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Angiotensin receptor neprilysin inhibitor (ARNI) decreases renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous systems (SNS) activity promoting vasodilation, decreasing myocardial hypertrophy and fibrosis. Beyond the SNS, RAAS and natriuretic peptide systems, ARNI results in increased circulatory and myocardial nitric oxide levels activating cGMP and protein kinase G, which reduces oxidative stress, myocyte hypertrophy, cell death and has anti-thrombotic effects. ARNIs have a class I indication by heart failure (HF) guidelines in HFrEF patients with NYHA class II to III symptoms. Beyond HFrEF, the use of ARNIs has also been expanded to other clinical settings including HF with preserved ejection fraction (EF, HFpEF), acute HF, advanced HF, hypertension, arrhythmias and chronic kidney disease. This paper reviews the clinical benefits of ARNIs in both HF and the aforementioned cardiovascular conditions. We also discuss the combined use of ARNI with SGLT2i and their potential synergistic benefits on cardiovascular outcomes.

Purpose: Effective use of mechanical plaque control devices can depend on individual manual dexterity levels. The purpose of this component of a 12-week, virtually-supervised clinical trial was to investigate the role of manual dexterity on clinical outcomes for gingivitis, as measured by the relationship between manual dexterity scores on the Purdue Pegboard Test (PPT) and the effects of various mechanical and chemotherapeutic oral hygiene regimens. Methods: This was a single-center, examiner blinded, randomized, four-treatment arm, parallel group, 12-week plaque and gingivitis study. At baseline, healthy adult volunteers with evidence of gingivitis were assessed for manual dexterity and were then examined for plaque, gingivitis and bleeding. After a dental prophylaxis, participants were randomized into four treatment groups: brush only (BO); brush/rinse (BR); brush/floss (BF); and brush/floss/rinse (BFR). The flossing groups received instruction in flossing. The PPT was used to assess manual dexterity and was performed by a licensed occupational therapist. Virtual supervision was required once each weekday and the oral hygiene regimen was unsupervised on evenings and weekends. Results: Of the 213 subjects enrolled, 209 completed the trial. Improvements from baseline to week 12 in interproximal percent nonbleeding healthy sites (Expanded Bleeding Index (EBI)=0 and Modified Gingival Index (MGI)=0 or 1) were dependent on the participant's dexterity score. Participants with the lowest dexterity scores (9 or lower) in the BFR treatment group demonstrated the greatest improvement interproximally based on the indices (EBI and MGI). In comparison, the BF test group subjects with dexterity scores 9 or lower had limited change in improvement interproximally. There was a direct correlation between flossing effectiveness and dexterity scores. Conclusions: Less manual dexterity can limit dental flossing effectiveness. Flossing is a difficult daily task that requires functional bilateral dexterity to be perform correctly. Individuals with lower levels of manual dexterity were shown to benefit from the addition of an essential oil mouthrinse to a regimen of toothbrushing and flossing in this clinical trial. The addition of an essential oil mouthrinse improved interproximal gingival health and mitigated the manual dexterity variable., (Copyright © 2022 The American Dental Hygienists’ Association.)

Purpose: The purpose of this survey was to investigate how flossing and rinsing behaviors impact individual beliefs about oral disease risk, the efficacy of floss and mouthrinse, and the perceived benefits and barriers of floss and mouthrinse. Methods: Participants in this required component of a 12-week plaque and gingivitis randomized clinical trial on flossing and rinsing regimens completed a paper questionnaire prior to randomization and baseline/screening measurements. Results: All of the clinical trial participants (n=213) completed the questionnaire. Respondents were grouped as habitual or non-habitual users of floss or mouthrinse if the product was used at least once daily; 16% (n=34) were habitual users of floss and 17% (n=36) were habitual users of mouthrinse. Perceived barriers included fear of gingival bleeding and pain, forgetting, and not including flossing or rinsing as part of the daily oral care routine. Non-habitual users were less likely to believe in the intangible benefits of flossing or rinsing and much more likely to perceive barriers to using floss or mouthrinse. Risk perception of developing oral disease was not shown to predict product usage. Respondents viewed their risk of developing gingivitis as relatively low despite this diagnosis being confirmed clinically among the participants. Conclusions: While respondents strongly believed that brushing, flossing, and mouthrinse use carry unique benefits and that combining all three methods would be optimal, these respondents still had high perceived barriers to using floss and mouthrinse regularly and consequently these habits were not included in their daily oral hygiene regimen. Understanding the perceptions regarding oral health behaviors may help drive more effective interventions and assist practitioners in improving their patients' oral health outcomes., (Copyright © 2022 The American Dental Hygienists’ Association.)

Purpose: Flossing is a well-known component of daily recommended oral care regimens, but patients often find it challenging to perform effectively on a regular basis. The purpose of this 12-week supervised clinical trial was to investigate the effects of twice daily rinsing with a mouthrinse containing a fixed combination of four essential oils (4EO) and supervised daily dental flossing regimens as compared to a negative control 5% hydroalcohol rinse (NC) on the prevention and reduction of plaque, gingivitis, and gingival bleeding. Methods: Volunteer participants who met the inclusion criteria were randomized into the following groups for the 12- week trial: 1) NC; 2) mouthrinse containing 4EO; 3) professional flossing performed by a dental hygienist (FBH); 4) supervised self-flossing (FUS). All participants received a professional dental prophylaxis prior to beginning the trial. On weekday mornings, all participants brushed on site. After brushing, the rinse groups used their products under supervision, and the floss groups had their teeth flossed by a dental hygienist or self-flossed under supervision. Participants performed their assigned regimen in the evenings and the twice-daily weekend use at home. Each individual assessment of oral hard and soft tissue, plaque, gingivitis, and gingival bleeding at weeks 4 and 12, probing depth and bleeding on probing at week 12 was made by the same calibrated examiner. Results: Of 156 randomized participants, 149 completed the trial. Use of the 4EO mouthrinse statistically significantly reduced plaque, gingivitis, and gingival bleeding on probing after 12 weeks as compared to the NC rinse. Both flossing interventions statistically significantly reduced interproximal gingivitis and gingival bleeding at 12 weeks compared to the NC rinse; neither flossing intervention significantly reduced interproximal plaque after 12 weeks compared to the NC rinse. Conclusions: Rinsing with a 4EO mouthrinse statistically significantly improved all oral health outcome measures at all time points compared to a NC rinse in this 12-week clinical trial. While professional and supervised flossing improved gingival health compared to use of the NC rinse, statistically significant plaque reduction with dental flossing was not attained at the end of the 12-week trial., (Copyright © 2022 The American Dental Hygienists’ Association.)

Purpose: Various mechanical and chemotherapeutic methods are used to control dental plaque accumulation and prevent or reduce gingivitis. The purpose of this 12-week clinical trial was to investigate the effects of various combinations of supervised mechanical and chemotherapeutic regimens on the prevention and reduction of plaque, gingivitis, and gingival bleeding. Methods: Volunteers presenting with some evidence of gingivitis and no severe periodontitis were randomized into four groups: brush only (BO); brush/rinse (BR); brush/floss (BF); brush/floss/rinse (BFR) for this examiner-blinded clinical trial. Toothbrush, toothpaste, floss and a mouthrinse containing a fixed combination of four essential oils (EO) and training/instructions were provided to participants as per their assigned group. Participants performed their regimen at home, under virtual supervision, once each weekday; the second daily and weekend uses were unsupervised. Assessments included oral hard and soft tissue, plaque, gingivitis, and gingival bleeding (weeks 4, 12); probing depth and bleeding on probing (week 12). Results: Of 213 enrolled participants, 209 completed the study. After 12 weeks, plaque, gingivitis, and gingival bleeding were significantly reduced in groups BR (35.8%, 50.8%, and 71.0% respectively, p <0.001) and BFR (32.8%, 54.1%, and 78.2% respectively, p <0.001) compared to BO. After 12 weeks, gingivitis and gingival bleeding were significantly reduced in the BF group (9.2%, p =0.013 and 17.5%, p =0.003, respectively), however there were no significant reductions in plaque in the BF group as compared to the BO group ( p =0.935). Conclusions: Oral care regimens that included a mouthrinse containing a fixed combination of four EOs (BR and BFR), demonstrated statistically significantly reduced plaque, gingivitis, and gingival bleeding as compared to BO and BF after 12 weeks. The BF regimen statistically significantly reduced gingivitis and gingival bleeding but did not statistically significantly reduce plaque compared to BO after 12 weeks., (Copyright © 2022 The American Dental Hygienists’ Association.)

Objective: Bacteremia is a leading cause of morbidity and mortality in children undergoing hematopoietic cell transplantation (HCT). Infections of vancomycin-resistant enterococci (VRE) and multidrug resistant (MDR) gram-negative rods (GNRs) are common in this population. Our objective was to assess whether experimental bath wipes containing silver were more effective than standard bath wipes containing soap at reducing skin colonization by VRE and MDR GNRs, and nonmucosal barrier injury bacteremia. Study Design: Patients undergoing autologous or allogeneic HCT in a tertiary referral center were randomized to receive experimental or standard bath wipes for 60 days post-HCT. Skin swabs were collected at baseline, discharge, and day +60 post-HCT. The rate of VRE colonization was chosen as the marker for efficacy. Results: Experimental bath wipes were well tolerated. Before the study, the rate of colonization with VRE in HCT recipients was 25%. In an interim analysis of 127 children, one (2%) patient in the experimental arm and two (3%) in the standard arm were colonized with VRE. Two (3%) patients had nonmucosal barrier injury bacteremia in the standard arm, with none in the experimental arm. MDR GNRs were not isolated. The trial was halted because the interim analyses indicated equivalent efficacy of the two methods. Conclusions: Skin cleansing with silver-containing or standard bath wipes resulted in very low and equivalent rates of bacteremia and colonization with VRE and MDR GNRs in children post-HCT. Future studies in other high-risk populations are needed to confirm these results.

T-cell depletion of an HLA-haploidentical (haplo) graft is often used to reduce the risk of graft-versus-host disease (GVHD), but the lack of donor T cells in the infused product may lead to graft failure, slow T-cell reconstitution, infections, and relapse. More selective T-cell depletion targeting CD45RA can effectively deplete naive T cells but preserve large numbers of memory T cells leading to robust engraftment of diverse T-cell populations and reduction of viremia in the early posttransplant period. Herein, we report the outcome of 143 pediatric and young adult hematologic malignancy patients receiving a first allogeneic hematopoietic cell transplantation (HCT) on six consecutive ex vivo T-cell depleted haploHCT protocols over the past 15 years at a single institution-including the first 50 patients on an active CD45RA-depleted haploHCT study in which patients also received NK-cells and pharmacological GvHD prophylaxis post transplant. Our data demonstrated an increase in the 3-year overall survival and event-free survival in nonchemorefractory recipients receiving CD45RA-depleted grafts (78.9% and 77.7%, respectively) compared with historic T-cell depleted haploHCT cohorts (46.7% and 42.7%, respectively, p = 0.004, and 0.003). This improvement was primarily due to a reduction in transplant related mortality without significant increase in the rates of GVHD.

Purpose: To determine the ocular complications in school-age children and adolescents surviving at least 1 year following allogeneic bone marrow transplantation., Design: Retrospective cohort study., Methods: In this institutional study, 162 patients (7-18 years old) met our inclusion criteria with a mean age of 13.4 years at bone marrow transplantation. Follow-up ranged from 13 months to 12 years (mean 4 years; median 3.2 years). Patient charts were screened for cataract formation, dry eye, and other anterior and posterior segment diseases., Results: Cataract formation was noted in 57 patients. Univariate analysis showed that fractionated total body irradiation, race, and use of cytarabine significantly increased the incidence of cataract formation (P < 0.05). Multivariate analysis of significant variables showed that total body irradiation was a risk factor for cataract formation. Of the 57 patients (97 eyes) who developed cataracts after bone marrow transplantation, 4 patients (6 eyes) required cataract surgery. After surgery, all patients had visual acuities of 20/20 to 20/25. Of the 162 patients, 51 developed dry eyes. Univariate analysis showed that age at transplantation; steroid use, chronic graft-versus-host disease; use of fludarabine, melphalan, and thiotepa; and receiving no pre-transplantation conditioning regimen prior to bone marrow transplant significantly increased the risk of dry eye syndrome (P < 0.05). In multivariate analysis, chronic graft-versus-host disease was a significant risk factor for dry eye syndrome., Conclusions: Due to the high incidence of cataract formation and dry eye disease in this population, this study proposes these patients be screened using examinations by a pediatric or general ophthalmologist at least every year., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: For the advances of pediatric oncology next generation sequencing (NGS) research to equitably benefit all children, a diverse and representative sample of participants is needed. However, little is known about demographic and clinical characteristics that differentiate families who decline enrollment in pediatric oncology NGS research., Methods: Demographic and clinical data were retrospectively extracted for 363 pediatric oncology patients (0-21 years) approached for enrollment on Genomes for Kids (G4K), a study examining the feasibility of comprehensive clinical genomic analysis of tumors and paired normal samples. Demographic and clinical factors that significantly differentiated which families declined were subsequently compared to enrollment in Clinical Implementation of Pharmacogenetics (PG4KDS) for 348 families, a pharmacogenomics study with more explicit therapeutic benefit examining genes affecting drug responses and metabolism., Results: Fifty-three (14.6%) families declined enrollment in G4K. Race/ethnicity was the only variable that significantly differentiated study refusal using multivariate logistic regression, with families of black children more likely to decline enrollment compared to families of non-Hispanic or Hispanic white children. Reasons for declining G4K were generally consistent with other pediatric genomics research, with feeling overwhelmed and insurance discrimination fears most frequently cited. Families of black children were also more likely to decline enrollment in PG4KDS. Thirteen (3.7%) of the 348 families approached for both studies declined PG4KDS., Conclusion: Race/ethnicity differentiated study declination across two different pediatric oncology genomics studies, suggesting enrollment disparities in the context of pediatric oncology genomics research. Genomics research participant samples that do not fully represent racial and ethnic minorities risk further exacerbating health disparities. Additional work is needed to understand the nuances of parental decision making in genomic research and facilitate enrollment of diverse patient populations.

Cardiogenic shock (CS) is a complex condition characterized by end-organ hypoperfusion and requiring pharmacologic and/or mechanical circulatory support. It is caused by a decline in cardiac output due to a primary cardiac disorder. CS is frequently complicated by multiorgan system dysfunction that requires a multidisciplinary approach in a critical care setting. Appropriate use of diagnostic data using tools available in a modern cardiac intensive care unit should guide optimal management incorporating both pharmacologic and nonpharmacologic therapies to minimize morbidity and mortality., Competing Interests: Conflict of Interest Disclosure: The authors have completed and submitted the Methodist DeBakey Cardiovascular Journal Conflict of Interest Statement and none were reported., (© 2020 Houston Methodist Hospital Houston, Texas.)

Vitamins and minerals are dietary supplements used by almost half of the US adult population based on the presumption that they help prevent or treat cardiovascular disease. Many studies, including randomized trials, have investigated the possible role of these substances in cardiovascular disease. We reviewed the available data on multivitamins/multiminerals, antioxidants, folic acid, vitamin E, niacin (B3), and beta-carotene. Despite extensive investigation, the evidence to date fails to support the use of exogenous supplements of vitamins and minerals for the prevention or treatment of cardiovascular disease. Here, we review some of the common supplements used by adults for cardiovascular health and the available evidence for risks/benefits., Competing Interests: Conflict of Interest Disclosure: The authors have completed and submitted the Methodist DeBakey Cardiovascular Journal Conflict of Interest Statement and none were reported., (© 2019 Houston Methodist Hospital Houston, Texas.)

Recurrent/refractory hematologic malignancies have a poor prognosis, and there is a need for novel treatment regimens that can be tolerated by this heavily pretreated patient group. Clofarabine has antileukemic activity with an acceptable toxicity profile. In a phase I clinical trial (NCT00824135), we substituted clofarabine for fludarabine in a well-established reduced-intensity conditioning regimen for a T cell-depleted, mismatched-related (haploidentical) donor transplant backbone and explored the maximum tolerated dose of clofarabine in this combination in 15 patients undergoing hematopoietic cell transplantation for recurrent/refractory or secondary leukemia. Clofarabine was well tolerated at a dose of 50 mg/m/d for 5 days in this regimen, with minimal treatment-related mortality in a heavily pretreated group of high-risk patients. All patients exhibited quick hematopoietic recovery, with median times to neutrophil and platelet engraftment being 11 and 16 days, respectively. Transient elevation of transaminases was the most common toxicity-observed in 13 patients (86.7%), with 6 (40%) grade III or above. Three patients (20%) developed hepatic veno-occlusive disease. Eleven patients (73.3%) died, with the most common cause of death being disease relapse (in 9 patients [60%]), followed by treatment-related mortality (in 2 patients [13.3%]). Four (26.6%) of the patients are long-term survivors.

Purpose: To investigate ocular complications associated with bone marrow transplant and associated continued maintenance therapy in a preschool population., Methods: The medical records of patients <7 years of age were reviewed retrospectively. Patient charts were screened for cataract formation, dry eye, and other anterior and posterior segment disease., Results: Of 270 cases reviewed, 91 met inclusion criteria. Mean age at diagnosis was 3.17 years. Average follow-up was 5.8 years (range, 1.9 months-14.1 years). Of the 91, 37 patients developed cataracts (35 bilaterally) over a 14-year period. Cumulative incidence corrected for competing event (death before cataract) for the study population was found to be 58.4% after 14 years. Univariate analysis for cataract formation showed statistical significance for total body irradiation dose, age at diagnosis, race, donor type (related vs unrelated), product type, diagnosis type, survival status, calcineurin inhibitor use, and bisulfan, cytarabine, and thiotepa use. Multivariate analysis for competing event (death), showed that total body irradiation dose was not statistically significant; however, when studied in a binary logistic regression model, total body irradiation dose was statistically significant. Notably, steroid use and presence of graft-versus-host disease did not show statistical significance for cataract development. No other ocular complication was found in sufficient quantities to allow statistical analyses., Conclusions: Due to the high incidence of cataract formation in this population, especially those enduring a treatment regimen with total body irradiation, we propose screening examinations by a pediatric or general ophthalmologist at least annually. We also urge a low threshold for treatment of dry eye syndrome., (Copyright © 2018 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Acute kidney injury (AKI) is a common adverse event after hematopoietic cell transplantation (HCT). AKI is associated with early death or chronic kidney disease among transplant survivors. However, large-scale pediatric studies based on standardized criteria are lacking. We performed a retrospective analysis of 1057 pediatric patients who received allogeneic HCT to evaluate the incidence and risk factors of AKI according to AKI Network criteria within the first 100 days of HCT. We also determined the effect of AKI on patient survival. The 100-day cumulative incidences of all stages of AKI, stage 3 AKI, and AKI requiring renal replacement therapy (RRT) were 68.2% ± 1.4%, 25.0% ± 1.3%, and 7.6% ± .8%, respectively. Overall survival at 1 year was not different between patients without AKI and those with stage 1 or 2 AKI (66.1% versus 73.4% versus 63.9%, respectively) but was significantly different between patients without AKI and patients with stage 3 AKI with or without RRT requirement (66.1% versus 47.3% versus 7.5%, respectively; P < .001). Age, year of transplantation, donor type, sinusoidal obstruction syndrome (SOS), and acute graft-versus-host disease (GVHD) were independent risk factors for stages 1 through 3 AKI. Age, donor, conditioning regimen, number of HCTs, SOS, and acute GVHD were independent risk factors for AKI requiring RRT. Our study revealed that AKI was a prevalent adverse event, and severe stage 3 AKI, which was associated with reduced survival, was common after pediatric allogeneic HCT. All patients receiving allogeneic HCT, especially those with multiple risk factors, require careful renal monitoring according to standardized criteria to minimize nephrotoxic insults., (Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Abnormal pulmonary function is prevalent in survivors of allogeneic hematopoietic cell transplantation (HCT). Post-transplantation recovery of pulmonary function, and its effect on survival, in children are not known. This retrospective cohort study of 308 children followed for 10 years after HCT at a single institution included 2 groups of patients. Group 1 comprised 188 patients with 3 or more pulmonary function test (PFT) results, of which at least 1 was abnormal, and group 2 comprised 120 patients with 3 or more PFTs, all of which were normal. Pulmonary function normalized post-transplantation in 51 patients (27%) in group 1. Obstructive lung disease, restrictive lung disease, mixed lung disease, and normal pattern were seen in 43%, 25%, 5%, and 27% of patients, respectively, at a median of 5 years (range, 0.5 to 11.9 years) post-transplantation. Lung volumes recovered better than spirometric indices. Pulmonary complications were seen in 80 patients (43%) in group 1. Patients who recovered pulmonary function had better overall survival (P = .006), which did not differ significantly from that in patients in group 2 with normal lung function post-transplantation (P = .80). After adjusting for duration of follow-up, pulmonary complications (P = .01), and lower pretransplantation forced vital capacity z-scores (P = .01) were associated with poor recovery. T cell depletion (P < .001), lower pretransplantation forced expired volume in 1 second z-scores (P = .006), and chronic graft-versus-host disease (P < .001) increased the risk for pulmonary complications. Nonrecovery of lung function with pulmonary complications (P = .03), acute graft-versus-host disease (P = .004), and mechanical ventilation (P < .001) were risk factors for nonrelapse mortality. Normalization of pulmonary function is possible in long-term survivors of allogeneic HCT. Strategies to decrease the risk of pulmonary complications may improve outcomes., (Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Coronary artery fistulae are rare abnormalities of the coronary arteries that are usually discovered incidentally on coronary angiogram. Most patients remain asymptomatic, and significant hemodynamic consequences are rarely observed. The following report describes the case of a patient presenting with symptoms of congestive cardiac failure due to multiple coronary artery fistulae., Competing Interests: The authors have completed and submitted the Methodist DeBakey Cardiovascular Journal Conflict of Interest Statement and none were reported.

The diagnostic utility of obtaining chest and abdomen computed tomography (CT) to evaluate for invasive fungal infection (IFI) before and after hematopoietic stem cell transplant (HSCT) remains unclear. The study was conducted as a quality improvement project. Chest and abdomen CT of patients who underwent an allogeneic HSCT over a 13-month period were reviewed. Scans included those performed pretransplant in all patients and days 0 to 100 post-transplant in selected patients. Sixty-six patients had chest and abdomen CT scans pretransplant. Chest CT was suggestive of IFI in 9 patients (13.6%), including 3 patients with prior history of IFI. After transplant, 37 patients had an initial chest CT and 14 patients an initial abdominal CT. The first chest CT post-transplant was suggestive of IFI in 3 patients; all had an abnormal CT pretransplant. After the initial post-transplant evaluation, 15 patients had 28 additional CT scans of the chest and 12 patients 19 additional CT scans of the abdomen. An abnormal chest CT with proven evidence of IFI was seen in only 1 patient. None of the 99 abdominal CT scans performed pre- or post-transplant had evidence of IFI. There is little benefit in obtaining abdominal CT scans in HSCT patients for detecting IFI either pre- or post-transplant., (Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Adenoviremia adversely affects prognosis in the post-hematopoietic stem cell transplant setting., Methods: We sought to determine retrospectively the cutoff load of adenovirus in the stool as a predictor of adenoviremia, in children who underwent an allogeneic hematopoietic stem cell transplant. The prevalence of sapovirus, norovirus and astrovirus in the stool was also studied., Results: The study cohort consisted of 117 patients, of which 71 (60%) had diarrhea. Adenovirus was detected in the stool in 39 of 71 (55%) patients. Age ≤10 years (P = 0.05; odds ratio: 2.57; 95% confidence interval: 0.98-6.75) and male sex (P = 0.04; odds ratio: 2.67; 95% confidence interval: 1.02-6.99) increased risk for detection of adenovirus in stool on univariate analysis. Coinfections with enteric pathogens were infrequent. Viral load >10 copies/g stool predicted adenoviremia with a sensitivity and specificity of 82%. Sapovirus, norovirus and astrovirus were detected in 3, 4 and 1 patient, respectively., Conclusions: Quantitative detection of adenovirus in stool may have implications for preemptive therapy. Testing for other enteric viruses may have implications for infection control.

After hematopoietic stem cell transplantation (HSCT), successful engraftment and immune recovery is necessary to protect the patient from relapse and infection. Many studies highlight the importance of conventional αβ T cell recovery after HSCT, but the impact of γδ T cell recovery has not been well described. Here, we investigate the recovery of γδ T cells in 102 pediatric patients with acute leukemia in first clinical remission who underwent allogeneic HSCT at St. Jude Children's Research Hospital from 1996 to 2011. Mean patient age was 10.5 ± 5.9 years (range, .6 to 25.2), and mean survivor follow-up was 2.7 ± 1.8 years (range, .12 to 6.0). Diagnoses included 59% patients with acute lymphoblastic leukemia and 41% patients with acute myelogenous leukemia. Multivariate analysis demonstrated significant impact of the maximum number of CD3(+), CD4(+), and CD8(+) T cells and donor source on the γδ T cell recovery (P < .0001, P < .0001, P < .0001, and P < .004, respectively). Univariate and multivariate models found the number of γδ T cells after HSCT to be associated with infections (P = .026 and P = .02, respectively). We found the probability of infections for patients with an elevated number of γδ T cells was significantly lower compared with patients with low or normal γδ T cells after HSCT (18% versus 54%; P = .025). Bacterial infections were not observed in patients with elevated γδ T cells. Finally, event-free survival was significantly higher in patients with enhanced γδ T cell reconstitution compared with patients with low/normal γδ T cell reconstitution after HSCT (91% versus 55%; P = .04). Thus, γδ T cells may play an important role in immune reconstitution after HSCT., (Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Rationale: Pulmonary complications are a significant cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation., Objectives: The relationship between pretransplant pulmonary function tests (PFTs) and development of post-transplant pulmonary complications in children was studied., Methods: This is a retrospective single institution cohort study of 410 patients who underwent pretransplant PFT and were monitored to 10 years posttransplant., Measurements and Main Results: Pulmonary complications were observed in 174 (42%) patients. Children with pulmonary complications had significantly lower forced expiratory flow at 25-75% of vital capacity (P = 0.02) derived using conventional predicted equations for age, and the Global Lung Initiative-2012 predicted equations (P = 0.01). T-cell depletion (P = 0.001), acute grade 3-4 graft-versus-host disease (P = 0.008), and chronic graft-versus-host disease (P = 0.01) increased risk for pulmonary complications. Patients who had pulmonary complications had a 2.8-fold increased risk of mortality (P < 0.0001). The cumulative incidence of death due to pulmonary complications was significantly higher in children who had low lung volumes, FRC less than 50% (P = 0.005), TLC less than 50% (P = 0.0002), residual volume less than 50% (P = 0.007), and T-cell depletion (P = 0.01). Lower FEV1 (P = 0.0005), FVC (P = 0.0005), TLC (P  <  0.0001), residual volume less than 50% (P = 0.01), and restrictive lung disease (P = 0.01) predicted worse overall survival., Conclusions: Abnormal pretransplant PFT significantly increased risk after transplant. These patients may benefit from modified transplant strategies to reduce morbidity and mortality.

The safety, pharmacokinetics, and biological effect of plerixafor in children as part of a conditioning regimen for chemo-sensitization in allogeneic hematopoietic stem cell transplantation (HSCT) have not been studied. This is a phase I study of plerixafor designed to evaluate its tolerability at dose of .24 mg/kg given intravenously on day -4 (level 1); day -4 and day -3 (level 2); or day -4, day -3, and day -2 (level 3) in combination with fludarabine, thiotepa, melphalan, and rabbit antithymocytic globulin for a second allogeneic HSCT in children with refractory or relapsed leukemia. Immunophenotype analysis was performed on blood and bone marrow before and after plerixafor administration. Twelve patients were enrolled. Plerixafor at all 3 levels was well tolerated without dose-limiting toxicity. Transient gastrointestinal side effects of National Cancer Institute-grade 1 or 2 in severity were the most common adverse events. The area under the concentration-time curve increased proportionally to the dose level. Plerixafor clearance was higher in males and increased linearly with body weight and glomerular filtration rate. The clearance decreased and the elimination half-life increased significantly from dose level 1 to 3 (P < .001). Biologically, the proportion of CXCR4(+) blasts and lymphocytes both in the bone marrow and peripheral blood increased after plerixafor administration., (Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: : The data on human rhinovirus, coronavirus, bocavirus, metapneumovirus, Chlamydophila pneumoniae, Mycoplasma pneumoniae and Bordetella pertussis infections in children with cancer is limited., Methods: : We sought to determine prospectively the prevalence of respiratory pathogens in these children, using multiplexed-polymerase chain reaction., Results: : We enrolled 253 children with upper or lower respiratory tract infection (LRTI) during a 1-year period. A respiratory virus was detected in 193 (76%) patients; 156 (81%) patients had upper respiratory tract infection. Human rhinovirus was the most common virus detected in 97 (62%) and 24 (65%) patients with upper respiratory tract infection and LRTI, respectively. Leukemia or lymphoma was the most common underlying diagnosis in 95 (49%) patients followed by solid tumor 47 (24%), posthematopoietic stem cell transplant 28 (15%) and brain tumor in 23 (12%) patients. By multiple logistic regression analysis, human bocavirus was the most commonly detected respiratory virus in patients with LRTI (P = 0.008; odds ratio, 4.52; 95% confidence interval: 1.48-13.79). Coinfection with >1 virus was present in 47 (24%) patients, and did not increase the risk for LRTI. Two (0.7%) patients succumbed to LRTI from parainfluenza virus-3 and respiratory syncytial virus/human rhinovirus infection, respectively. C. pneumoniae and M. pneumoniae were detected in 4 and 3 patients, respectively., Conclusions: : Human rhinovirus was the most common virus detected in children with cancer and posthematopoietic stem cell transplant hospitalized with an acute respiratory illness, and was not associated with increased morbidity. Prospective studies with viral load determination and asymptomatic controls are needed to study the association of these emerging respiratory viruses with LRTI in children with cancer and posthematopoietic stem cell transplant.

Detection of respiratory viruses by molecular methods, in children without respiratory symptoms undergoing hematopoietic cell transplantation (HCT), has not been well described. A prospective study of 33 asymptomatic children detected respiratory viruses in 8 of 33 (24%) patients before HCT. Human rhinovirus (HRV) was detected in five patients, and human adenovirus (hADV) in three patients. Two additional patients shed HRV, and one shed human coronavirus (hCoV), post-HCT. Two patients had co-infections. Of the 11 asymptomatic patients where respiratory virus was detected, 3 (27%) later developed an upper respiratory tract infection, from the same virus., (Copyright © 2012 Wiley Periodicals, Inc.)