No child left behind: Enrolling children and adults simultaneously in critical care randomized trials.

Objective: : Randomized clinical trials of novel critical care interventions are currently tested in children only after documenting their safety in adults. Although this practice may protect children from research risks, it may paradoxically threaten children's well-being by depriving them of evidence to guide their care. We sought to evaluate the ethical, methodologic, and practical arguments for and against studying critical care interventions in adults and children simultaneously rather than sequentially.

Corticosteroids for the prevention and treatment of post-extubation stridor in neonates, children and adults.

Background: Post-extubation stridor may prolong length of stay in the intensive care unit, particularly if airway obstruction is severe and re-intubation proves necessary. Some clinicians use corticosteroids to prevent or treat post-extubation stridor, but corticosteroids may be associated with adverse effects ranging from hypertension to hyperglycaemia, so a systematic assessment of the efficacy of this therapy is indicated.

Objectives: To determine whether corticosteroids are effective in preventing or treating post-extubation stridor in critically ill infants, children, or adults.

Management of acute lung injury and acute respiratory distress syndrome in children.

Background: Acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome (ARDS), are devastating disorders of overwhelming pulmonary inflammation and hypoxemia, resulting in high morbidity and mortality.

Aim: To provide the clinician with a summary of the literature on the epidemiology, diagnosis, and an evidence-base for management of ALI/ARDS in children.

Data Selection: PubMed search for clinical trials, selected literature review of other relevant studies on epidemiology and diagnosis.

The unique challenges of enrolling patients into multiple clinical trials.

Multiple interventions are implemented to save the lives of a critically ill patients. The therapeutic value of most of these interventions remains untested. Enrollment of patients in the intensive care unit into multiple studies could improve the efficiency of testing interventions in the intensive care unit.

Spontaneous regression of hepatocellular carcinoma is possible and might have implications for future therapies.

Hepatocellular carcinoma is a potentially challenging cancer with very high mortality. Medical therapies are generally ineffective in achieving complete remission, especially for aggressive types or for advanced stage cancers. Spontaneous regression of these tumors is a rare and fascinating phenomenon.

SPINK1 and PRSS1 mutations in benign pancreatic hyperenzymemia.

Unlabelled: The aim of this study was to determine whether mutations in SPINK1/PRSS1 genes are associated with benign pancreatic hyperenzymemia (BPH).

Methods: Sixty-eight subjects with BPH (including 13 familial cases) were studied. In all, we sequenced germline DNA for all the exons and intro-exon boundaries of PRSS1 and SPINK1.

Prevalence of Barrett's esophagus in patients with moderate to severe erosive esophagitis.

Aim: To investigate the proportion of patients with moderate-severe erosive esophagitis (EE) who will have Barrett's esophagus (BE) after healing of inflammation.

Methods: Patients with EE of Los Angeles (LA) class B, C and D who underwent follow-up endoscopy documenting complete mucosal healing.

Results: A total of 86/169 patients were suspected of having BE (38 before healing and 48 after healing of EE) and, 46/86 eventually had the histological confirmation.

Addressing the unit of analysis in medical care studies: a systematic review.

Objective: We assessed the frequency that patients are incorrectly used as the unit of analysis among studies of physicians' patient care behavior in articles published in high impact journals.

Methods: We surveyed 30 high-impact journals across 6 medical fields for articles susceptible to unit of analysis errors published from 1994 to 2005. Three reviewers independently abstracted articles using previously published criteria to determine the presence of analytic errors.

Corticosteroids for the prevention and treatment of post-extubation stridor in neonates, children and adults.

Background: Post-extubation stridor may prolong length of stay in the intensive care unit, particularly if airway obstruction is severe and re-intubation proves necessary. Corticosteroids, however, may be associated with adverse effects ranging from hypertension to hyperglycemia, and a more systematic assessment of the efficacy of this therapy is indicated prior to widespread adoption of this practice.

Objectives: To determine whether corticosteroids are effective in preventing or treating post-extubation stridor in critically ill infants, children, or adults.

Anemia, blood loss, and blood transfusions in North American children in the intensive care unit.

Rationale: Minimizing exposure of children to blood products is desirable.

Objectives: We aimed to understand anemia development, blood loss, and red blood cell (RBC) transfusions in the pediatric intensive care unit (PICU).

Methods: Prospective, multicenter, 6-month observational study in 30 PICUs.

Gender differences in research grant applications and funding outcomes for medical school faculty.

Purpose: To evaluate whether there were differences in acquisition of research grant support between male and female faculty at eight Harvard Medical School-affiliated institutions.

Methods: Data were obtained from the participating institutions on all research grant applications submitted by full-time faculty from 2001 through 2003. Data were analyzed by gender and faculty rank of applicant, source of support (federal or nonfederal), funding outcome, amount of funding requested, and amount of funding awarded.

Real-time evaluation of patient monitoring algorithms for critical care at the bedside.

Rapid interpretation of physiological time-series data and accurate assessment of patient state are crucial to patient monitoring in critical care. Algorithms that use artificial intelligence techniques have the potential to help achieve these tasks, but their development requires well-annotated patient data. In this study, we designed a data acquisition system for synchronized collection of physiological time-series data and clinical event annotations at the bedside to support the evaluation of alarm algorithms in real time, and implemented this system in a pediatric intensive care unit (ICU).

Reduced likelihood of metastases in patients with microsatellite-unstable colorectal cancer.

Purpose: The outcome of patients with colorectal cancer is more favorable when the tumor exhibits high-frequency microsatellite instability (MSI). Although associated with earlier-stage tumors, MSI has been proposed as an independent predictor of survival. We tested the prognostic value of MSI in a large series of patients diagnosed with colorectal cancer in the last decade.

Surfactant therapy for acute respiratory failure in children: a systematic review and meta-analysis.

Introduction: Exogenous surfactant is used to treat acute respiratory failure in children, although the benefits and harms in this setting are not clear. The objective of the present systematic review is to assess the effect of exogenous pulmonary surfactant on all-cause mortality in children mechanically ventilated for acute respiratory failure.

Methods: We searched the MEDLINE, EMBASE, CINAHL and Ovid Healthstar databases, the bibliographies of included trials and review articles, conference proceedings and trial registries.

The financial impact of underestimating personnel needs associated with implementing a computerized patient record in the intensive care unit.

Purpose: We tracked the cost of implementing a computerized patient record across 3 intensive care units at a large pediatric hospital.

Materials And Methods: This is a descriptive case study. We compared our initial budget estimates at the time of purchase with the actual expenditures during phase 1 implementation.

Ribavirin for respiratory syncytial virus infection of the lower respiratory tract in infants and young children.

Background: Respiratory syncytial virus (RSV) is a common cause of lower respiratory tract infection in infants and is responsible for many hospitalizations annually. Ribavirin is approved for treatment of these infections, but its use is controversial because of questions about its efficacy, concerns about occupational exposure, and its high cost.

Objectives: The objective of this review is to assess the efficacy of aerosolized ribavirin for infants and children with lower respiratory tract infection due to RSV.

Potential for donation after cardiac death in a children's hospital.

Objectives: A task force was convened to decide whether a donation after cardiac death policy should be implemented at Children's Hospital Boston. As part of this process, we sought to determine the number of potential kidney donation after cardiac death donors in our PICUs.

Methods: We examined all 254 deaths in the Medical/Surgical ICU and the Cardiac ICU from 2002 to 2004 and identified potential donation after cardiac death donors.

N-glycosylation of MDA-7/IL-24 is dispensable for tumor cell-specific apoptosis and "bystander" antitumor activity.

Biochemical and genetic mutation-based analyses confirm that the MDA-7/IL-24 protein can induce transformed cell-specific apoptosis through a mechanism involving endoplasmic reticulum (ER) stress-associated pathways. Covalent modifications by N-linked glycans in the ER contribute to the conformational maturation and biological functions of many proteins. Because MDA-7/IL-24 is a glycosylated protein, we investigated the role of glycosylation in mediating the specific biological and "bystander" antitumor activities of this cytokine.

BiP/GRP78 is an intracellular target for MDA-7/IL-24 induction of cancer-specific apoptosis.

Melanoma differentiation-associated gene-7/interleukin-24 (mda-7/IL-24) is a unique member of the IL-10 gene family that induces cancer-selective growth suppression and apoptosis in a wide spectrum of human cancers in cell culture and animal models. Additionally, recent clinical trials confirm safety and document significant clinical activity of mda-7/IL-24 in patients with diverse solid cancers and melanomas. Despite intensive study the molecular basis of tumor-cell selectivity of mda-7/IL-24 is not well characterized.

Molecular target-based therapy of pancreatic cancer.

Pancreatic cancer is genetically complex, and without effective therapy. Mutations in the Kirsten-ras (K-ras) oncogene occur early and frequently (approximately 90%) during pancreatic cancer development and progression. In this context, K-ras represents a potential molecular target for the therapy of this highly aggressive cancer.

Activation of the nuclear factor kappaB pathway by astrocyte elevated gene-1: implications for tumor progression and metastasis.

Astrocyte elevated gene-1 (AEG-1) was initially identified as an HIV-1- and tumor necrosis factor alpha (TNF-alpha)-inducible transcript in primary human fetal astrocytes by a rapid subtraction hybridization approach. Interestingly, AEG-1 expression is elevated in subsets of breast cancer, glioblastoma multiforme and melanoma cells and AEG-1 cooperates with Ha-ras to promote transformation of immortalized melanocytes. Activation of the transcription factor nuclear factor kappaB (NF-kappaB), a TNF-alpha downstream signaling component, is associated with several human illnesses, including cancer, and NF-kappaB controls the expression of multiple genes involved in tumor progression and metastasis.

mda-9/Syntenin: a positive regulator of melanoma metastasis.

Metastasis is a significant event in cancer progression and continues to pose the greatest challenge for a cancer cure. Defining genes that control metastasis in vivo may provide new targets for intervening in this process with profound therapeutic implications. Melanoma differentiation associated gene-9 (mda-9) was initially identified by subtraction hybridization as a novel gene displaying biphasic expression during terminal differentiation in human melanoma cells.

Cumulative fluid intake minus output is not associated with ventilator weaning duration or extubation outcomes in children.

Objective: The effect of fluid balance on respiratory outcomes for critically ill children has not been evaluated. The only indicator of fluid balance routinely recorded across our intensive care units was estimated fluid intake and output. We sought to determine whether cumulative intake minus output (I-O) at the start of weaning predicted weaning duration and whether cumulative I-O at extubation predicted extubation failure.

Targeted virus replication plus immunotherapy eradicates primary and distant pancreatic tumors in nude mice.

Pancreatic cancer is an aggressive neoplasm with no current viable, effective treatment options. In the majority of cases, at first diagnosis, pancreatic cancer has already become metastatic so that conventional treatment regimens provide minimal, if any, clinical benefit in prolonging life or ameliorating the negative prognosis of this disease. These harsh realities underscore the need for developing improved treatment paradigms for this cancer, with gene therapy and immunotherapy currently being evaluated as potential therapeutic options.

Defining the domains of human polynucleotide phosphorylase (hPNPaseOLD-35) mediating cellular senescence.

To fully comprehend cellular senescence, identification of relevant genes involved in this process is mandatory. Human polynucleotide phosphorylase (hPNPase(OLD-35)), an evolutionarily conserved 3', 5' exoribonuclease mediating mRNA degradation, was first identified as a predominantly mitochondrial protein overexpressed during terminal differentiation and senescence. Overexpression of hPNPase(OLD-35) in human melanoma cells and melanocytes induces distinctive changes associated with senescence, potentially mediated by direct degradation of c-myc mRNA by this enzyme.