Evaluation of single domain antibodies as nuclear tracers for imaging of the immune checkpoint receptor human lymphocyte activation gene-3 in cancer.

Recent advancements in the field of immune-oncology have led to a significant increase in life expectancy of patients with diverse forms of cancer, such as hematologic malignancies, melanoma and lung cancer. Unfortunately, these encouraging results are not observed in the majority of patients, who remain unresponsive and/or encounter adverse events. Currently, researchers are collecting more insight into the cellular and molecular mechanisms that underlie these variable responses. As an example, the human lymphocyte activation gene-3 (huLAG-3), an inhibitory immune checkpoint receptor, is increasingly studied as a therapeutic target in immune-oncology. Noninvasive molecular imaging of the immune checkpoint programmed death protein-1 (PD-1) or its ligand PD-L1 has shown its value as a strategy to guide and monitor PD-1/PD-L1-targeted immune checkpoint therapy. Yet, radiotracers that allow dynamic, whole body imaging of huLAG-3 expression are not yet described. We here developed single-domain antibodies (sdAbs) that bind huLAG-3 and showed that these sdAbs can image huLAG-3 in tumors, therefore representing promising tools for further development into clinically applicable radiotracers.

Inter-rater reliability of shoulder measurements in middle-aged women.

OBJECTIVES: To investigate inter-rater reliability of a set of shoulder measurements including inclinometry [shoulder range of motion (ROM)], acromion-table distance and pectoralis minor muscle length (static scapular positioning), upward rotation with two inclinometers (scapular kinematics) and pain pressure thresholds (muscle tenderness) in middle-aged women. DESIGN: Observational study. PARTICIPANTS: Thirty symptom-free middle-aged women (first cohort) were measured by two raters. All measurements with an intraclass correlation coefficient (ICC) below 0.75 were retested after an additional training period in a second cohort of 30 symptom-free middle-aged women. MAIN OUTCOME MEASURES: Inter-rater reliability of all variables was measured with the ICC (95% confidence interval) and standard error of measurement (SEM). RESULTS: Acromion-table distance (ICC=0.91, SEM 0.22 to 0.28% of body length), pectoralis minor muscle length (ICC=0.91, SEM 0.16% of body length), pain pressure thresholds (ICC=0.78 to 0.85, SEM 0.39 to 0.70kg) and abduction ROM (ICC=0.77, SEM 5°) showed good to excellent inter-rater reliability in the first cohort. After an additional training period, forward flexion ROM showed good inter-rater reliability (ICC=0.83, SEM 5°), scapular upward rotation in resting position showed moderate reliability (ICC=0.52, SEM 2°), and other scaption angles showed weak reliability (ICC=0.26 to 0.43, SEM 3 to 8°). CONCLUSIONS: In a battery of clinical tools to evaluate factors contributing to shoulder pain, static scapular positioning and pressure pain thresholds were found to have good to excellent inter-rater reliability in middle-aged women. Additional training is recommended for measurements with a gravity inclinometer.

Pelvic floor muscle training for erectile dysfunction and climacturia 1 year after nerve sparing radical prostatectomy: a randomized controlled trial.

This study aimed to determine whether patients with persistent erectile dysfunction (ED), minimum 12 months after radical prostatectomy (RP), experienced a better recovery of erectile function (EF) with pelvic floor muscle training (PFMT) compared with patients without this intervention. Second, we aimed to investigate the effect of PFMT on climacturia. All patients, who underwent RP, with persistent ED of minimum 1 year post operation were eligible. The treatment group started PFMT immediately at 12 months post operation and the control group started at 15 months after RP. All patients received PFMT during 3 months. The sample size needed to detect with 80% power a 6 points-difference regarding the EF-domain of the International Index of Erectile Function (IIEF), was at least 12 subjects per group. Patients were evaluated using the IIEF and questioned regarding climacturia. Differences between groups at 15 months were evaluated with Mann-Whitney U-test and Fisher's exact test. As a result, the treatment group had a significantly better EF than the control group at 15 months after surgery (P=0.025). Other subdomains of the IIEF remained constant for both groups. The effect of PFMT was maintained during follow-up. At 15 months, a significantly higher percentage of patients in the treatment group showed an improvement regarding climacturia (P=0.004).

Cross-cultural Psychometric Evaluation of the Dutch McGill-QoL Questionnaire for Breast Cancer Patients.

AIM OF THE STUDY: Assessing the cross-cultural psychometric properties of the Dutch-MQoL for breast cancer patients. METHODS: 26 patients were recruited at the Antwerp University Hospital. Eligible patients filled in the MQoL on different moments in time in order to evaluate clinimetric properties. To determine the validity; MQoL was correlated to the EORTC QLQ-C30. Internal consistency was analysed using Cronbach's and test-retest reliability was determined by ICC. For statistical responsiveness, S.E.M and MDC were calculated. RESULTS: A strong correlation was found between the 'QoL score' of the MQoL and the domain 'existential well- being' of the EORTC QLQ-C30 (r = 0.72). An excellent test-retest reliability (ICC (1,1)) was demonstrated with intraclass coefficients ranging from 0.82 to 0.92. A MDC in total score of only 1.22 (12%) was seen, needed to detect a factual change within a patients' QoL. Psychometric properties of the Dutch MQoL were found comparable to the properties of the original questionnaire. CONCLUSION: The Dutch version of the MQoL is a valid and reliable questionnaire for breast cancer patients and shows statistical responsiveness. Due to the strong to excellent reliability, this version of the MQoL is useful in clinical as well as scientific setting.

Systematic review of breast cancer related lymphoedema: making a balanced decision to perform an axillary clearance.

AIM: Breast cancer-related lymphoedema (BCRL) is a disabling complication developing after breast cancer treatment in a proportion of patients. Its impact on quality of life becomes more substantial as survival after breast cancer diagnosis increases. The incidence of BCRL following breast cancer treatment varies due to a lack of -uniform definition and measurement criteria. This review aims to determine the prevalence of BCRL following axillary lymph node dissection (ALND) as a benchmark to be used in a risk-benefit medical decision whether to proceed with ALND or not. The risk of leaving unresected non-sentinel metastatic lymph nodes with a presumed inherent risk of local recurrence will be balanced against the risk of BCRL following a potentially unnecessary ALND. METHODS: Pubmed and Embase databases were searched for all publications on BCRL in order to estimate its -incidence and to decide on the most appropriate measurement method to use in clinical practice. RESULTS: 51 articles were identified on BCRL incidence and measurement technique. Most studies measured BCRL based on differences in arm circumference (n = 18) or by self-reported symptoms (n = 18). The weighted average of BCRL incidence following ALND measured by self-report and circumference method was 28% and 16%, respectively. CONCLUSION: The importance of ALND and irradiation as part of the treatment of operable breast carcinoma is well established, but its morbidity is less well documented. We argue self-report as the most appropriate method to -establish a diagnosis of BCRL. Therefore a 28% risk of finding non-sentinel lymph node metastases in a completion ALND will be regarded as the cut-off in a medical decision to proceed with ALND.

Short- and long-term recovery of upper limb function after axillary lymph node dissection.

All breast cancer patients, suspected with lymph node invasion, need an axillary lymph node dissection. This study investigated the short- and long-term effects of the treatment for breast cancer on shoulder mobility, development of lymphoedema, pain and activities of daily living. Patients who had a modified radical mastectomy (33%) or a breast-conserving procedure (67%) in combination with axillary lymph node dissection were included. Shoulder mobility, lymphoedema, pain and activities of daily living were evaluated at 3 months and at 3.4 years after surgery. At long term, 31% of the patients experienced impaired shoulder mobility, 18% developed lymphoedema, 79% had pain and 51% mentioned impaired daily activities. Between 3 months and 3.4 years after surgery, impaired shoulder mobility decreased from 57% to 31%. The incidence of lymphoedema increased from 4% to 18%. Patients experienced an equal amount of pain but fewer problems with daily activities. At 3.4 years, no significant differences between mastectomy and breast-conserving procedure were found. In conclusion, at long term, significant number of breast cancer survivors still had impaired shoulder mobility, developed lymphoedema, had pain and experienced difficulties during daily activities. Shoulder mobility, pain and daily activities evolved positively, while the incidence of lymphoedema increased.

A new device to measure upper limb circumferences: validity and reliability.

AIM: The aim of this paper was to examine the reliability and validity of a new measurement device that counters the disadvantages of the traditional method of arm circumference measurements. METHODS: We measured the arm on the non-operated side of breast cancer patients. Sixty-four patients were measured twice by the same assessor and 48 patients were measured twice by two different assessors. The arm circumferences were measured at the olecranon and each 4 cm proximal and distal of the olecranon. The measurements were performed with a self-developed device consisting of a stainless steel bar on which a tapeline was fixed at every 4 cm distance. The arm volume was calculated from the circumference measurements with the frustrum formula and was also measured directly with the water displacement method. RESULTS: For the circumference measurements, intrarater and interrater ICCs ranged between 0.942 and 0.998. ICCs for the calculated arm volume were also very high. No systematic changes between the first to the second assessment could be found. The standard error of measurement for the circumference measurements as well as for the calculated arm volume was low (between 0.8% and 2.0%). An increase of 1.0 cm or more of the arm circumference at any measurement side and of 55 ml or more of the calculated arm volume was clinically significant. CONCLUSION: Arm circumferences and also the calculated arm volume can be measured quickly and accurately with a simple and inexpensive device.

The regulated expression of an intrabody produces a mutant phenotype in Drosophila.

Intrabodies show great promise for controlling gene expression. As an initial attempt to evaluate the intrabody technology in Drosophila, the gene poxn was used as target. Transgenic flies harboring different anti-Poxn scFv genes integrated into various chromosomes were obtained. In one transformant, a phenocopy resembling the hypomorphic poxn-phenotype was produced in embryos and larvae following induction of expression of alpha-Poxn2 intrabody. The antisense approach was used as control. Parameters that can affect the success of intrabody technology are described.