INK4A/ARF deletions are acquired at relapse in childhood acute lymphoblastic leukaemia: a paired study on 25 patients using real-time polymerase chain reaction

Current risk-adjusted intensive therapies for childhood acute lymphoblastic leukaemia (ALL) are expected to result in an event-free survival of greater than 75%. In sharp contrast, relapsed paediatric ALL is a difficult disease to treat. In this study, 25 paediatric patients with ALL were analysed at diagnosis and relapse for their p16 (exon 2) status using the most accurate method of detection, real-time polymerase chain reaction (PCR). The median time to relapse for the group was 27 months. At diagnosis, the incidence of p16 homozygous and hemizygous deletion in this group was 32% and 20% respectively. The incidence of homozygous p16 deletion at relapse was 64%. A large number of patients, eight of 16 (50%), developed p16 homozygous deletion at relapse. Of those eight patients, four were hemizygous and four were germline at diagnosis. At diagnosis, those patients with a homozygous or hemizygous p16 deletion relapsed sooner than those germline for p16. We have shown that p16 alterations are frequently present in relapsed lymphoblastic leukaemia in children.     

Efficacy of bupropion for relapse prevention in smokers with and without a past history of major depression

BACKGROUND: This study evaluated the efficacy of bupropion for relapse prevention in smokers with and without a past history of major depressive disorder. Changes in depressive symptoms were also examined. DESIGN: Data were gathered prospectively from a randomized, double-blind relapse prevention trial of bupropion conducted at five study sites. A total of 784 smokers (54% female, 97% white) were enrolled. Using the Structured Clinical Interview for Depression, 17% of the subjects reported a past history of major depressive disorder at baseline. All subjects received open-label bupropion SR (300 mg/d) for 7 weeks. Subjects abstinent from smoking at the end of 7 weeks (N = 429) were randomized to bupropion SR (300 mg/d) or placebo for the remainder of the year and followed for 1 year off medication. The primary outcome measures were median time to relapse to smoking and the 7-day point-prevalence smoking abstinence rate. Self-reported abstinence from smoking was verified by expired air carbon monoxide. The Beck Depression Inventory was used to assess depressive symptoms at baseline and at weeks 8 and 12. RESULTS: Median time to relapse did not differ by past history of major depressive disorder. Bupropion was associated with higher point-prevalence smoking abstinence at the end of medication compared to placebo (P = .007), independent of a past history of major depressive disorder. Moreover, change in depressive symptoms during the double-blind phase did not differ for those with and without a past history of major depressive disorder. CONCLUSIONS: Extended use of bupropion for relapse prevention is effective for smokers with and without a history of major depression.     

Clonal evolution of high‐grade serous ovarian carcinoma from primary to recurrent disease

High‐grade serous carcinoma (HGSC) is the most common and fatal form of ovarian cancer. While most tumours are highly sensitive to cytoreductive surgery and platinum‐ and taxane‐based chemotherapy, the majority of patients experience recurrence of treatment‐resistant tumours. The clonal origin and mutational adaptations associated with recurrent disease are poorly understood. We performed whole exome sequencing on tumour cells harvested from ascites at three time points (primary, first recurrence, and second recurrence) for three HGSC patients receiving standard treatment. Somatic point mutations and small insertions and deletions were identified by comparison to constitutional DNA. The clonal structure and evolution of tumours were inferred from patterns of mutant allele frequencies. TP53 mutations were predominant in all patients at all time points, consistent with the known founder role of this gene. Tumours from all three patients also harboured mutations associated with cell cycle checkpoint function and Golgi vesicle trafficking. There was convergence of germline and somatic variants within the DNA repair, ECM, cell cycle control, and Golgi vesicle pathways. The vast majority of somatic variants found in recurrent tumours were present in primary tumours. Our findings highlight both known and novel pathways that are commonly mutated in HGSC. Moreover, they provide the first evidence at single nucleotide resolution that recurrent HGSC arises from multiple clones present in the primary tumour with negligible accumulation of new mutations during standard treatment.     

An evaluation of symptom domains in the 2 years before pregnancy as predictors of relapse in the perinatal period in women with severe mental illness

BackgroundSymptoms may be more useful prognostic markers for mental illness than diagnoses. We sought to investigate symptom domains in women with pre-existing severe mental illness (SMI; psychotic and bipolar disorder) as predictors of relapse risk during the perinatal period.MethodsData were obtained from electronic health records of 399 pregnant women with SMI diagnoses from a large south London mental healthcare provider. Symptoms within six domains characteristically associated with SMI (positive, negative, disorganization, mania, depression, and catatonia) recorded in clinical notes 2 years before pregnancy were identified with natural language processing algorithms to extract data from text, and associations investigated with hospitalization during pregnancy and 3 months postpartum.ResultsSeventy-six women (19%) relapsed during pregnancy and 107 (27%) relapsed postpartum. After adjusting for covariates, disorganization symptoms showed a positive association at borderline significance with relapse during pregnancy (adjusted odds ratio [aOR] = 1.36; 95% confidence interval [CI] = 0.99–1.87 per unit increase in number of symptoms) and depressive symptoms negatively with relapse postpartum (0.78; 0.62–0.98). Restricting the sample to women with at least one recorded symptom in any given domain, higher disorganization (1.84; 1.22–2.76), positive (1.50; 1.07–2.11), and manic (1.48; 1.03–2.11) symptoms were associated with relapse during pregnancy, and disorganization (1.54; 1.08–2.20) symptom domains were associated with relapse postpartum.ConclusionsPositive, disorganization, and manic symptoms recorded in the 2 years before pregnancy were associated with increased risk of relapse during pregnancy and postpartum. The characterization of routine health records from text fields is relatively transferrable and could help inform predictive risk modelling.     

精神分裂症患者5年内复发再入院情况分析

目的调查分析精神分裂症患者5年内复发再入院情况。方法采用回顾性分析法了解患者在5年内复发再入院情况,比较复发入院者和未复发者基本情况的差异。结果5年内患者复发入院率达33．70％,患者性别（X2：4．84,P=0．028）、年龄（X2=13．89,P=0．ooo）、婚姻（X2=11．31,P=0．001）、受教育程度（r=4．83,P=0．028）对其复发住院情况有显著影响。结论精神分裂症患者有较高的复发入院率,应及早进行复发干预。     

Postoperative stability of conventional bimaxillary surgery compared with maxillary impaction surgery with mandibular autorotation for patients with skeletal class II retrognathia

We aimed to compare the postoperative stability of conventional bimaxillary surgery (with bilateral sagittal split osteotomy) with that of maxillary impaction surgery (with mandibular autorotation without bilateral sagittal split osteotomy) in patients with skeletal class II retrognathia. Patients were assigned to have conventional bimaxillary surgery (conventional group, n = 6) or mandibular autorotation (experimental group, n = 7). Measurements were made using serial lateral cephalometric radiographs taken immediately preoperatively (T0), immediately postoperatively (T1), and one year later (T2) to assess the variation in operative change (T1-T0) and relapse (T2-T1). There was no significant difference in median (range) surgical change in the anterior movement at point B (conventional group, 4.5 (3.0–11.0) mm; experimental group 4.1 (2.1–6.4) mm). However, there was a significant difference in median (range) surgical posterior movement relapse at point B (conventional group −1.7 (−2.3 to −0.5) mm; experimental group −0.6 (−1.0 to 1.0) mm; p = 0.032). Mandibular advancement with mandibular autorotation is therefore a more stable procedure than mandibular advancement with bilateral sagittal split osteotomy in patients with skeletal class II retrognathia.     

阿司匹林、氯吡格雷不同联合阿托伐他汀钙治疗对短暂缺血性脑缺血发作患者住院期间复发进展率的影响

目的： 分析短暂性脑缺血发作（TIA）患者中,应用阿司匹林、氯吡格雷联合他汀类药物治疗的效用。方法： 选取在其院接受治疗的116例TIA患者,收治的时间为2017年3月-2019年10月,按照不同的治疗方法将所有的患者分为3组,其中A组32例（给予阿司匹林+阿托伐他汀钙片治疗）,B组20例（给予氯吡格雷+阿托伐他汀钙片）,C组64例（给予氯吡格雷+阿托伐他汀钙片+阿司匹林治疗）。将3组治疗后的复发进展率、TIA发作时间、血小板计数、凝血功能、治疗效果以及不良反应发生情况进行对比。结果： 经分析,B组、C组的治疗总有效率均高于A组,差异有显著性意义（P<0.05）,C组的治疗总有效率高于B组（P<0.05）;经重复测量方差分析,3组患者治疗前后不同时间的PT值比较,差异无显著性（P>0.05）;3组患者治疗前后不同时间的APTT水平比较,差异具有显著性（P<0.05）;经两两比较,C组的PT水平明显低于A组和B组（P<0.05）;经重复测量方差分析,3组患者治疗前后TIA发作时间比较,差异具有显著性（P<0.05）。治疗后,C组的复发进展率较A组和B组低（P<0.05）;3组用药后的不良反应发生率相比不具有显著性（P>0.05）。结论： 给予阿司匹林+阿托伐他汀钙片+氯吡格雷联合应用于TIA时,可以发挥协同作用,改善凝血功能,抑制血小板的聚集,机体状态改善明显,进而降低了进展复发率,且用药安全性高。