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Background: Tumour, nodes, and metastases (TNM) staging has been deficient in prognosticating in patients suffering from non-small cell lung cancer (NSCLC). To supplement TNM staging, this systematic review and meta-analysis aimed to evaluate the prognostic value of the regulatory T cells (Treg)., Methods: A keyword search was conducted in MEDLINE and EMBASE for full-text original human studies from any region published in English during the last 12 years. Eligible for inclusion were studies evaluating the prognostic value of the number of Treg cells in NSCLC except case studies, case series, systematic reviews, and meta-analyses. Two reviewers (one reviewer used an automation tool) independently screened the studies and assessed risk-of-bias using the Quality in Prognosis Studies (QUIPS) tool. Meta-analysis was done for studies reporting significant multivariate hazard ratio (HR)., Results: Out of 809 retrievals, 24 studies were included in the final review. The low number of Treg cells was found significantly associated with improved overall survival (pooled log OR, 1.646; 95% CI, 1.349, 1.944; p (2-tailed) < .001; SE, 0.1217), improved recurrence-free survival (HR, 1.99; 95% CI, 1.15, 3.46; p = .01), improved progression-free survival (pooled log OR, 2.231; 95% CI, 0.424, 4.038; p (2-tailed) .034; SE, 0.4200), and worse disease-free survival (pooled log OR, 0.992; 95% CI, 0.820, 1.163; p (2-tailed) .009; SE, 0.0135), especially when identified by forkhead box P3 (FOXP3), in any stage or non-metastatic NSCLC., Conclusion: A low number of Treg cells indicated better survival, suggesting its potential use as a prognostic biomarker in NSCLC., Systematic Review Registration: The protocol of this review was prospectively registered on PROSPERO on August 28, 2021, and was assigned the registration number CRD42021270598. The protocol can be accessed from PROSPERO website., (© 2024. The Author(s).)

Background: If symptomatic in infants, the autosomal recessive disease lysosomal acid lipase deficiency (LAL-D; sometimes called Wolman disease or LAL-D/Wolman phenotype) is characterized by complete loss of LAL enzyme activity. This very rare, rapidly progressive form of LAL-D results in severe manifestations leading to failure to thrive and death, usually by 6 months of age. We report results from 2 open-label studies of enzyme replacement therapy with sebelipase alfa, a recombinant human LAL, in infants with LAL-D: the phase 2/3 Survival of LAL-D Infants Treated With Sebelipase Alfa (VITAL) study (NCT01371825) and a phase 2 dose-escalation study (LAL-CL08 [CL08]; NCT02193867). In both, infants received once-weekly intravenous infusions of sebelipase alfa., Results: The analysis population contained 19 patients (9 in VITAL; 10 in CL08). Kaplan-Meier estimates of survival to 12 months and 5 years of age were 79% and 68%, respectively, in the combined population, and the median age of surviving patients was 5.2 years in VITAL and 3.2 years in CL08. In both studies, median weight-for-age, length-for-age, and mid-upper arm circumference-for-age z scores increased from baseline to end of study. Decreases in median liver and spleen volume over time were noted in both studies. Short-term transfusion-free hemoglobin normalization was achieved by 100% of patients eligible for assessment in VITAL, in an estimated median (95% confidence interval [CI]) time of 4.6 (0.3-16.6) months. In CL08, short-term transfusion-free hemoglobin normalization was achieved by 70% of patients eligible for assessment, in an estimated median (95% CI) time of 5.5 (3.7-19.6) months. No patient discontinued treatment because of treatment-emergent adverse events. Most infusion-associated reactions (94% in VITAL and 88% in CL08) were mild or moderate in severity., Conclusions: The findings of these 2 studies of infants with rapidly progressive LAL-D demonstrated that enzyme replacement therapy with sebelipase alfa prolonged survival with normal psychomotor development, improved growth, hematologic parameters, and liver parameters, and was generally well tolerated, with an acceptable safety profile.

Background: Infants presenting with lysosomal acid lipase deficiency have marked failure to thrive, diarrhea, massive hepatosplenomegaly, anemia, rapidly progressive liver disease, and death typically in the first 6 months of life; the only available potential treatment has been hematopoietic stem cell transplantation, which is associated with high morbidity and mortality in this population. The study objective was to evaluate safety and efficacy (including survival) of enzyme replacement with sebelipase alfa in infants with lysosomal acid lipase deficiency. This is an ongoing multicenter, open-label, phase 2/3 study conducted in nine countries. The study enrolled infants with growth failure prior to 6 months of age with rapidly progressive lysosomal acid lipase deficiency; they received once-weekly doses of sebelipase alfa initiated at 0.35 mg/kg with intrapatient dose escalation up to 5 mg/kg. The main outcome of interest is survival to 12 months and survival beyond 24 months of age., Results: Nine patients were enrolled; median age at baseline was 3.0 months (range 1.1-5.8 months). Sixty-seven percent (exact 95% CI 30%-93%) of sebelipase alfa-treated infants survived to 12 months of age compared with 0% (exact 95% CI 0%-16%) for a historical control group (n = 21). Patients who survived to age 12 months exhibited improvements in weight-for-age, reductions in markers of liver dysfunction and hepatosplenomegaly, and improvements in anemia and gastrointestinal symptoms. Three deaths occurred early (first few months of life), two patients died because of advanced disease, and a third patient died following complications of non-protocol-specified abdominal paracentesis. A fourth death occurred at 15 months of age and was related to other clinical conditions. The five surviving patients have survived to age ≥24 months with continued sebelipase alfa treatment; all have displayed marked improvement in growth parameters and liver function. Serious adverse events considered related to sebelipase alfa were reported in one of the nine infants (infusion reaction: tachycardia, pallor, chills, and pyrexia). Most infusion-associated reactions were mild and non-serious., Conclusion: Sebelipase alfa markedly improved survival with substantial clinically meaningful improvements in growth and other key disease manifestations in infants with rapidly progressive lysosomal acid lipase deficiency TRIAL REGISTRATION: Clinicaltrials.gov NCT01371825 . Registered 9 June 2011.

The efficacy and safety of plerixafor + G-CSF in enhancing hematopoietic stem cell mobilization and collection has been demonstrated in two phase III studies involving patients with NHL or MM. In these pivotal studies, plerixafor + G-CSF significantly increased the proportion of patients achieving target stem cell yields, compared to placebo + G-CSF. In this analysis, we compare the efficacy and safety of plerixafor + G-CSF versus placebo + G-CSF in patients enrolled in the two phase III studies, stratified by age: ≥60 years of age and <60 years of age. The proportion of older patients who achieved target stem cell yields was significantly higher in the plerixafor group than in placebo group (NHL: 50.9 vs. 25.4%, P < 0.001; MM: 69.6 vs. 23.7%, P < 0.001). In this older cohort, the median times to neutrophil and to platelet engraftment following autologous stem cell transplant were comparable between the plerixafor and placebo groups. Similar efficacy findings were observed in the younger age group. The most common adverse events (all grades) reported among older patients in the plerixafor group included diarrhea (41.3%), nausea (38.9%), fatigue (30.2%), and injection-site reaction (29.4%). The frequency of adverse events was similar between the older and the younger age groups. Taken together, our subanalysis demonstrate that plerixafor + G-CSF can be safely and effectively used in adult patients of all ages, including those ≥60 years, to support optimal stem cell mobilization for autologous stem cell transplantation., (Copyright © 2013 Wiley Periodicals, Inc.)

Autologous hematopoietic stem cell transplantation (ASCT) is an established treatment for patients with hematologic malignancies, yet the impact of transplanted CD34(+) cell dose on clinical outcomes is unresolved. We conducted post hoc analyses of transplanted CD34(+) cell dose and hematopoietic recovery following ASCT in 438 patients with non-Hodgkin lymphoma (NHL) or multiple myeloma (MM), using data from 2 multicenter phase 3 clinical studies that compared plerixafor plus granulocyte-colony stimulating factor (G-CSF) versus placebo plus G-CSF as stem cell mobilization regimens. Days to engraftment and the proportion of patients who reached predetermined blood count thresholds were compared across 3 CD34(+) cell dose levels: 2-4 × 10(6) cells/kg, 4-6 × 10(6) cells/kg, and >6 × 10(6) cells/kg, regardless of mobilization treatment. Short-term neutrophil and platelet engraftment times were similar regardless of cell dose. A significant linear trend was observed between transplanted CD34(+) cell dose and the proportion of patients with platelet count >150 × 10(9)/L at 100 days (P < .001), 6 months (P = .026), and 12 months (P = .020) in patients with NHL, and at 100 days in patients with MM (P = .004). A linear trend was also observed between transplanted cell dose and the proportion of patients with platelet count >100 × 10(9)/L at 100 days (P < .001) and 6 months (P = .023) in patients with NHL. A higher cell dose was associated with a lower percentage of NHL patients requiring red blood cell transfusions (P = .006). Our analyses confirm previous findings that transplanted CD34(+) cell dose may be associated with better long-term platelet recovery after ASCT., (Copyright © 2011 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: The presence of aortic atherosclerosis has been identified as a major risk factor for stroke after coronary artery bypass grafting (CABG). Whether aortic atherosclerosis is similarly related to the risk of acute renal failure (ARF), a common and important complication of CABG, is unknown., Methods: Rates of postoperative ARF were analyzed using data from 1,117 randomized patients in a multicenter controlled trial comparing standard CABG with CABG plus an experimental aortic catheter. Aortic atherosclerosis was prospectively measured using transesophageal echocardiography. The association of aortic atherosclerosis with postoperative renal failure was analyzed using multivariable logistic regression to adjust for confounding by baseline and intraoperative conditions., Results: Baseline creatinine clearance <40 ml/min and systolic hypertension were strong predictors of postoperative acute renal failure. Neither mild nor moderate aortic atherosclerosis was associated with the development of acute renal failure. Patients with moderate aortic atherosclerosis had a lower risk of acute renal failure (odds ratio = 0.53, p = 0.20) than those with lesser degrees of atherosclerosis., Conclusions: Our results demonstrate that the presence of significant aortic atherosclerosis does not increase the risk of acute renal failure following CABG, and they suggest that cholesterol embolization from the aorta to the renal circulation is an infrequent cause of acute renal failure after bypass surgery. Strategies to decrease cholesterol embolization from the aorta are unlikely to significantly lower the rate of renal failure following bypass surgery.