Clinical and biologic features of childhood T-cell leukemia with the t(11;14)

Cytogenetic analysis of cells from 622 consecutive patients with newly diagnosed acute lymphoblastic leukemia (ALL) and successful G-banding chromosome studies disclosed seven cases with the t(11;14)(p13;q11) and one with the t(11;14)(p15;q11). Leukemia cells in all eight cases had a T-cell immunophenotype. The t(11;14)(p13;q11) occurred in 6.8% and the t(11;14)(p15;q11) in 1% of T-cell ALL cases (n = 103). The t(11;14) was associated with presenting clinical features typical of T-cell ALL: male predominance (n = 6), age greater than 10 years (n = 3), hyperleukocytosis (white blood cells greater than 100 x 10(9)/L, n = 5), relatively high hemoglobin level (median, 10.8 g/dL), high serum lactic dehydrogenase level (median, 3248 U/L), presence of mediastinal mass (n = 6), and central nervous system leukemia (n = 2). While there were no significant differences in presenting features between T-cell ALL cases with or without the t(11;14), leukemic cells from patients with the translocations were more likely to coexpress CD4 and CD8 antigens (6 of 6 v 35 of 86 cases tested, P less than .05). Adverse events have occurred in six patients: three central nervous system relapses [including the one with t(11;14)(p15;q11)], two secondary acute myeloid leukemia, and one hematologic relapse. Our results indicate that the t(11;14)(p13;q11) occurs exclusively in T-cell malignancies of intermediate- or late-stage thymocyte differentiation. Additional studies are needed to determine the prognostic implications of these translocations.     

Cutaneous lymphoblastic lymphoma with pre-B markers

Two children with cutaneous convoluted lymphoblastic lymphoma are reported. Malignant cells from both patients contained cytoplasmic Mu heavy chains characteristic of pre-B-cells and expressed CALLA and la antigens as well. Most cases of convoluted lymphoblastic lymphoma are T- cell-derived neoplasms. The non-T, non-B phenotype found in these two children demonstrates that histology does not necessarily predict immunophenotype. The association of the pre-B phenotype with cutaneous lymphoma has not been previously reported, but may represent a unique clinical-histopathologic-immunologic entity that occurs in young children.     

Early migration of tibial components is associated with late revision: A systematic review and meta-analysis of 21,000 knee arthroplasties

Purpose

We performed two parallel systematic reviews and meta-analyses to determine the association between early migration of tibial components and late aseptic revision.

Methods

One review comprised early migration data from radiostereometric analysis (RSA) studies, while the other focused on revision rates for aseptic loosening from long-term survival studies. Thresholds for acceptable and unacceptable migration were determined according to that of several national joint registries: < 5% revision at 10 years.

Results

Following an elaborate literature search, 50 studies (involving 847 total knee prostheses (TKPs)) were included in the RSA review and 56 studies (20,599 TKPs) were included in the survival review. The results showed that for every mm increase in migration there was an 8% increase in revision rate, which remained after correction for age, sex, diagnosis, hospital type, continent, and study quality. Consequently, migration up to 0.5 mm was considered acceptable during the first postoperative year, while migration of 1.6 mm or more was unacceptable. TKPs with migration of between 0.5 and 1.6 mm were considered to be at risk of having revision rates higher than 5% at 10 years.

Interpretation

There was a clinically relevant association between early migration of TKPs and late revision for loosening. The proposed migration thresholds can be implemented in a phased, evidence-based introduction of new types of knee prostheses, since they allow early detection of high-risk TKPs while exposing only a small number of patients.Worldwide, several hundred thousand total knee prostheses (TKPs) are implanted each year and this number is expected to increase by a factor of 6 within the next 2 decades (Kurtz et al. 2005, 2007). Most of the new TKP designs have been introduced to the market without being shown to be safe or effective (Sheth et al. 2009). This has resulted in the widespread use of TKPs with failure rates exceeding 10 times the standard of national joint registries (< 5% failures at 10-year follow-up), such as the Accord, St Leger, and Journey-Deuce (Norton et al. 2002, Gilbert et al. 2009, Sheth et al. 2009, Palumbo et al. 2011 (personal communication)). To guarantee patient safety, several countries have developed guidelines, e.g. the NICE guidelines for total hip prostheses (2003). Furthermore, it has become increasingly evident that a phased, evidence-based introduction, as is common for pharmaceuticals, is needed to regulate the introduction of new TKPs to the market (Malchau 2000, McCulloch et al. 2009, Schemitsch et al. 2010). This should include systematic assessment and early detection of the major cause of TKP failure, which is aseptic loosening of the tibial component necessitating revision surgery (2003, AJR 2010).Although it can take 10 years before loosening causes symptoms, it is possible to detect loosening early postoperatively using radiostereometric analysis (RSA) (Selvik 1989, Grewal et al. 1992, Karrholm et al. 1994, Ryd et al. 1995). Since RSA allows in vivo, 3D measurement of the migration of TKPs with an accuracy of 0.2 mm for translations and 0.5 degrees for rotations, only a small number of patients need be exposed to potentially unsafe TKPs (Grewal et al. 1992, Ryd et al. 1995, Nelissen et al. 1998). RSA could therefore play an important role in the phased, evidence-based introduction of new TKPs (Selvik 1989, Karrholm et al. 1994, Ryd et al. 1995). However, the evidence for the relationship between early migration and TKP revision for aseptic loosening is limited to a few studies from the 1990s (Grewal et al. 1992, Ryd et al. 1995). Furthermore, the applicability of these studies is restricted, because surgical technique, fixation methods, implant design, and polyethylene have evolved since their publication.We hypothesized that early migration of the tibial component, measured through RSA, is associated with late revision for aseptic loosening of TKPs. We therefore systematically reviewed the association between early migration and late aseptic revision for the tibial component in TKPs. This could ultimately lead to clinical guidelines to be used in a phased introduction of new TKPs.     

胶原诱导性关节炎的评定与T细胞受体-热休克蛋白70DNA疫苗的保护作用

目的:纯化制备含有编码T细胞受体(TCR)Vβ5.2/8.2基因片段与结核杆菌热休克蛋白(HSP)70的一段保守序列P111-125的嵌合DNA疫苗,观察其对胶原诱导性关节炎的保护性作用。方法:实验于2006-07/2007-02在首都医科大学免疫学系实验室完成。①实验分组:36只Lewis大鼠随机分为6组,即正常对照组、胶原诱导性关节炎对照组、空质粒组、pTARGET-TCRVβ5.2-HSP70重组质粒治疗组、pTARGET-TCRVβ8.2-HSP70重组质粒治疗组及pTARGET-TCRVβ5.2-HSP70和pTARGET-TCRVβ8.2-HSP70重组质粒联合治疗组,每组6只。②实验方法:大量纯化制备重组DNA疫苗pTARGET-TCRVβ5.2-HSP70、pTARGET-TCRVβ8.2-HSP70和空质粒pTARGET,观察重组DNA疫苗对胶原诱导性关节炎的保护效果,包括关节炎指数评分、Eli-spot法测定脾细胞分泌的干扰素γ和白细胞介素4的水平、ELISA法测定血清中抗Ⅱ型胶原抗体的水平;光镜下观察大鼠后肢足关节的病理学变化。结果:36只Lewis大鼠均进入结果分析。重组DNA疫苗pTARGET-TCRVβ5.2-HSP70和pTARGET-TCRVβ8.2-HSP70对胶原诱导性关节炎有较好的保护性作用,与胶原诱导性关节炎对照组相比,关节炎指数(P<0.05)下降,炎性细胞因子干扰素γ水平(P<0.05)和抗Ⅱ型胶原抗体水平(P<0.01)降低,抑制性细胞因子白细胞介素4水平(P<0.05)升高,病理学改变较轻。且两种重组质粒联合治疗的效果要比单种质粒好。结论:重组DNA疫苗pTARGET-TCRVβ5.2-HSP70和pTARGET-TCRVβ8.2-HSP70能明显减轻胶原诱导性关节炎大鼠的关节炎症状和病理改变,二者联合应用效果更佳。     

云南红豆杉中四个新紫杉烷类四环二萜成分的分离和鉴定

从云南红豆杉(Taxus yunnanensis ChengetL.K.Fu)树皮的二氯甲烷部分又分离得到四个新紫杉烷类四环二萜化合物,分别命名为taxayuntin A,B,C和D。应用¹HNMR,¹³CNMR,¹H-¹HCOSY,¹³C-¹HCOSY及¹³C-¹HCOLOC等方法进行结构测定,证明它们都有5/7/6三环稠合的基本骨架,并在C₄和C₅上连有环氧丙烷。     

健骨冲剂对去势大鼠骨质疏松作用的研究

目的:研究健骨冲剂防治骨质疏松的作用。方法:观察去势大鼠骨密度、生物力学和血雌二醇、甲状旁腺素、降钙素、血钙、骨钙素的变化。结果:健骨冲剂能明显升高去势大鼠全身、腰椎和股骨骨密度;能增加股骨三点弯曲试验的屈服强度、最大载荷和断裂载荷;但不能提高去势大鼠血雌二醇的水平。结论:表明健骨冲剂能防治因雌二醇下降所致的骨质疏松症,但其作用机制不一定通过提高卵巢功能来实现。     

云南红豆杉化学成分的研究IV：二个新紫杉烷类三环二萜成分的分离和鉴定

在继续从云南红豆杉（ＴａｓｕｓｙｕｎｎａｎｅｎｓｉｓＣｈｅｎｇｅｔＬ．Ｋ．Ｆｕ）树皮中寻找抗肿瘤活性成分的研究中，又分离出７个紫杉烷类二萜化合物，经光谱解析（ＭＳ，１ＨＮＭＲ，１Ｈ－１ＨＣＯＳＹ，１３ＣＮＭＲ，１３Ｃ－１ＨＣＯＳＹａｎｄ１３Ｃ－１ＨＣＯＬＯＣ），鉴定其中５个为已知化合物：７－ｅｐｉ－１０－ｄｅａｃｅｔｙｌｔａｘｏｌ（Ｉ），７－ｅｐｉ－１０－ｄｅａｃｅｔｙｌｃｅｐｈａｌｏｍａｎｎｉｎｅ（ＩＩ），１０－ｄｅａｃｅｔｙｌｔａｘｏｌ（ＩＩＩ），１０－ｄｅａｃｅｔｙｌｃｅｐｈａｌｏｍａｎｎｉｎｅ（ＩＶ）和１０－ｄｅａｃｅｔｙｌｂａｃｃａｔｉｎＩＩＩ（ＶＩＩ）；２个新化合物是１３（２′，３′－ｄｉｈｙｄｒｏｘｙ－３′－ｐｈｅｎｙｌ）－ｐｒｏｐｉｏｎｙｌｂａｃｃａｔｉｎ，ＩＩＩ（Ｖ）和９－ｄｅｏｘｏ－９α－ｈｙｄｒｏｘｙｔａｘｏｌ（ＶＩ），分别命名为云南红豆杉醇（ｙｕｎｎａｎｘｏｌ）和云南红豆杉胺（ｙｕｎｎａｎｘａｍｉｎｅ）。     

东北红豆杉枝叶化学成分的研究

东北红豆杉(Taxus cuspidata SibeetZucc)枝叶乙醇提取物的二氯甲烷溶部分显示有较强的抗肿瘤活性,从这部分中已分离出十二个紫杉烷类二萜化合物,经理化常数测定和光谱解析证明其中十个为已知化合物taxinine(I),taxinineA(II),taxinineB(III),taxacin(V),taxagifine(VI),taxol(VII),cephalomannine(VIII),taxinineM(IX),10-deacetyl baccatinIII(X)和taxayuntin(XI),另二个化合物为新成分,分别命名为10-deacetyl taxinineB(IV)和taxacustin(XII),其中化合物VII,VIII,IX,X和XI均为首次从该植物枝叶中分离得到。     

Detection of circulating tumour DNA after neoadjuvant chemoradiotherapy in patients with locally advanced oesophageal cancer

Active surveillance instead of standard surgery after neoadjuvant chemoradiotherapy (nCRT) has been proposed for patients with oesophageal cancer. Circulating tumour DNA (ctDNA) may be used to facilitate selection of patients for surgery. We show that detection of ctDNA after nCRT seems highly suggestive of major residual disease. Tumour biopsies and blood samples were taken before, and 6 and 12 weeks after, nCRT. Biopsies were analysed with regular targeted next-generation sequencing (NGS). Circulating cell-free DNA (cfDNA) was analysed using targeted NGS with unique molecular identifiers and digital polymerase chain reaction. cfDNA mutations matching pre-treatment biopsy mutations confirmed the presence of ctDNA. In total, 31 patients were included, of whom 24 had a biopsy mutation that was potentially detectable in cfDNA (77%). Pre-treatment ctDNA was detected in nine of 24 patients (38%), four of whom had incurable disease progression before surgery. Pre-treatment ctDNA detection had a sensitivity of 47% (95% CI 24–71) (8/17), specificity of 85% (95% CI 42–99) (6/7), positive predictive value (PPV) of 89% (95% CI 51–99) (8/9), and negative predictive value (NPV) of 40% (95% CI 17–67) (6/15) for detecting major residual disease (>10% residue in the resection specimen or progression before surgery). After nCRT, ctDNA was detected in three patients, two of whom had disease progression. Post-nCRT ctDNA detection had a sensitivity of 21% (95% CI 6–51) (3/14), specificity of 100% (95% CI 56–100) (7/7), PPV of 100% (95% CI 31–100) (3/3), and NPV of 39% (95% CI 18–64) (7/18) for detecting major residual disease. The addition of ctDNA to the current set of diagnostics did not lead to more patients being clinically identified with residual disease. These results indicate that pre-treatment and post-nCRT ctDNA detection may be useful in identifying patients at high risk of disease progression. The addition of ctDNA analysis to the current set of diagnostic modalities may not improve detection of residual disease after nCRT. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.