoid residual lesions or reoperation.     

Can the patient pinpoint where the ingested fish bone is impacted?: A single-center,retrospective study

Among the plethora of foreign body impactions, fish bones are common examples that patients may struggle to properly disclose in clinical situations. This study investigated whether patients could pinpoint where the ingested fish bone was lodged. In addition, we investigated the differences between fish bone and other foreign bodies, the usefulness of computed tomography (CT), and the related risk factors for hospitalization. The cases of patients who underwent an endoscopic removal of fish bone between April 2008 and April 2020 were retrospectively reviewed. The clinical outcomes, X-ray scan, CT, and complications of each patient were investigated. A total of 96 patients were included in this study. The mean size of the impacted fish bone was 23.78 mm, and most were found in the upper esophagus (n = 38). There was a weak correlation between pain location and the actual lesion location (r = 0.419, P < .001). Compared to those of other foreign bodies, the location of impacted fish bones was different (P < .001), the X-ray detection rate of fish bones was lower (P < .001), and the complication incidence was higher (P = .030). CT (95.89%) showed higher sensitivity than X-ray scanning (11.24%) (P < .001). Foreign body size (P = .004) and door-to-endoscopy time (P = .029) were related to admission. Patients only managed to point out the approximate location of the ingested fish bone. CT detected fish bones well, but scans should include at least the entire esophagus instead of solely the area where pain is felt. Fish bone impaction has different clinical characteristics from other foreign bodies. Endoscopic removal without delay can reduce the admission rates.     

Assessment of functioning in Dutch primary care: Development study of a consultation tool for patients with chronic conditions and multimorbidity

BackgroundIn primary care, a shift from a disease‐oriented approach for patients with multimorbidity towards a more person‐centred approach is needed.AimTo transform a self‐report questionnaire for patients with chronic conditions in primary care, the Primary Care Functioning Scale (PCFS), into an understandable, visually attractive and feasible consultation tool for patients and health care providers. The consultation tool consists of a web‐based version of the PCFS, which is filled in by the patient and is processed to a feedback report that summarizes and visualizes the main findings. The feedback report can be discussed with the patient to facilitate a more person‐centred conversation for patients with chronic conditions and multimorbidity in general practice.Design and SettingIn this qualitative study, we developed the consultation tool by using design thinking in a participatory developmental process.MethodsIn the first phase, we constructed five different feedback report templates to summarize and display the results of a completed PCFS questionnaire in a series of two expert meetings with patients and general practitioners (GPs). In the second phase, we performed an exploratory qualitative interview study involving dyads of patients with chronic conditions and their practice nurses. In an iterative process, we explored their experiences with the consultation tool.ResultsPatients, as well as GPs, preferred a clear manner of presenting the results of the questionnaire in a feedback report. In 18 interviews with patients and practice nurses during three different interview rounds, we adjusted the feedback report and consultation tool based on the input from patients and practice nurses. After the final interview round, patients and practice nurses consented that the consultation tool was useful for having a more in‐depth consultation about functioning and patients'' preferences when integrated into the regularly scheduled consultations.ConclusionWe were able to develop an understandable and feasible consultation tool that is applicable in already existing chronic disease management programmes in general practice in the Netherlands.Patient or Public ContributionTo increase the understandability and feasibility of the consultation tool, we collaborated with end‐users and actively involved patients, GPs and practice nurses in a participatory development process.     

心脑血管疾病用药不良反应与药品品种关系的聚类分析

目的寻找心脑血管疾病用药的不良反应与药品品种间聚类关系,促进临床安全合理用药。方法运用数据挖掘技术中的两阶段聚类算法对药品的严重不良反应与药品品种间的关系进行聚类分析。结果由聚类结果可知,在使用心脑血管疾病用药时,出现的严重和新的严重不良反应为肝功能异常、肾功能异常、呼吸困难、横纹肌溶解,导致这些严重不良反应的药物有受体类药物、钙离子拮抗剂、降低胆固醇类药物。结论在选择心脑血管疾病用药时,受体类药物、钙离子拮抗剂、降低胆固醇类药物应慎用、少用,尽量避免严重的不良反应发生。     

Cocktails of Mycotoxins,Phytoestrogens, and Other Secondary Metabolites in Diets of Dairy Cows in Austria: Inferences from Diet Composition and Geo-Climatic Factors

Dairy production is a pivotal economic sector of Austrian and European agriculture. Dietary toxins and endocrine disruptors of natural origin such as mycotoxins and phytoestrogens can affect animal health, reproduction, and productivity. This study characterized the profile of a wide spectrum of fungal, plant, and unspecific secondary metabolites, including regulated, emerging, and modified mycotoxins, phytoestrogens, and cyanogenic glucosides, in complete diets of lactating cows from 100 Austrian dairy farms. To achieve this, a validated multi-metabolite liquid chromatography/electrospray ionization–tandem mass spectrometric (LC/ESI–MS/MS) method was employed, detecting 155 of >800 tested metabolites. Additionally, the most influential dietary and geo-climatic factors related to the dietary mycotoxin contamination of Austrian dairy cattle were recognized. We evidenced that the diets of Austrian dairy cows presented ubiquitous contamination with mixtures of mycotoxins and phytoestrogens. Metabolites derived from Fusarium spp. presented the highest concentrations, were the most recurrent, and had the highest diversity among the detected fungal compounds. Zearalenone, deoxynivalenol, and fumonisin B1 were the most frequently occurring mycotoxins considered in the EU legislation, with detection frequencies >70%. Among the investigated dietary factors, inclusion of maize silage (MS) and straw in the diets was the most influential factor in contamination with Fusarium-derived and other fungal toxins and metabolites, and temperature was the most influential among the geo-climatic factors.     

基于肿瘤临床前模型建立头颈癌新型药物基因组学的必要性及展望

头颈癌是全球第七大恶性肿瘤类型,超过60％患者初次确诊即为中晚期.靶向治疗和免疫治疗的发展已经显著推动了头颈癌治疗策略的转型,但是临床获益有待进一步提升.肿瘤临床前模型保留了患者肿瘤的基因和表型的异质性,已广泛应用于临床前药物筛选和验证体系.药物基因组学通过将基因组学和药物响应进行匹配,能够基于肿瘤异质性基础进行患者分...