Physical Activity Is Associated with Slower Cognitive Decline in Older Adults with Type 2 Diabetes.

BACKGROUND: Physical activity is associated with slower cognitive decline in old age. Type 2 diabetes (T2d) is a risk factor for dementia and cognitive decline. Physical activity protects against several T2d complications. Yet, little is known about the contribution of physical activity to cognitive health among the elderly with T2d. OBJECTIVES: To examine the association between physical activity and cognitive decline in older adults with T2d. DESIGN: This is a prospective longitudinal study using data from the Israel Diabetes and Cognitive Decline (IDCD) study. SETTING: ICDC study (N=1,213), is a population-based cohort of adults over the age of 65, diagnosed with type 2 diabetes, who were cognitively normal at baseline and followed up every 18 months. PARTICIPANTS: Participants with at least one follow-up assessment who were in the same physical activity group consistently and had complete demographic data. MEASUREMENTS: Physical activity was measured using Minnesota Leisure Time Activity Questionnaire, cognitive functioning was measured using a broad neuropsychological assessment measuring Executive Functioning, Attention/Working Memory, Semantic Categorization and Episodic Memory. RESULTS: Participants were classified into physical activity groups based on self-reported physical activity at baseline and all follow ups: "active" - participation in recreational physical activity (n=286); "non-active"- the only physical activity was walking from place to place (n=93) and "sedentary" (n=19). Linear mixed effects models were applied to adjust for key demographic and cardiovascular risk factors. Participants were 72.4 (SD 4.6) years old, had 13.3 (SD 3.6) years of education, and 163 (41%) were female. In the fully adjusted model, compared to the non-active group the active group had significantly slower rate of decline in Global Cognition (p=0.005), Executive Functioning (p=.014), and Attention/Working Memory (p=.01). There were no significant group differences for Semantic Categorization (p=.17) and Episodic Memory (p=.88). CONCLUSIONS: Among initially cognitively normal and independent older adults with T2d, a physically active lifestyle was associated with a slower rate of cognitive decline. Future research should examine whether promoting physical activity may prevent or delay onset of dementia in this high-risk population.

Patients' preferences for telemedicine versus in-clinic consultation in primary care during the COVID-19 pandemic.

BACKGROUND: The Hybrid Patient Care system integrates telehealth and in-clinic consultation. While COVID-19 increased telehealth use, healthcare providers are still seeking the best combination of virtual and in-clinic consultation. Understanding patients' tele-consultation-related preferences is vital for achieving optimal implementation. The discrete choice experiment (DCE) is the stated preference technique for eliciting individual preferences and is increasingly being used in health-related applications. The study purpose was to evaluate attributes and levels of the DCE regarding patients' preferences for telemedicine versus traditional, in-clinic consultation in primary care during the COVID-19 pandemic, in order to facilitate successful implementation. METHODS: A three-phase structure was used in the qualitative stage of the DCE: (1) a literature review and preparation of interview guides; (2) Eight focus group interviews comprised of 26 patients and 33 physicians; and (3) Attribute selection: a ranking exercise among 48 patients. The Think Aloud technique, in which respondents are asked to verbalize their thoughts, was used in the focus groups. Interview data were analyzed by thematic analysis. RESULTS: Eight attributes were proposed by the patients in the focus groups. The four most important attributes were then selected in pre-testing, and are described in this study: Availability, time until the appointment, severity of the medical problem, patient-physician relationship, and flexible reception hours. CONCLUSIONS: This study has a theoretical contribution in post-COVID-19 patients' preferences in Hybrid Medicine patient care. This provides a foundation to assess the rigors of this stage and provide additional evidence to the limited existing literature on attributes development for DCE patient preferences.

The relation between gain in cognition during rehabilitation on functional outcome among hip fracture adult patients with and without pre- hip fracture dementia.

The purpose of the present study was focused on the relationship between change in cognition and the functional outcome during rehabilitation in demented and non-demented adult hip fracture patients. We studied seventy consecutive adult patients with hip fracture admitted to our rehabilitation wards. Functional outcome was assessed by the Functional Independence Measure (FIM). The gain in cognition during the rehabilitation process was measured by the difference in Mini Mental State Examination scores at admission and discharge. Data was analyzed by t-test, chi square-test and linear regression. Patients without dementia presented and discharged from the rehabilitation ward with statistically significant higher total, motor, and gain functional independence measure scores compared to patients with dementia. In a multiple regression analyses, gain in Mini Mental State scores examination were not independently associated with higher total and motor functional independence measure scores at discharge (beta = 0.086, p = 0.194; beta = 0.077, p = 0.309, respectively). Our findings suggest that there is no association between functional outcome and cognitive gain at the end of the rehabilitation process among adult hip fracture patients with and without dementia. However hip fracture adult patients with dementia should not be deprived of a post-acute rehabilitation.

Principles of effective communication with patients who have intellectual disability among primary care physicians.

OBJECTIVE: Examine physicians' implementation of effective communication principles with patients with intellectual disabilities (ID) and its predictors. METHODS: Focus groups helped construct a quantitative questionnaire. The questionnaire (completed by 440 physicians) examined utilization of effective communication principles, attitudes toward individuals with ID, subjective knowledge and number of patients with ID. RESULTS: Subjective knowledge of ID and more patients with ID increased utilization of effective communication principles. Provision of knowledge that allows patients to make their own medical decisions was predicted by more patients with ID, lower attitudes that treatment of this population group is not desirable, less negative affect and greater perception that treatment of this group is part of the physician's role. Effective preparation of patients with ID for treatment was predicted by higher perception of treatment of this group as part of the physician's role, lower perception of this field as undesirable and higher perception of these individuals as unable to make their own choice. Simplification of information was predicted by a greater perception of treatment of this group as part of the physician's role and more negative affect. CONCLUSION: Greater familiarity may enhance care for these patients. PRACTICE IMPLICATIONS: Increase exposure to patients with ID within training.

Diabetes prevention program in a Mediterranean environment: individual or group therapy? An effectiveness evaluation.

INTRODUCTION: Diabetes as a multifactorial disorder requires prevention measures based upon the modification of several risk factors simultaneously; otherwise, there is insufficient potential for prevention. Following the success of the American Diabetes Prevention Program (DPP), we implemented an intervention program in a large Israeli healthcare organization with an emphasize on Mediterranean Diet (MedDiet) and physical activity. The objective was to evaluate the effectiveness of two types of intervention, individual and group therapies, in reducing risk factors and in preventing or delaying the development of type 2 diabetes. METHODS: Out of 180 primary care physicians, 85 who agreed to participate, were randomly assigned, between the years 2005 and 2006, into two groups: those who would refer pre-diabetes adult patients for individual therapy and those who would refer for group therapy. The two groups of patients consisted of 111 and 112 in each group. The intervention lasted for 6 months and discussed: the benefits of MedDiet, planning nutritional behavior and mindful eating, and the importance of physical activity. All patients were invited to participate in walking groups. Follow up lasted for 24 months and logistic, mixed models, and Cox regressions were employed. RESULTS: No statistically significant differences were detected between the two intervention groups in age; gender and clinical measurements at recruitment. Thirty nine percent of both groups developed diabetes (entered the DR by 2012), including 38.7% from the individual therapy and 39.3% from the group therapy (P=0.933). The mean time from 2005 until entry to the Diabetes Registry (DR) was 2.9 and 2.5 years for the individual and group therapy respectively (P=0.542). CONCLUSION: Both interventions were equally effective in achieving the desired outcomes and time until entry to the DR. For large health organizations with a high number of pre-diabetes patients and scarce resources, group therapy, where 12 people are reached out by one team member are preferable and more costly effective, than a one on one therapy.

A changed pattern of insulin use following the introduction of basal analog insulin treatment in primary care.

AIMS: We analyzed the impact of the removal of administrative restrictions on basal analog insulin prescribing by primary care physicians in the year 2008 in a large HMO. METHODS: This cross-sectional database study of patients with diabetes study was conducted in Maccabi Healthcare Services, the second largest HMO in Israel, insuring 1.9 million members countrywide. The research population included men over 40 and women over the age of 45 from MHS diabetes registry during the time period 1.1.2002-31.12.2009. RESULTS: After removal of basal analog insulin prescription restrictions, more primary care physicians initiated treatment with basal analog insulin than with other types of insulin and did so with fewer referrals for specialty diabetes consultation. No growth in the relative number of patients commencing insulin use was observed, nor did we find an earlier initiation of insulin. CONCLUSION: In the first year following the relaxation of prescribing restrictions on the use of basal analog insulin we observed an increase in its use amongst patients previously treated with other types of insulin. The administrative changes did not result in an overall increase in the use of insulin in the study population.

Primary care intervention programme to improve early detection of hearing loss in the elderly.

OBJECTIVE: To improve audiology screening in general practice, using an intervention programme aiming to empower older adults and their general practitioners. METHODS: We conducted a quasi-experimental community study comparing 206 patients and two control groups (the first being 101 people registered with the same general practitioner, and the second 87 people registered with another general practitioner). Outcome measures were: rates of hearing tests in the six months before interview, and screening recommendation by the general practitioner. RESULTS: Amongst patients, there was a significant increase in numbers undergoing a hearing test, from 19 per cent before the intervention to 49 per cent two years later, while in the two control groups there was little change. Twenty-two per cent of patients and 19 per cent of the first control group reported that their physicians suggested undergoing a hearing test; the second control group subjects (whose general practitioners received no specific educational intervention) showed no change. CONCLUSION: The two crucial factors for improving hearing screening uptake in the elderly are general practitioner education and patient empowerment.

Strategies for diagnosis and treatment of iatrogenic tracheal ruptures.

BACKGROUND: Management of tracheal ruptures in critically ill patients is challenging. Conservative treatment has been described, but in mechanically ventilated patients with distal tracheal ruptures surgical repair might be inevitable. Strategies for diagnosis and treatment of tracheal ruptures and handling of mechanical ventilation remain to be clarified. Our aim was to comprise a structured diagnostic and treatment protocol for patients suspicious of tracheal injury, including detailed principles of mechanical ventilation and specific indications for conservative or surgical treatment. METHODS: Patients with tracheal ruptures were compared in accordance to the need of mechanical ventilation and to indication for surgical repair. In patients suffering from tracheal ruptures affecting the whole tracheal wall and with protrusion of mediastinal structures into the lumen surgery was indicated. We compared ventilatory, hemodynamic and clinical parameters between the different patient groups. We report our structured approach in diagnostics and treatment of tracheal ruptures and place special emphasis on respiratory management. RESULTS: Seventeen patients with tracheal rupture were identified. In 8 patients surgical repair was performed 1.8±1.5 days after diagnosis. Previous to surgery, ventilation parameters improved significantly: plateau pressure decreased, percentage of assisted spontaneous breathing increased and compliance improved. Conservative treatment was successful in long-term ventilated patients (13.7±8 days) even when suffering from distal lesions. CONCLUSION: Invasiveness of mechanical ventilation and obstruction of tracheal lumen might indicate conservative or surgical treatment strategies in long-term ventilated patients suffering from iatrogenic tracheal rupture. Indications for surgical repair remain to be further clarified.

Assessment of the underestimation of childhood diarrhoeal disease burden in Israel.

We determined the extent by which mandatory reporting on isolates of Shigella and Salmonella underestimates the burden of diarrhoeal diseases in individuals aged <17 years in Israel and examined paediatricians' knowledge, attitudes and practices related to patient visits with diarrhoeal diseases. Sources of data were a nationwide population-based telephone survey for presence of diarrhoeal diseases, Maccabi Healthcare Services databases and a mail survey among its paediatricians. Monte Carlo simulation and rate estimates for all stages, from visit to physician to reporting on a culture-confirmed case of shigellosis or salmonellosis, were used to determine the underestimation factor. Of 1492 children, 5·7% reported a diarrhoeal episode during the 2 weeks prior to interview. The rate of visiting a physician with and without fever was 86% and 16%, respectively. A stool culture was performed for around 20% of patients and the isolation rates were 7·1% for Shigella and 2·1% for Salmonella. Paediatricians (n=214) ranked very young age of patient and the complaint 'bloody diarrhoea' as the most important determinants. We estimated that one reported isolate of Shigella or Salmonella represented 152 diarrhoeal episodes of all aetiologies. This estimate is important for further assessments of the true burden of diarrhoeal diseases.

The importance of measuring self-efficacy in patients with diabetes.

OBJECTIVES: Self-efficacy is an important factor influencing diabetes self-management behaviours. Previous studies have examined self-efficacy as a general measure in diabetes care for all self-care treatment recommendations together. This current study was designed to examine if low self-efficacy in each of the measured self-care treatment recommendations is related to decreased adherence for each specific recommendation. METHODS: The self-efficacy was measured in 119 patients for four different treatment recommendations: blood glucose self-monitoring, exercise, diet and oral medication intake and correlated with The Resistance to Treatment Questionnaire. RESULTS: Significant and positive Pearson's correlations were found between the frequency of adherence to treatment recommendations and the self-efficacy regarding different recommendations. The correlation between self-efficacy and diet and physical activity was 0.5 and 0.67, respectively. The higher the resistance to treatment score, the less confident the patient is in his or her ability to adhere with treatment recommendations. This pattern was not present in adherence to medication intake. CONCLUSIONS: Self-efficacy impacts adherence to treatment and therefore plays a role in the clinical outcome. The practical implication is that assessment of self-efficacy in people with diabetes may be a first step in the development of individually tailored interventions.

Remifentanil reduces the incidence of post-operative delirium.

A secondary exploratory analysis of data from an observational study was used to study the influence of the opioid used for intraoperative anaesthesia on the incidence of post-operative delirium. Patients who had been admitted to the recovery room following elective general anaesthesia were divided into those who had received fentanyl or remifentanil. For unbiased patient analysis, matched pairs were built with respect to gender, age, physical status, anaesthetic type and surgery duration. In 752 patients, the overall incidence of delirium was 9.9% in the recovery room and 3.8% on the first post-operative day. Compared with the remifentanil group, the fentanyl group had a significantly higher incidence of delirium in the recovery room (12.2% versus 7.7%) and on the first post-operative day (5.8% versus 1.9%). Delirium in the recovery room and on the first post-operative day were both associated with a significantly prolonged post-operative hospital stay. The choice of intraoperative opioid influences the incidence of post-operative delirium. Remifentanil was associated with a lower incidence of post-operative delirium in the early post-operative period.

The risk of overt diabetes mellitus among women with gestational diabetes: a population-based study.

AIMS: To determine the incidence of postpartum diabetes mellitus in the years following a diagnosis of gestational diabetes mellitus (GDM) and to determine whether the severity of GDM, represented by the magnitude of the deviation of diagnostic tests from the normal values or requirement for medications, is associated with the development of diabetes. METHODS: A retrospective cohort study was performed among 185 416 pregnant women who had glucose challenge test or 3 h oral glucose tolerance test (OGTT) in a large health maintenance organization in Israel. Subsequent diagnosis of diabetes was ascertained by using an automated patient registry. RESULTS: A total of 11 270 subjects were diagnosed with GDM, comprising 6.07% of the cohort. During a total follow-up period of 1 049 334 person-years there were 1067 (16.9 per 1000 person-years) and 1125 (1.1 per 1000 person-years) diagnoses of postpartum diabetes among GDM and non-GDM women, respectively. The cumulative risk of incident diabetes in GDM patients with up to 10 years of follow-up was 15.7%, compared with 1% among the non-GDM population. Gestational diabetes mellitus was associated with nearly an eightfold higher risk of postpartum diabetes after adjusting for important confounders, such as socioeconomic status and body mass index. Among women with a history of GDM, the number of abnormal OGTT values and use of insulin were associated with a substantially higher risk for developing diabetes. CONCLUSIONS: Three or four abnormal OGTT values and GDM requiring insulin or oral hypoglycaemic medications are important predictors of postpartum diabetes risk in women with a history of GDM.

Delayed treatment of delirium increases mortality rate in intensive care unit patients.

Delirium in the intensive care unit (ICU) is a serious complication associated with a poor outcome in critically ill patients. In this prospective observational study of the effect of a delay in delirium therapy on mortality rate, 418 ICU patients were regularly assessed using the Delirium Detection Score (DDS). The departmental standard required that if delirium was diagnosed (DDS >7), therapy should be started within 24 h. In total, 204 patients (48.8%) were delirious during their ICU stay. In 184 of the delirious patients (90.2%), therapy was started within 24 h; in 20 patients (9.8%), therapy was delayed. During their ICU stay, patients whose delirium treatment was delayed were more frequently mechanically ventilated, had more nosocomial infections (including pneumonia) and had a higher mortality rate than patients whose treatment was not delayed. Thus, it would appear that a delay in initiating delirium therapy in ICU patients was associated with increased mortality.

School closure may be effective in reducing transmission of respiratory viruses in the community.

Proposed measures to contain pandemic influenza include school closure, although the effectiveness of this has not been investigated. We examined the effect of a nationwide elementary school strike in Israel in 2000 on the incidence of influenza-like illness. In this historical observational study of 1.7 million members of a preferred provider organization, we analysed diagnoses from primary-care visits during the winter months in 1998-2002. We calculated the weekly ratio of influenza-like diagnoses to non-respiratory diagnoses, and fitted regression models for school-aged children, children's household members, and all other individuals aged >12 years. For each population the steepest drop in the ratio of influenza-like diagnoses to non-respiratory diagnoses occurred in the strike year 2 weeks after the start of the strike. The changes in the weekly ratio of influenza-like diagnoses to non-respiratory diagnoses were statistically significant (P=0.0074) for school children for the strike year compared to other years. A smaller decrease was also seen for the adults with no school-aged children in 1999 (P=0.037). The Chanukah holiday had a negative impact on the ratio for school-aged children in 1998, 1999 and 2001 (P=0.008, 0.006 and 0.045, respectively) and was statistically significant for both adult groups in 1999 and for adults with no school-aged children in 2001. School closure should be considered part of the containment strategy in an influenza pandemic.

Long-term trends in hepatitis A incidence following the inclusion of Hepatitis A vaccine in the routine nationwide immunization program.

For many years hepatitis A was one of the most common vaccine preventable diseases in Israel. In 1999, Israel became the first country to introduce an inactivated hepatitis A vaccine into its national childhood vaccination program. The objectives of the present study were to study trends in disease incidence after the implementation of the new vaccination policy and to assess vaccination coverage among children and adults in Israel. We used the databases of the second largest HMO in Israel (1.7 million members) to identify patients who had evidence of hepatitis A in 1998 and 2007 and to collect information on all subjects who received at least one dose of hepatitis A vaccine during the study period. Hepatitis A vaccination coverage in children <5 years and 5-14 years of age increased from 9% and 15% in 1998 to 89% and 68% in 2007, respectively. During this period the annual incidence of hepatitis A dropped from 142.4 per to 7.6 per 100 000. The most prominent reduction in the age-specific annual incidence rates was calculated in children <5 years from 239.4 per 100 000 in 1998 to 2.2 per 100 000 in 2007 and from 310.3 per 100 000 to 3.0 per 100 000 in children aged 5-14 years. In endemic areas, vaccination of infants and children against hepatitis A can greatly reduce the total burden of the disease.

Diabetes as a risk factor for herpes zoster infection: results of a population-based study in Israel.

BACKGROUND: Studies showed that diabetes mellitus (DM) is often accompanied by impaired cell-mediated immunity, which potentially may increase the risk for infectious diseases, including herpes zoster (HZ). However, data on the relation between DM and HZ are scarce. This case-control study explored the association between DM and HZ. PATIENTS AND METHODS: This study was nested within a cohort of all members of a large health maintenance organization (HMO) in Israel. Cases totaled 22,294 members who were diagnosed with HZ between 2002 and 2006. Controls (n=88,895) were randomly selected from the remaining HMO population using frequency-matched age, sex, and duration of follow-up. Personal data on history of DM, lymphoma, leukemia, or AIDS, were obtained from computerized medical records. RESULTS: Adjusted analyses showed that the risk of HZ was associated with history of leukemia, lymphoma, use of steroids or antineoplastic medications, and AIDS, particularly among patients below 45 years of age. In a multivariate analysis, DM was associated with an increased risk of HZ (OR=1.53; 95% CI: 1.44-1.62). CONCLUSIONS: The data suggest that individuals with DM are at increased risk of HZ. Well-designed cohort studies may help to clarify the nature of this association.

The association between glycemic, lipids and blood pressure control among Israeli diabetic patients.

BACKGROUND: It is recommended that in diabetes mellitus patients all risk factors for cardiovascular disease should be controlled. AIM: To evaluate the rate of reaching all glycemic, lipids and blood pressure target levels among diabetic patients in Israel and to analyze demographic and clinical parameters associated with it. DESIGN: A cross-sectional study. METHODS: The study was conducted in Maccabi Healthcare Services, Israel's second largest health maintenance organization. All patients (n = 41 936), older than 20 years, who were listed on Maccabi Healthcare Service's diabetes mellitus computerized database and had all three study parameters (HbA1c, LDL-C and blood pressure levels during 2005) were eligible for the study. The rate of reaching HbA1c <7.0%, LDL-C <100 mg/dl and blood pressure <130/85 mmHg, as well as its association with various demographic and clinical parameters were analyzed. RESULTS: Only 13% of all study patients achieved all three target levels. The parameters which were significantly associated with goal achievement were compliance to medical treatment for all three parameters (OR 1.56, 95% CI 1.44-1.69, P = 0.0001), male gender (OR 1.42, 95% CI 1.31-1.54, P = 0.0001), comorbidity with ischemic heart disease (OR 1.23, 95% CI 1.13-1.34, P = 0.0001), and >12 visits per year to family physician (OR 1.10, 95% CI 1.02-1.19, P = 0.012). CONCLUSION: Non-compliance with treatment and sub-optimal follow-up by family physicians are associated with increased risk of failure to control major risk factor among diabetic patients.

Conceptualization and measurement of resistance to treatment: the resistance to treatment questionnaire for people with diabetes.

OBJECTIVE: This research describes the process of building a tool which allows assessment of resistance to treatment and its intensity among patients with diabetes. METHODS: This study was undertaken in Maccabi Health care Services a preferred provider health care organization. This is a multistage study using both qualitative and quantitative methods. A semi-structured interview using 14 key questions identified the reasons for resistance to treatment among 64 people with diabetes. A questionnaire was built based on these themes and then validated with a further 123 people with diabetes. A further validation was undertaken comparing our questionnaire with that of Kavookjian. RESULTS: This resulted in a four theme, 40-item questionnaire which can be administered in about 10 minutes. Resistance patterns and their intensity were different in each patient. This resistance questionnaire identifies the core reasons for non-compliance: lack of faith or dissatisfaction with the treatment or with the medical team, emotional reasons, specific problems or constraints and factors connected to despair and failure. CONCLUSIONS: We present a tool 'The Resistance to Treatment Questionnaire' which may be used by medical personnel to identify the barriers to treatment for each individual and in turn improve patient compliance to treatment.

Hyperactive delirium and blood glucose control in critically ill patients.

Delirium is a common complication of critically ill patients and is often associated with metabolic disorders. One of the most frequent metabolic disorders in intensive care unit (ICU) patients is hyperglycaemia. The aim of this retrospective study of 196 adult ICU patients was to determine if there is an association between hyperactive delirium and blood glucose levels in ICU patients. Hyperactive delirium was diagnosed using the delirium detection score. Blood glucose levels were monitored by blood gas analysis every 4 h. Hyperactive delirium was detected in 55 (28%) patients. Delirious patients showed significantly higher blood glucose levels than non-delirious patients Higher overall complication rates, length of ventilation, ICU stay and mortality rates were seen in the delirium group. In a multivariate analysis, glucose level, alcohol abuse, APACHE II score, complication by hospital-acquired pneumonia and a diagnosis of polytrauma on-admission all significantly influenced the appearance of delirium.

Role of bone morphogenetic protein 2 in the crosstalk between endothelial progenitor cells and mesenchymal stem cells.

In recent studies, we and others have demonstrated that bone morphogenetic protein-2 (BMP-2) promotes vascularization, inhibits hypoxic cell death of cancer cells and may be involved in tumor angiogenesis. The activation of circulating endothelial progenitor cells (EPCs) and mesenchymal stem cells (MSCs) represents a crucial factor in the process of postnatal neovascularization. BMP-2 protein expression has been detected in several tumor tissues and BMP receptors are expressed in EPCs and MSCs. We therefore analysed the influence of recombinant human (rh) BMP-2 on the function of human EPCs and human bone marrow derived MSCs. Treatment of EPCs isolated from peripheral blood with rhBMP-2 did not induce any significant changes in EPC viability but induced a dose-dependent activation of chemotaxis. Incubation of human MSCs isolated from bone marrow aspirates with rhBMP-2 revealed no significant effect on MSC proliferation. Incubation of EPCs with supernatants of MSCs significantly increased the cell viability compared to controls cultivated with endothelial cell medium. Protein and mRNA expression of the vascular endothelial growth factor (VEGF) family member, placental growth factor (PlGF), which is known to be involved in the expansion and recruitment of EPCs, was induced in MSCs after treatment with rhBMP-2. We conclude that tumor- associated BMP-2 secretion might promote tumor angiogenesis by chemotactic effects on EPCs circulating in the peripheral blood and by increased secretion of paracrine angiogenic growth factors including PlGF in MSCs of the tumor stroma.