Medical Emergency Team call within 24 h of medical admission with a focus on sepsis: a retrospective review.

BACKGROUND AND AIMS: Clinical deterioration within the first 24 h of patient admission triggering a Medical Emergency Team (MET) call is a common occurrence. A greater understanding of these events, with a focus on the recognition and management of sepsis, could lead to quality improvement interventions. METHODS: A retrospective observational review of general and subspecialty medical admissions triggering a MET call within 24 h of admission at a quaternary Australian hospital. RESULTS: 2648 MET calls occurred (47.9/1000 admissions), 527 (20% of total MET events, 9.5/1000 admissions) within 24 h of admission, with the trigger more likely to be hypotension (odds ratio: 1.5, P = 0.0013). There were 263 MET calls to 217 individual medical patients within 24 h of admission, of which 84 (38.7%) were admitted with suspected infection, 69% of which fulfilled sepsis criteria. Of these, 36.2% received antimicrobial therapy within the recommended timeframe and 39.6% received antibiotics in line with hospital guidelines. Sepsis was initially missed in 11% of patients. Afferent limb failure occurred in 29% of patients with 40.5% experiencing a failure of the ward-based response to deterioration prior to MET call. Median hospital length of stay was increased in patients admitted with suspected infection (7 vs 5 days, P = 0.015) and in those with sepsis not receiving antimicrobial therapy within guideline timeframes (9 vs 4 days, P = 0.017). CONCLUSION: There is a significant opportunity to improve care for patients who trigger a MET within 24 h of admission. This study supports the implementation of a hospital sepsis management guideline.

Management of surgical patients on opioid replacement therapy: An audit of current practice.

Patients on opioid replacement therapy hospitalised with acute pain represent a clinical challenge and have poorer perioperative outcomes. There is limited evidence relating to acute pain management of this complex cohort. The primary objectives of this retrospective audit was to establish the number of patients who are admitted on opioid replacement therapy with an acute pain condition under surgical services and evaluate the management of these patients to determine consistency of pain management practices. Secondarily, we aimed to evaluate the documentation of opioid replacement therapy in clinical notes to determine adherence to operational protocols and record clinically relevant outcomes including infection or postoperative complication rates. Forty-four episodes of care for buprenorphine patients and 19 episodes of care for methadone patients were included. There was significant variability in inpatient opioid prescribing, including practice of dose modification, and there was high utilisation of additional opioids, although agent choice varied. Multimodal analgesia was utilised, especially following acute pain service review. There was an 11% readmission rate for complications of the initial presentation. Documentation at transitions of care was poor. There is a need for further clinical studies into specific acute pain management strategies, and their effect on clinically relevant outcomes, to guide consistent management practices.

Highly conserved sperm function-related transcripts across three species: human, rat and mouse.

Assessing male reproductive toxicity of environmental and therapeutic agents relies on the histopathology of the testis and epididymis in a pre-clinical setting. Animal histopathology poorly correlates with human sperm parameters, and none of these current methods are strong indicators of sperm health or reproductive potential. Therefore, there is an urgent need to identify a translatable, non-invasive and reliable approach to monitor environmental and therapeutic agents' effects on male reproductive health. mRNA sequences were analyzed in mouse, rat and human sperm samples to identify sperm transcriptomic similarities across species that could be used as biomarkers to predict male reproductive toxicity in animal models. Semen specimens were collected from men aged 18 to 55 years with proven fertility. Rat and mouse semen specimens were collected via needle punctures of the cauda epididymides. Sperm RNAs were extracted using an optimized sperm RNA isolation protocol and subjected to polyA-purified mRNA-sequencing. Bioinformatics analyses, including differential abundance and gene set enrichment analysis, were used to investigate the biological and molecular functions of all shared and differentially abundant transcripts across species. Transcriptome profiling identified 6,684 similarly expressed transcripts within the three species of which 1,579 transcripts were found to be involved in spermatogenic functions. Our findings have shown that sperm transcriptome is highly species dependent, however, there are some key similarities among transcripts that are required for fertility. Based on these similarities, sperm mRNA biomarker may be developed to monitor male reproductive toxicity where rodent models would make suitable laboratory substitutes for human.

Direct reprogramming of oligodendrocyte precursor cells into GABAergic inhibitory neurons by a single homeodomain transcription factor Dlx2.

Oligodendrocyte precursor cells (NG2 glia) are uniformly distributed proliferative cells in the mammalian central nervous system and generate myelinating oligodendrocytes throughout life. A subpopulation of OPCs in the neocortex arises from progenitor cells in the embryonic ganglionic eminences that also produce inhibitory neurons. The neuronal fate of some progenitor cells is sealed before birth as they become committed to the oligodendrocyte lineage, marked by sustained expression of the oligodendrocyte transcription factor Olig2, which represses the interneuron transcription factor Dlx2. Here we show that misexpression of Dlx2 alone in postnatal mouse OPCs caused them to switch their fate to GABAergic neurons within 2 days by downregulating Olig2 and upregulating a network of inhibitory neuron transcripts. After two weeks, some OPC-derived neurons generated trains of action potentials and formed clusters of GABAergic synaptic proteins. Our study revealed that the developmental molecular logic can be applied to promote neuronal reprogramming from OPCs.

Quality of life assessment in interventional radiology.

The aim of this review was to describe quality of life (QoL) questionnaires relevant to interventional radiology. Interventional radiologists perform a large number of palliative procedures. The effect of these therapies on QoL is important. This is particularly true for cancer therapies where procedures with marginal survival benefits may result in tremendous QoL benefits. Image-guided minimally invasive procedures should be compared to invasive procedures, with respect to QoL, as part of comparative effectiveness assessment. A large number of questionnaires have been validated for measurement of overall and disease-specific quality of life. Use of applicable QoL assessments can aid in evaluating clinical outcomes and help to further substantiate the need for minimally invasive image-guided procedures.

Quality-of-life assessment after palliative interventions to manage malignant ureteral obstruction.

PURPOSE: Malignancies may cause urinary tract obstruction, which is often relieved with placement of a percutaneous nephrostomy tube, an internal double J nephro-ureteric stent (double J), or an internal external nephroureteral stent (NUS). We evaluated the affect of these palliative interventions on quality of life (QoL) using previously validated surveys. METHODS: Forty-six patients with malignancy related ureteral obstruction received nephrostomy tubes (n = 16), double J stents (n = 15), or NUS (n = 15) as determined by a multidisciplinary team. QoL surveys were administered at 7, 30, and 90 days after the palliative procedure to evaluate symptoms and physical, social, functional, and emotional well-being. Number of related procedures, fluoroscopy time, and complications were documented. Kruskal-Wallis and Friedman's test were used to compare patients at 7, 30, and 90 days. Spearman's rank correlation coefficient was used to assess correlations between clinical outcomes/symptoms and QoL. RESULTS: Responses to QoL surveys were not significantly different for patients receiving nephrostomies, double J stents, or NUS at 7, 30, or 90 days. At 30 and 90 days there were significantly higher reported urinary symptoms and pain in those receiving double J stents compared with nephrostomies (P = 0.0035 and P = 0.0189, respectively). Significantly greater fluoroscopy time was needed for double J stent-related procedures (P = 0.0054). Nephrostomy tubes were associated with more frequent minor complications requiring additional changes. CONCLUSION: QoL was not significantly different. However, a greater incidence of pain in those receiving double J stents and more frequent tube changes in those with nephrostomy tubes should be considered when choosing palliative approaches.

Ultrastructural and clinical evidence of subretinal debris accumulation in type 2 macular telangiectasia.

AIMS: To describe subretinal debris found on ultrastructural examination in an eye with macular telangiectasia (MacTel) type 2 and on optical coherence tomography (OCT) in a subset of patients with MacTel type 2. METHODS: Blocks from the mid-periphery and temporal perifovea of an eye with clinically documented MacTel type 2 were examined with electron microscopy (EM). Cases came from the Sydney centre of the MacTel project and the practices of the authors. RESULTS: On EM examination, subretinal debris was found in the perifovea with accumulation of degenerate photoreceptor elements in the subretinal space. Despite the substantial subretinal debris, there was minimal retinal pigment epithelial (RPE) reaction. Focal defects were seen in the inner limiting membrane in the perifovea. Of the 65 Sydney MacTel project participants, three (5%) had prominent yellow material at the fovea. OCT revealed smooth mounds between the RPE and the ellipsoid region. The material was hyperautofluorescent. CONCLUSIONS: This study suggests that subretinal accumulation of photoreceptor debris may be a feature of MacTel type 2. Ultrastructural and OCT evidence of disease beyond the vasculature, involving photoreceptors and Muller cells, is presented.

Multidisciplinary management of blunt pelvic trauma.

Pelvic fractures account for ∼3% of all fractures and usually occur in patients with polytrauma. Pelvic fractures usually indicate high energy transfer and a significant mechanism of injury, and they can involve massive hemorrhage. For this reason, mortality from pelvic trauma is high, ranging from 40% to 60% among patients in shock, and up to 90% in patients considered to be in extremis. Multidisciplinary approaches in the treatment of patients with pelvic fractures have resulted in improved outcomes for these complex and challenging injuries. In this article, we describe a case of a pediatric patient who suffered severe pelvic fracture with massive hemorrhage, requiring a multidisciplinary approach for control of hemorrhage and definitive repair of injuries.

Bullet embolization: multidisciplinary approach by interventional radiology and surgery.

Bullet embolization after penetrating trauma is an infrequent but important phenomenon. It presents an unexpected sequelae to the otherwise predictable injury pattern of penetrating missile injury mechanism and poses a challenging diagnostic and therapeutic dilemma. Bullets from penetrating wounds can gain access to the vasculature and migrate to nearly every large vascular bed. Patients can be asymptomatic, but the potential complications can be devastating including limb-threatening ischemia, sepsis, endocarditis, cardiac valvular incompetence, pulmonary embolism, stroke, and even death. The exact incidence of bullet embolization is unknown, but it was estimated to be 0.3% during the Vietnam War and 1.1% in the recent conflict in Afghanistan and Iraq. The scarcity of the condition and the lack of concentrated experience at any single institution contribute to the controversies pertaining to the management approach. Traditionally, surgical extraction of embolized bullets may involve difficult and invasive surgical exposures. Recent advancement in endovascular techniques provides an additional option in this treatment algorithm. In this article, we describe a case of venous bullet embolization from the left iliac vein treated by a combined endovascular and surgical approach.

Transcatheter treatment of liver laceration from blunt trauma.

Blunt hepatic trauma is a fairly common pathology seen in trauma centers. We describe a pediatric patient who suffered blunt hepatic trauma that was managed successfully with a combination of exploratory laparotomy and liver packing, followed by hepatic artery embolization by interventional radiology (IR) after he continued to have significant arterial extravasation. Also discussed are trends in overall blunt hepatic trauma management and the technique of IR management.

A family history demonstration project among women in an urban Appalachian community.

BACKGROUND: Family health history (FHH) is promoted to consumers by the Surgeon General as a tool to improve health and prevent disease. However, few FHH resources exist for medically underserved populations such as the urban Appalachian community in Southwest Ohio. OBJECTIVES: To engage and educate urban Appalachian women about the importance and collection of their own FHH. METHODS: Researchers partnered with six community organizations to develop a model Family History Demonstration Project. Focus groups were held with urban Appalachian women to determine how they would like to learn about their FHH. Resources and an educational intervention were developed based on focus group findings with input from the academic and community partners. Participants in the project recorded their family history and evaluated the education sessions and materials. RESULTS: Eleven fact sheets and four educational presentations were developed based on feedback from the target community. One hundred women participated in two family history education sessions. Learning objectives for both education sessions were met. All participants recorded their family history electronically or on paper and 91% of participants found the first education session (ES1) very helpful at teaching the importance of FHH. CONCLUSIONS: Community organizations and university researchers partnered to develop a model Family History Demonstration Project with input from community members. Evaluations of the project were positive. Future efforts should focus on sustainable dissemination of the educational programs and resulting health outcomes.

Vertebral augmentation with a flexible curved needle: preliminary results in 17 consecutive patients.

This report details a trial demonstrating the viability of a blunt-tipped curved needle for use as a cement injection device for vertebral body augmentation. Between January and September 2007, 17 consecutive patients (eight men and nine women; average age, 76 years; age range, 52-97 years) underwent vertebral body augmentation with a blunt-tipped curved nitinol injection needle via a single pedicle to treat pain due to acute vertebral body compression fractures. All patients were successfully treated without complication. The results of the trial demonstrate that a curved blunt-tipped nitinol needle is a viable alternative to a rigid injection cannula when performing vertebral body augmentation with cement.

Early in vivo experience with the pediatric Jarvik 2000 heart.

The need for smaller, more efficient ventricular assist devices that can be used in a more chronic setting have led to exploration of mechanical circulatory support in the pediatric population. The pediatric Jarvik 2000 heart (child size), under development, was implanted in six juvenile sheep and studied for both acute fit and chronic performance evaluation. Daily hemodynamic measurements of cardiac output and pump output at varying pump speeds were taken. In addition, plasma free hemoglobin, lactic acid dehydrogenase, and platelet activation from blood samples were determined at baseline, after implantation, and twice a week thereafter. The measured flow through the outflow graft at increasing speeds from 10,000 rpm to 14,000 rpm with an increment of 1,000 rpm were 1.47 +/- 0.43, 1.89 +/- 0.52, 2.36 +/- 0.61, 2.80 +/- 0.73, and 3.11 +/- 0.86 (L/min). The baseline plasma free hemoglobin was 11.95 +/- 4.76 (mg/dL), with subsequent mean values being <30 mg/dL at postimplantation and weekly postimplantation measurements. Both lactic acid dehydrogenase and platelet activation showed an acute increase within the first week after implantation with subsequent return to baseline by 2 weeks after surgery. Our initial animal in vivo experience with the pediatric Jarvik 2000 heart shows that a small axial flow pump can provide partial to nearly complete circulatory support with minimal adverse effects on blood components.

Beating heart direct left atrial access balloon cryoablation: safety and efficacy of pulmonary vein isolation in an ovine model.

OBJECTIVE: : Clinical experience with endocardial cryoablation for the surgical treatment of atrial fibrillation has demonstrated safety and efficacy. Direct access to the left atrium via a thoracoscopic or pericardial approach with a balloon-tipped cryoablation catheter might facilitate endocardial cryoablation on the beating heart. We investigated the ability of a novel cryoballoon to produce endocardial pulmonary vein ostial cryolesions on the beating heart in a large-animal model. METHODS: : Six sheep underwent small left thoracotomy. A 10.5F catheter with a 23-mm cryoballoon was inserted directly into the left atrium under fluoroscopic and intracardiac echo (ICE) guidance. Cryoablation of the pulmonary vein ostia was performed. Animals were killed at 14 days. Pulmonary venous electrical isolation was assessed immediately before the animals were killed. RESULTS: : All animals survived balloon cryoablation with no periprocedural complications. Balloon occlusion was well tolerated hemodynamically, with minimal change in blood pressure (-4 ± 6 mm Hg systolic BP) and no change in heart rate. ICE demonstrated an absence of intracardiac air or ice embolization during ablation. Mean balloon temperature was -67 ± 8°C. All animals were neurologically intact after the procedure. Five of 6 (83%) veins exhibited circumferential exit block. Phrenic nerve function was intact in all animals. On gross inspection, all lesions were circumferential and continuous without evidence of endocardial thrombus. Pathology confirmed circumferential transmurality in all treated veins. CONCLUSIONS: : Direct left atrial access cryoballoon ablation was effective for isolating pulmonary veins. This technology may be an important component of a minimally invasive beating heart CryoMaze procedure for the treatment of atrial fibrillation.

Strain-related regional alterations of calcium-handling proteins in myocardial remodeling.

BACKGROUND: Cardiac remodeling has been shown to have deleterious effects at both the global and local levels. The objective of this study is to investigate the role of strain in the initiation of structural and functional changes of myocardial tissue and its relation to alteration of calcium-handling proteins during cardiac remodeling after myocardial infarction. METHODS: Sixteen sonomicrometry transducers were placed in the left ventricular free wall of 9 sheep to measure the regional strain in the infarct, adjacent, and remote myocardial regions. Hemodynamic, echocardiographic, and sonomicrometry data were collected before myocardial infarction, after infarction, and 2, 6, and 8 weeks after infarction. Regional myocardial tissues were collected for calcium-handling proteins at the end study. RESULTS: At time of termination, end-systolic strains in 3 regionally distinct zones (remote, adjacent, and infarct) of myocardium were measured to be -14.65 +/- 1.13, -5.11 +/- 0.60 (P < or = .05), and 0.92 +/- 0.56 (P < or = .05), respectively. The regional end-systolic strain correlated strongly with the abundance of 2 major calcium-handling proteins: sarcoplasmic reticulum Ca2+ adenosine triphosphatase subtype 2a (r2 = 0.68, P < or = .05) and phospholamban (r2 = 0.50, P < or = .05). A lesser degree of correlation was observed between the systolic strain and the abundance of sodium/calcium exchanger type 1 protein (r2 = 0.17, P < or = .05). CONCLUSIONS: Regional strain differences can be defined in the different myocardial regions during postinfarction cardiac remodeling. These differences in regional strain drive regionally distinct alterations in calcium-handling protein expression.

Matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases in the human lens: implications for cortical cataract formation.

PURPOSE: To characterize the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) in human cortical cataract and to determine whether there is a correlation with the localization of cortical cataract. To evaluate the expression and activity of MMPs and TIMPs after cytokine and UV-B exposure in a human lens epithelial cell line. METHODS: Twenty-eight human donor eyes with cortical cataract and 21 normal human donor eyes were photographed. Thirteen cortical cataract and six normal lenses were immunohistochemically analyzed for MMP-1, -2, -3, and -9 and TIMP-1, -2, and -3. Twelve fresh cortical cataract and 12 normal lenses were divided into quadrants to quantify, by ELISA, the expression of MMP-1, -2, -3, and -9 and TIMP-1. Three fresh cortical cataract and three control lenses were assessed for MMP-1, -2, and -9 activity by SDS-PAGE zymography. Human lens epithelial cells (HLE-SRA-01/04) were exposed to proinflammatory cytokines and UV-B radiation to determine the protein expression profiles of MMP-1, -2, -3, and -9 and TIMP-1 and -2. RESULTS: Immunohistochemical analysis revealed specific localization of MMP-1 within lens epithelium and cortical lens fibers of cortical cataract. Normal lenses had equally low MMP-1, -2, -3, and -9 and TIMP-1, -2, and -3 immunoreactivity, expression, and activity in all lens quadrants. IL-1 and TNF-alpha upregulated the expression of MMP-2, -3, and -9, and UV-B upregulated the expression of MMP-1 in the SRA-01/04 HLE cell line. CONCLUSIONS: This is the first study to localize the expression of MMP-1 in cataracts with clinically observed opacification in vivo and to examine the expression induced by UV-B, in vitro.

Development of a balloon volume sensor for pulsating balloon catheters.

Helium pulsed balloons are integral components of several cardiovascular devices, including intraaortic balloon pumps (IABP) and a novel intravenous respiratory support catheter. Effective use of these devices clinically requires full inflation and deflation of the balloon, and improper operating conditions that lead to balloon under-inflation can potentially reduce respiratory or cardiac support provided to the patient. The goal of the present study was to extend basic spirographic techniques to develop a system to dynamically measure balloon volumes suitable for use in rapidly pulsating balloon catheters. The dynamic balloon volume sensor system (DBVSS) developed here used hot wire anemometry to measure helium flow in the drive line from console to catheter and integrated the flow to determine the volume delivered in each balloon pulsation. An important component of the DBVSS was an algorithm to automatically detect and adjust flow signals and measured balloon volumes in the presence of gas composition changes that arise from helium leaks occurring in these systems. The DBVSS was capable of measuring balloon volumes within 5-10% of actual balloon volumes over a broad range of operating conditions relevant to IABP and the respiratory support catheter. This includes variations in helium concentration from 70-100%, pulsation frequencies from 120-480 beats per minute, and simulated clinical conditions of reduced balloon filling caused by constricted vessels, increased driveline, or catheter resistance.

Proliferative effects of heparin-binding epidermal growth factor-like growth factor on pterygium epithelial cells and fibroblasts.

PURPOSE: To investigate the growth promoting and chemotactic effects of heparin binding epidermal growth factor-like growth factor (HB-EGF), recently shown to be upregulated by ultraviolet irradiation in pterygium-derived epithelium cells (PECs) and pterygium fibroblasts (PFs). METHODS: PECs and PFs were incubated with various concentrations of HB-EGF. Cell proliferation was evaluated by measurement of [3H]thymidine incorporation. The potential chemotactic effect of HB-EGF on these two cell lines was assessed with migration assays, using modified Boyden chambers and checkerboard analysis. RESULTS: Incubation of PECs and PFs with HB-EGF resulted in a significant increase in [3H]thymidine incorporation compared with that of control cells. HB-EGF stimulated chemotaxis of both PECs and PFs. Maximum stimulation occurred at 1 ng/mL for PFs and 10 ng/mL for PECs. These effects were abolished by the addition of a neutralizing antibody to HB-EGF. CONCLUSIONS: The findings demonstrate the potential proliferative and chemotactic effects of HB-EGF on both PECs and PFs. This is the first study to illustrate the positive effect of a specific growth or chemotactic factor on the cellular elements of a pterygium.

The role of ultraviolet irradiation and heparin-binding epidermal growth factor-like growth factor in the pathogenesis of pterygium.

Ultraviolet (UV) light is one of the major factors implicated in the pathogenesis of pterygium. The mechanism by which UV light induces this disease remains elusive. The aim of this study was to evaluate the effects of UVB irradiation on the expression of growth factors in cultured pterygium epithelial cells and to demonstrate their distribution within pterygium. We cultured pterygial epithelial cells from pterygium explants and these cells were exposed to 20 mJ/cm(2) of UVB. Total RNA was extracted at 0, 6, and 12 hours after irradiation. (32)P-labeled cDNA was synthesized and analyzed using microarray technology to determine the differential expression of 268 growth factor and cytokine related genes. Semiquantitative reverse transcriptase-polymerase chain reaction was used to corroborate this data. Conditioned media derived from cells exposed to UVB irradiation was analyzed for protein expression by enzyme-linked immunosorbent assay. Immunohistochemistry was used to evaluate the distribution of heparin-binding epidermal growth factor-like growth factor (HB-EGF) in pterygium tissue. Analysis of the hybridization signals revealed that the genes encoding HB-EGF, fibroblast growth factor 3, and cytotoxic trail ligand receptor were consistently elevated at 6 and 12 hours after UVB treatment. HB-EGF mRNA was elevated 6.8-fold at 6 hours after irradiation and was augmented in culture supernatants after the same treatment. Furthermore, HB-EGF reactivity was identified in the epithelium and vasculature of pterygium by immunohistochemistry. HB-EGF was present in normal limbal epithelium, although it was not induced in cultured limbal epithelial cells by UV irradiation. HB-EGF is a potent mitogen, localized in pterygium tissue, and significantly induced by UVB in pterygium-derived epithelial cells. We postulate that this growth factor is a major driving force in the development of pterygia and a means by which UV irradiation causes the pathogenesis of pterygium.