The war between colloids and crystalloids wages on. In a large multinational survey of fluid prescribing practices in critically ill patients, we have a new and intriguing snapshot of global fluid resuscitation practices. Colloids are more often used for impaired perfusion or low cardiac output, and the choice of colloid or crystalloid varies enormously between countries. Why are some ICUs prescribing colloids more often than crystalloids when there is little convincing evidence that colloids are superior for fluid resuscitation? Are colloids advantageous in certain diseases, or in specific regional patient populations that have not yet been elucidated? Perhaps we should look inwards: the answer may not be more randomized clinical trials, but better adherence to current guidelines and treatment recommendations.
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Timothy S. Fenske;
Mehdi Hamadani;
Jonathon Cohen;
Luciano J. Costa;
Brad Kahl;
Andrew M. Evens;
Paul A. Hamlin;
Hillard M. Lazarus;
Effie Petersdorf;
Christopher Bredeson
Non-Hodgkin lymphoma (NHL) constitutes a collection of lymphoproliferative disorders with widely varying biological, histological, and clinical features. For the B cell NHLs, great progress has been made due to the addition of monoclonal antibodies and, more recently, other novel agents including B cell receptor signaling inhibitors, immunomodulatory agents, and proteasome inhibitors. Autologous hematopoietic cell transplantation (auto-HCT) offers the promise of cure or prolonged remission in some NHL patients. For some patients, however, auto-HCT may never be a viable option, whereas in others, the disease may progress despite auto-HCT. In those settings, allogeneic HCT (allo-HCT) offers the potential for cure. Over the past 10 to 15 years, considerable progress has been made in the implementation of allo-HCT, such that this approach now is a highly effective therapy for patients up to (and even beyond) age 75 years. Recent advances in conventional lymphoma therapy, peritransplantation supportive care, patient selection, and donor selection (including the use of alternative hematopoietic cell donors), has allowed broader application of allo-HCT to patients with NHL. As a result, an ever-increasing number of NHL patients over age 60 to 65 years stand to benefit from allo-HCT. In this review, we present data in support of the use of allo-HCT for patients with diffuse large B cell lymphoma, follicular lymphoma, and mantle cell lymphoma. These histologies account for a large majority of allo-HCTs performed for patients over age 60 in the United States. Where possible, we highlight available data in older patients. This body of literature strongly supports the concept that allo-HCT should be offered to fit patients well beyond age 65 and, accordingly, that this treatment should be covered by their insurance carriers.
Background: Glioblastoma multiforme (GBM) is an umbrella designation that includes a heterogeneous group of primary brain tumors. Several classification strategies of GBM have been reported, some by clinical course and others by resemblance to cell types either in the adult or during development. From a practical and therapeutic standpoint, classifying GBMs by signal transduction pathway activation and by mutation in pathway member genes may be particularly valuable for the development of targeted therapies. Methodology/Principal Findings: We performed targeted proteomic analysis of 27 surgical glioma samples to identify patterns of coordinate activation among glioma-relevant signal transduction pathways, then compared these results with integrated analysis of genomic and expression data of 243 GBM samples from The Cancer Genome Atlas (TCGA). In the pattern of signaling, three subclasses of GBM emerge which appear to be associated with predominance of EGFR activation, PDGFR activation, or loss of the RAS regulator NF1. The EGFR signaling class has prominent Notch pathway activation measured by elevated expression of Notch ligands, cleaved Notch receptor, and downstream target Hes1. The PDGF class showed high levels of PDGFB ligand and phosphorylation of PDGFRβ and NFKB. NF1-loss was associated with lower overall MAPK and PI3K activation and relative overexpression of the mesenchymal marker YKL40. These three signaling classes appear to correspond with distinct transcriptomal subclasses of primary GBM samples from TCGA for which copy number aberration and mutation of EGFR, PDGFRA, and NF1 are signature events. Conclusions/Significance: Proteomic analysis of GBM samples revealed three patterns of expression and activation of proteins in glioma-relevant signaling pathways. These three classes are comprised of roughly equal numbers showing either EGFR activation associated with amplification and mutation of the receptor, PDGF-pathway activation that is primarily ligand-driven, or loss of NF1 expression. The associated signaling activities correlating with these sentinel alterations provide insight into glioma biology and therapeutic strategies.
Background: Although radiofrequency (RF) has been used to treat several types of chronic osteoarthritic pain, the role of percutaneous thermal RF ablation and pulsed RF in treating nonmalignant hip pain has not been well established.
Objective: To estimate the effectiveness of thermal and pulsed RF therapy in treating nonmalignant hip pain and encourage further research.
Study Design: A systematic review of English and non-English articles was performed on 1/20/2017 using the following databases:
PubMed (1960-2017), Cochrane Controlled Trials Register (1960-2017), and EMBASE (1966-2017). Studies for which complete articles were not accessible were excluded if primary authors could not be successfully contacted after attempts via at least 2 different mediums.
Search terms included RF, hip, and human (“radiofrequency”[All Fields] AND (“hip”[MeSH Terms] AND “humans”[MeSH Terms]).
Results: Two clinical trials for hip RF (n = 32) and a collection of 7 case series or studies (n = 25) met our inclusion criteria. Both trials used percutaneous RF of the periarticular sensory branches of the obturator and femoral nerves near the hip joint. Ten studies were found to be eligible after screening title, abstract, and full text for inclusion and exclusion criteria. Both clinical
trials saw improved post procedure pain scores when compared with standard conservative treatment for inoperable chronic hip pain. The overall complication rate of pooled cohort of all cases reviewed was 9.5% (6/57), but did not result in any self-reported injury.
Conclusions: There is low quality evidence to suggest that thermal or pulsed RF therapy is a suitable option for chronic inoperable hip pain. Higher quality trials are needed for stronger recommendations.
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David T. Selewski;
Jonathan P. Troost;
Danyelle Cummings;
Susan F. Massengill;
Rasheed A. Gbadegesin;
Larry Greenbaum;
Ibrahim F. Shatat;
Yi Cai;
Gaurav Kapur;
Diane Hebert;
Michael J. Somers;
Howard Trachtman;
Priya Pais;
Michael E. Seifert;
Jens Goebel;
Christine B. Sethna;
John D. Mahan;
Heather E. Gross;
Emily Herreshoff;
Yang Liu;
Noelle E. Carlozzi;
Bryce B. Reeve;
Darren A. DeWalt;
Debbie S. Gipson
Background: Nephrotic syndrome represents a condition in pediatric nephrology typified by a relapsing and remitting course, proteinuria and the presence of edema. The PROMIS measures have previously been studied and validated in cross-sectional studies of children with nephrotic syndrome. This study was designed to longitudinally validate the PROMIS measures in pediatric nephrotic syndrome.
Methods: One hundred twenty seven children with nephrotic syndrome between the ages of 8 and 17years participated in this prospective cohort study. Patients completed a baseline assessment while their nephrotic syndrome was active, a follow-up assessment at the time of their first complete proteinuria remission or study month 3 if no remission occurred, and a final assessment at study month 12. Participants completed six PROMIS measures (Mobility, Fatigue, Pain Interference, Depressive Symptoms, Anxiety, and Peer Relationships), the PedsQL version 4.0, and two global assessment of change items.
Results: Disease status was classified at each assessment: nephrotic syndrome active in 100% at baseline, 33% at month 3, and 46% at month 12. The PROMIS domains of Mobility, Fatigue, Pain Interference, Depressive Symptoms, and Anxiety each showed a significant overall improvement over time (p < 0.001). When the PROMIS measures were compared to the patients' global assessment of change, the domains of Mobility, Fatigue, Pain Interference, and Anxiety consistently changed in an expected fashion. With the exception of Pain Interference, change in PROMIS domain scores did not correlate with changes in disease activity. PROMIS domain scores were moderately correlated with analogous PedsQL domain scores.
Conclusion: This study demonstrates that the PROMIS Mobility, Fatigue, Pain Interference, and Anxiety domains are sensitive to self-reported changes in disease and overall health status over time in children with nephrotic syndrome. The lack of significant anchoring to clinically defined nephrotic syndrome disease active and remission status may highlight an opportunity to improve the measurement of HRQOL in children with nephrotic syndrome through the development of a nephrotic syndrome disease-specific HRQOL measure.
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Radek Bukowski;
Nellie I. Hansen;
Halit Pinar;
Marian Willinger;
Uma M. Reddy;
Corette B. Parker;
Robert M. Silver;
Donald J. Dudley;
Barbara Stoll;
George R. Saade;
Matthew A. Koch;
Carol Hogue;
Michael W. Varner;
Deborah L. Conway;
Donald Coustan;
Robert L. Goldenberg
Background: Worldwide, stillbirth is one of the leading causes of death. Altered fetal growth and placental abnormalities are the strongest and most prevalent known risk factors for stillbirth. The aim of this study was to identify patterns of association between placental abnormalities, fetal growth, and stillbirth.
Methods and findings: Population-based case-control study of all stillbirths and a representative sample of live births in 59 hospitals in 5 geographic areas in the U.S. Fetal growth abnormalities were categorized as small ( < 10th percentile) and large ( > 90th percentile) for gestational age at death (stillbirth) or delivery (live birth) using a published algorithm. Placental examination by perinatal pathologists was performed using a standardized protocol. Data were weighted to account for the sampling design. Among 319 singleton stillbirths and 1119 singleton live births at ≥24 weeks at death or delivery respectively, 25 placental findings were investigated. Fifteen findings were significantly associated with stillbirth. Ten of the 15 were also associated with fetal growth abnormalities (single umbilical artery; velamentous insertion; terminal villous immaturity; retroplacental hematoma; parenchymal infarction; intraparenchymal thrombus; avascular villi; placental edema; placental weight; ratio birth weight/placental weight) while 5 of the 15 associated with stillbirth were not associated with fetal growth abnormalities (acute chorioamnionitis of placental membranes; acute chorioamionitis of chorionic plate; chorionic plate vascular degenerative changes; perivillous, intervillous fibrin, fibrinoid deposition; fetal vascular thrombi in the chorionic plate). Five patterns were observed: placental findings associated with (1) stillbirth but not fetal growth abnormalities; (2) fetal growth abnormalities in stillbirths only; (3) fetal growth abnormalities in live births only; (4) fetal growth abnormalities in stillbirths and live births in a similar manner; (5) a different pattern of fetal growth abnormalities in stillbirths and live births.
Conclusions: The patterns of association between placental abnormalities, fetal growth, and stillbirth provide insights into the mechanism of impaired placental function and stillbirth. They also suggest implications for clinical care, especially for placental findings amenable to prenatal diagnosis using ultrasound that may be associated with term stillbirths.
Background: Timing and trajectories of cardiovascular risk factor (CVRF) development in relation to atrial fibrillation (AF) have not been described previously. We assessed trajectories of CVRF and incidence of AF over 25 years in the ARIC study (Atherosclerosis Risk in Communities). Methods: We assessed trajectories of CVRF in 2456 individuals with incident AF and 6414 matched control subjects. Subsequently, we determined the association of CVRF trajectories with the incidence of AF among 10 559 AF-free individuals (mean age, 67 years; 52% men; 20% blacks). Risk factors were measured during 5 examinations between 1987 and 2013. Cardiovascular events, including incident AF, were ascertained continuously. We modeled the prevalence of risk factors and cardiovascular outcomes in the period before and after AF diagnosis and the corresponding index date for control subjects using generalized estimating equations. Trajectories in risk factors were identified with latent mixture modeling. The risk of incident AF by trajectory group was examined with Cox models. Results: The prevalence of stroke, myocardial infarction, and heart failure increased steeply during the time close to AF diagnosis. All CVRFs were elevated in AF cases compared with controls > 15 years before diagnosis. We identified distinct trajectories for all the assessed CVRFs. In general, individuals with trajectories denoting long-term exposure to CVRFs had increased AF risk even after adjustment for single measurements of the CVRFs. Conclusions: AF patients have increased prevalence of CVRF many years before disease diagnosis. This analysis identified diverse trajectories in the prevalence of these risk factors, highlighting their different roles in AF pathogenesis.
BACKGROUND: There is little consensus on the most efficacious vehicle substance for vitamin D supplements. Fat malabsorption may impede the ability of patients with cystic fibrosis (CF) to absorb vitamin D in an oil vehicle. We hypothesized that vitamin D contained in a powder vehicle would be absorbed more efficiently than vitamin D contained in an oil vehicle in patients with CF. METHODS: In this double-blind, randomized controlled trial, hospitalized adults with CF were given a one-time bolus dose of 100,000 IU of cholecalciferol (D3) in a powder-based or oil-based vehicle. Serum D3, 25-hydroxyvitamin D, and parathyroid hormone concentrations were analyzed at 0, 12, 24, and 48 hours posttreatment. The area under the curve for serum D3 and the 12-hour time point were also assessed as indicators of D3 absorption. RESULTS: This trial was completed by 15 patients with CF. The median (interquartile range) age, body mass index, and forced expiratory volume in 1 second were 23.7 (19.9-33.2) years, 19.9 (18.6-22.6) kg/m(2), and 63% (37%-80%), respectively. The increase in serum D3 and the area under the curve was greater in the powder group (P = .002 and P = .036, respectively). Serum D3 was higher at 12 hours in the powder group compared with the oil group (P = .002), although levels were similar between groups by 48 hours. CONCLUSIONS: In adults with CF, cholecalciferol is more efficiently absorbed in a powder compared with an oil vehicle. Physicians should consider prescribing vitamin D in a powder vehicle in patients with CF to improve the absorption of vitamin D from supplements.
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Aaron U. Blackham;
Doug S. Swords;
Edward A. Levine;
Nora F. Fino;
Malcolm H. Squires;
George Poultsides;
Ryan C. Fields;
Mark Bloomston;
Sharon M. Weber;
Timothy M. Pawlik;
Linda X. Jin;
Gaya Spolverato;
Carl Schmidt;
David Worhunsky;
Clifford S. Cho;
Shishir Maithel;
Konstantinos I. Votanopoulos
Background: Current staging and treatment guidelines for gastric adenocarcinoma do not differentiate between linitis plastic (LP) and non-LP cancers. Significant controversy exists regarding the surgical management of LP patients.
Methods: Using the multi-institutional U.S. Gastric Cancer Collaborative database, 869 gastric cancer patients who underwent resection between 2000 and 2012 were identified. Clinicopathologic and outcomes data of 58 LP patients were compared to 811 non-LP patients.
Results: Stage III/IV disease was more common at presentation in LP patients compared with non-LP patients (90 vs. 44 %, p < 0.01). Despite the fact that most LP patients underwent total gastrectomy (88 vs. 39 %, p < 0.01), final positive margins were more common in LP patients (33 vs. 7 %, p < 0.01). The use of frozen section allowed 15 intraoperative positive margins in 38 patients to be converted to negative final margins. Median overall survival (OS) was significantly worse in patients with LP (11.6 vs. 37.8 months, p < 0.01). There was no difference in median OS of LP patients based on stage (I/II, 17.3 mo; III, 10.6 mo; IV, 12.0 mo; p = 0.46). LP and non-LP patients who underwent optimal resection (negative margin and D2/3 lymphadenectomy) had better survival compared with those with nonoptimal resections. The median OS for optimally resected stage III LP (n = 22) and stage III non-LP (n = 185) patients was nearly identical (26.7 vs. 25.3 mo; p = 0.69).
Conclusions: Future staging systems and treatment guidelines should differentiate between LP and non-LP gastric cancers. Long-term survival in select LP patients who undergo optimal resections is comparable to optimally resected non-LP patients.
Urbanization is expected to increase in low and middle-income countries (LMICs), and might contribute to the increased disease burden. The association between urbanization and CKD is incompletely understood among LMICs. Recently, Inoue et al., explored the association of urbanization on renal function from the China Health and Nutrition Survey. The study found that individuals living in an urban environment had a higher odds of reduced renal function independent of behavioral and cardiometabolic measures, and this effect increased in a dose dependent manner. In this commentary, we discuss the results of these findings and explain the need for more surveillance studies among LMICs.