Single‐agent lenalidomide in relapsed/refractory mantle cell lymphoma: results from a UK phase II study suggest activity and possible gender differences

We present data from a phase II study investigating a novel treatment strategy for relapsed/refractory mantle cell lymphoma (MCL). Twenty‐six patients received lenalidomide 25 mg/d (days 1–21 of a 28‐d cycle) for up to 6 cycles followed by low‐dose maintenance lenalidomide (15 mg) in responding patients. Eight patients achieved complete or partial response to give an overall response rate of 31% with median response duration of 22·2 months [95% confidence interval (CI) 0·0–53·6] and median progression‐free survival (PFS) of 3·9 months (95% CI 0·0–11·1). An additional six patients (23%) achieved stable disease. Eleven patients received maintenance with median PFS of 14·6 months (95% CI 7·3–21·9). Correlative studies showed that peripheral T and Natural Killer (NK) cells increased in responding patients by 40–60% over the first 6 cycles with an initial dip in NK cells suggestive of tumour infiltration. Peripheral regulatory T cells were increased in MCL patients (P = 0·001) and expanded further following lenalidomide. Sequential plasma analysis showed increased IL12 p40 and IL7 alongside decreased MMP9, IL10, and adiponectin. Finally, a significant correlation (P = 0·02) between gender and response suggested that female MCL patients were more sensitive to lenalidomide than males. In summary, we confirm the activity, safety and immunomodulatory properties of lenalidomide in MCL and highlight its potential as a low‐dose maintenance agent.     

长期口服小剂量阿司匹林不能预防健康女性患2型糖尿病

慢性无临床症状的炎症与2型糖尿病的发生有关,流行病学资料认为这种关联在妇女表现得更为强烈。虽然小型临床研究显示短期口服大剂量阿司匹林具有明显的降糖效果,但是并没有随机试验直接评估临床可接受的剂量的阿司匹林预防糖尿病的效果。在美国一项随机、双盲、安慰剂-对照的女性健康研究（Women＇s Health Study）中,38716名45岁以上的且无临床糖尿病的健康女性随机口服小剂量的阿司匹林（n=19326）或安慰剂（n=19390）,     

Stereotypes on Nodding syndrome: responses of health workers in the affected region of northern Uganda

Background

Nodding Syndrome is a debilitating disorder of yet unknown etiology that has affected children and adolescents aged 3 – 18 years in parts of sub Saharan African countries including Uganda, South Sudan, Tanzania and Liberia.

Objective

To identify stereotypes and negative attitudes held by primary care health workers about nodding syndrome.

Method

Of one hundred health workers invited by the Uganda Ministry of Health for training on nodding syndrome from the three most affected districts of Pader, Lamwo and Kitgum forty were interviewed using a predesigned tool. Content and thematic analysis was applied.

Results

There were 22 females. The median age was 33 years (range 23–54 years). The participants included Psychiatric Clinical Officers, Medical Clinical Officers, Laboratory Technicians, Midwives, Registered and Enrolled Nurses. Overall, four broad categories of negative stereotypes were identified; Nodding syndrome is 1) an incurable disease, 2) is associated with evil spirits and curses, 3) is disabling, making the patient a burden to society and 4) is a fatal illness.

Conclusion

Primary health care workers who lead the care of patients with nodding syndrome have several negative stereotypes that may potentially impact negatively on the quality of care they provide.     

儿童肥胖症的综合干预研究

本文以３３例１２－１４岁的青春前期单纯性肥胖儿童为治疗组，另设同性别、同年龄的肥胖对照组２９例和正常体重对照组３２例作对比研究。治疗前对三组儿童均进行体格测量及生化检测，只对肥胖治疗组儿童进行综合性干预，包括家庭行为疗法、饮食指导和运动训练，为肥胖儿童制定减肥计划，内含中介行为、目标行为、奖惩手段、制约方法等，由专业人员定期家访指导，学校老师监督执行。经过二年的治疗观察，肥胖治疗组儿童肥胖度明显下降，身高的增长与正常对照组儿童一致，接受治疗的肥胖儿童血压、总胆固醇、甘油三酯、体脂含量均有不同程度的降低，不良饮食、运动行为得到不同程度的矫正，体育成绩提高，热卡摄入量比治疗前有所减少，而肥胖对照组儿童上述各指标无明显变化。     

Effect of Dataset Size and Medical Image Modality on Convolutional Neural Network Model Performance for Automated Segmentation: A CT and MR Renal Tumor Imaging Study

The aim of this study is to investigate the use of an exponential-plateau model to determine the required training dataset size that yields the maximum medical image segmentation performance. CT and MR images of patients with renal tumors acquired between 1997 and 2017 were retrospectively collected from our nephrectomy registry. Modality-based datasets of 50, 100, 150, 200, 250, and 300 images were assembled to train models with an 80–20 training-validation split evaluated against 50 randomly held out test set images. A third experiment using the KiTS21 dataset was also used to explore the effects of different model architectures. Exponential-plateau models were used to establish the relationship of dataset size to model generalizability performance. For segmenting non-neoplastic kidney regions on CT and MR imaging, our model yielded test Dice score plateaus of \(0.93\pm 0.02\) and \(0.92\pm 0.04\) with the number of training-validation images needed to reach the plateaus of 54 and 122, respectively. For segmenting CT and MR tumor regions, we modeled a test Dice score plateau of \(0.85\pm 0.20\) and \(0.76\pm 0.27\), with 125 and 389 training-validation images needed to reach the plateaus. For the KiTS21 dataset, the best Dice score plateaus for nn-UNet 2D and 3D architectures were \(0.67\pm 0.29\) and \(0.84\pm 0.18\) with number to reach performance plateau of 177 and 440. Our research validates that differing imaging modalities, target structures, and model architectures all affect the amount of training images required to reach a performance plateau. The modeling approach we developed will help future researchers determine for their experiments when additional training-validation images will likely not further improve model performance.

     

A pilot randomized trial comparing CD34‐selected versus unmanipulated hemopoietic stem cell transplantation for severe,refractory rheumatoid arthritis

Objective

Evidence from animal studies, case reports, and phase I studies suggests that hemopoietic stem cell transplantation (HSCT) can be effective in the treatment of rheumatoid arthritis (RA). It is unclear, however, if depletion of T cells in the stem cell product infused after high‐dose chemotherapy is beneficial in prolonging responses by reducing the number of infused autoreactive T cells. This pilot multicenter, randomized trial was undertaken to obtain feasibility data on whether CD34 selection (as a form of T cell depletion) of an autologous stem cell graft is of benefit in the HSCT procedure in patients with severe, refractory RA.

Methods

Thirty‐three patients with severe RA who had been treated unsuccessfully with methotrexate and at least 1 other disease‐modifying agent were enrolled in the trial. The patients received high‐dose immunosuppressive treatment with 200 mg/kg cyclophosphamide followed by an infusion of autologous stem cells that were CD34 selected or unmanipulated. Safety, efficacy (based on American College of Rheumatology [ACR] response criteria), and time to recurrence of disease were assessed on a monthly basis for up to 12 months.

Results

All patients were living at the end of the study, with no major unexpected toxicities. Overall, on an intent‐to‐treat basis, ACR 20% response (ACR20) was achieved in 70% of the patients. An ACR70 response was attained in 27.7% of the 18 patients who had received CD34‐selected cells and 53.3% of the 15 who had received unmanipulated cells (P = 0.20). The median time to disease recurrence was 147 days in the CD34‐selected cell group and 201 days in the unmanipulated cell group (P = 0.28). There was no relationship between CD4 lymphopenia and response, but 72% of rheumatoid factor (RF)–positive patients had an increase in RF titer prior to recurrence of disease.

Conclusion

HSCT can be performed safely in patients with RA, and initial results indicate significant responses in patients with severe, treatment‐resistant disease. Similar outcomes were observed in patients undergoing HSCT with unmanipulated cells and those receiving CD34‐selected cells. Larger studies are needed to confirm these findings.