Treatment of Skin Reaction Induced by Nivolumab Combined with Radiotherapy in Non-small Cell Lung Cancer:A Case Report

Skin reaction or dermatological toxicities induced by immunotherapy is common.It usually manifests skin rash or erythema and can be cured by skin lotion or steroid.Nivolumab,a human IgG4 programmed cell death protein 1(PD-1)inhibitor,blocks T cells activation preventing signal and allows the immune system to clear cancer cells.Nivolumab was approved in the second-line therapy in squamous cell lung cancer by FDA,with less than 10%unusual skin reaction,like sensory neuropathy,peeling skin,erythema multiforme,vitiligo,and psoriasis.Radiotherapy could aggravate this skin reaction through inflammatory response and promotion of immunity.The combined treatment of anti-PD-1 and radiotherapy represented a new promising therapeutic approach in many studies,but the risk of side effects may be high.We reported a patient with advanced squamous cell lung cancer who suffered from serious skin immune-related adverse events when he was treated with nivolumab and radiotherapy.The immune overreaction of the treatment of anti-PD-1 treatment and radiotherapy might cause these serious skin adverse events.Our report warranted careful workup to reduce the risk of side effects by combinative therapy with anti-PD-1 and radiotherapy.

Multikinase inhibitor-associated hand-foot skin reaction as a predictor of outcomes in patients with hepatocellular carcinoma treated with sorafenib

AIM To investigate the relationship between the onsets of multikinase inhibitor(MKI)-associated hand-foot skin reaction(HFSR) and prognosis under intervention by pharmacists after the introduction of sorafenib.METHODS We conducted a retrospective study involving 40 patients treated with sorafenib. Intervention by pharmacists began at the time of treatment introduction and continued until the appearance of symptomatic exacerbation or non-permissible adverse reactions. We examined the relationship between MKI-associated HFSR and overall survival(OS) after the initiation of treatment.RESULTS The median OS was 10.9 mo in the MKI-associated HFSR group and 3.4 mo in the no HFSR group, showing a significant difference in multivariate analysis. A multivariate analysis of the time to treatment failure indicated that the intervention by pharmacists and MKI-associated HFSR were significant factors. The median cumulative dose and the mean medication possession ratio were significantly higher in the intervention group than in the non-intervention group. A borderline significant difference was observed in terms of OS in this group.CONCLUSION Intervention by pharmacists increased drug adherence. Under increased adherence, MKI-associated HFSR was an advantageous surrogate marker. Intervention by healthcare providers needs to be performed for adequate sorafenib treatment.

Skin reactions caused by bone-anchored hearing aid(BAHA) implantation

Objective: To report a case of intractable skin reactions caused by bone-anchored hearing aid (BAHA) implantation to improve our under-standing and treatment of BAHA implantation-caused skin reactions. Methods:We reported a case of severe skin reactions caused by BAHA implantation. Related literature were also reviewed. Results:We found grade IV skin reactions, including hyperplasia around the implant, which led to the removal of the BAHA implant 10 months after implantation. The findings indicated poor skin hygiene, allergy to titanium and inadequate surgicals skills as the possible causes of the skin reaction. Conclusion: Skin adverse reactions, usually rare in BAHA implantation patients, may cause implant removal and implantation failure. We suggest to further investigate the mechanisms underlying titanium allergy. Copyright ? 2016, PLA General Hospital Department of Otolaryngology Head and Neck Surgery. Production and hosting by Elsevier (Singapore) Pte Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Traditional Chinese Medicine for Treatment of Apatinib-induced Hand and Foot Skin Reaction:A case report

Squamous cell carcinoma arising at maxillary sinus is a rare neoplasm, characterized by aggressive growth pattern and glooming prognosis. A 78-year-old woman presented with left maxillary sinus carcinoma. The patient received four courses of chemotherapy after surgery in our center. Eight months after treatment, the patient experienced local progress, severe gastrointestinal reactions and asthenia. Then apatinib was used as third-line treatment. Good curative effect was achieved with 250 mg apatinib per day, while adverse reaction such as hand and foot skin reaction affected the quality of her life. Traditional Chinese medicine exhibits good results and no obvious side effects in relieving hand and foot skin reaction. Traditional Chinese medicine is Chinese treasure, it remains challenging, and further investigations are needed.

Clinical Efficacy and Adverse Reactions of Photodynamic Therapy in the Treatment of Malignant Skin Tumors and Precancerous Skin Diseases

The purpose of the study was to investigate the efficacy and safety of photodynamic therapy in the treatment of malignant skin tumors and precancerous skin diseases.First of all,100 patients with malignant skin tumor and pre-cancer skin disease admitted to our hospital from January 20,2018 to September 18,2018 were selected,and all of them adopted photodynamic therapy.The 100 patients included 40 cases of basal cell carcinoma,14 cases of squamous cell carcinoma,7 cases of proliferative erythema,9 cases of Bowen’s disease and 39 cases of solar keratosis.Among the 100 patients,77 cases had excellent curative effect,18 cases had good effect and 5 cases had poor effect,and the overall effective rate was 95%(95/100).After 6 months of follow-up,5 cases of basal cell carcinoma,2 cases of squamous cell carcinoma,0 cases of proliferative erythra,1 case of Bowen’s disease and 3 cases of solar keratosis recurred,with an overall recurrence rate of 14%(14/100).The adverse reactions of pruritus were 90%(90/100),81%(81/100),90%(90/100)and 3%(3/100).Therefore,the application of photodynamic therapy in the treatment of malignant skin tumors and precancerous skin diseases is not only effective,but also safe and not easy to relapse.

吴煜基于“火郁发之”论治靶向药物相关手足皮肤反应经验

手足皮肤反应是接受抗肿瘤治疗过程中使用靶向药物后常见的不良反应,严重降低患者生活质量,甚至导致药物减量或中断,影响抗肿瘤疗效。西医学对症治疗效果欠佳,中医药防治手足皮肤反应收效良好。吴煜教授临证经验丰富,基于“火郁发之”理论治疗靶向药物相关手足皮肤反应,归纳其病机以“热毒、湿、瘀交阻为标,气阴亏虚为本”,临床可辨证分型为热毒蕴结型、湿热瘀阻型、阴虚血燥型,分别清热解毒、透邪外出以泻火,祛湿通瘀、凉血活血以散火,补虚扶正、滋阴养血以生肌,临床效果满意,并附验案一则以证其效。

Tacrolimus may play a role in dermatitis and radiation-induced skin injury through cellular senescence

Skin Exposure of skin to ionizing radiation can induce acute or chronic biological effects,resulting in radiation-induced skin injury(RSI).Premature cellular senescence,caused by oxidative stress and/or DNA damage from chemical or physical agents,leads to the decrease of cellular proliferation and physiological function.Persistent DNA damage and accumulation of senescent cells are associated with the progression of radiation-induced injury.Atopic dermatitis and RSI have similar inflammatory symptoms.The treatment of tacrolimus(TAC)in atopic dermatitis may be associated with premature cellular senescence.TAC can prevent the onset of cellular senes-cence by inactivating the p38 mitogen-activated protein kinase(p38 MAPK).The activation of p38 MAPK can induce the senescence-associated secretory phenotype(SASP)by enhancing the transcriptional activity of nuclear factor kappa-B(NF-κB),which ultimately leads to premature cellular senescence.FK506 binding protein 51(FKBP51)exhibits resistance to ionizing radiation,but the mechanism of TAC regulation of ionizing radiation-induced premature senescence still needs further study.This review discusses the mechanism of cellular senes-cence in RSI and the role of TAC in both dermatitis and RSI.

Configurational information entropy analysis of fragment mass cross distributions to determine the neutron skin thickness of projectile nuclei

Configurational information entropy(CIE)analysis has been shown to be applicable for determining the neutron skin thickness(δnp)of neutron-rich nuclei from fragment production in projectile fragmentation reactions.The BNN+FRACS machine learning model was adopted to predict the fragment mass cross-sections(σ_(A))of the projectile fragmentation reactions induced by calcium isotopes from ^(36)Ca to ^(56)Ca on a ^(9)Be target at 140MeV/u.The fast Fourier transform was adopted to decompose the possible information compositions inσA distributions and determine the quantity of CIE(S_(A)[f]).It was found that the range of fragments significantly influences the quantity of S_(A)[f],which results in different trends of S_(A)[f]~δnp correlation.The linear S_(A)[f]~δnp correlation in a previous study[Nucl.Sci.Tech.33,6(2022)]could be reproduced using fragments with relatively large mass fragments,which verifies that S_(A)[f]determined from fragmentσAis sensitive to the neutron skin thickness of neutron-rich isotopes.

Sequence Analysis of Attachment Gene of Lumpy Skin Disease and Sheep Poxviruses

In Egypt,protection of cattle against lumpy skin disease (LSD) was carried out using a sheep poxvirus (Kenyan strain) vaccination strategy.In the present study 15 skin nodules from LSD suspected cows and 5 scab samples from sheep pox (SP) suspected sheep were collected.Hyperimmune rabbit sera to Lumpy skin disease virus (LSDV)/Ismailyia88 strain and sheep pox virus (SPV)/ Kenyan vaccinal strain were prepared.The causative agent in the collected samples was identified using immunoflourescence (IF) and immunoperoxidase techniques.Of the 15 skin nodules suspected of LSD,10 showed a positive reaction and 3 out of 5 skin scabs suspected of sheeppox were found to be positive.An antigenic correlation between field skin isolate of LSDV,tissue culture adapted LSDV/Ismailyia88 strain,field skin isolate of SPV and SPV/Kenyan vaccinal strain was studied using prepared hyperimmune sera.Also,nucleotide sequence of the PCR amplified attachment gene fragments of field skin isolate of LSDV,tissue culture adapted LSDV/Ismailyia88 strain,field skin isolate of SPV and SPV /Kenyan vaccinal strain were compared.The results revealed that the four used viruses were antigenically identical.Sequence analysis indicated that field skin LSDV isolate is more related to tissue culture adapted LSDV/Ismailyia88 strain than to vaccinal SPV/ Kenyan strain and the skin isolate of SPV is more closely related to field skin isolate of LSDV than to SPV/Kenyan vaccinal strain.Thus,further study should be applied on the advantage of a LSD vaccine prepared from LSDV in protection of cattle against LSD compared to the commonly used sheep pox vaccine.

Assistive Navigation Device for Visually Impaired—A Study on Reaction Time to Tactile Modality Stimuli

A tactile system to support severe visually-impaired or blind people in the world for their orientation and navigation had been developed. To optimize the design, some parameters of tactile display device were evaluated. In the present paper,we focused on the reaction time to tactile stimuli. In the test, the stimuli were produced through a vibration belt that was worn around the participants’ waist. In the choice reaction time task, the participants had to click corresponding arrow keys according to the location of a tactile signal. The findings of this study provided a reference of the reaction time range, so as to design a more effective and safe tactile navigation system.

Clinical Effect of Photodynamic Therapy Combined Cryotherapy on Nonmelanoma Skin Cancer

The purpose of this study was to investigate the clinical efficacy of photodynamic combined freezing in patients with non-melanoma skin cancer(NMSC).First,according to the treatment regimen,96 patients with NMSC were divided into study group(n=50)and control group(n=46).The control group was treated with 5-amino-ketovalic acid photodynamic therapy(ALAPDT),while the study group was treated with ala-PDT combined with cryotherapy.Visual analogue scale(VAS)scores,visual satisfaction,clinical efficacy,adverse reactions,and progression-free survival were compared between the two groups.The results showed that VAS score in the study group was slightly higher than that in the control group,but the difference was not statistically significant(P>0.05).The appearance satisfaction and total effective rate of patients in the study group were higher than those in the control group,and the difference was statistically significant(P<0.05).The total incidence of adverse reactions in the study group was slightly higher than that in the control group,but the difference was not statistically significant(P>0.05).3 years progressionfree survival time and 3 years progression-free survival rate were compared between the two groups,and the difference was not statistically significant(P>0.05).Therefore,the combination of PDT and cryotherapy for non-melanoma skin cancer has a good clinical effect,which is conducive to the recovery of skin lesions,high patient satisfaction,fewer adverse reactions,and longer progression-free survival.In addition,the combined therapy can provide a new treatment idea for non-melanoma skin cancer patients who are not suitable for surgical treatment.

奥马珠单抗注射剂治疗哮喘致迟发型皮肤过敏反应1例分析

目的 提示临床奥马珠单抗注射剂联合治疗中重度过敏性哮喘使用过程中需加以关注可能引起的迟发型皮肤过敏反应。方法 分析1例奥马珠单抗注射剂联合治疗中重度过敏性哮喘过程中,发生迟发型过敏大面积皮疹,通过不良反应相关性分析鉴别该患者发生不良反应的可能药物和处理措施。结果 患者不良反应为迟发型大面积过敏皮疹,排除患者病情和合并用药情况,判断引起患者严重大面积皮疹的原因为注射使用奥马珠单抗。不良反应相关性评价为“肯定”,立即予以停药并对症处理后患者好转,未发生后遗症。结论 临床应加强监测奥马珠单抗注射剂引起的迟发型不良反应并及时采取措施,以免造成严重后果。

卢传坚教授从脾肾论治慢性荨麻疹经验撷英

介绍卢传坚教授从脾肾论治慢性荨麻疹的临床经验。认为慢性荨麻疹风团之标象,从病理角度看实际属于“水湿”范畴,其发生和反复发作与“水湿运化不利”密不可分,其根本责之于“脾肾阳虚”,慢性荨麻疹的核心病机为“脾肾阳虚为其本,风湿相搏为其标”;强调以“温肾健脾治其本、祛风化湿治其标”为治疗法则,并创制“固本抗敏方”为核心方进行辨证论治,疗效显著。并附验案1则。

基于生理指标的儿童牙科恐惧与焦虑的评估模型

目的探索口腔治疗场景下患者恐惧焦虑情绪所伴随的神经生理表征,并构建一种基于生理指标的儿童牙科恐惧与焦虑(DFA)的评估模型。方法纳入在北京儿童医院口腔科就诊的166例14周岁以下儿童。采用改良中文版儿童畏惧调查表-牙科分量表(CFSS-DS)评定儿童DFA得分。使用腕式生理数据采集设备对儿童患者就诊期间的心率(HR)和皮肤电(GSR)进行全程连续测量。用重复测量方差分析对治疗前、中和后的生理数据进行差异检验;用皮尔逊(Pearson)相关分析对治疗前、中和后的生理数据与CFSS-DS分数做相关分析;建立最小绝对收缩和选择算法(LASSO)回归模型对儿童牙科恐惧与焦虑进行评估,用留一法(LOO)进行交叉验证。结果生理数据各维度在治疗前、中和后的变化差异显著(P<0.05);LASSO模型预测值与CFSS-DS原始分数之间皮尔逊相关系数r=0.30,P<0.05,说明本模型有较好的预测准确性。结论评估模型可以实现对儿童牙科恐惧与焦虑的客观、自动化的测量。

调Q激光与强脉冲光治疗面部雀斑的疗效比较

目的:探究调Q激光与强脉冲光治疗面部雀斑的疗效及对皮损情况和不良反应的影响。方法:选取2021年1月-2022年9月就诊于笔者医院的130例面部雀斑患者,按就诊顺序随机分为对照组和观察组,每组65例。对照组采用强脉冲光治疗,观察组采用调Q激光治疗。比较两组治疗前后皮肤生理特征、美学效果及疗程、皮损情况、不良反应、患者美观满意度。结果:两组患者治疗期间不良反应总发生率比较差异无统计学意义(P>0.05),停止治疗3~6个月后均自行恢复。治疗前,两组患者斑点,纹理,皱纹,毛孔评分,皮损面积、颜色评分比较差异无统计学意义(P>0.05)。治疗1次后,两组皮肤生理状况及皮损状况均得到明显改善,且观察组上述评分均低于对照组(P<0.05);观察组美容治疗总有效率高于对照组(P<0.05)。观察组治疗时间及次数少于对照组(P<0.05)。两组患者美观满意度比较差异无统计学意义(P>0.05)。随访6个月后,所有患者无复发。随访1年后,两组复发率比较差异无统计学意义(P>0.05)。结论:与强脉冲光相比,调Q激光改善皮肤生理特征效果更好,治疗面部雀斑疗效更确切。调Q激光与强脉冲光治疗雀斑的近期疗效良好,但远期复发率较高。强脉冲光治疗雀斑的皮损情况少于调Q激光治疗。两者不良反应均较少,美观满意度相当。

双相情感障碍患者人类白细胞抗原-B^(*)1502基因检测分析及用药风险评估

目的通过检测并分析双相情感障碍(BD)患者人类白细胞抗原-B^(*)1502(HLA-B^(*)1502)基因多态性,评估拉莫三嗪诱发皮肤不良反应的风险。方法回顾性收集2019年1月至2022年8月在枣庄市妇幼保健院就诊并在初次使用拉莫三嗪前采用荧光染色原位杂交测序技术检测HLA-B^(*)1502基因型和用药指导的510例患者作为研究对象,分析其基因型与皮肤型药物不良反应发生情况。结果患者HLA-B^(*)1502基因中阳性结果的占比低于阴性结果,差异有统计学意义(P<0.05)。HLA-B^(*)1502基因阳性结果中,杂合突变型占比高于纯合突变型,差异有统计学意义(P<0.01)。结论临床在初次使用拉莫三嗪控制和治疗双相情感障碍患者的过程中,为降低拉莫三嗪诱发皮肤不良反应的风险,有必要进行HLA-B^(*)1502基因检测。

肿瘤免疫检查点抑制剂相关皮肤毒性管理的证据总结

目的评价并总结免疫检查点抑制剂相关皮肤毒性管理的相关证据,为医护人员对肿瘤免疫检查点抑制剂相关皮肤毒性患者进行管理提供依据。方法系统检索国内外相关网站和数据库,查询关于肿瘤免疫检查点抑制剂相关皮肤毒性管理方面的指南、专家共识、证据总结、系统评价等证据。检索时间为建库至2024年4月30日,由2名具有循证护理知识的研究人员独立对文献进行质量评价和证据级别评定。结果共纳入19篇文献,包括指南7篇、专家共识10篇、系统评价1篇、临床决策1篇,从预防、评估、检查、治疗与护理、监测5个方面形成19条最佳证据。结论有效管理免疫检查点抑制剂相关皮肤毒性可改善皮肤症状,提高患者的生活质量。医护人员需考虑患者的意见,结合临床情境,为肿瘤免疫检查点抑制剂相关皮肤毒性患者提供个性化的指导。

甲基莲心碱通过调节AMPK/mTOR/NLRP3信号通路减轻慢性皮肤溃疡大鼠的炎症反应

目的:探讨甲基莲心碱(Nef)调节AMP活化蛋白激酶(AMPK)/哺乳动物雷帕霉素靶蛋白(mTOR)/NOD样受体热蛋白结构域相关蛋白3(NLRP3)信号通路对慢性皮肤溃疡(CSU)大鼠炎症反应的影响。方法:将90只大鼠随机分为空白对照组(NC组)、CSU组、Nef组、AMPK抑制剂(Compound C)组、Nef+Compound C组,每组18只大鼠。除NC组外的其他各组大鼠通过剪开创口注射氢化可的松以及喷洒金黄色葡萄球菌构建CSU大鼠模型。造模完成后,Nef组和Compound C组分别将20%Nef、10μmol·L^(-1) Compound C与50 mL的20%高渗盐水凝胶混合敷在伤口处,Nef+Compound C组将20%Nef和10μmol·L^(-1) Compound C一起添加到20%高渗盐水凝胶中敷在伤口处,持续治疗2周,NC组、CSU组用等量盐水凝胶处理伤口。观察大鼠皮肤创面愈合情况;ELISA法检测血清白细胞介素(IL)-1β、IL-8、TNF-α水平;水解法检测创面肉芽组织中羟脯氨酸(HyP)水平;HE染色检测肉芽组织病理学变化;Western blotting检测CCL4、CCL2、CXCL12以及AMPK/mTOR/NLRP3信号通路蛋白表达水平。结果:CSU组大鼠可看到新生肉芽组织,并且有大量炎症细胞浸润现象,CSU组较NC组IL-1β、IL-8、TNF-α含量显著升高(P<0.05);与CSU组相比,Nef组创面愈合率、HyP含量、p-AMPK/AMPK蛋白水平显著增加(P<0.05),IL-1β、IL-8、TNF-α含量、CCL2、CXCL12、CCL4、mTOR、NLRP3蛋白水平显著下降(P<0.05),而Compound C组趋势相反(P<0.05);Compound C消除了Nef对CSU大鼠炎症反应的减轻作用。结论:Nef可能通过调控AMPK/mTOR/NLRP3信号通路减轻CSU大鼠炎症反应。

应用DPRA替代方法评价3种香豆素类化合物的皮肤致敏性

应用直接多肽反应试验(DPRA)方法,对化妆品植物提取物原料中存在的蛇床子素、滨蒿内酯、东莨菪内酯3种未知致敏性的香豆素类化合物进行评价。3种香豆素类化合物与半胱氨酸多肽和赖氨酸多肽模拟的皮肤蛋白共同孵育,使用高效液相色谱法检测3种化合物的多肽消耗率。在标准色谱条件下,蛇床子素和滨蒿内酯与两种多肽的反应体系峰型均正常,东莨菪内酯与赖氨酸反应体系峰型异常,以体积分数0.1%的甲酸水-乙腈流动相体系对标准流动相体系进行优化后检测。结果表明:蛇床子素与半胱氨酸反应体系在反应24 h前产生沉淀,致敏性结果为不确定;滨蒿内酯多肽消耗率均值为6.95%,判定致敏性为阳性,反应等级为弱反应;东莨菪内酯的半胱氨酸多肽消耗率为75.82%,优化色谱条件后的赖氨酸多肽消耗率为80.46%,判定致敏性为阳性,反应等级为中度反应。阳性和阴性对照化合物的结果均与小鼠淋巴结试验(LLNA)致敏性结果一致,实验结果可为3种香豆素类化合物的致敏性提供参考和依据。

维生素B1注射液皮肤过敏试验反应性和治疗安全性分析

目的 分析维生素B1注射液皮肤过敏试验结果和治疗安全性。方法 收集2020年1月至2021年12月行维生素B1皮试患者的临床资料,分析患者皮试阳性率和相关因素,皮试后维生素B1肌注或使用其他维生素B1制剂的不良反应发生率。结果 维生素B1皮试阳性率为17.07%。共549例皮试阴性患者肌注维生素B1注射液,不良反应发生率为0.95%,其中1例为严重过敏反应。59例皮试阳性患者接受静脉补充复方水溶性维生素或口服含维生素B1制剂治疗,均未发现不良反应。结论 维生素B1皮试阳性率高,可能存在假阳性和假阴性,需更深入探讨维生素B1皮试预测过敏的价值,完善相关规章制度。