LI Group Research Articles

Genomic Evaluation of Primiparous High-Producing Dairy Cows: Inbreeding Effects on Genotypic and Phenotypic Production-Reproductive Traits.

Simple SummaryImproving the genomic prediction methodologies in high-producing dairy cattle is a key factor for the selection of suitable individuals to ensure better productivity. However, the most advanced prediction tools based on genotyping show ~75% reliability. Nowadays, the incorporation of new indices to genomic prediction methods, such as the Inbreeding Index (II), can significantly facilitate the selection of reliable production and reproductive traits for progeny selection. Thus, the objective of this study was to determine the impact of II (low: LI and high: HI), based on genomic analysis, and its effect on production and reproductive phenotypic traits in high-producing primiparous dairy cows. Individuals with II between ≥2.5 and ≤5.0 have shown up to a two-fold increase in negative correlations comparing LI versus HI genomic production and reproductive parameters, severely affecting important traits such as Milk Production at 305 d, Protein Production at 305 d, Fertility Index, and Daughter Pregnancy Rate. Therefore, high-producing dairy cows face an increased risk of negative II-derived effects in their selection programs, particularly at II ≥ 2.5.The main objective of this study was to analyze the effects of the inbreeding degree in high-producing primiparous dairy cows genotypically and phenotypically evaluated and its impacts on production and reproductive parameters. Eighty Holstein–Friesian primiparous cows (age: ~26 months; ~450 kg body weight) were previously genomically analyzed to determine the Inbreeding Index (II) and were divided into two groups: low inbreeding group (LI: <2.5; n = 40) and high inbreeding group (HI: ≥2.5 and ≤5.0; n = 40). Genomic determinations of production and reproductive parameters (14 in total), together with analyses of production (12) and reproductive (11) phenotypic parameters (23 in total) were carried out. Statistically significant differences were obtained between groups concerning the genomic parameters of Milk Production at 305 d and Protein Production at 305 d and the reproductive parameter Daughter Calving Ease, the first two being higher in cows of the HI group and the third lower in the LI group (p < 0.05). For the production phenotypic parameters, statistically significant differences were observed between both groups in the Total Fat, Total Protein, and Urea parameters, the first two being higher in the LI group (p < 0.05). Also, significant differences were observed in several reproductive phenotypic parameters, such as Number of Services per Conception, Calving to Conception Interval, Days Open Post Service, and Current Inter-Partum Period, all of which negatively influenced the HI group (p < 0.05). In addition, correlation analyses were performed between production and reproductive genomic parameters separately and in each consanguinity group. The results showed multiple positive and negative correlations between the production and reproductive parameters independently of the group analyzed, being these correlations more remarkable for the reproductive parameters in the LI group and the production parameters in the HI group (p < 0.05). In conclusion, the degree of inbreeding significantly influenced the results, affecting different genomic and phenotypic production and reproductive parameters in high-producing primiparous cows. The determination of the II in first-calf heifers is crucial to evaluate the negative effects associated with homozygosity avoiding an increase in inbreeding depression on production and reproductive traits.

The impact of a randomized controlled trial of a lifestyle intervention on postpartum physical activity among at-risk hispanic women: Estudio PARTO.

To assess the impact of a culturally modified, motivationally targeted, individually-tailored intervention on postpartum physical activity (PA) and PA self-efficacy among Hispanic women. Estudio PARTO was a randomized controlled trial conducted in Western Massachusetts from 2013-17. Hispanic women who screened positive for gestational diabetes mellitus were randomized to a Lifestyle Intervention (LI, n = 100) or to a comparison Health and Wellness (HW, n = 104) group during late pregnancy. Exercise goals in LI were to meet American College of Obstetrician & Gynecologists guidelines for postpartum PA. The Pregnancy Physical Activity Questionnaire (PPAQ) and the Self-Efficacy for Physical Activity Questionnaire were administered at 6 weeks, 6 months, and 1 year postpartum. Compared to baseline levels, both groups had significant increases in moderate-to-vigorous PA at 6 months and one year postpartum (i.e., LI: mean change = 30.9 MET-hrs/wk, p = 0.05; HW: 27.6 MET-hrs/wk, p = 0.01), with only LI group experiencing significant increases in vigorous PA (mean change = 1.3 MET-hrs/wk, p = 0.03). Based on an intent-to-treat analysis using mixed effects models, we observed no differences in pattern of change in PA intensity and type over time between intervention groups (all p > 0.10). However, there was the suggestion of a greater decrease in sedentary activity in the LI group compared to the HW group (β = -3.56, p = 0.09). In this randomized trial among high-risk Hispanic women, both groups benefitted from participation in a postpartum intervention.

Open Problem‐Based Instruction Improves Student Outcome on Short Answer Critical Thinking Physiology Questions

Classroom instruction has historically focused on teacher‐centered, lecture‐based instruction. However, evidence suggests student‐centered and team‐based approaches stimulate greater knowledge retention, student involvement, and investment in the information. Therefore, we hypothesized that students receiving problem‐based instruction would show greater performance on assessments with regards to total points as well as level of understanding compared to traditional lecture style of instruction. To test this, a quasi‐experimental study was conducted in an upper‐level (junior/senior students) animal physiology course. Students were enrolled in different course sections based on scheduling only and students had no prior knowledge of the instruction style of the course. Three sections were presented with lecture‐based instruction (LI, n=66) and two sections were presented with open problem‐based instruction (OPBI, n=40). The same professor designed and taught all sections and identical course materials were provided to students regardless of instructional group. Students were assessed with 3 exams consisting of 50% multiple choice and 50% short answer questions. Exams were scored blindly. We previously reported that students in OPBI‐based instruction performed better on short answer questions than those in the LI group (LI 47.6 ± 1.1 points vs OPBI 52.0 ± 1.8 points; out of 65 points; p&lt;0.05 t‐test). The present study aimed to assess the short answer responses to determine whether OPBI was associated with higher level responses to critical‐thinking short‐answer questions. This was done through qualitative analysis of questions from exam 1, which covers cellular physiology, membrane potentials, and neuronal function. Responses for these questions were blindly analyzed and scored with a rubric for the following factors: accuracy (0–2 points) based on whether what was written was correct; sufficiency (0–4 points) based on the detail and level of thinking presented in the short‐answer response; and use of technical vocabulary (0–2 points) based on inclusion of physiological terminology. OPBI students scored higher in 2 out of 6 SA questions (Q3 LI 8.9 ± 0.4 points vs OPBI 10.3 ± 0.3 points; Q5: LI 10.1 ± 0.5 vs OPBI 11.8 ± 0.2; out of 12 points each; p&lt;0.05 t‐test). Accuracy (LI 1.5 ± 0.5 vs OPBI 1.8 ± 0.3 points), sufficiency (LI 2.8 ± 1.0 vs OPBI 3.3 ± 0.8 points), and technical vocabulary usage (LI 1.4 ± 0.5 vs OPBI 1.7 ± 0.4 points) were higher for students in OPBI compared to LI for both questions (p&lt;0.05 t‐test). Students in OPBI exhibit greater perceived understanding and technical vocabulary usage, resulting in more sufficient and accurate in‐depth responses to questions that challenge students to think critically. This strongly suggests that an open‐problem, active‐learning based instructional style not only results in retention of information, but a deeper level of understanding. Future studies include comparing additional responses and exam question wording to investigate why OPBI may have better prepared students for some questions but not all.

Isolated Cyclic Loading During Adolescence Improves Tibial Bone Microstructure and Strength at Adulthood.

ABSTRACTBone is a unique living tissue, which responds to the mechanical stimuli regularly imposed on it. Adolescence facilitates a favorable condition for the skeleton that enables the exercise to positively influence bone architecture and overall strength. However, it is still dubious for how long the skeletal benefits gained in adolescence is preserved at adulthood. The current study aims to use a rat model to investigate the effects of in vivo low‐ (LI), medium‐ (MI), and high‐ (HI) intensity cyclic loadings applied during puberty on longitudinal bone development, morphometry, and biomechanics during adolescence as well as at adulthood. Forty‐two young (4‐week‐old) male rats were randomized into control, sham, LI, MI, and HI groups. After a 5 day/week for 8 weeks cyclic loading regime applied on the right tibia, loaded rats underwent a subsequent 41‐week, normal cage activity period. Right tibias were removed at 52 weeks of age, and a comprehensive assessment was performed using μCT, mechanical testing, and finite element analysis. HI and MI groups exhibited reduced body weight and food intake at the end of the loading period compared with shams, but these effects disappeared afterward. HI cyclic loading increased BMD, bone volume fraction, trabecular thickness, trabecular number, and decreased trabecular spacing after loading. All loading‐induced benefits, except BMD, persisted until the end of the normal cage activity period. Moreover, HI loading induced enhanced bone area, periosteal perimeter, and moment of inertia, which remained up to the 52nd week. After the normal cage activity at adulthood, the HI group showed increased ultimate force and stress, stiffness, postyield displacement and energy, and toughness compared with the sham group. Overall, our findings suggest that even though both trabecular and cortical bone drifted through age‐related changes during aging, HI cyclic loading performed during adolescence can render lifelong benefits in bone microstructure and biomechanics. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Sarcopenia assessed by the quantity and quality of skeletal muscle is a prognostic factor for patients undergoing cardiac surgery.

Sarcopenia was assessed as a prognostic factor for patients undergoing cardiac surgery by evaluating the quantity and quality of skeletal muscle. Sarcopenia was assessed by perioperative abdominal computed tomography using the total psoas muscle index (TPI) and intra-muscular adipose tissue content (IMAC). Patients were classified into high- (HT, n = 143) and low- (LT, n = 63) TPI groups and low- (LI, n = 122) and high- (HI, n = 84) IMAC groups. There were significantly more complications in the LT and HI groups than in the HT and LI groups. (HT 15.4% vs. LT 30.2%, P = 0.014) (LI 11.5% vs. HI 31.1%, P < 0.001). There were more respiratory complications in the LT group (HT 0% vs. LT 6.3%, P = 0.002) and more surgical site infections in the HI group than in the LI group (LI 0.8% vs. HI 7.1%, P = 0.014). A multivariable analysis showed that low TPI and high IMAC significantly predicted more major complications than other combinations (odds ratio [OR] 2.375; 95% confidence interval [CI] 1.152-5.783; P = 0.036, OR 3.973; 95% CI 1.737-9.088; P = 0.001). Sarcopenia is a risk factor for complications. The quantity and quality of muscle must be assessed to predict operative outcomes. UMIN000027077.

Cardiopulmonary exercise test indices of respiratory buffering before and after aerobic exercise training in women with pulmonary hypertension: Differentiation by magnitudes of change in six-minute walk test performance.

To compare post-aerobic exercise training adaptations in cardiorespiratory functional capacity across three groups of patients with PH: those with high (HI), low (LI) and negative (NEG) post-training increases in 6MWD. Participants were 25 females (age 54±11 years; BMI 31±7kg/m2) who completed a vigorous, 10-week, thrice weekly, supervised treadmill walking exercise program. Cardiopulmonary exercise tests (CPET) and 6MWT were completed before and after training. Ten of the 25 participants were classified as HI (range=47-143m), 11 were classified as LI (range=4-37m) and 4 were classified as NEG (range=-17 to -53m). Peak CPET duration, WR and time to anaerobic threshold (AT) were significantly higher (p<0.05) after training in both the LI and HI groups but not in the NEG group. There was a significant improvement in VE/VCO2 (p=0.042), PETCO2 (p=0.011) and TV (p=0.050) in the HI group after training, but not in the NEG or LI group. These findings suggest that sustained ventilatory inefficiency and restricted respiratory buffering may mediate exercise intolerance and impede the ability to adapt to exercise training in some patients with PH.

Facile synthesis of lithium containing polyhedral oligomeric phenyl silsesquioxane and its superior performance in transparency, smoke suppression and flame retardancy of epoxy resin

Massive release of toxic volatiles and smoke during combustion is one of the biggest problems facing epoxy resin composites, therefore, it is still a huge challenge to obtain a flame retardant that can simultaneously improve the flame retardancy and reduce the evolution of smoke and toxic gases. Herein, a novel lithium containing polyhedral oligomeric phenyl silsesquioxane (Li-Ph-POSS) has been prepared via hydrolysis condensation of phenyltriethoxysilane in the presence of LiOH·H2O. FTIR, NMR, and MALDI-TOF-MS were used to identify the structure of Li-Ph-POSS, which indicate that it is a hepta-phenyl POSS comprised of incompletely condensed Si–OH and Si–O–Li groups. The excellent compatibility and dispersion of Li-Ph-POSS in EP/Li-Ph-POSS nanocomposites were detected by SEM and TEM. The effective smoke suppression and flame retardancy of EP/Li-Ph-POSS nanocomposites were investigated using cone calorimeter, smoke density and limited oxygen index measurements. Compared with pure EP, the EP with 4 wt% Li-Ph-POSS made the peak of heat release rate (p-HRR), total heat release (THR), peak of smoke production rate (p-SPR) and peak of CO production rate (p-COP) reduce by 61%, 36%, 44%, and 72%, respectively. This work provides a new strategy of mitigating the fire hazard of EP using phosphorus- and halogen-free metal-POSS.

Effects of mild intrauterine hypoperfusion in the second trimester on memory and learning function in rat offspring.

Mild intrauterine hypoperfusion (MIUH) is a serious pathological event that affects the growth and development of fetuses and offspring. MIUH can lead to growth restriction, low birth weight, neurodevelopmental disorders, and other adverse clinical outcomes. To study the effects of MIUH on learning and memory function in offspring, a model of MIUH was established by placing a coil (length 2.5 mm, diameter 0.24 mm) on the uterine artery and ovarian uterine artery of Sprague-Dawley rats in the second trimester of pregnancy (day 17). Next, 120 mg/kg lithium chloride (the MIUH + Li group) or normal saline (the MIUH group) was injected intraperitoneally into these rats. In addition, 120 mg/kg lithium chloride (the Li group) or normal saline (the SHAM group) was injected intraperitoneally into pregnant rats without coil placement. The Morris water maze was used to detect changes in learning and memory ability in the offspring at 4 weeks after birth. In the MIUH group, the escape latency and journey length before reaching the platform were both increased, and the number of times that the platform was crossed and the activity time in the target quadrant within 90 seconds were both decreased compared with the SHAM group. Immunofluorescence double staining and western blot assays demonstrated that hippocampal nestin and Ki67 (both cell-proliferation-related proteins) expression was significantly downregulated in the MIUH group compared with the SHAM group. Furthermore, western blot assays were conducted to investigate changes in related signaling pathway proteins in the brains of offspring rats, and revealed that glycogen synthase kinase 3β (GSK3β) expression was upregulated and β-catenin expression was downregulated in the MIUH group compared with the SHAM group. In addition, compared with the MIUH group, the expression levels of p-GSK3β and β-catenin were upregulated in the MIUH + Li group. These results suggest that MIUH may affect learning and memory function in rat offspring by regulating the GSK3β signaling pathway. The experimental procedures were approved by Animal Ethics Committee of Shengjing Hospital of China Medical University (approval No. 2018PS07K) in June 2018.

BDNF Gene Frequency Distribution in Li and Han Ethnic Groups in Hainan Province and Its Comparison with Other Countries and Regions

Objective: To explore the distribution characteristics of BDNF gene frequency in Li and Han nationalities in Hainan province. Methods: In June 2018-2019 and march to the people’s hospital of Hainan province health volunteers, 152 cases (Li 80, Han, 72), the application of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method to detect the polymorphism of BDNF gene (rs6265), and compared with other countries and regions of ethnic comparison between BDNF gene frequency distribution. Results: No statistical difference was found in rs6265 genotype distribution of BDNF gene in Li and Han ethnic groups (P = 0.3358, P = 0.0892, P = 0.1549). Comparison of BDNF allele frequency between Li and other ethnic groups showed statistically significant differences with other ethnic groups in China and Europe (P = 0.0384, P = 0.0000), but not statistically significant differences with Japan (P = 0.1164). Conclusion: BDNF gene (rs6265) has polymorphism in both Li and Han ethnic groups in Hainan Province. Compared with ethnic groups in other countries and regions, the polymorphism distribution is ethnically different.

A Study on the Association between Patients with Post-Traumatic Stress Disorder in Li and Han Ethnic Groups in Hainan Province and DNA Methylation of Brain-Derived Neurotrophic Factor Genes

Objective: To explore the pathogenesis of PTSD in the brain-derived neurotrophic factor (BDNF) gene methylation of patients with posttraumatic stress disorder (Posttraumatic Stress Disorder, PTSD) in Hainan Province, the relationship between the influence of BDNF gene methylation and the influence of PTSD. Methods: A case-control study method was adopted, strictly in accordance with DSM-IV and PTSD diagnosis, and 150 Li PTSD patients matched with gender and age of 300 Han PTSD patients were selected as the research objects. The peripheral venous whole blood of the subjects was drawn, genomic DNA was extracted, modified with bisulfite, and directly sequenced to quantitatively detect the methylation status of the CpG island in the promoter region of brain-derived neurotrophic factor (BDNF). Results: The results showed that the methylation levels of CPGl, CPG2, CPG3, CPG4, CPG5, CPG6, CPG7, CPG9, CPGl2, CPGl3, CPGl4, CPGl5, CPGl6, CPGl7, and CPGl8 in THE BDNF promoter were significantly different between the HAN PTSD group and the Li PTSD group (P Conclusion: It is suggested that CPG methylation in the promoter region of BDNF gene is closely related to patients with PTSD. There is a statistical difference in the level of CpG methylation in the promoter region of BDNF gene in PTSD between Li and Han ethnic groups in Hainan Province. CpG methylation in the promoter region of BDNF gene may be used as a biomarker for the diagnosis of PTSD.

Frailty Checkup Supporters' Intentions to Participate in Human-Resource Development and Training Activities.

Frailty prevention is one of social prescriptions for an aging society. That requires community level intervention. This study examined frailty checkup supporters' (FCSs') intentions to engage in human-resource development and training activities (i.e., leadership activities) and related factors. Cross-sectional study. Three municipalities in suburban area, Eastern Japan. Forty-five of 59 FCSs completed anonymous self-administered questionnaires. Questionnaire sought information regarding their sociodemographic data, their perceptions and experiences of FCS activities, and their intentions to participate in human-resource development and training activities. Participants were divided into a high intention (HI) and low intention group (LI). The two groups were compared using quantitative and qualitative data. Eleven FCSs reported intending to engage in leader-related activities. Factors associated with FCSs' intentions were finding FCS activities rewarding and the willingness to continue performing FCS activities. The participants who changed their daily activities (p = .041) and perceptions regarding contributing to the community (p = .018) showed significantly higher intention than LI participants. Free description about the changes in perceptions and lifestyles as a consequence of participating in FCS activities were analyzed qualitatively. FCSs who changed their daily activities and perspectives about contributing to the community described positive changes in both the groups. Meanwhile, FCSs who did not change their daily activities and perspectives about contributing to the community described their reason only in the LI group. The results might encourage FCSs to participate in training and guidance activities, as they have positive experiences and receive recognition obtained through participation in such activities.

Forensic features, genetic diversity and structure analysis of three Chinese populations using 47 autosomal InDels

Insertion/deletion polymorphisms (InDels), which combine the desirable features of both short tandem repeats (STRs) and single-nucleotide polymorphisms (SNPs), have become widely used genetic markers for forensic investigations, anthropology and population genetics. The AGCU InDel 50 kit is a newly developed panel that contains 47 autosomal InDels (A-InDels), 2 Y-chromosomal InDels (Y-InDels) and Amelogenin and is designed to provide a higher discriminatory power in Chinese populations compared with the Qiagen DIPplex kit. In this study, 542 unrelated individuals were first genotyped to evaluate the forensic efficiency of this novel panel in three Chinese ethnicities (Hainan Han, Hainan Li and Zunyi Gelao groups). Additionally, genetic relationships among the three investigated populations (geographically close but linguistically different populations: Han and Li; geographically diverse but from the same language family: Li and Gelao) and 31 worldwide populations were analyzed using pairwise genetic distances, multidimensional scaling (MDS), phylogenetic tree, principal component analysis (PCA) and STRUCTURE. The combined powers of discrimination (CPD) for the Han, Li and Gelao groups were 0.999999999999999999635, 0.999999999999999997668 and 0.999999999999999999840, respectively, and the combined powers of exclusion (CPE) were 0.999715, 0.999283 and 0.999575, respectively. The genetic relationship between the Hainan Han and Zunyi Gelao groups was relatively closer than that between the Hainan Li and Zunyi Gelao groups, demonstrating that there was little gene communication between Li and Han living on Hainan Island as well as between Li and Gelao in the Tai-Kadai language family. The aforementioned results suggest that the AGCU InDel 50 kit is an effective tool that is appropriate for personal identification and population genetics.

A Case-Control Study of Skin Microbiome in Patients with Lamellar Ichthyosis

Abstract Introduction: Lamellar ichthyosis is a genetic disorder of keratinization and the frequent skin infections in these patients may be a result of change in normal skin flora acting in addendum to breach in the physical barrier. Material and Methods: A comparative retrospective study was performed in patients with lamellar ichthyosis and age/ sex controlled matched patients attending the dermatology IPD/OPD with positive skin swab results from July 1st 2015 to June 31st 2016. The two groups were then compared in terms of bacterial culture results. Results: The mean gestational age of the study subjects at birth was 35.56 weeks (range: 30–39 weeks). The study sample consisted of 6 males and 3 females in LI group and 12 males and 6 females in the control group. Methicillin resistant Staphylococcusaureus (MRSA) was exclusively seen in LI patients, and Gram negative rods, Fusobacterium and Candida were found more in the LI patients than in the control group. The Bacteroidetes to Firmicutes ratio, lipophilic diphtheroids, Propionibacterium acnes, Fusobacterium and Micrococci were present more in the control group than in the LI patients. Conclusion: By knowing this microbiota, undue reliance on antibiotics can be reduced as these microorganisms may form normal commensals for the given micro environment. Furthermore, these organisms may be responsible for perpetuating the disease process by compounding the genetic keratinocyte barrier. What is known: Frequent skin infections are not uncommon in patients of lamellar ichthyosis. What is new: Methicillin resistant Staphylococcus aureus (MRSA) are commonly present in LI patients, and Gram negative rods, Fusobacterium and Candida are commoner in the LI patients than in the control group of patients.

Effects of level of feed intake and season on digestibility of dietary components, efficiency of microbial protein synthesis, rumen fermentation and ruminal microbiota in yaks

Yaks (Poephagus grunniens) are raised under the harsh conditions of the Qinghai-Tibetan Plateau (QTP) and, traditionally, they graze only natural grasslands all year round without receiving any supplements. The pasture peaks in biomass and quality during the summer when yaks usually gain body weight; however, it is sparse and of poor quality in winter when yaks generally lose body weight. Yaks are well adapted to the extreme conditions and are able to cope with low energy and nitrogen intakes. We hypothesized that the level of feed intake would affect the digestibility of nutrients and the efficiency of microbial protein synthesis (EMPS, as g microbial N/kg organic matter intake) and predicted that at very low dietary intakes in yaks, dietary components would be digested at a higher rate but that there would be little, if any effect on EMPS. We also predicted that the EMPS in yaks would be higher than values reported for cattle. To test these predictions, we offered six yaks a dry matter intake of 0.010 to 0.011 BW (low intake: LI) and six yaks a dry matter intake of 0.020 to 0.021 BW (high intake: HI) both in summer and in winter. Apparent digestibilities of dry matter (DM, P = 0.04), organic matter (OM, P = 0.048) and crude protein (CP, P = 0.04) were greater in the LI yaks than in the HI yaks in winter. The HI group was in positive N balance in summer and in winter, whereas the LI group was in positive N balance in summer, but not in winter. The total volatile fatty acids (TVFA) tended or was greater (P = 0.09 in summer; 0.053 in winter) and estimated microbial N yield was greater (P < 0.001) in the HI than in the LI yaks in both seasons. The EMPS did not differ between seasons (P = 0.51) or between feed levels (P = 0.26) and, in general, was higher in yaks than in cattle. The proportion of Fibrobacter succinogenes, a major fibrolytic ruminal bacterium, was significantly greater in LI than in HI yaks (P =0.007). We concluded that in yaks: 1) the apparent digestibilities of the dietary components increase at low level dietary intakes in winter when the forage is of poor quality; 2) EMPS does not differ between feed levels and is generally higher in yaks than for reported values in cattle; and 3) the higher digestion of NDF and ADF in the LI yaks than in the HI yaks in winter when the pasture is of poor quality, was due, at least in part, to a greater proportion of ruminal Fibrobacter succinogenes bacterium.

Impact of Bridging Chemotherapy on Clinical Outcomes of CD19 CAR T Therapy in Relapse/Refractory Diffuse Large B- Cell Lymphoma in Real World Experience

Background: Autologous chimeric antigen receptor (CAR) T cell therapy has shown to be effective in relapsed or refractory (R/R) diffuse large B cell lymphoma (DLBCL) but requires in real world and in Europe at least a 4 weeks period of cell processing. During this "bridging period", patients are vulnerable to disease progression and complications. We sought to characterize bridging therapy strategies. Methods: We performed a retrospective review of patients (pts) with R/R DLBCL treated with commercialized CD19 CAR T cells, either Axicabtagene Ciloleucel (Yescarta) or tisagenlecleucel (Kymriah). Bridging therapy (BT) was defined by any therapy given from enrolment to cell infusion. We divided bridging therapy in 2 groups: high intensity BT (HI, including chemotherapy+/-immunotherapy) and low intensity BT (LI, including monoclonal antibodies rituximab, brentuximab, dexamethasone, lenalidomide). We evaluated toxicity (cytokine releasing syndrome (CRS), CAR-related encephalopathy syndrome (CRES), infections) and efficacy (OS, PFS) after infusion according to the intensity of the BT. Results: 46 pts were enrolled for commercialized CAR T cells (Kymriah n=25, Yescarta n=21) including R/R DLBCL (n=35), TFL (n=5) or PMBL (n=6) between June 2018 and April 2019. The median age was 57 (IQR, 42 to 64). Number of pts with aaIPI &gt; 2 was 20. The median number of previous lines was 3 (range 3-5), including 15 autologous stem cell transplants and 2 allotransplants. Median time between enrollment and infusion, and between collection and infusion were 59 (35 to 118) and 40 (32 to 90) days, respectively. Overall, 30 (65%) pts received a HI and 16 (35%) a LI or no bridging therapy. Median number of BT cycles was 2 (range, 1-4). 13 patients had various regimen because of uncontrolled disease. Pts receiving HI presented at enrollment with more elevated LDH (60% vs 31%), more involved extranodal sites (n&gt; 2, 32% vs 0%), higher IPI (&gt;2, 77% vs 43%, p=.049), and higher total metabolic tumor volume (TMTV) measured on FDG PET/CT (median, 90 vs 10, p=.002). After BT, 44 pts were infused. 2 pts died before infusion because of a pulmonary infection (n=1) and a lymphoma progression (n=1), both in the HI group. At infusion response evaluation showed that 25 (57%) pts progressed during BT, without difference in the HI or the LI groups (61 % vs 50%). Median TMTV in HI and LI was 95 (10 -256) vs 18 (8 - 44), respectively. After CAR T infusion, 14 pts (32%) developed an infectious disease (7 in the LI group, 7 in the HI group, p=0.31). Median duration of neutropenia (PNN &lt; 1000) was 8 days, 7 in the LI and 9 in the HI (p= 0.21). In the LI and HI groups, 11 and 19 pts developed a CRS (0 grade 3-4), 1 and 11 pts developed a CRES (1 and 3 grade 3-4), respectively. The HI/LI did not impact the occurrence of CRS (p=1.00) but that of CRES (p=0.03). Pts with abnormal LDH (p=0.02), high number of courses (p=0.03) or PS&gt;0 (p=0.049) had a higher risk of CRS, whereas patients with high IPI (p=0.03), and high values of CRP (P=0.02) or decreased albumin levels (p=0.008) had a higher risk of CRES. After CAR T cells infusion, with a median follow up of 5.7 months, the median PFS was not reached in the LI group, and was of 3 months in the HI group (p=0.06). The median OS was not reached in the LI group, and was of 12.5 months in the HI group (p=0.09). In multivariate analyses, IPI was predictor of better PFS, whereas low IPI and TMTV were predictors of better OS. No evidence of any effect of intensity of the BT on OS or PFS was observed in these multivariate analyses. Conclusion: The type of bridging therapies was very heterogeneous. Its intensity was closely related to tumor burden at enrolment. There was no significant difference in terms of efficacy between the HI and LI groups, but a higher frequency of CRES in the HI group. Disclosures Paillassa: Janssen: Other: Bibliography board with young hematologists. Di Blasi:Novartis: Honoraria. Thieblemont:Roche: Honoraria, Research Funding; Gilead: Honoraria; Novartis: Honoraria; Kyte: Honoraria; Janssen: Honoraria; Celgene: Honoraria; Cellectis: Membership on an entity's Board of Directors or advisory committees.

Effect of Short-Term Cardiac Rehabilitation on Quality of Life According to Socioeconomic Status

BackgroundCardiac rehabilitation (CR) lowers the recurrence of cardiovascular disease and has strong and posi-tive physical and psychological effects. The purpose of this study was to analyze the quality of life (QoL) of CR participants according to their monthly income and education levels in the early phase after percutaneous coronary intervention (PCI). Material and methodsThere were 128 participants (98 men and 30 women). Their socioeconomic status (SES) was evaluated and QoL was assessed using the 36-item Short Form Health Survey. CR was initiated 3 weeks after treatment and remeasured after 3 months. The pre-post analysis was performed using the paired t-test. The participants’ education levels were defined in terms of a middle school group (low education [LE]), high school group (middle education [ME]), and above college group (high education [HE]). Monthly household income was divided into tertiles: up to US$2000 (low income [LI]), up to US$4000 (middle income [MI]), and more than US$4000 (high income [HI]). ResultsThere was a significant increase in mental health status—from 54.9 to 63.3—in the HE group, but no significant changes were observed in the LE and ME groups. Physical changes were observed in all education-level groups.The physical changes in the group according to monthly income significantly increased by 9.1% (66.8– 73.5) in the LI group, 7.8% (65.9–71.5) in the MI group, and 12.1% (62.7–71.3) in the HI group. Physical changes were observed in all monthly income groups. Changes in occupational physical activity levels sig-nificantly improved physical and mental status in the middle and high activity groups, but not in the low activity group. ConclusionChanges in QoL as an effect of short-term CR were effective. Changes in mental QoL were significant in higher SES levels and physical QoL was effective in all groups.

High Impact Exercise Improves Bone Microstructure and Strength in Growing Rats

Physical activity is beneficial for skeletal development. However, impact sports during adolescence, leading to bone growth retardation and/or bone quality improvement, remains unexplained. This study investigated the effects of in vivo low (LI), medium (MI), and high (HI) impact loadings applied during puberty on bone growth, morphometry and biomechanics using a rat model. 4-week old rats (n = 30) were divided into control, sham, LI, MI, and HI groups. The impact was applied on the right tibiae, 5 days/week for 8 weeks mimicking walking (450 µε), uphill running (850 µε) and jumping (1250 µε) conditions. Trabecular and cortical parameters were determined by micro-CT, bone growth rate by calcein labeling and toluidine blue staining followed by histomorphometry. Bio-mechanical properties were evaluated from bending tests. HI group reduced rat body weight and food consumption compared to shams. Bone growth rate also decreased in MI and HI groups despite developing thicker hypertrophic and proliferative zone heights. HI group showed significant increment in bone mineral density, trabecular thickness, cortical and total surface area. Ultimate load and stiffness were also increased in MI and HI groups. We conclude that impact loading during adolescence reduces bone growth moderately but improves bone quality and biomechanics at the end of the growing period.

Computer-Based Cognitive Rehabilitation in Patients with Visuospatial Neglect or Homonymous Hemianopia after Stroke

Objectives: The purpose of this pilot study was to investigate the feasibility and effects of computer-based cognitive rehabilitation (CBCR) in patients with symptoms of visuospatial neglect or homonymous hemianopia in the subacute phase following stroke. Method: A randomized, controlled, unblinded cross-over design was completed with early versus late CBCR including 7 patients in the early intervention group (EI) and 7 patients in the late intervention group (LI). EI received CBCR training immediately after inclusion (m = 19 days after stroke onset) for 3 weeks and LI waited for 3 weeks after inclusion before receiving CBCR training for 3 weeks (m = 44 days after stroke onset). Results: CBCR improved visuospatial symptoms after stroke significantly when administered early in the subacute phase after stroke. The same significant effect was not found when CBCR was administered later in the rehabilitation. The difference in the development of the EI and LI groups during the first 3 weeks was not significant, which could be due to a lack of statistical power. CBCR did not impact mental well-being negatively in any of the groups. In the LI group, the anticipation of CBCR seemed to have a positive impact of mental well-being. Conclusion: CBCR is feasible and has a positive effect on symptoms in patients with visuospatial symptoms in the subacute phase after stroke. The study was small and confirmation in larger samples with blinded outcome assessors is needed.

Combination of lithium and electroconvulsive therapy (ECT) is associated with higher odds of delirium and cognitive problems in a large national sample across the United States

BackgroundLithium is a helpful adjunct to patients undergoing ECT. However, only case reports and limited data suggest increase risk of delirium. Thus, this continues to be a controversial issue. ObjectiveIn this study, we examine 1) The association and odds of delirium and cognitive problems with ECT and lithium (ECT + Li) combination compared to ECT alone, 2) If positively associated, would this association vary by both type of mood episode and type of disorder? MethodsA national sample of 64,728 adult psychiatric inpatients across the US (identified from a total data of about 70 million total discharges annually) was analyzed using linear-by-linear association and logistic regression to assess the odds ratio (OR) for delirium and cognitive impairment for those treated with lithium (N = 158), ECT (N = 64148), or ECT + Li (N = 422) after adjusting for demographics and psychiatric diagnoses. ResultsThe prevalence of delirium was higher in the ECT + Lithium group (5.7%) vs. ECT only (0.6%) or lithium only groups (0%). Patients managed with ECT + Lithium have 11.7-fold higher odds (95% CI 7.55–17.99, P < 0.001) of delirium compared to ECT alone. In the ECT + Li group, delirium prevalence was 7.8% in unipolar depression, 3.4% in bipolar depressed, 0% in bipolar mania. ConclusionThese results are surprising given the fading concern about delirium association with ECT + lithium combination. The high odds in the combination group warrant clinical caution, use of lower lithium doses (if combinations cannot be avoided), and vigilance regarding early signs of delirium. These results warrant replication in future studies.

Ventilatory Efficiency Among Patients With Pulmonary Hypertension With Varying Levels Of Adaptation To Exercise Training

The 6-minute walk test (6MWT) is universally accepted as a measure of functional capacity in patients with pulmonary hypertension (PH). While aerobic exercise training (AET) has generally been shown to improve exercise tolerance and 6MWT distance in patients with PH, some patients have been observed to adapt differently to AET, with minimal or even negative changes in 6MWT distance being reported. Differences in patient characteristics and peak ventilatory efficiency to AET have not been characterized and compared in these subset of patients. PURPOSE: To determine differences in ventilatory efficiency, defined as peak ventilatory equivalents for O2 uptake (VE/VO2), peak ventilatory equivalents for CO2 output (VE/VCO2), end-tidal CO2 (PETCO2) and tidal volume (TV), in patients with high (HI, >42 meters), low (LI, 0-42 meters) and negative (NEG, <0 meters) change in 6MWT distance after AET. METHODS: Subjects were 25 females (age 54±11 years; BMI 31±7 kg/m2) enrolled in the NIH Exercise Therapy for Advanced Lung Disease Trial. Participants completed 24-30 supervised treadmill walking exercise sessions, over 10 consecutive weeks, at a training intensity of 70% to 80% of heart rate reserve. The thrice-weekly sessions were 30-45 minutes in duration. A cardiopulmonary exercise test and 6MWT was completed before and after the 10-weeks of training. Ten of the 25 subjects were classified as HI (range = 47-143 meters), 11 were classified as LI (range = 4 - 37 meters) and 4 were classified as NEG (range = -17-53 meters). RESULTS: After AET, peak values in VE/VO2 (p=0.02), VE/VCO2 (p=0.002), PETCO2 (p=0.016) and TV (p=0.016) were improved for the HI versus NEG group. Peak values for VE/VCO2 (p=0.003) and TV (p=0.041) were improved for the LI versus NEG group. CONCLUSION: Previous studies suggest that reduced ventilatory efficiency (VE/VCO2) is associated with a poor prognostic outcome in patients with PH. To our knowledge this is the first study to look at changes in ventilatory efficiency after AET, specifically in HI, LI and NEG subsets. Findings from this study suggest that reduced ventilatory efficiency may also contribute to reduced functional capacity in patients with PH, contributing to the etiological basis for the association between 6MWD and mortality in these patients. Funding NIH IRP [1 Z01 CL060068-05 CC].