Association between intra-operative cardiac arrest and country Human Development Index status: a systematic review with meta-regression analysis and meta-analysis of observational studies.

Intra-operative cardiac arrests differ from most in-hospital cardiac arrests because they reflect not only the patient's condition but also the quality of surgery and anaesthesia care provided. We assessed the relationship between intra-operative cardiac arrest rates and country Human Development Index (HDI), and the changes occurring in these rates over time. We searched PubMed, EMBASE, Scopus, LILACS, Web of Science, CINAHL and SciELO from inception to 29 January 2020. For the global population, rates of intra-operative cardiac arrest and baseline ASA physical status were extracted. Intra-operative cardiac arrest rates were analysed by time, country HDI status and ASA physical status using meta-regression analysis. Proportional meta-analysis was performed to compare intra-operative cardiac arrest rates and ASA physical status in low- vs. high-HDI countries and in two time periods. Eighty-two studies from 25 countries with more than 29 million anaesthetic procedures were included. Intra-operative cardiac arrest rates were inversely correlated with country HDI (p = 0.0001); they decreased over time only in high-HDI countries (p = 0.040) and increased with increasing ASA physical status (p < 0.0001). Baseline ASA physical status did not change in high-HDI countries (p = 0.106), while it decreased over time in low-HDI countries (p = 0.040). In high-HDI countries, intra-operative cardiac arrest rates (per 10,000 anaesthetic procedures) decreased from 9.59 (95%CI 6.59-13.16) pre-1990 to 5.17 (95%CI 4.42-5.97) in 1990-2020 (p = 0.013). During the same time periods, no improvement was observed in the intra-operative cardiac arrest rates in low-HDI countries (p = 0.498). Odds ratios of intra-operative cardiac arrest rates in ASA 3-5 patients were 8.48 (95%CI 1.67-42.99) times higher in low-HDI countries than in high-HDI countries (p = 0.0098). Intra-operative cardiac arrest rates are related to country-HDI and decreased over time only in high-HDI countries. The widening gap in these rates between low- and high-HDI countries needs to be addressed globally.

Diagnostic point-of-care ultrasound: applications in obstetric anaesthetic management.

Complications during pregnancy are not frequent, but may occur abruptly. Point-of-care ultrasound is a non-invasive, non-ionising diagnostic tool that is available at the bed-side when complications occur. This review covers the use of ultrasound in various clinical situations. Gastric ultrasound can identify stomach contents that put the woman at risk for pulmonary aspiration. In the future, this tool will probably be used routinely before induction of anaesthesia to determine the presence of stomach contents above a particular risk threshold. Difficult tracheal intubation, and the potential for 'can't intubate, can't oxygenate', is more frequent in pregnant women. Point-of-care ultrasound of the airway allows accurate identification of the cricothyroid membrane, permitting rapid and safer establishment of front-of-neck airway access. Combined cardiac and lung ultrasound can determine the potential risk:benefit of fluid administration in the pregnant patient. Such prediction is of critical importance, given the tendency of pregnant women to develop pulmonary oedema. Combined echocardiography and lung ultrasound can be combined with ultrasound of the leg veins to differentiate between the various causes of acute respiratory failure, and guide treatment in this situation. Finally, as shown in the general population, multi-organ point-of-care ultrasound allows early diagnosis of the main causes of circulatory failure and cardiac arrest at the bed-side. As the importance of point-of-care ultrasound in critical patients is increasingly recognised, it is emerging as an important tool in the therapeutic armoury of obstetric anaesthetists.

Can point-of-care ultrasound predict spinal hypotension during caesarean section? A prospective observational study.

Spinal anaesthesia for elective caesarean section is associated with maternal hypotension, secondary to alteration of sympathetic tone and hypovolemia, in up to 70% of cases. Measurement of the subaortic variation in the velocity time integral (VTI) after passive leg raising allows prediction of fluid responsiveness. Our objective, in this prospective single-centre observational study, was to assess the ability of change in VTI after 45° passive leg raising to predict hypotension after spinal anaesthesia. Ultrasound measurements were performed just before elective caesarean section. Anaesthesia, intravenous coloading and prophylactic vasopressor treatment were standardised according to current guidelines. We studied 40 women. Hypotension occurred in 17 (45%) women. The area (95%CI) under the receiver operating characteristics (ROC) curve for the prediction of spinal hypotension was 0.8 (0.6-0.9; p = 0.0001). Seventeen women had a change in VTI with leg elevation ≤ 8%, which was predictive for not developing hypotension, and 11 had a change ≥ 21%, predictive for hypotension. The grey zone between 8% and 21%, with inconclusive values, included 12 women. We suggest that cardiac ultrasound provides characterisation of the risk of hypotension following spinal anaesthesia at elective caesarean section, and therefore may allow individualised strategies for prevention and management.

Performance of non-invasive stroke volume variation during passive leg raising as a predictor of hypotension following induction of spinal anesthesia for elective cesarean delivery: a single cohort study.

BACKGROUND: Spinal anesthesia for cesarean delivery is accompanied by hypotension in up to 70% of cases. To date, there is no gold standard for predicting hypotension after spinal anesthesia for cesarean delivery. The Clearsight™ device is a non-invasive system that uses a digital cuff to calculate stroke volume. We hypothesized that stroke volume variation induced with passive leg raising before spinal anesthesia for elective cesarean delivery could predict the occurrence of hypotension. METHODS: We conducted a prospective observational study, including third trimester parturients undergoing elective cesarean delivery with spinal anesthesia. We analyzed the stroke volume variation performance for predicting hypotension. Stroke volume was collected in the semi-recumbent position (baseline) and during passive leg raising before spinal anesthesia. Systolic arterial blood pressure measurement was followed for 15 min after spinal anesthesia. Hypotension was defined as a ≥20% decrease from the baseline measurement. All parturients received appropriate hypotension prophylaxis. RESULTS: Data from 42 parturients were analyzed. Hypotension occurred in 45%. The area-under-the curve for predicting hypotension using the stroke volume variation was 0.83 (95% CI 0.68 to 0.98; P=0.001). The best cut-off value for predicting hypotension was 7%, having a sensitivity of 87% (95% CI 0.70 to 0.99) and a specificity of 83% (95% CI 0.69 to 0.97). CONCLUSION: In our study of third trimester parturients undergoing cesarean delivery and receiving appropriate hypotension prophylaxis, a digital non-invasive monitoring device of stroke volume variation analysis was useful for predicting the occurrence of hypotension after spinal anesthesia.

The time is now: addressing the need for training in maternal critical care medicine.

Amongst many high-income countries, indirect medical conditions (e.g. cardiovascular disease, sepsis) now account for the majority of maternal deaths. In response to this concerning rise in indirect causes of maternal deaths, professional societies have developed guidelines that regionalize high-risk obstetric care and prioritize critical care expertise as a requirement for designated 'top' maternity hospitals. Critical care proficiency is mandated by the Accreditation Council for Graduate Medical Education for graduating obstetric anesthesiology fellows. Despite these requirements, no formal obstetric critical care educational curricula or fellowship pathways, combining critical care medicine and obstetric anesthesiology, currently exist. Dual subspecialty training in both obstetric anesthesiology and critical care medicine represents one strategy to improve the care of critically-ill obstetric patients and reduce maternal mortality and morbidity, which is one of the pressing healthcare issues of our time.

Epidemiology, ventilation management and outcome in patients receiving intensive care after non-thoracic surgery - Insights from the LAS VEGAS study.

INTRODUCTION AND OBJECTIVES: Information about epidemiology, ventilation management and outcome in postoperative intensive care unit (ICU) patients remains scarce. The objective was to test whether postoperative ventilation differs from that in the operation room. MATERIAL AND METHODS: This was a substudy of the worldwide observational LAS VEGAS study, including patients undergoing non-thoracic surgeries. Of 146 study sites participating in the LAS VEGAS study, 117 (80%) sites reported on the postoperative ICU course, including ventilation and complications. The coprimary outcomes were two key elements of ventilator management, i.e., tidal volume (VT) and positive end-expiratory pressure (PEEP). Secondary outcomes included the proportion of patients receiving low VT ventilation (LTVV, defined as ventilation with a median VT < 8.0 ml/kg PBW), and the proportion of patients developing postoperative pulmonary complications (PPC), including ARDS, pneumothorax, pneumonia and need for escalation of ventilatory support, ICU and hospital length of stay, and mortality at day 28. RESULTS: Of 653 patients who were admitted to the ICU after surgery, 274 (42%) patients received invasive postoperative ventilation. Median postoperative VT was 8.4 [7.3-9.8] ml/kg predicted body weight (PBW), PEEP was 5 [5-5] cm H2O, statistically significant but not meaningfully different from median intraoperative VT (8.1 [7.3-8.9] ml/kg PBW; P < 0.001) and PEEP (4 [2-5] cm H2O; P < 0.001). The proportion of patients receiving LTVV after surgery was 41%. The PPC rate was 10%. Length of stay in ICU and hospital was independent of development of a PPC, but hospital mortality was higher in patients who developed a PPC (24 versus 4%; P < 0.001). CONCLUSIONS: In this observational study of patients undergoing non-thoracic surgeries, postoperative ventilation was not meaningfully different from that in the operating room. Like in the operating room, there is room for improved use of LTVV. Development of PPC is associated with mortality.

Impact of time to antibiotic therapy on clinical outcome in patients with bacterial infections in the emergency department: implications for antimicrobial stewardship.

BACKGROUND: Rapid initiation of antibiotic treatment is considered crucial in patients with severe infections such as septic shock and bacterial meningitis, but may not be as important for other infectious syndromes. A better understanding of which patients can tolerate a delay in start of therapy is important for antibiotic stewardship purposes. OBJECTIVES: To explore the existing evidence on the impact of time to antibiotics on clinical outcomes in patients presenting to the emergency department (ED) with bacterial infections of different severity of illness and source of infection. SOURCES: A literature search was performed in the PubMed/MEDLINE database using combined search terms for various infectious syndromes (sepsis/septic shock, bacterial meningitis, lower respiratory tract infections, urinary tract infections, intra-abdominal infections and skin and soft tissue infections), time to antibiotic treatment, and clinical outcome. CONTENT: The literature search generated 8828 hits. After screening titles and abstracts and assessing potentially relevant full-text papers, 60 original articles (four randomized controlled trials, 43 observational studies) were included. Most articles addressed sepsis/septic shock, while few studies evaluated early initiation of therapy in mild to moderate disease. The lack of randomized trials and the risk of confounding factors and biases in observational studies warrant caution in the interpretation of results. We conclude that the literature supports prompt administration of effective antibiotics for septic shock and bacterial meningitis, but there is no clear evidence showing that a delayed start of therapy is associated with worse outcome for less severe infectious syndromes. IMPLICATIONS: For patients presenting with suspected bacterial infections, withholding antibiotic therapy until diagnostic results are available and a diagnosis has been established (e.g. by 4-8 h) seems acceptable in most cases unless septic shock or bacterial meningitis are suspected. This approach promotes the use of ecologically favourable antibiotics in the ED, reducing the risks of side effects and selection of resistance.

Rationale and evidence on the use of tocilizumab in COVID-19: a systematic review.

BACKGROUND: Tocilizumab is an IL-6 receptor-blocking agent proposed for the treatment of severe COVID-19. The aim of this systematic review was to describe the rationale for the use of tocilizumab for the treatment of COVID-19 and to summarize the available evidence regarding its efficacy and safety. METHODS: MEDLINE, PubMed, EMBASE, pre-print repositories (bioRxiv and medRxiv) and two trial Registries were searched for studies on the use of tocilizumab in COVID-19 or SARS-CoV-2 infection, viral pneumonia, and/or sepsis until 20th June 2020. RESULTS: We identified 3 indirect pre-clinical studies and 28 clinical studies including 5776 patients with COVID-19 (13 with a comparison group, 15 single-arm). To date, no randomized trials have been published. We retrieved no studies at low risk of bias. Forty-five ongoing studies were retrieved from trial registries. CONCLUSIONS: There is insufficient evidence regarding the clinical efficacy and safety of tocilizumab in patients with COVID-19. Its use should be considered experimental, requiring ethical approval and clinical trial oversight.

Lopinavir/ritonavir for the treatment of SARS, MERS and COVID-19: a systematic review.

OBJECTIVE: Lopinavir/ritonavir has been used for the treatment of Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) coronavirus infections. It has been suggested that, based on this experience, this drug should also be studied in SARS-CoV2 infection. MATERIALS AND METHODS: We performed a systematic review of the literature regarding the use of lopinavir/ritonavir for the treatment of these three infections. We systematically searched the PubMed database from inception to April 30th, 2020, to identify in-vitro and animal studies and any reports of human use of lopinavir/ritonavir for the treatment of SARS, MERS and COVID-19. We also searched the Clinicatrial.gov to identify ongoing trials. RESULTS: Five in-vitro studies evaluated the effect of lopinavir/ritonavir in SARS. Three additional in-vitro studies reported the EC50 of the antiviral activity of lopinavir/ritonavir in MERS. We identified no in vitro studies evaluating the effect of lopinavir/ritonavir on the novel coronavirus. Two retrospective matched-cohort studies reported the use of lopinavir/ritonavir in combination with ribavirin for SARS patients. Three case reports and one retrospective study described the use of lopinavir/ritonavir in MERS. Twenty-two papers describe the use of lopinavir/ritonavir in adult patients with COVID-19. CONCLUSIONS: The existing literature does not suffice for assessing whether Lopinavir/ritonavir has any benefit in SARS, MERS or COVID-19.

Hand placement during chest compressions in parturients: a pilot study to identify the location of the left ventricle using transthoracic echocardiography.

BACKGROUND: Current guidelines for maternal cardiopulmonary resuscitation recommend the hands be placed on the lower half of the sternum for compressions. We sought to evaluate the effect of the gravid uterus and left uterine displacement on the position of the left ventricle (LV) using transthoracic echocardiography. METHODS: We enrolled 20 women in the third trimester of a singleton pregnancy. Transthoracic echocardiography images in the supine and left lateral position, using a 30° wedge, were acquired. Parasternal long and short axis views of the LV were obtained at the lower half of the sternum and at the ideal imaging window (best image of mid-LV at 90° transducer orientation) The primary aim was to evaluate the distance between the distal end of the xiphoid and the location of the best imaging window of the LV. RESULTS: The cohort included women without prior anatomical cardiac disease. The LV was best visualized 5.8 (±2) cm cranial to the distal end of the xiphoid in the supine position and 6.1 (±2) cm in the lateral position (P=0.6), using the left parasternal border as a reference. No lateral cardiac displacement was evidenced in either position. CONCLUSIONS: This pilot study used transthoracic echocardiography to document the position of the LV during the third trimester of pregnancy. The LV was located approximately 6 cm cranial to the distal tip of the xiphoid process. Further validation is required before recommending changes in hand placement during maternal cardiopulmonary resuscitation.

Mediastinitis in the intensive care unit patient: a narrative review.

BACKGROUND: Mediastinitis is a rare but severe infection, defined as an inflammation of the connective tissues and structures within the mediastinum. Due to its proximity to vital structures, mediastinitis represents a highly morbid pathological process associated with a high risk of mortality. In most cases mediastinitis requires treatment in the intensive care unit. OBJECTIVES: To highlight to the reader the clinical features of mediastinitis, to attempt to define each clinical scenario, to describe the responsible pathogens and finally to depict both the medical and surgical treatments. SOURCES: We performed a literature search of the PubMed and Cochrane libraries, limited for articles published between January 2003 and December 2018, reporting on acute mediastinitis. CONTENT: The term covers different entities of different aetiologies including deep sternal wound infection related to sternotomy; oesophageal perforation or anastomosis leakage; and finally descending necrotizing mediastinitis, often secondary to oropharyngeal abscess. The responsible pathogens and therefore subsequent management depends on the underlying aetiology. Empirical antimicrobial therapy should cover the suspected microorganisms while surgery and supportive measures should aim to reduce the inoculum of pathogens by providing adequate drainage and debridement. IMPLICATIONS: Literature concerning mediastinitis in the intensive care unit is relatively scarce. We have collated the evidence and reviewed the different causes and treatment options of acute mediastinitis with a particular focus on microbiological epidemiology. Future research in larger cohorts is needed to better understand the treatment of this difficult disease.

Walking reduces the post-void residual volume in parturients with epidural analgesia for labor: a randomized-controlled study.

BACKGROUND: The post-void residual volume is higher among parturients who received epidural analgesia than those who received no or alternative analgesia. METHODS: This prospective, randomized, controlled, non-blinded study was performed in a tertiary referral center labor suite. The post-void residual volume was measured by a transabdominal ultrasound following a voiding attempt. Healthy parturients with low-dose epidural analgesia in active labor were randomized either to walk to the toilet or to use a bedpan for voiding. The primary outcome measure (post-void residual volume in labor) was compared between the study groups. RESULTS: The toilet group (n=34) and the bedpan group (n=28) demonstrated similar post-void residual volumes (212 +/- 100 vs. 168 +/- 93 ml, P=0.289). Twenty patients (59%) randomized to the toilet group were unable to walk and actually voided in a bedpan. A secondary analysis was performed analyzing the groups as treated. The post-void residual volume was significantly lower in the actual toilet group (n=14, 63 +/- 24 ml) vs. the bedpan group (n=48, 229 +/- 200 ml), P=0.0052. Thirteen (93%) women who walked to the toilet managed to void before the ultrasound measurement vs. 20/48 (42%) using the bedpan, P=0.001. Fewer women who managed to walk to the toilet required urinary bladder catheterization during the labor than women who used the bedpan (6/14, 43% vs. 36/48, 75%) P=0.028. CONCLUSION: Women who were randomized to walk to the bathroom with epidural analgesia and were able to do so during labor had a significantly reduced post-void residual volume and a reduced requirement for urinary catheterization.

Epidemiology of obstetric critical illness.

Obstetric intensive care unit (ICU) admissions comprise only a small part of severe maternal morbidity. The incidence rate of both remains relatively unclear due to inconsistent definitions across publications, although this has begun to be addressed. There is a relative paucity of information regarding disease-specific survival following obstetric ICU admission, but outcomes are clearly related to the cause of admission and the quality of care. The ratio between maternal near-miss cases (many of whom are admitted to ICUs) and maternal death may provide insight into the preventability of death. Hemorrhage and pre-eclampsia constitute the leading causes of ICU admission and have relatively low mortality rates, perhaps demonstrating the impact of informed care in managing obstetric critical illness. Obstetric sepsis, heart disease and anesthesia complications should be the focus of future research. The incidence of obstetric sepsis has been increasing in the last decade, with mortality rates remaining relatively high. The incidence of obstetric heart disease is increasing and maternal complications have been attributed to fractionated care of mothers within this category. Anesthesia complications remain a predominant cause of maternal death and likely intensive care admission. Data are lacking regarding the relative proportion of cases per disease that remain treated outside the ICU; and the outcomes of various management strategies. The only study of the health status of survivors of obstetric ICU admission revealed that six months after hospital discharge, one in five women still had a poorer health-related quality of life than those of a reference age- and sex-matched cohort.

High flow nasal cannula compared with conventional oxygen therapy for acute hypoxemic respiratory failure: a systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis summarizes the safety and efficacy of high flow nasal cannula (HFNC) in patients with acute hypoxemic respiratory failure. METHODS: We performed a comprehensive search of MEDLINE, EMBASE, and Web of Science. We identified randomized controlled trials that compared HFNC to conventional oxygen therapy. We pooled data and report summary estimates of effect using relative risk for dichotomous outcomes and mean difference or standardized mean difference for continuous outcomes, with 95% confidence intervals. We assessed risk of bias of included studies using the Cochrane tool and certainty in pooled effect estimates using GRADE methods. RESULTS: We included 9 RCTs (n = 2093 patients). We found no difference in mortality in patients treated with HFNC (relative risk [RR] 0.94, 95% confidence interval [CI] 0.67-1.31, moderate certainty) compared to conventional oxygen therapy. We found a decreased risk of requiring intubation (RR 0.85, 95% CI 0.74-0.99) or escalation of oxygen therapy (defined as crossover to HFNC in the control group, or initiation of non-invasive ventilation or invasive mechanical ventilation in either group) favouring HFNC-treated patients (RR 0.71, 95% CI 0.51-0.98), although certainty in both outcomes was low due to imprecision and issues related to risk of bias. HFNC had no effect on intensive care unit length of stay (mean difference [MD] 1.38 days more, 95% CI 0.90 days fewer to 3.66 days more, low certainty), hospital length of stay (MD 0.85 days fewer, 95% CI 2.07 days fewer to 0.37 days more, moderate certainty), patient reported comfort (SMD 0.12 lower, 95% CI 0.61 lower to 0.37 higher, very low certainty) or patient reported dyspnea (standardized mean difference [SMD] 0.16 lower, 95% CI 1.10 lower to 1.42 higher, low certainty). Complications of treatment were variably reported amongst included studies, but little harm was associated with HFNC use. CONCLUSION: In patients with acute hypoxemic respiratory failure, HFNC may decrease the need for tracheal intubation without impacting mortality.

Retrospective study to investigate fresh frozen plasma and packed cell ratios when administered for women with postpartum hemorrhage, before and after introduction of a massive transfusion protocol.

BACKGROUND: Administration of packed red blood cells (PRBC) and fresh frozen plasma (FFP) to women with postpartum hemorrhage (PPH) before and after introduction of a massive transfusion protocol. METHODS: The retrospective PPH study cohort of two tertiary centers was identified using blood bank records, verified by patient electronic medical records. We identified women transfused with ≥3 units PRBC in a short time period within 24 hours of delivery. Since 2010, both centers have used a protocol using 1:1 FFP:PRBC ratios. Demographic, obstetric, and blood management data were retrieved from medical records. Outcome measures included estimated blood loss, blood product administration, and hematologic variables. RESULTS: 273 women were included, 112 (41.0%) prior to introduction of the protocol (2004-2009) and 161 (59.0%) afterwards (2010-2014). The frequency of women managed with 1:1 FFP:PRBC ratios was similar before 55/112 (49.1%) and after 83/161 (51.6%) introduction of the protocol (P=0.69). There was strong correlation between PRBC units transfused and the FFP:PRBC transfusion ratio (R-square 0.866, P <0.0001), demonstrating that as the number of transfused PRBC units increased, FFP:PRBC ratios became closer to 1:1. There were no outcome differences between women managed before and after introduction of the protocol. CONCLUSIONS: Among women with PPH receiving ≥3 PRBC units within a short period of time, it appears that factors other than the existence of our massive transfusion protocol influence the number and ratio of PRBC and FFP units transfused. Blood products were not transfused according to exact ratios, even when guided by a protocol.

Management of invasive candidiasis and candidaemia in critically ill adults: expert opinion of the European Society of Anaesthesia Intensive Care Scientific Subcommittee.

OBJECTIVE: The global burden of invasive fungal disease is increasing. Candida albicans remains the leading cause of fungal bloodstream infections, although non-albicans candidal infections are emerging. Areas of controversy regarding diagnosis and management are hampering our ability to respond effectively to this evolving threat. The purpose of this narrative review is to address current controversies and provide recommendations to supplement guidelines. DIAGNOSIS OF INVASIVE CANDIDIASIS: Diagnosis of invasive candidiasis requires a combination of diagnostic tests and patient risk factors. Beta-D glucan and Candida albicans germ tube antibody are both used as biomarkers as adjuncts to diagnosis, although direct culture remains the gold standard. Scoring systems are available to help distinguish between colonization and invasive disease. TREATMENT OF INVASIVE CANDIDIASIS: Echinocandins are recommended as first-line therapy in candidaemia, with de-escalation to fluconazole when clinical stability is achieved. Empirical therapy is highly recommended in high-risk patients, but a more targeted pre-emptive approach is now being favoured. The evidence for prophylactic therapy remains weak. SUMMARY: Mortality attributable to invasive candidiasis may be as high as 70%. Prompt diagnosis and treatment, in conjunction with source control, are the key to improving outcomes.

Molecular and cellular characterization of mesenchymal progenitors for skeletal biomedical devices.

Mesenchymal cells are successfully used to create cell-loaded devices in tissue engineering. Molecular properties of the cells and interaction with polymer scaffolds regulate the development of desired tissues. The present study compared the molecular markers in mesenchymal pleuripotent C3H10T1/2 and osteogenic MBA-15 cells. The cells express transcription factors (TF) of chondro-ostegenic pathway (cbfa-1 and c-fos) and MyoD - TF of muscle differentiation pathway, but not myogenin. Analyzed cells expressed receptors for glucocorticoids, growth hormone, prolactin, and PTH, which indicates their potential responsiveness to systemic signals. Analysis of mRNA encoding for receptors of TGFbeta, TNF, and various interleukins revealed differential expression of IL-2r and TGFbeta-1r receptors, which were expressed by MBA-15 but not by C3H10T1/2 cells. Expression of functional genes indicates differences in the stages of cell differentiation: ALK was present in MBA-15 only, while both cell types expressed collagen-I. Furthermore, we evaluated the expression of adhesion proteins that mediate cell-polymer interactions by flow cytometry analysis. Cell adhesion molecules (CAMs) analyzed were integrinalpha-M (CD11b), selectin-E (CD62E), and PECAM-1 (CD31), which have shown differential expression on cells cultured on plastic, poly(L-lactic acid) (PLLA) or poly(DL-lactide-glycolide acid) (PDLGA) polymer films. Detailed molecular characterization of mesenchymal cells will enable optimization of culture conditions for successful creation of implantable cell-loaded constructs.

Attitudes of medical practitioners towards "Do Not Resuscitate" orders.

When the desires of a patient are unknown or cannot be ascertained, cardio-pulmonary resuscitation (CPR) is the default procedure. Explicit, Do Not Resuscitate (DNR), orders are required to prevent implementation of CPR. We studied the response of general medical internists in specific clinical situations demanding consideration of DNR orders and respect for patient preferences; their current practice regarding slow codes and participation in CPR attempts considered futile provide information as to how often they discuss DNR issues with patients or families. Eighty-five internists attending the monthly meeting of the Internal Medicine Forum participated in the study. The physicians demonstrated their consent to participate by accepting a remote transmitter that elicited a response 2-3 minutes following the presentation of case vignettes or practice-related questions. The survey showed that 73% of the physicians agreed to assign a DNR order for a terminally ill patient unable to express her preferences. Only 55% agreed to do the same for a competent patient who specifically requested that CPR be withheld in the event of a cardiopulmonary arrest (p<0.05). 77% reported to have performed CPR, at least three times, in situations where they expected no benefit. 59% affirmed that their team had performed a partial CPR (slow code) at least once. Only 28% discussed the subject of DNR with patients or family more than 5 times a year. Paternalism, disregard for patients' preferences and poor communication skills influence normative behaviour in end-of-life decision-making.