Parameters affecting successful stem cell collections for genetic therapies in sickle cell disease

Emerging cellular therapies require the collection of peripheral blood hematopoietic stem cells (HSC) by apheresis for in vitro manipulation to accomplish gene addition or gene editing. These therapies require relatively large numbers of HSCs within a short time frame to generate an efficacious therapeutic product. This review focuses on the principal factors that affect collection outcomes, especially relevant to gene therapy for sickle cell disease.     

The effects of using virtual patients on the history-taking ability of nursing interns: A non-randomized controlled study

ObjectivesThe aim of this study was to examine the effects of the SYSU-NEP virtual patients (VPs) on the history-taking ability and self-efficacy of nursing interns.BackgroundAn easy to use, freely accessible and objective training software program on WeChat named Sun Yat-sen University Nursing Education Platform (SYSU-NEP) was developed to help nursing students improve their history-taking skills.DesignThis was a non-randomized controlled study.MethodsA total of 90 nursing interns (44 in the intervention group and 46 in the control group), who practiced in internal medicine departments at a single teaching hospital, were recruited between July 2017 and December 2018. The data collected comprised demographic and academic data, Nursing History-taking Assessment Scale (NHTAS) and Academic Self-Efficacy Scale (ASES) scores. The chi-square test, t test and Wilcoxon test were used to test the differences in the variables between the two groups. The t test or Wilcoxon test was used to compare the differences between pre-intervention and post-intervention NHTAS and ASES scores in each group and to compare the changes (post-intervention – pre-intervention) in NHTAS and ASES scores between the control and intervention groups.ResultsBoth the control and intervention groups had higher post-intervention NHTAS scores compared with their pre-intervention scores (control group: 83.50 VS 61.00, P < 0.001; intervention group: 106.00 VS 77.00, P < 0.001). However, the intervention group had a much greater improvement in the NHTAS score than the control group (29.00 VS 9.00, P < 0.001). There were no significant differences in the ASES score within groups (control group: 80.50 VS 80.00, P = 0.292; intervention group: 81.50 VS 79.00, P = 0.979) or between groups (2.00 VS 0.00, P = 0.430). The most frequently used VPs were associated with the respiratory, gastroenterology and cardiovascular systems, accounting for 70.4% among all VP cases.ConclusionsThe SYSU-NEP VPs can improve the history-taking ability of nursing interns. They can provide autonomous, repeatable training opportunities for nursing interns and help them prepare well for real clinical encounters.     

Assessing gait efficacy in older adults: An analysis using item response theory

BackgroundAssessing confidence in walking in older adults is important, as mobility is a critical aspect of independence and function, and self-report provides complementary information to performance-based measures. The modified Gait Efficacy Scale (mGES) is a self-report measure used to examine confidence in walking.Research Question: What are the psychometric properties of the mGES at the item level? Are there opportunities for improvement?MethodsWe performed a secondary analysis of baseline data from a cluster randomized trial of 424 community-dwelling older adults and reliability data from 123 participants. We fitted a graded response model to dissect the mGES to the item and individual response level and examined opportunities to improve and possible shorten the mGES. We examined psychometric characteristics such as internal consistency, test-retest reliability and construct validity with respect to other relevant measures.ResultsMobility tasks such as navigating stairs and curbs with separate items for going up and down largely provide the same information on confidence, with downward direction providing slightly more. It may be reasonable to consider removal of walking 1/2 mile, stepping down and/or stair tasks with railings items due to little or duplicate information contributed compared to other items. The shortened scales proposed by removing the above items had similar psychometric properties to mGES.SignificanceThe mGES has good psychometric properties, but can be potentially shortened to substantially reduce responder burden. The upward direction curb and stairs items can be removed to result in a 7-item scale with virtually no loss of desirable psychometrics. An alternative 3-item version, level surface walking, stepping down curb and climbing up stairs without a railing items, entails only a minimal loss in psychometric properties.     

Dealing With High-Risk AL Amyloidosis Patients: A Single Hematologic Center Experience

PurposeTo assess the feasibility and the results of Bortezomib-based treatment of “high-risk” AL-amyloidosis patients in a hematology ward.MethodsWe report on 52 high-risk amyloidosis patients treated with first-line bortezomib-based chemotherapy.ResultsAt day 30 from the beginning of the therapy, 23 patients (44%) achieved a hematological response (complete response plus very good partial response); 14 patients (27%) achieved a partial response; 15 patients (29%) were non-responders. After a median follow-up of 28.5 months, the survival rates were 18/23 (78%) for responders; 9/14 (64%) for partial responders and 3/15 (20%) for nonresponders with a median overall survival of 43, 24 and 11 months, respectively (log-rank test: P < .001). NHYA class I-II, NTproBNP < 6500 ng/L, the hematologic response, and the partial hematological response at day 30 independently predicted the survival. There has been no significant difference (P = .173) in survival between revised Mayo stage III and IV patients although there was a trend toward a better prognosis for Mayo stage III. A suboptimal hematological response at day 30 allowed a later organ response in 12/14 patients (85%) even without therapy change and no modification of the hematological status.ConclusionsThese results show that high-risk AL-amyloidosis patients can be managed safely and effectively in a hematology ward. A partial hematologic response may herald a later better response, organ response, and can allow a subsequent second-line therapy and a good survival.     

Beneficiaries of radical surgery among clinical complete responders to neoadjuvant chemoradiotherapy in rectal cancer

This study aimed to identify patients who benefit from radical surgery among those with rectal cancer who achieved clinical complete response (cCR). Patients with locally advanced rectal cancer (LARC; stage II/III) who achieved cCR after neoadjuvant chemoradiotherapy (nCRT) were included (n = 212). Univariate/multivariate Cox analysis was performed to validate predictors for distant metastasis-free survival (DMFS). A decision tree was generated using recursive partitioning analysis (RPA) to categorize patients into different risk stratifications. Total mesorectal excision (TME) was compared with the watch-and-wait (W&W) strategy in each risk group. Two molecular predicators of CEA and CA19-9 were selected to establish the RPA-based risk stratification, categorizing LARC patients into low-risk (n = 139; CA19-9 < 35 U/mL and CEA < 5 ng/mL) and high-risk (n = 73; CA19-9 ≥ 35 U/mL or CEA ≥5 ng/mL) groups. Superior 5-y DMFS was observed in the low-risk group vs. the high-risk group (92.9% vs. 76.2%, P = .002). Low-risk LARC patients who underwent TME had significantly improved 5-y DMFS compared with their counterparts receiving the W&W strategy (95.9% vs. 84.3%; P = .028). No significant survival difference was observed in high-risk patients receiving the 2 treatment modalities (77.9% vs. 94.1%; P = .143). LARC patients with cCR who had both baseline CA19-9 < 35 U/mL and CEA < 5 ng/mL may benefit from radical surgery.     

Inclusion of L5–S1 in oblique lumbar interbody fusion–techniques and early complications–a single center experience

Background contextThe oblique prepsoas retroperitoneal approach to the lumbar spine for interbody fusion or oblique lumbar interbody fusion (OLIF) provides safe access to nearly all lumbar levels. A wide interval between the psoas and aorta allows for a safe and straightforward left-sided oblique approach to the discs above L5. Inclusion of L5–S1 in this approach, however, requires modifications in the technique to navigate the complex and variable vascular anatomy distal to the bifurcation of the great vessels. While different oblique approaches to L5–S1 have been described in the literature, to our knowledge, no previous study has provided guidance for the choice of technique.PurposeOur objectives were to evaluate our early experience with the safety of including L5–S1 in OLIF using 3 different approach techniques, as well as to compare early complications between OLIF with and without L5–S1 inclusion.Study designRetrospective cohort study.Patient sampleOf the 87 patients who underwent lumbar interbody fusion at 167 spinal levels via an OLIF approach, 19 included L5–S1 (group A) and 68 did not (group B).Outcome measuresDemographics, levels fused, indications, operative time (ORT), estimated blood loss (EBL), vascular ligation, intraoperative blood transfusion, length of stay (LOS), discharge to rehabilitation facility, and complications (intraoperative, early ≤90 days, and delayed >90 days) were retrospectively assessed and compared between the groups.MethodsA retrospective chart and imaging review of all consecutive patients who underwent OLIF at a single institution was performed. Indications for OLIF included symptomatic lumbar degenerative stenosis, deformity, and spondylolisthesis. The L5–S1 level, when included, was approached via one of the following 3 techniques: (1) a left-sided intrabifurcation approach; (2) left-sided prepsoas approach; and (3) right-sided prepsoas approach. Vascular anatomic variations at the lumbosacral junction were evaluated using the preoperative magnetic resonance imaging (MRI), and a “facet line” was proposed to assess this relationship. A minimum of 6 months of follow-up data were assessed for approach-related morbidities.ResultsDemographics and operative indications were similar between the groups. The mean follow-up was 10.8 (6–36) months. ORT was significantly longer in group A than in group B (322 vs. 256.3 min, respectively; p=.001); however, no difference in ORT between the two groups was found in the subanalyses for 2- and 3-level surgeries. Differences in EBL (260 vs. 207.91 cc, p=.251) and LOS (2.76 vs. 2.48 days, p=.491) did not reach statistical significance. Ligation of the iliolumbar vein, segmental veins, median sacral vessels, or any vascular structure, as needed for adequate exposure, was required in 13 (68.4%) patients from group A and 4 (5.9%) from group B (p<.00001). Two patients suffered minor vascular injuries (1 in each group); however, no major vascular injuries were seen. Complications were not significantly different between groups A and B, or between the three approaches to L5–S1, and trended lower in the latter part of the series as the learning curve progressed.ConclusionsInclusion of L5–S1 in OLIF is safe and feasible through three different approaches but likely involves greater operative complexity. In our early experience, inclusion of L5–S1 showed no increase in early complications. This is the first series that reports the use of 3 different oblique approaches to L5–S1. The proposed “facet line” in the preoperative MRI may guide the choice of approach.