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Improved immune recovery after transplantation of TCRαβ/CD19-depleted allografts from haploidentical donors in pediatric patients
Immune recovery was retrospectively analyzed in a cohort of 41 patients with acute leukemia, myelodysplastic syndrome and nonmalignant diseases, who received αβ T- and B-cell-depleted allografts from haploidentical family donors. Conditioning regimens consisted of fludarabine or clofarabine, thiotepa, melphalan and serotherapy with OKT3 or ATG-Fresenius. Graft manipulation was carried out with anti-TCRαβ and anti-CD19 Abs and immunomagnetic microbeads. The γδ T cells and natural killer cells remained in the grafts. Primary engraftment occurred in 88%, acute GvHD (aGvHD) grades II and III–IV occurred in 10% and 15%, respectively. Immune recovery data were available in 26 patients and comparable after OKT3 (
n
=7) or ATG-F (
n
=19). Median time to reach >100 CD3+ cells/μL, >200 CD19+ cells/μL and >200 CD56+ cells/μL for the whole group was 13, 127 and 12.5 days, respectively. Compared with a historical control group of patients with CD34+ selected grafts, significantly higher cell numbers were found for CD3+ at days +30 and +90 (267 vs 27 and 397 vs 163 cells/μL), for CD3+4+ at day +30 (58 vs 11 cells/μL) and for CD56+ at day +14 (622 vs 27 cells/μL). The clinical impact of this accelerated immune recovery will be evaluated in an ongoing prospective multicenter trial.
Journal Article
A role for microfluidic systems in precision medicine
Precision oncology continues to challenge the “one-size-fits-all” dogma. Under the precision oncology banner, cancer patients are screened for molecular tumor alterations that predict treatment response, ideally leading to optimal treatments. Functional assays that directly evaluate treatment efficacy on the patient’s cells offer an alternative and complementary tool to improve the accuracy of precision oncology. Unfortunately, traditional Petri dish-based assays overlook much tumor complexity, limiting their potential as predictive functional biomarkers. Here, we review past applications of microfluidic systems for precision medicine and discuss the present and potential future role of functional microfluidic assays as treatment predictors.
Precision oncology is important for patient treatment. Here the authors review the current applications of microfluidic systems to cancer precision medicine, and discuss the issues that must be addressed prior to getting these technologies into the clinic.
Journal Article
Small teaching online : applying learning science in online classes
\"BUILDS OFF OUR PREVIOUS SUCCESS: Small Teaching (9781118944493, February 2016) has sold 27,498 units life-to-date. We are building off of our success with that title to address the specific challenges that online instructors face in higher education. Author James Lang is partnering with eLearning expert Flower Darby to write and promote the book. RAPIDLY GROWING SEGMENT OF STUDENT POPULATION: According to the Online Learning Consortium, in 2016, 5.8 million students were enrolled in at least one online course. This represents a 263% increase over the last decade. Two-thirds of these 5.8 million students take online courses through public institutions. ONLINE LEARNING IS PREFERRED BY TODAY'S LEARNER: The Online Learning Consortium study also shows that 90% of today's student believes online learning is as good as or better than the traditional classroom experience. INCREASED ENGAGEMENT WITH EDTECH: A survey of university Chief Information Officers shows that 96% believe adaptive technology has potential to improve student outcomes, while 87% believe technology provides a richer experience for students. Students agree, except that 4 out of 5 would also say universities should be doing more with technology-based learning experiences. This book will help higher education instructors do that\"-- Provided by publisher.
Book
Long-term interplay between COVID-19 and chronic kidney disease
Purpose
The COVID-19 pandemic may have an impact on the long-term kidney function of survivors. The clinical relevance is not clear.
Methods
This review summarises the currently published data.
Results
There is a bidirectional relationship between chronic kidney disease and COVID-19 disease. Chronic kidney diseases due to primary kidney disease or chronic conditions affecting kidneys increase the susceptibility to COVID-19 infection, the risks for progression and critical COVID-19 disease (with acute or acute-on-chronic kidney damage), and death. Patients who have survived COVID-19 face an increased risk of worse kidney outcomes in the post-acute phase of the disease. Of clinical significance, COVID-19 may predispose surviving patients to chronic kidney disease, independently of clinically apparent acute kidney injury (AKI). The increased risk of post-acute renal dysfunction of COVID-19 patients can be graded according to the severity of the acute infection (non-hospitalised, hospitalised or ICU patients). The burden of chronic kidney disease developing after COVID-19 is currently unknown.
Conclusion
Post-acute COVID-19 care should include close attention to kidney function. Future prospective large-scale studies are needed with long and complete follow-up periods, assessing kidney function using novel markers of kidney function/damage, urinalysis and biopsy studies.
Journal Article
GM-CSF-based treatments in COVID-19: reconciling opposing therapeutic approaches
Therapeutics against coronavirus disease 2019 (COVID-19) are urgently needed. Granulocyte–macrophage colony-stimulating factor (GM-CSF), a myelopoietic growth factor and pro-inflammatory cytokine, plays a critical role in alveolar macrophage homeostasis, lung inflammation and immunological disease. Both administration and inhibition of GM-CSF are currently being therapeutically tested in COVID-19 clinical trials. This Perspective discusses the pleiotropic biology of GM-CSF and the scientific merits behind these contrasting approaches.Recombinant granulocyte–macrophage colony-stimulating factor (GM-CSF) as well as antibodies targeted at GM-CSF or its receptor are being tested in clinical trials for coronavirus disease 2019 (COVID-19). This Perspective introduces the pleiotropic functions of GM-CSF and explores the rationale behind these different approaches.
Journal Article
Pulmonary Hypertension in Heart Failure. Epidemiology, Right Ventricular Function, and Survival
Abstract
Rationale
Patients with pulmonary hypertension due to left heart disease (PH-LHD) and a diastolic pulmonary vascular pressure gradient ≥7 mm Hg, representing PH out of proportion to pulmonary arterial wedge pressure, have pulmonary vascular disease and increased mortality. Little information exists on this condition, recently labeled as “combined pre- and post-capillary PH” (Cpc-PH).
Objectives
To investigate epidemiology, risk factors, right ventricular function, and outcomes in patients with chronic heart failure and Cpc-PH.
Methods
The study population was identified from a retrospective chart review of a clinical database of 3,107 stable patients who underwent first diagnostic right heart catheterization and from a prospective cohort of 800 consecutive patients at a national university-affiliated tertiary center.
Measurements and Main Results
The retrospective cohort had 664 patients with systolic heart failure (SHF) and 399 patients with diastolic heart failure (DHF), 12% of whom were classified as Cpc-PH. The prospective cohort had 172 patients with SHF (14% Cpc-PH) and 219 patients with DHF (12% Cpc-PH). Chronic obstructive pulmonary disease (P = 0.034) and the tricuspid annular plane systolic excursion to systolic pulmonary artery pressure ratio (P = 0.015) predicted Cpc-PH in SHF. Younger age (P = 0.004), valvular heart disease (P = 0.046), and the tricuspid annular plane systolic excursion to systolic pulmonary artery pressure ratio predicted Cpc-PH in DHF (P = 0.016). Right ventricular–pulmonary vascular coupling was worse in Cpc-PH patients (end-systolic elastance to effective arterial elastance [Ees/Ea]: SHF: 1.05 ± 0.25; P = 0.002; DHF: 1.17 ± 0.27; P = 0.027) than in those with isolated post-capillary PH (Ees/Ea: SHF: 1.52 ± 0.51; DHF: 1.45 ± 0.29).
Conclusions
Cpc-PH is rare in chronic heart failure. Right ventricular–pulmonary vascular coupling is poor in Cpc-PH and could be one explanation for dismal outcomes.
Journal Article