Tumor-associated high endothelial venules mediate lymphocyte entry into tumors and predict response to PD-1 plus CTLA-4 combination immunotherapy

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Robust antibody response after a third BNT162b2 vaccine compared to the second among immunocompromised and healthy individuals,a prospective longitudinal cohort study

PurposeAs protection from COVID-19 following two doses of the BNT162b2 vaccine showed a time dependent waning, a third (booster) dose was administrated. This study aims to compare the antibody response following the third dose versus the second and to evaluate post-booster seroconversion.MethodsA prospective observational study conducted in Maccabi Healthcare Services. Serial SARS-CoV-2 Spike IgG tests, 1,2,3 and 6 months following the second vaccine dose and one month following the third were obtained. Neutralizing antibody levels were measured in a subset of participants. Per individual SARS-CoV-2 Spike IgG titer ratios were calculated one month after the booster administration compared to titers one month following the second dose and prior to booster.ResultsAmong 110 participants, 56 (51%) were women. Mean age was 61.7 ± 1.9 years and 66 (60%) were immunocompromised. One month after third dose, IgG titers were induced 7.83 (95 %CI 5.25–11.67) folds and 2.40 (95 %CI 1.90–3.03) folds compared to one month after the second, in the immunocompromised and immunocompetent groups, respectively. Of the 17 immunocompromised participants who were seronegative after the second dose, 4 (24%) became seropositive following the third. Comparing the titers prior to the third dose, an increase of 50.7 (95 %CI 32.5–79.1) fold in the immunocompromised group and 25.7 (95 %CI 19.1–34.7) fold in and immunocompetent group, was observed.ConclusionA third BNT162b2 vaccine elicited robust humoral response, superior to the response observed following the second, among immunocompetent and immunocompromised individuals.     

De novo p.G696S mutation in COL4A1 causes intracranial calcification and late-onset cerebral hemorrhage: A case report and review of the literature

BackgroundThe collagen type IV alpha 1 chain (COL4A1) is an essential component of the basement membrane in small vessels. Pathogenic variants in COL4A1 cause perinatal cerebral hemorrhages in an autosomal-dominant fashion. However, little is known about the long-term outcomes of patients with mildly affecting COL4A1 mutations.Case reportWe report a 17-year-old boy, who presented with recurrent intracranial hemorrhages in the periventricular white matter. He had been followed-up as a child with cerebral palsy bearing intracranial calcifications, developmental delay and epilepsy. Screening tests in infancy provided negative results for intrauterine infections. Severe motor and cognitive deficits persisted after admission. Carbazochrome was introduced on day 19 of admission, which appeared to prevent extension and reactivation of cerebral hemorrhages for over 6 months after discharge.ResultsTargeted sequencing of NOTCH3 and TREX1 excluded causal mutations in these genes. The whole-exome sequencing revealed that he carried a de novo mutation in COL4A1 (p.Gly696Ser). An overview of the literature for 345 cases with COL4A1 mutations supported evidence that p.Gly696Ser is associated with the unique phenotype of late-onset hemorrhage among patients with COL4A1-associated cerebral angiopathy.ConclusionsThis case first demonstrates that infants with COL4A1-associated leukoencephalopathy and calcifications have a risk for developing the rupture of small vessels in the cerebral white matter after 10 years of age.     

冠状动脉心肌桥的临床特点与治疗

目的探讨冠状动脉心肌桥的冠脉造影特点、临床意义及治疗方法。方法回顾性分析293例冠状动脉造影中检出的8例心肌桥患者的临床资料。结果共检出心肌桥8例,均位于前降支,心肌桥发生率为2.7%,心肌桥长度8～25mm,平均14.5mm。依据Nobel分级法,Ⅰ级3例,Ⅱ级4例,Ⅲ级1例。1例Ⅲ级患者同时并发冠脉粥样硬化,病变位于回旋支中段,狭窄<50%。8例患者应用β受体阻滞剂或钙拮抗剂治疗后症状均明显缓解。结论选择性冠脉造影可用于心肌桥的诊断,心肌桥可能引起心肌缺血表现,应用β受体阻滞剂或钙拮抗剂等药物治疗有效。     

趾蹼血管分型的临床认识

目的分析120例足趾移植再造手指病例，对趾蹼间的血管形态和交通情况进行观察，并阐述其临床意义。方法临床观察120例156侧趾蹼，对第一跖骨背动脉和第一趾底动脉在趾蹼间的走向、口径以及两者的交通支情况进行记录并进行分型。结果按孙博的分型方法：Ⅰ型72侧，占46．2％；Ⅱ型57侧，占36．5％；Ⅱ型7侧，占4．5％；Ⅳ型3侧，占1．9％；Ⅴ型15侧，占9．6％；另有2侧（占1．3％）第一跖骨背血管口径〉1mm，虽发出趾背动脉供养蹲趾胫侧和第二趾腓侧，但在趾蹼内与趾底血管无吻合，故称之为孙博Ⅵ型。结论（1）从解剖形态看应增加孙博Ⅵ型较全面；（2）从临床实用角度出发，趾蹼间血管可以简单分为三型：Ⅰ型交通支口径在0．5mm以上。Ⅱ型交通支在0．5mm以下。Ⅲ型无交通；（3）手术中采用第一套或第二套供血系统，首先要看趾蹼间血管的交通支，即按本组的分型属Ⅰ型采用第一套供血系统，Ⅱ、Ⅲ型采用第二套供血系统。     

带浅静脉干逆行皮瓣早期微血管构筑变化的体视学研究

目的 探讨带浅静脉干的逆行皮瓣早期微血管构筑变化的特点以供临床实践参考。方法 应用生物体视学技术测量带浅静脉干皮瓣微血管体积密度，结合组织学观察，与不带静脉干皮瓣作对照比较。结果 带浅静脉干皮瓣组微血管密度整体水平高于不带静脉干皮瓣组（P〈0．05）。结论 浅静脉干的存在有利于皮瓣的血管化进程，保留浅静脉干对皮瓣成活有利。     

冠状动脉旁路移植手术67例

目的报告2002年4月至2004年12月67例冠状动脉旁路移植手术(CABG).方法男性58例,女性9例,年龄41～76岁,平均58.5岁.合并二尖瓣病变同期手术3例,3支血管病变39例,2支血管病变28例.采取体外循环下手术(on-pump-CABG)和非体外循环下手术(off-pump-CABG)两种方式,各有其适应指征.结果全组死亡1例,其余治愈出院,随诊1～18个月,心绞痛消失,疗效满意.结论冠状动脉旁路移植手术安全,有很好的发展前景.