The impact of proton therapy on cardiotoxicity following radiation treatment

Journal of Thrombosis and Thrombolysis - Cardiac disease following radiation therapy represents a major consideration in the treatment of a variety of malignancies. Damage to the heart can manifest...     

Identification of somatic JAK1 mutations in patients with acute myeloid leukemia

Somatic mutations in JAK2 are frequently found in myeloproliferative diseases, and gain-of-function JAK3 alleles have been identified in M7 acute myeloid leukemia (AML), but a role for JAK1 in AML has not been described. We screened the entire coding region of JAK1 by total exonic resequencing of bone marrow DNA samples from 94 patients with de novo AML. We identified 2 novel somatic mutations in highly conserved residues of the JAK1 gene (T478S, V623A), in 2 separate patients and confirmed these by resequencing germ line DNA samples from the same patients. Overexpression of mutant JAK1 did not transform primary murine cells in standard assays, but compared with wild-type JAK1, JAK1^T478S, and JAK1^V623A expression was associated with increased STAT1 activation in response to type I interferon and activation of multiple downstream signaling pathways. This is the first report to demonstrate somatic JAK1 mutations in AML and suggests that JAK1 mutations may function as disease-modifying mutations in AML pathogenesis.     

Low–Molecular-Weight-Heparins as Periprocedural Anticoagulation for Patients on Long-Term Warfarin Therapy: A Standardized Bridging Therapy Protocol

Background: Over 2 million patients in North America are on warfarin anticoagulation therapy for prevention of thromboembolism. Suspension of warfarin therapy is often required to prepare patients for invasive procedures or surgeries. To protect these patients against thromboembolism while they are off warfarin, shorter-acting parenteral agents such as low-molecular-weight heparins (LMWHs) are often used. We conducted a retrospective observational study of our anticoagulation clinic patients to assess the safety and efficacy of LMWHs using a standardized protocol for periprocedural anticoagulation therapy.Methods: We included 69 consecutive patients who required interruption of their long-term warfarin therapy between August 2001 and August 2002, and were deemed by the treating physician to be at high enough risk for perioperative thromboembolism to justify bridging anticoagulation. We used a standard bridging therapy protocol in our anticoagulation clinic. Sixty-six patients received enoxaparin and three patients received tinzaparin for a mean duration of 7.7 days postoperatively. Outcomes were assessed for 30 days post-procedure. Safety outcomes included major bleeding and minor bleeding. Efficacy outcomes included thromboembolic event or death.Results: There were two major bleeding events, one minor bleeding event, and no cases of thromboembolism. Twelve patients experienced some bruising around the injection site.Conclusions: LMWH administration using our standard outpatient bridging protocol for perioperative anticoagulation appears to be relatively safe and efficacious, offering an alternative to inpatient administration of intravenous unfractionated heparin (UFH). Our study provides additional evidence to the limited published observational data regarding the safety and efficacy of LMWH as bridging therapy in the perioperative and periprocedural setting. Large, multicenter, randomized controlled trials are necessary to fully assess the safety and efficacy of LMWH for perioperative anticoagulation.Abbreviated Abstract We conducted a retrospective observational study of 69 consecutive anticoagulation clinic patients on warfarin between August 2001 and August 2002, who were undergoing a procedure or surgery. The study was done to assess the safety and efficacy of an outpatient LMWH bridging protocol. Sixty-six patients received enoxaparin and three patients received tinzaparin for a mean duration of 3 days preoperatively and 7.7 days postoperatively. Outcomes were assessed for 30 days post-procedure. Safety outcomes included major bleeding and minor bleeding. Efficacy outcomes included thromboembolic event or death. There were two major bleeding events, one minor bleeding event, and no cases of thromboembolism. Twelve patients experienced some bruising around the injection site.     

Bedside echocardiography is useful in assessing children with fluid and inotrope resistant septic shock

Objective:

To report changes in the cardiovascular management of fluid and inotropic resistant septic shock in children based on echocardiography.

Design:

Retrospective case series.

Setting:

Tertiary care Pediatric Intensive Care Unit (PICU), Chennai.

Patients:

Twenty-two patients with unresolved septic shock after 60 ml/kg fluid plus inotropic agents in the first hour.

Interventions:

Bedside echocardiography (echo) within 6 h of admission to the PICU.

Results:

Over a 28-month period, of 37 patients with septic shock, 22 children remained in shock despite 60 ml/kg fluid and dopamine and/or dobutamine infusions as per guidelines. On clinical exam, 12 patients had warm shock and ten had cold shock, however, six exhibited an unusual pattern of cold shock with wide pulse pressures on invasive arterial monitoring. The most common echocardiographic finding was uncorrected hypovolemia in 12/22 patient while ten patients had impaired left ± right ventricular function. Echocardiography permitted an appreciation of the underlying disordered pathophysiology and a rationale for adjustment of treatment. Shock resolved in 17 (77%) and 16 patients (73%) survived to discharge.

Conclusions:

Bedside echo provided crucial information that was not apparent on clinical assessment and affords a simple noninvasive tool to determine the cause of low cardiac output in patients who remain in shock despite 60 ml/kg fluid and inotropic support. Most patients in our series had vasodilatory shock with wide pulse pressures and most common finding on echo was uncorrected hypovolemia. The echo findings allowed adjustment of therapy which was not possible based on clinical examination alone.     

Clinical profile of acute kidney injury in a pediatric intensive care unit from Southern India: A prospective observational study

Background:

Although the term acute renal failure was replaced by acute kidney injury (AKI) recently, there is a paucity of data on the incidence and profile of AKI in critically ill children from the developing world.

Objectives:

The objective of this study is to determine the incidence, etiology, short term outcome and predictors of fatality in critically ill children admitted to the pediatric intensive care unit (PICU) with AKI, aged 1 month to 13 years.

Materials and Methods:

In this prospective observational study, from June 2010 to March 2011, 215 children admitted to the PICU were screened for AKI, defined according to the AKI Network criteria. The patients with AKI were followed-up until discharge/death. Their clinical and biochemical data were recorded.

Results:

The incidence of AKI among 215 patients screened was 54 (25.1%). The common etiologies were infections, [34 (62.9%)], acute glomerulonephritis (7.6%), snake envenomation (5.7%), hemolytic uremic syndrome (3.8%) and congestive cardiac failures (3.8%). Among infections, pneumonia and septicemia constituted 26.5% each, meningoencephalitis accounted for 23.5%, and dengue, scrub typhus, tuberculosis and malaria constituted 9.3% of children with AKI. 27.8% of patients required dialysis. Overall mortality was 46.3%. On logistic regression analysis, requirement of mechanical ventilation was an independent predictor of fatality in AKI.

Conclusions:

Besides the high incidence of AKI in critically ill-children admitted to the PICU (25.1%), the condition was associated with adverse outcomes, including high mortality (46.3%) and need for dialysis (27.8%). Infections dominated the etiological profile. Requirement of mechanical ventilation predicted an adverse outcome in our patient population.     

Photoacoustic dual-scan mammoscope: results from 38 patients

We have developed a photoacoustics-based imaging system, the dual-scan mammoscope (DSM), that combines optical contrasts with acoustic detection, to obtain the angiographic features in human breast. In this study, we investigated whether the system can differentiate malignant tumor and healthy breast. We have imaged 38 patients with various tumor types and compared results of tumor-bearing breast with healthy breast for each patient. We also compared the photoacoustic and ultrasound imaging results with clinical US. Vascular features in and around the tumor mass were visualized. We found that tumor-bearing breast contained vessels of larger caliber and exhibited stronger variations in the background signals than those in the contralateral healthy breasts. Preliminary data on photoacoustic and ultrasound images also indicate that the technique has potential in differentiating different tumor types. Overall, our results indicate that combining photoacoustic and ultrasound images can improve breast cancer screening.     

Novel integrative genomic tool for interrogating lithium response in bipolar disorder

We developed a novel integrative genomic tool called GRANITE (Genetic Regulatory Analysis of Networks Investigational Tool Environment) that can effectively analyze large complex data sets to generate interactive networks. GRANITE is an open-source tool and invaluable resource for a variety of genomic fields. Although our analysis is confined to static expression data, GRANITE has the capability of evaluating time-course data and generating interactive networks that may shed light on acute versus chronic treatment, as well as evaluating dose response and providing insight into mechanisms that underlie therapeutic versus sub-therapeutic doses or toxic doses. As a proof-of-concept study, we investigated lithium (Li) response in bipolar disorder (BD). BD is a severe mood disorder marked by cycles of mania and depression. Li is one of the most commonly prescribed and decidedly effective treatments for many patients (responders), although its mode of action is not yet fully understood, nor is it effective in every patient (non-responders). In an in vitro study, we compared vehicle versus chronic Li treatment in patient-derived lymphoblastoid cells (LCLs) (derived from either responders or non-responders) using both microRNA (miRNA) and messenger RNA gene expression profiling. We present both Li responder and non-responder network visualizations created by our GRANITE analysis in BD. We identified by network visualization that the Let-7 family is consistently downregulated by Li in both groups where this miRNA family has been implicated in neurodegeneration, cell survival and synaptic development. We discuss the potential of this analysis for investigating treatment response and even providing clinicians with a tool for predicting treatment response in their patients, as well as for providing the industry with a tool for identifying network nodes as targets for novel drug discovery.     

Association of an abnormal exercise heart rate recovery with pulmonary function abnormalities

BACKGROUND: Heart rate recovery (HRR) after exercise correlates with decreased vagal tone and mortality. Patients with COPD may have altered autonomic tone. We sought to determine the association of HRR with spirometry measures of pulmonary function. METHODS: We analyzed 627 patients (mean [+/- SD] age, 58 +/- 12 years; 65% men; mean FEV(1), 2.6 +/- 0.9 L, 80 +/- 20% predicted; patients receiving inhaled beta(2) agonist therapy, 10%; patients receiving inhaled anticholinergic therapy, 3%; patients receiving inhaled steroids, 5%; patients receiving oral prednisone, 4%) who had undergone maximal exercise testing and had undergone pulmonary function tests < 1 year apart. Patients with heart failure, pacemakers, and atrial fibrillation were excluded. Abnormal HRR was defined as a fall in heart rate during the first minute after exercise of 相似文献   

Valve repair in rheumatic heart disease in pediatric age group

Valve repair in children is technically demanding but more desirable than valve replacement. From April 2004 to September 2005, 1 boy and 8 girls with rheumatic heart disease, aged 2-13 years (median, 9 years), underwent valve repair for isolated mitral regurgitation in 5, combined mitral and aortic regurgitation in 2, mitral stenosis in 1, and mitral regurgitation associated with atrial septal defect in 1. Chordal shortening in 7, annular plication in 6, commissurotomy in 1, reconstruction of commissural leaflets in 7 were performed for mitral valve disease. Plication and reattachment of the aortic cusps was carried out in 2 patients. Annuloplasty rings were not used. All patients survived the operation, 8 had trivial or mild residual mitral regurgitation, and 1 had trivial aortic regurgitation. Mean left atrial pressure decreased from 14 to 7 mm Hg postoperatively. During follow-up of 3-18 months, all children were asymptomatic and enjoyed normal activity. None required reoperation. In addition to chordal shortening and annular plication, reconstruction of the commissural leaflets is considered the most important aspect of valve repair. It can be achieved without annuloplasty rings, giving good early and midterm results.