肿瘤免疫检查点抑制剂相关的肝毒性

肿瘤免疫检查点抑制剂治疗为肿瘤患者带来生存获益的同时,也面临了许多挑战,例如免疫介导的肝毒性的发生。深入了解免疫检查点抑制剂治疗肿瘤过程中导致肝损伤的发生情况、可能机制、危险因素等,有助于更好地临床管理。     

Differentiating autoimmune pancreatitis from pancreatic ductal adenocarcinoma with CT radiomics features

PurposeThe purpose of this study was to determine whether computed tomography (CT)-based machine learning of radiomics features could help distinguish autoimmune pancreatitis (AIP) from pancreatic ductal adenocarcinoma (PDAC).Materials and MethodsEighty-nine patients with AIP (65 men, 24 women; mean age, 59.7 ± 13.9 [SD] years; range: 21–83 years) and 93 patients with PDAC (68 men, 25 women; mean age, 60.1 ± 12.3 [SD] years; range: 36–86 years) were retrospectively included. All patients had dedicated dual-phase pancreatic protocol CT between 2004 and 2018. Thin-slice images (0.75/0.5 mm thickness/increment) were compared with thick-slices images (3 or 5 mm thickness/increment). Pancreatic regions involved by PDAC or AIP (areas of enlargement, altered enhancement, effacement of pancreatic duct) as well as uninvolved parenchyma were segmented as three-dimensional volumes. Four hundred and thirty-one radiomics features were extracted and a random forest was used to distinguish AIP from PDAC. CT data of 60 AIP and 60 PDAC patients were used for training and those of 29 AIP and 33 PDAC independent patients were used for testing.ResultsThe pancreas was diffusely involved in 37 (37/89; 41.6%) patients with AIP and not diffusely in 52 (52/89; 58.4%) patients. Using machine learning, 95.2% (59/62; 95% confidence interval [CI]: 89.8–100%), 83.9% (52:67; 95% CI: 74.7–93.0%) and 77.4% (48/62; 95% CI: 67.0–87.8%) of the 62 test patients were correctly classified as either having PDAC or AIP with thin-slice venous phase, thin-slice arterial phase, and thick-slice venous phase CT, respectively. Three of the 29 patients with AIP (3/29; 10.3%) were incorrectly classified as having PDAC but all 33 patients with PDAC (33/33; 100%) were correctly classified with thin-slice venous phase with 89.7% sensitivity (26/29; 95% CI: 78.6–100%) and 100% specificity (33/33; 95% CI: 93–100%) for the diagnosis of AIP, 95.2% accuracy (59/62; 95% CI: 89.8–100%) and area under the curve of 0.975 (95% CI: 0.936–1.0).ConclusionsRadiomic features help differentiate AIP from PDAC with an overall accuracy of 95.2%.     

Vaccines and autoimmunity during the COVID-19 pandemic

To control the pandemic, efficient vaccines must be applied to the population, including patients with autoimmune diseases. Therefore, one can expect that coronavirus disease 2019 (COVID-19) vaccines may influence the underlying autoimmune processes in these patients. Additionally, it is essential to understand whether COVID-19 vaccines would be effective, safe, and provide long-lasting immunological protection and memory. However, the currently available and approved COVID-19 vaccines turned out to be safe, effective, and reliable in patients with autoimmune inflammatory and rheumatic diseases. Furthermore, most patients said they felt safer after getting vaccinations for COVID-19 and reported enhanced overall quality of life and psychological wellbeing. In general, the COVID-19 vaccines have been highly tolerated by autoimmune patients. Such findings might comfort patients who are reluctant to use COVID-19 vaccines and assist doctors in guiding their patients into receiving vaccinations more easily and quickly.     

Case of autoimmune neutropenia with severe marginal periodontitis

Early onset periodontitis is rarely seen in infants, though often leads to an acute and serious clinical course when encountered in such patients. Autoimmune neutropenia presents systemic and dental symptoms, as depressed resistance to bacterial infection is caused by a disorder that reduces the number of neutrophils. This disease can result in not only gingival inflammation but also destruction of periodontal tissues, such as attachment loss, alveolar bone absorption, and early tooth loss in primary as well as mixed dentition. Here, we report treatment of a child with marginal periodontitis from the age of 3 years–7 years 9 months. No systemic manifestations were noted until 3 years of age, thus the patient had never received a detailed examination or medication related to the disease. Following examinations at our department, we referred the patient to a pediatrician at our university hospital for possible systemic disease, who made a diagnosis of autoimmune neutropenia. Although administration of antibiotics and professional dental care were continued, neutrophil count was not increased and progressive periodontal destruction was observed. Extraction of teeth with poor prognosis was performed and a prosthetic strategy for the missing teeth developed. It is important to recognize that periodontitis along with autoimmune neutropenia can appear in infants, even though the incidence is quite low. Early detection and early treatment of this disease is necessary for delaying progression of periodontitis and optimal occlusal induction of permanent teeth.     

Peripheral whole blood FOXP3 TSDR methylation: a potential marker in severity assessment of autoimmune diseases and chronic infections

Immune dysregulation is a cardinal feature of autoimmune diseases and chronic microbial infections. In particular, regulatory T cells are downregulated in autoimmune diseases while upregulated in chronic microbial infections. FOXP3 is the master regulator of Treg development. Treg-specific demethylated region (TSDR) is a highly conserved locus on the FOXP3 gene that is fully demethylated in natural Tregs but methylated in effector T cells. In our study, we used high resolution melt-polymerase chain reaction (HRM-PCR) to determine the FOXP3 TSDR methylation status in autoimmune diseases and chronic microbial infections. We found that FOXP3 TSDR to have the highest mean melting temperature (highly methylated) in active SLE patients compared to all the other groups (p?<?0.001). The psoriasis group also had a significantly high mean melting temperature (78.62?±?0.20) when compared with the inactive SLE group (78.49?±?0.29, p?<?0.05) and control group (78.44?±?0.25, p?<?0.01). There was no significant difference in melting temperature between inactive SLE and healthy controls. Disease activity in SLE was directly associated with methylation of the FOXP3 TSDR. On the other hand, patients with chronic microbial infections had significantly lower FOXP3 TSDR mean melting temperature (demethylated) when compared with healthy controls (78.28?±?0.21 vs 78.44?±?0.25, p?<?0.05). Our results suggest that the use of HRM-PCR to detect FOXP3 TSDR methylation status is a reliable and easy method to predict natural regulatory T cell levels in peripheral blood in different disease conditions. Determining FOXP3 TSDR methylation status can be a useful tool in diagnosis, and monitoring the severity of autoimmune diseases and chronic microbial infections.     

含化复方新诺明引起过敏性休克一例

含化复方新诺明引起过敏性休克一例患者，女，３０岁，因咽峡炎于１９９２年８月７日晚１０时自行含化复方新诺明（广州白云山制药厂）两片、约７分钟后，出现全身搔痒，当即肌注苯海拉明２０ｍｇ，静推１０％葡萄糖酸钙１０ｍｌ，旋即全身泛起荨麻疹，奇痒难忍，眼睑轻度水肿，嘴唇发麻，咽部“发紧”，发音困难，烦躁，立即给予吸氧，静推地塞米松１０ｍｇ，皮下注射肾上腺素０．５ｍｇ，与此同时，患者脸色苍白、鼻尖、未梢发凉，口唇紫绀，时吸暂停，意识丧失，脉搏１４０次／分，细数，血压测不到，再次给予皮下注射肾上腺素０．５ｍｇ，静点地塞米松１５ｍｇ，并给予扩容、纠酸，约一分钟后，欲行气管切开时，患者呼吸渐恢复、继而意识清楚，紫绀减轻，血压１０／１６ｋＰａ，遂休克纠正。复方新诺明片致过敏性休克者尚属少见，该患者有青霉素过敏史，局部用药又易致过敏，考虑喉头痉挛与药物含化有关。（长治市人民医院王爱军，崔文华，郭天然）含化复方新诺明引起过敏性休克一例@王爱军，崔文华，郭天然$长治市人民医院     

自身免疫性白内障的晶状体代谢与生理改变研究

目的 :探讨自身免疫性白内障 (AIC)的病理生理学机制。　方法 :采用酶组织化学方法以及晶状体生理功能检查 ,观察AIC模型动物晶状体生理功能与组织内主要酶活性的变化。　结果 :晶状体组织内Na K ATP酶活性降低与晶状体调节力下降、裂隙灯下显微镜混浊改变之间存在着相关性。　结论 :自身免疫性晶状体损伤 ,进而造成晶状体组织内相关酶代谢异常是AIC的病理基础     

碘和甲状腺球蛋白诱导大鼠自身免疫性甲状腺炎的研究

目的　研究碘与自身免疫性甲状腺炎 (EAT)的关系。方法　用碘和甲状腺球蛋白 (TG)诱导SD大鼠建立甲状腺炎模型 ,随机分为 5组 ,每组 10只。正常对照组 (NC组 ) ;少量碘组 (LI组 ) :饮 5 0 0 μg/L碘化钠水 ;大量碘组 (HI组 ) :饮 5 0 0mg/L碘化钠水 ;TG组 :于实验第 15天大鼠接受皮内多点注射完全福氏佐剂乳化的TG各 10 0 μg作为初次免疫 ,2周后以不完全福氏佐剂乳化的TG加强免疫 ,以后每周加强免疫 1次至第 6周末实验结束 ;TG HI组 :TG及HI给药方法同上。至第 6周末实验结束处死所有动物 ,用放免法检测血清TG抗体 (TGAb)及甲状腺过氧化物酶抗体 (TPOAb)效价 ,并于光镜下观察甲状腺组织淋巴细胞浸润程度。结果　TG HI组、HI组及TG组甲状腺滤泡破坏及淋巴细胞浸润均较明显 ,TG HI组及HI组与NC组比较 ,P<0 .0 5 ,TG组与NC组比较有增高趋势 ,但无统计学意义。 3组TGAb、TPOAb均明显高于NC组及LI组 (P<0 .0 1;仅HI组TPOAbP<0 .0 5 )。各组TGAb及TPOAb水平与甲状腺病理分级呈正相关关系 (r =0 .9,P<0 .0 5 )。结论　高碘可诱发SD鼠EAT发生 ,TG与高碘结合诱导SD大鼠EAT的作用更明显     

免疫反应在实验性游离型腰椎间盘突出自然吸收中的意义

目的：通过检测CD3和IgG在实验性游离型腰椎间盘突出自然吸收中的表达，探讨腰椎间盘突出后能否自然吸收及其可能的吸收机制。方法：将25只成年狗平均分成5组，从L2/3切取髓核组织，置于L5处的硬脊膜外，于术后2，4，6，8，12周，取动物标本以及正常部位的髓核组织，用CD3抗体和抗IgG进行免疫组化检测。结果：约30%的标本局部为脂肪组织，54%的标本局部硬脊膜与骨粘连，16%的标本既无粘连也无脂肪，免疫组化测定显示，随着时间的推移，CD3^ 细胞的浸润程度呈递减趋势，而IgG沉积的分布程度呈递增趋势，正常髓核无CD3^ 细胞浸润，IgG沉积分布极少。结论：在椎管内，狗游离的髓核组织8-12周后可部分或全部自然吸收，其吸收机制是机体自身免疫反应的结果。