Effects of monoclonal antibody therapy in patients with chronic lymphocytic leukemia

A phase I clinical trial was initiated to treat patients with stage IV B-derived chronic lymphocytic leukemia (CLL) with the IgG2a murine monoclonal antibody T101. This antibody binds to a 65,000-mol wt (T65) antigen found on normal T lymphocytes, malignant T lymphocytes, and B- derived CLL cells. All of the patients had a histologically confirmed diagnosis of advanced B-derived CLL and were refractory to standard therapy, and more than 50% of their leukemia cells reacted with the T101 antibody in vitro. The patients received T101 antibody two times per week, over two to 50 hours by intravenous administration in 100 mL of normal saline containing 5% human albumin. Twelve patients were treated with a fixed dosage of 1, 10, 50, or 100 mg, and one patient was treated with 140 mg of antibody. It was demonstrated that patients given two-hour infusions of 50 mg developed pulmonary toxicity, with shortness of breath and chest tightness. This toxicity was eliminated when infusions of 50 or 100 mg of T101 were prolonged to 50 hours. All dose levels caused a rapid but transient decrease in circulating leukemia cell counts. In vivo binding to circulating and bone marrow leukemia cells was demonstrated at all dose levels with increased binding at higher dosages. Antimurine antibody responses were not demonstrated in any patients at any time during treatment. Circulating free murine antibody was demonstrated in the serum of only the two patients treated with 100 mg of antibody as a 50-hour infusion and the patient treated with 140 mg of antibody over 30 hours. Antigenic modulation was demonstrated in patients treated at all dose levels but was particularly apparent in patients treated with prolonged infusions of 50 and 100 mg of antibody. We were also able to demonstrate antigenic modulation in lymph node cells, which strongly suggests in vivo labeling of these cells. Overall, T101 antibody alone appears to have a very limited therapeutic value for patients with CLL. The observations of in vivo labeling of tumor cells, antigenic modulation, antibody pharmacokinetics, toxicity, and antimurine antibody formation may be used in the future for more effective therapy when drugs or toxins are conjugated to the antibody.     

Radiation Exposure from Diagnostic Imaging Studies Among Patients with Inflammatory Bowel Disease in a Safety-Net Health-Care System

Background/Aims

Radiographic imaging studies are important in the management of patients with inflammatory bowel disease (IBD), but are associated with radiation exposure. IBD patients in a safety-net health-care system may be at risk of high exposure to radiation. Our purpose was to identify associations of high-dose radiation exposure among an ethnically diverse cohort of IBD patients in a safety-net health-care system.

Methods

A study was performed on patients with IBD receiving care from the Harris County Hospital District. Radiation exposure was calculated using total number of imaging studies performed between from 2000 and 2010 and estimates of radiation dose per study. Associations of high-dose radiation exposure, defined as a cumulative effective dose (CED) >50 mSv, were identified by using univariate and multivariate logistic regression.

Results

The study cohort of 278 patients with IBD was ethnically diverse, with 30 % Caucasian, 44 % African–American, and 26 % Hispanic. The median CED was 10.40 mSv (SD 20.02). Annualized radiation doses were 3.45 mSv/year among patients with Crohn’s disease (CD) and 1.27 mSv/year among patients with ulcerative colitis, p < 0.02. Approximately 13 % of IBD patients received a CED >50 mSv. There were no differences in radiation exposure based on age, gender, or race/ethnicity.

Conclusions

A small proportion of IBD patients in a safety-net health-care system received high doses of diagnostic radiation exposure. Use of diagnostic imaging studies that limit radiation exposure should be encouraged.     

乳腺浸润性导管癌超声影像特征分析

 目的 分析超声各特征性影像表现在乳腺浸润性导管癌中的诊断价值。方法 选取解放军总医院第六医学中心 2018-01至2019-12两年内收治的 135例乳腺浸润性导管癌患者纳入本研究,分析乳腺浸润性导管癌的超声影像特征、体检自检发现率以及淋巴结转移与病变大小、位置的相关性。结果 (1)单因素分析显示:形态不规则(91.11%)、边界不清楚(64.44％)、血流信号(44.44％)、微钙化(37.78%)、纵横比＞1(17.78％)、后方回声衰减(15.56％)超声诊断指标,与浸润性导管癌的诊断具有相关性;(2)与其他三个象限相比较,内上象限浸润性导管癌更容易被患者自检发现,占自检发现病例的34.93%;(3)内上象限及外上象限的浸润性导管癌更容易发生淋巴结转移(转移率为:内上:25.53%,内下:0.00%,外上:64.70%,外下:11.76%);(4)对＜3 cm的浸润性导管癌,其大小与腋窝淋巴结的转移没有相关性。结论 超声表现以形态不规则在乳腺浸润性导管癌中的发生率最高,且在早期病变中即表现出来;乳腺病变的自检检出率、乳腺癌淋巴转移率均与乳腺病变的大小和位置密切相关。     

The use of bisphosphonates in children: review of the literature and guidelines for dental management

Bisphosphonates are inhibitors of osteoclastic bone resorption with therapeutic benefit in a variety of bone disorders in both adults and children. While these agents have been routinely used in adults for the past three decades, their more recent introduction into paediatric medicine means there is a paucity of data on long‐term safety and effects on dental development. There is uncertainty regarding the dental management of children treated with bisphosphonates, particularly when invasive dental procedures, such as extractions and oral surgical procedures, are required. There are limited data with which to make recommendations about the dental management of patients treated with bisphosphonates, and there are no published recommendations that specifically address paediatric patients. This paper aims to outline paediatric uses and adverse effects of bisphosphonates and present recommendations on the dental management of children receiving bisphosphonates.     

Validation of family history of breast cancer and identification of the BRCA1 and other syndromes using a population-based cancer registry

A major risk factor for breast cancer is family history of the disease in first-degree relatives. This study evaluates the validity of family history information on breast cancer in mothers and sisters of breast cancer probands from the cancer registry (CR) compared to personal interviews (PI) of 359 consecutive population-based cases of breast cancer. Breast cancer is seen in mothers of 14% of probands by CR compared to 12% by PI. Further, 13% of probands have a sister with breast cancer using CR compared to 12% by PI. Using PI as the standard, the sensitivity of the CR family history data in mothers is 92% and the specificity is 99%, while in sisters they are 88% and 99%, respectively. These estimates were calculated on cases where family history information is available in the CR. Sensitivity and specificity are recalculated, recording an “error” whenever family history information is not available, and they are 75% and 68%, respectively, for mothers and 72% and 70%, respectively, for sisters. Estimates of proband-mother and proband-sisters familial breast cancer from CR and PI are sufficiently similar to warrant the use of CR family history data in studies of genetic epidemiology. The family phenotype consistent with the BRCA1 syndrome was found in four (1.1%) probands, all below age 50 years, while for BRCA2 there were five (1.4%) probands, three below age 50 years and two 50 years or older. Site-specific familial breast cancer was found in 23 (6.4%) probands. Population-based multiple-case breast cancer families can rapidly be identified through CR. These families can make substantial contributions to the study of genetic and environmental etiology of the disease as well as benefit from preventive and therapeutic efforts. As new knowledge and tools in molecular genetics become available, there is an urgent need for large population-based registries of families at high risk for cancer. © 1996 Wiley-Liss, Inc.     

Impact of COVID-19 on cancer management in military hospitals of Saudi Arabia

Objectives:To evaluate the impact of COVID-19 on cancer management in Saudi Arabia’s military hospitals.Methods:This multi-centric, retrospective study compared cancer patients diagnosed from February-July 2019 and 2020, focusing on the time duration for acceptance and time for oncologic treatment initiation. Eligibility and referral status were recorded. Clinical data of COVID-19-positive cancer patients were collected and evaluated their outcomes and survival.Results:Data of 1574 cancer patients (mean age, 57.1 years) were collected. Mean time for acceptance was 7.3 days in 2019 and 8 days in 2020, with no statistically significant difference. Mean time for oncology treatment initiation was 38.4 days in 2019 and 44.3 days in 2020, with no statistically significant difference. The number of new cancer patients decreased in 2020 but increased in peripheral hospitals. It decreased in Riyadh and Jeddah hospitals. Concerning referral status, a statistically significant modification was recorded only in Riyadh and Tabuk hospitals. No significant changes observed in time duration for acceptance of new patients and oncology treatment initiation from 2019-2020. A total of 76 COVID-19-positive cancer patients recorded; 72% were symptomatic, 73.6% recovered, 22.3% died due to COVID-19 complications, and 8% died due to cancer; cancer progressed in 7 patients.Conclusion:COVID-19 did not affect oncology service in Saudi Arabia’s military hospitals. New cancer cases reduced during the pandemic. Cancer patients are at increased risk for COVID-19 complications, including death.     

基于层次分析法（AHP）的保健食品原料评价体系构建及分析

目的建立保健食品原料评价体系(Functional Food Crude Materials Evaluation System,FUFMES),为保健食品原料目录排名提供科学依据与技术保障。方法首先,利用文献调研和多轮专家访谈方法筛选FUFMES的指标并确定其层级关系;第二,使用层次分析法(Analytic Hierarchy Process,AHP)计算指标权重,具体方法是依据专家打分构建判断矩阵,利用R语言进行一致性检验与最大特征根检验,得出各级指标权重;第三,使用极值法计算原料的单个指标值;第四,利用线性加权综合法得到每种原料的评价指数并据此进行排名;最后,将获得的分析结果与专家评价结果进行比较。结果 FUFMES包括6个一级指标、39个二级指标、11个三级指标。利用FUFMES对9种保健食品原料进行评价,获得的评价指数依次是:西洋参(0.49)、人参(0.48)、银杏叶(0.21)、灵芝孢子粉(0.08)、鱼油(0.06)、螺旋藻(0.03)、辅酶Q10(0.02)、褪黑素(0.01)、大蒜油(-0.03)。基于该评价指数的排名结果与专家评价结果显示了较高一致性。结论构建了科学、完整的FUFMES,FUFMES将成为保健食品原料目录评价与排名的有力工具,为推进保健食品原料备案制提供科学依据与技术保障。