Summary
The effect of prolonged pulse therapy with vincristine and dexamethasone (VD) during maintenance therapy on the outcome of paediatric patients with TCF3‐PBX1 positive acute lymphoblastic ...leukaemia (ALL) remains uncertain. We conducted non‐inferiority analysis of 263 newly diagnosed TCF3‐PBX1 positive ALL children who were stratified and randomly assigned (1:1) to receive seven additional VD pulses (the control group) or not (the experimental group) in the CCCG‐ALL‐2015 clinical trial from January 2015 to December 2019 (ChiCTR‐IPR‐14005706). There was no significant difference in baseline characteristics between the two groups. With a median follow‐up of 4.2 years, the 5‐year event‐free survival (EFS) and 5‐year overall survival (OS) in the control group were 90.1% (95% confidence interval CI 85.1–95.4) and 94.7% (95% CI, 90.9–98.6) comparable to those in the experimental group 89.2% (95% CI 84.1–94.7) and 95.6% (95% CI 91.8–99.6), respectively. Non‐inferiority was established as a one‐sided 95% upper confidence bound for the difference in probability of 5‐year EFS was 0.003, and that for 5‐year OS was 0.01 by as‐treated analysis. Thus, omission of pulse therapy with VD beyond one year of treatment did not affect the outcome of children with TCF3‐PBX1 positive ALL.
Objectives
To examine levels of knowledge about dementia and attitudes towards dementia in low‐ and middle‐income countries (LMICs), identify sources to turn to for help, and explore the relationship ...between knowledge and attitudes.
Methods
This mixed methods study with both quantitative (a cross‐sectional survey) and qualitative (focus group interviews) components was conducted in Cambodia, the Philippines, and Fiji in 2017‐18. A survey was completed by the citizens of the three countries, and two focus group interviews were conducted in each country to generate a context‐specific understanding of dementia literacy within the local LMIC setting. The quantitative component utilized the Alzheimer's Disease Knowledge Scale and the Dementia Attitude Scale, while knowledge, attitudes, and views on seeking help for dementia was discussed in the focus group interviews (qualitative component).
Results
A total of 476 participants completed the survey. Another 54 participants (39 females and 15 males) were invited to join six focus group interviews to express their views on dementia. Positive attitudes were noted despite the level of dementia knowledge was low. Families and religious figures were viewed as the sources for help. Controlling for demographics, country‐specific predictors of positive attitudes towards dementia were found.
Conclusions
The involvement of family members and religious leaders in dementia education could enhance the recognition of dementia. Specific kinds of dementia knowledge should be targeted to educate the public in different countries.
There is no established effective treatment for patients with t(1;22)(p13;q13) acute megakaryoblastic leukemia (AMKL) and hepatic fibrosis.
Here we report the outcomes of 2 t(1;22)(p13;q13) AMKL ...patients with hepatic fibrosis. One patient died from liver failure despite the control of leukemia. The other patient was successfully treated with reduced-intensity chemotherapy and antifibrosis therapy with tretinoin and α-tocopheryl acetate, the hepatic fibrosis resolved and leukemia was in remission for 3 years.
Reduced-intensity chemotherapy plus antifibrosis therapy with tretinoin and α-tocopheryl acetate could be a treatment option for these patients with t(1;22)(p13;q13) AMKL and hepatic fibrosis.
We conducted a prospective randomized trial to compare the efficacy and survival outcome by chemoradiation with that by esophagectomy as a curative treatment. From July 2000 to December 2004, 80 ...patients with potentially resectable squamous cell carcinoma of the mid or lower thoracic esophagus were randomized to esophagectomy or chemoradiotherapy. A two- or three-stage esophagectomy with two-field dissection was performed. Patients treated with chemoradiotherapy received continuous 5-fluorouracil infusion (200 mg/m
2/day) from day 1 to 42 and cisplatin (60 mg/m
2) on days 1 and 22. The tumor and regional lymphatics were concomitantly irradiated to a total of 50–60 Gy. Tumor response was assessed by endoscopy, endoscopic ultrasonography, and computed tomography scan. Salvage esophagectomy was performed for incomplete response or recurrence. Forty-four patients received standard esophagectomy, whereas 36 were treated with chemoradiotherapy. Median follow-up was 16.9 months. The operative mortality was 6.8%. The incidence of postoperative complications was 38.6%. No difference in the early cumulative survival was found between the two groups (RR
=
0.89; 95% confidence interval, 0.37–2.17; log-rank test
P
=
0.45). There was no difference in the disease-free survival. Patients treated with surgery had a slightly higher proportion of recurrence in the mediastinum, whereas those treated with chemoradiation sustained a higher proportion of recurrence in the cervical or abdominal regions. Standard esophagectomy or chemoradiotherapy offered similar early clinical outcome and survival for patients with squamous cell carcinoma of the esophagus. The challenge lies in the detection of residue disease after chemoradiotherapy.
Haemoglobin Bart's hydrops fetalis syndrome was once considered a fatal condition. However, advances over the past two decades have enabled survival of affected patients. Data relating to their ...morbidities and outcomes will help medical specialists formulate a management plan and parental counselling.
All babies with the syndrome who survived beyond the neonatal period and were subsequently managed long-term in eight public hospitals in Hong Kong from 1 January 1996 to 31 December 2015 were included. Patient and parent characteristics, antenatal care, reasons for continuation of pregnancy, intrauterine interventions, perinatal course, presence of congenital malformations, stem-cell transplantation details, and long-term neurodevelopmental outcomes were reviewed.
A total of nine patients were identified, of whom five were female and four male. The median follow-up duration was 7 years. All were Chinese and were homozygous for the Southeast Asian α-thalassaemia deletion. Five of the nine mothers received antenatal care at a public hospital and opted to continue the pregnancy after antenatal diagnosis and counselling. Despite intrauterine transfusions, all babies were born with respiratory depression and required intubation and mechanical ventilation during the neonatal period. Hypospadias was identified in all four male infants. Growth retardation, global developmental delay, and residual neurological deficits were noted in two-thirds of the patients. Haematopoietic stem-cell transplantation was performed in two patients, who became transfusion-independent.
Survival of patients with Bart's hydrops fetalis syndrome is possible but not without short- and long-term complications; local epidemiology is comparable to that documented for an international registry. Detailed antenatal counselling of parents with a non-judgemental attitude and cautious optimism are imperative.
The outcome of infants with KMT2A-germline acute lymphoblastic leukaemia (ALL) is superior to that of infants with KMT2A-rearranged ALL but has been inferior to non-infant ALL patients. Here, we ...describe the outcome and prognostic factors for 167 infants with KMT2A-germline ALL enrolled in the Interfant-06 study.
Univariate analysis on prognostic factors (age, white blood cell count at diagnosis, prednisolone response and CD10 expression) was performed on KMT2A-germline infants in complete remission at the end of induction (EOI; n = 163). Bone marrow minimal residual disease (MRD) was measured in 73 patients by real-time quantitative polymerase chain reaction at various time points (EOI, n = 68; end of consolidation, n = 56; and before OCTADAD, n = 57). MRD results were classified as negative, intermediate (<5∗10−4), and high (≥5∗10−4).
The 6-year event-free and overall survival was 73.9% (standard error SE = 3.6) and 87.2% (SE = 2.7). Relapses occurred early, within 36 months from diagnosis in 28 of 31 (90%) infants. Treatment-related mortality was 3.6%. Age <6 months was a favourable prognostic factor with a 6-year disease-free survival (DFS) of 91% (SE = 9.0) compared with 71.7% (SE = 4.2) in infants >6 months of age (P = 0.04). Patients with high EOI MRD ≥5 × 10−4 had a worse outcome (6-year DFS 61.4% SE = 12.4, n = 16), compared with patients with undetectable EOI MRD (6-year DFS 87.9% SE = 6.6, n = 28) or intermediate EOI MRD <5 × 10−4 (6-year DFS 76.4% SE = 11.3, n = 24; P = 0.02).
We conclude that young age at diagnosis and low EOI MRD seem favourable prognostic factors in infants with KMT2A-germline ALL and should be considered for risk stratification in future clinical trials.
•Prognostic factors for infants with KMT2A-germline acute lymphoblastic leukaemia (ALL) are not well known.•Characteristics of 167 uniformly treated infants with KMt2A-germline ALL were analyzed.•Young age at diagnosis (<6 months) was associated with better outcome.•End of induction minimal residual disease (MRD), rather than end of consolidation MRD, was a prognostic factor for outcome.•Combined MRD and genetic-based stratification of KMT2A-g infants should be considered.
This study aims to establish the range of exophthalmometry values (EV) in the adult Hong Kong (HK) Chinese population, its relationship with various anthropometric parameters, and to compare it with ...the EV in different ethnic groups.About 1485 adult HK Chinese were drawn from a random sample from the community-based FAMILY Cohort. Participants were interviewed, and comprehensive ophthalmological assessments were conducted. EV was measured using the Hertel's exophthalmometer.EV of both eyes from 630 male (42.4%) and 855 female (57.6%) participants, mean age 54 ± 17.2 and 52 ± 16 respectively were analyzed. The mean EV were found to be 15.3 ± 2.8 mm in the right eye, 15.2 ± 2.9 mm in the left eye for men and 14.4 ± 2.7 mm in the right eye, 14.3 ± 2.7 mm in the left eye for women. There were no differences in the EV between right and left eyes (P > .05). Men had significantly higher EV than women (P < .05) and age was found to be negatively correlated to EV (P < .05). Body height (r = 0.20), weight (r = 0.25), waist (r = 0.11), hip circumference (r = 0.15), body mass index (r = 0.17), interpupillary distance (r = 0.54), and axial length (AL) (r = 0.20) were all found to have statistically significant positive correlations with EV (P < .01). Spherical equivalent was found to have statistically significant negative correlation with EV (P < .01).Our study provides normative data on EV in the HK Chinese population. Height, weight, interpupillary distance, waist, hip circumference, and AL had positive correlations with EV. Spherical equivalent had negative correlation with EV. There was no significant difference in EV between the right and left eye. Age and gender had significant effect on EV.
Abstract Gastric cancer is the second most common cancer and a leading cause of cancer-related death worldwide. The Kruppel-like factor 6 ( KLF6 ) tumour suppressor gene had been previously shown to ...be inactivated in a number of human cancers through loss of heterozygosity (LOH), somatic mutation, decreased expression and increased alternative splicing into a dominant negative oncogenic splice variant, KLF6 -SV1. In the present study, 37 gastric cancer samples were analysed for the presence of loss of heterozygosity (LOH) of the KLF6 locus and somatic mutation. In total, 18 of 34 (53%) of the gastric cancer samples analysed demonstrated KLF6 locus specific loss. Four missense mutations, such as T179I, R198G, R71Q and S180L, were detected. Interestingly, two of these mutations R71Q and S180L have been identified independently by several groups in various malignancies including prostate, colorectal and gastric cancers. In addition, decreased wild-type KLF6 (wtKLF6) expression was associated with loss of the KLF6 locus and was present in 48% of primary gastric tumour samples analysed. Functional studies confirmed that wtKLF6 suppressed proliferation of gastric cancer cells via transcriptional regulation of the cyclin-dependent kinase inhibitor p21 and the oncogene c-myc. Functional characterisation of the common tumour-derived mutants demonstrated that the mutant proteins fail to suppress proliferation and function as dominant negative regulators of wtKLF6 function. Furthermore, stable overexpression of the R71Q and S180L tumour-derived mutants in the gastric cancer cell line, Hs746T, resulted in an increased tumourigenicity in vivo . Combined, these findings suggest an important role for the KLF6 tumour suppressor gene in gastric cancer development and progression and identify several highly cancer-relevant signalling pathways regulated by the KLF6 tumour suppressor gene.
Background. Oxford Cognitive Screen is designed for assessing cognitive functions of poststroke patients. This study was aimed to assess the psychometric properties of the Chinese (Putonghua) version ...of the Oxford Cognitive Screen-Putonghua (OCS-P) for use among poststroke patients without neglect. Methods. Expert review panel evaluated content validity of the Chinese-translated items. After pilot tested the translated items, the patients and healthy participants completed the OCS-P as well as the Montreal Cognitive Assessment (MoCA-ChiB) and Goldenberg’s test. A group of patients completed OCS-P for the second time within seven days. Data analyses included confirmatory factor analysis, item difficulty and item-total correlation, inter- and intrarater reliability, internal consistency, and between-group discrimination. Results. One hundred patients and 120 younger (n=60) or older (n=60) healthy participants completed all the tests. Modifications were required for items in the “Picture Naming”, “Orientation”, and “Sentence Reading” subscales. Confirmatory factor analysis revealed a three-factor structure for the OCS-P subscales. The internal consistency coefficients for the three identified test dimensions were 0.30 to 0.52 (Cronbach’s alpha). Construct validity coefficients between the OCS-P and MoCA-ChiB subscales were 0.45 < r < 0.79 (p<0.001) and the “Praxis” subscale of OCS-P and Goldenberg’s test was r=0.72 (p<0.001). The interrater reliability coefficients for the subscales were in general higher than the intrarater reliability coefficients. The “Picture Naming” and “Numerical Cognition” subscales were the most significant (p=0.003) for differentiating patient participants from their older healthy counterpart. Conclusion. This study generated satisfactory evidence on the content validity, substantive validity, construct validity, inter- and intrarater reliability, and known-group discrimination of the OCS-P. They support its application among poststroke patients who speak Putonghua. Future studies could review the existing five-dimension domains for improving its structural validity and internal consistency as well as generate evidence of the OCS-P for use among the poststroke patients with neglect.
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