Automatic generation of alloreactivity-reduced donor lymphocytes and hematopoietic stem cells from the same mobilized apheresis product.

INTRODUCTION: In vitro or in vivo depletion of alloreactive T cells can facilitate haplo-identical hematopoietic stem cell transplantation (HSCT). Very satisfactory transplant outcomes were thus reported for TCRαß/CD19-depleted hematopoietic stem/progenitor cell (HSPC) grafts. The current semi-automatic manufacturing process on the CliniMACS Plus, although robust, still requires a significant amount of manual labor to be completed. Towards advancing and further facilitating large scale cell processing, a new TCRαß/CD19 depletion module combined with the previously described CD45RA depletion module (to serve as allo-reactivity attenuated donor lymphocyte infusion) was established on the CliniMACS Prodigy. METHODS: We evaluated six apheresis products from G-CSF-mobilized volunteer donors which were split automatically by the Prodigy, one portion each depleted of CD45RA+ or of TCRαß+ and CD19+ cells. We investigated critical quality attributes for both products. Products were assessed for recovery of HSPCs and mature subsets, as well as depletion efficiency of targeted cells using flow cytometry. Effects of apheresis and product age post 48 h storage at 2-6 °C as well as freeze-thawing on product viability and recovery of WBC and HPSCs were assessed by flow cytometry. RESULTS: Ten sequential automatic processes were completed with minimal hands-on time beyond tubing set installation. Depletion efficiency of CD45RA+ resp. TCRαß+ and CD19+ cells was equivalent to previous reports, achieving mean depletions of 4 log of targeted cells for both products. HSPC products retained TCRγδ+ and NK cells. 48 h storage of apheresis product was associated with the expected modest loss of HSPCs, but depletions remained efficient. Depleted products were stable until at least 72 h after apheresis with stem cell viabilities > 90%. Freeze-thawing resulted in loss of NK cells; post-thaw recovery of viable CD45+ and HSPCs was > 70% and in line with expectation. CONCLUSION: The closed, GMP-compatible process generates two separate medicinal products from the same mobilized apheresis product. The CD45RA-depleted products contained functional memory T cells, whereas the TCRαß/CD19-depleted products included HSPCs, TCRγδ+ and NK cells. Both products are predicted to be effectively depleted of GVH-reactivity while providing immunological surveillance, in support of haplo-identical HSCT.

Metronomic Temozolomide in Heavily Pretreated Patients With Recurrent Isocitrate Dehydrogenase Wild-type Glioblastoma: A Large Real-Life Mono-Institutional Study.

AIMS: Glioblastoma (GBM) is the most common primary malignant brain tumour in adults and frequently relapses. The aim of this study was to assess the efficacy and safety of metronomic temozolomide (TMZ) in the recurrent GBM population. MATERIALS AND METHODS: All patients treated at our centre between September 2013 and March 2021 were retrospectively reviewed. The main inclusion criteria were first-line therapy with the Stupp protocol, relapse after the first or subsequent line of therapy, treatment with a metronomic TMZ schedule (50 mg/m2 continuously) and histological diagnosis of isocitrate dehydrogenase wild-type GBM according to World Health Organization 2016 classification. RESULTS: In total, 120 patients were enrolled. The median follow-up was 15.6 months, the median age was 59 years, Eastern Cooperative Oncology Group performance status (ECOG-PS) was 0-2 in 107 patients (89%). O6-methylguanine-DNA-methyltransferase (MGMT) was methylated in 66 of 105 (62%) evaluable patients. The median number of prior lines of treatment was 2 (range 1-7). Three (2%) patients showed a partial response; 48 (40%) had stable disease; 69 (57%) had progressive disease. The median overall survival from the start of metronomic TMZ was 5.4 months (95% confidence interval 4.3-6.4), whereas the median progression-free survival (PFS) was 2.6 months (95% confidence interval 2.3-2.8). At univariate analysis, MGMT methylated and unmethylated patients had a median PFS of 2.9 and 2.1 months (P = 0.001) and a median overall survival of 5.6 and 4.4 months (P = 0.03), respectively. At multivariate analysis, the absence of MGMT methylation (hazard ratio = 2.3, 95% confidence interval 1.3-3.9, P = 0.004) and ECOG-PS ≤ 2 (hazard ratio = 0.5, 95% confidence interval 0.3-0.9, P = 0.017) remained significantly associated with PFS, whereas ECOG-PS ≤ 2 (hazard ratio = 0.4, 95% confidence interval 0.3-07, P = 0.001) was the only factor associated with overall survival. The most common grade 3-4 toxicities were haematological (lymphopenia 10%, thrombocytopenia 3%). CONCLUSIONS: Rechallenge with metronomic TMZ is a well-tolerated option for recurrent GBM, even in pretreated patients. Patients with methylated MGMT disease and good ECOG-PS seem to benefit the most from this treatment.

Accuracy of a spontaneous breathing trial for extubation of neonates.

BACKGROUND: Prevalence of extubation failure in neonates may be up to 80%, but evidence to determine if a neonate is ready for extubation remains unclear. We aim to evaluate a spontaneous breathing trial accuracy with minimum pressure support to predict success in neonates' extubation and identify variables related to failures. METHODS: This is a diagnostic accuracy study based on a cohort study in an intensive care unit with all eligible newborn infants subjected to invasive mechanical ventilation for at least 24 hours submitted to the trial for 10 minutes before extubations. The outcome was failures of extubations, considered if reintubation was needed until 72 hours. RESULTS: The incidence of failure was 14.7%among 170 extubations. There were 145 successful extubations; of these, 140 also passed the trial with a sensitivity of 96.5%(95%CI: 92.1-98.9). Of the 25 extubations that eventually failed, 16 failed the test with a specificity of 64.0%(95%CI: 42.5-82.0). The negative predictive value was 76.2%, and the positive predictive value was 94%. In stratifying by weight, the accuracy was >98.7%for neonates weighting >2500 g, but 72.5%for those weighing <1250 g. Extubation failures occurred more frequently in smaller (p = 0.01), preterm infants (p = 0.17), with longer ventilation time (p = 0.05), and having a hemodynamically significant persistent arterial duct (p = 0.01), compared with infants whose extubation was successful. CONCLUSION: The spontaneous breathing trial with minimum pressure support ventilation seems to predict extubation success with great accuracy in full-term and larger neonates.

Fertilizing a Patient Engagement Ecosystem to Innovate Healthcare: Toward the First Italian Consensus Conference on Patient Engagement.

Currently we observe a gap between theory and practices of patient engagement. If both scholars and health practitioners do agree on the urgency to realize patient engagement, no shared guidelines exist so far to orient clinical practice. Despite a supportive policy context, progress to achieve greater patient engagement is patchy and slow and often concentrated at the level of policy regulation without dialoguing with practitioners from the clinical field as well as patients and families. Though individual clinicians, care teams and health organizations may be interested and deeply committed to engage patients and family members in the medical course, they may lack clarity about how to achieve this goal. This contributes to a wide "system" inertia-really difficult to be overcome-and put at risk any form of innovation in this filed. As a result, patient engagement risk today to be a buzz words, rather than a real guidance for practice. To make the field clearer, we promoted an Italian Consensus Conference on Patient Engagement (ICCPE) in order to set the ground for drafting recommendations for the provision of effective patient engagement interventions. The ICCPE will conclude in June 2017. This document reports on the preliminary phases of this process. In the paper, we advise the importance of "fertilizing a patient engagement ecosystem": an oversimplifying approach to patient engagement promotion appears the result of a common illusion. Patient "disengagement" is a symptom that needs a more holistic and complex approach to solve its underlined causes. Preliminary principles to promote a patient engagement ecosystem are provided in the paper.

Comparison between rice husk ash grown in different regions for stabilizing fly ash from a solid waste incinerator.

The Stabilization of heavy metals from municipal solid waste incineration (MSWI) fly ash by rice husk ash (RHA) is under intense study as an effective strategy to recover and reuse industrial and agricultural waste together. We compare the metal entrapment performances of RHA from different Asian rice sources ­ namely from Japonica rice grown in Italy and Indica rice grown in India ­ Physicochemical and morphological characterization of the final stabilized material show that the same thermal treatment may result in marked structural differences in the silica contained in the two RHA. Remarkably, one of them displays a crystalline silica content, although obtained by a thermal treatment below 800 °C. We also find that the presence of an alkali metal ion (potassium) in the rice husk plays a crucial role in the attainment of the final silica phase. These physicochemical differences are mirrored by different stabilization yields by the two RHA.

'Engage me in taking care of my heart': a grounded theory study on patient-cardiologist relationship in the hospital management of heart failure.

OBJECTIVE: In approaching the study and practice of heart failure (HF) management, authors recognise that the patient-doctor relationship has a central role in engaging patients in their care. This study aims at identifying the features and the levers of HF patient engagement and suggestions for orienting clinical encounters. DESIGN: Using a grounded theory approach, we conducted 22 in-depth interviews (13 patients with HF, 5 physicians and 4 caregivers). Data were collected and analysed using open, axial and selective coding procedures according to the grounded theory principles. SETTINGS: All interviews were conducted in an office in a university hospital located in a metropolitan area of Milan, Italy. PARTICIPANTS: The data comprised a total of 22 patient, hospital cardiologist and caregiver interviews. Patients aged ≥18 years with New York Heart Association (NYHA) Functional Class of II or III were eligible to take part. Patients were recruited primarily through their referral cardiologist. RESULTS: The HF patient engagement process develops in four main phases that are characterised by different patients' emotional, cognitive and behavioural dynamics that contribute to shape the process of a patient's meaning making towards health and illness regarding their care. The emerging model illustrates that HF patient engagement entails a meaning-making process enacted by the patient after the critical event. This implies patients' ability to give sense to their care experience and to their disease, symptomatology and treatments, and their changes along their illness course. Doctors are recognised as crucial in fostering patients' engagement along all the phases of the process as they contribute to providing patients with self-continuity and give new meaning to their illness experience. CONCLUSIONS: This study identifies the core experiential domains and the main levers involved in driving patients with HF to effectively engage in their disease management. The model emerging from this study may help clinicians think in a fresh way about encounters with patients and their role in fostering their patients' health engagement.

Reliability of the assessment of peripheral muscle fatigue induced by high-intensity intermittent exercise.

AIM: Reliability of the assessment of peripheral fatigue induced in knee extensors by high-intensity intermittent running exercise (HIE) was established in ten amateur soccer players (age: 18±1, height: 178±5 cm, weight: 68±8 kg). METHODS: Transcutaneous electrical stimulations before and after HIE determined muscle contractile properties on three separate occasions (T1, T2 and T3), each separated by 7 days. RESULTS: No significant differences were noted for any of the parameters measured (P=0.101). The ICC values for peak torque (PT) varied from moderate to high, with the exception of PT at 10-Hz calculated comparing T2 vs. T1 (range PRE=0.78-0.92; POST=0.76-0.97). The ICC derived from PT percentage decrements data were all low, with the exception of PT decrements at 1 Hz calculated comparing T3 vs. T2 (ICC=0.85, moderate). The TE for all contractile parameters obtained using 1-Hz and 100-Hz electrical stimulations were below 10%, including some that demonstrated a TE lower than 5%. Muscle contractile properties determined using 10-Hz stimulations showed a higher level of TE (range: 3.2-15.1%). Similar results were obtained for maximal rate of torque development and torque relaxation. CONCLUSION: From the results of this study it can be concluded that muscle contractile properties express a good level of reliability in baseline and postexercise measures following familiarization.

Enabling eHealth as a Pathway for Patient Engagement: a Toolkit for Medical Practice.

Academic and managerial interest in patient engagement is rapidly earning attention and becoming a necessary tool for researchers, clinicians and policymakers worldwide to manage the increasing burden of chronic conditions. The concept of patient engagement calls for a reframe of healthcare organizations' models and approaches to care. This also requires innovations in the direction of facilitating the exchanges between the patients and the healthcare. eHealth, namely the use of new communication technologies to provide healthcare, is proved to be proposable to innovate healthcare organizations and to improve exchanges between patients and health providers. However, little attention has been still devoted to how to best design eHealth tools in order to engage patients in their care. eHealth tools have to be appropriately designed according to the specific patients' unmet needs and priorities featuring the different phases of the engagement process. Basing on the Patient Engagement model and on the Positive Technology paradigm, we suggest a toolkit of phase-specific technological resources, highlighting their specific potentialities in fostering the patient engagement process.

Effects of a 25-km trial on psychological, physiological and stroke characteristics of short- and mid-distance swimmers.

AIM: The aim of this paper was to evaluate the effects of a very long distance swimming task on psychological, biomechanical and physiological responses. Eight swimmers (age 21.0 ± 1.2 years; stature 1.80 ± 0.07 m; body mass 76.7 ± 11.0 kg; means ± SD) participated in a 25-km trial in a swimming pool. METHODS: Before and immediately after the trial, swimmers underwent a 50-m sprint test, during which we assessed velocity, stroke rate (SR), stroke length (SL) and psychological condition (rate of perceived exertion [RPE] and profile of mood state [POMS] questionnaire). During the 25-km trial we determined also elbow angle, heart rate (HR) and lactate concentration ([La]). RESULTS: Velocity, SR and SL during the sprint test after the trial decreased compared to before from 1.91 ± 0.01 m·s⁻¹, 0.94 ± 0.01 cycles·s⁻¹ and 1.99 ± 0.02 m·cycle⁻¹ to 1.45 ± 0.01 m·s⁻¹, 0.78 ± 0.01 cycles·s⁻¹ and 1.84 ± 0.03 m·cycle⁻¹, respectively (P<0.05). During the 25-km trial, velocity and SL decreased significantly, while SR and elbow angle did not change. Velocity and SR during the sprint test after the trial were significantly higher than those during the trial. RPE and fatigue (POMS subscale) increased significantly, while the other negative POMS subscales and vigor decreased significantly. HR decreased significantly at 20 km, then increasing significantly at 25 km, while [La] did not change. CONCLUSION: These results suggest that, despite the occurrence of fatigue, as evidenced by the drop in velocity and changes in psychological profile, swimmers were able to complete the 25-km trial by adopting a conservative pacing, unveiling also a reserve in maximum performance.

Patient Engagement: The Key to Redesign the Exchange Between the Demand and Supply for Healthcare in the Era of Active Ageing.

The last decades' changes in the epidemiological trends of chronic disease - also due to the ageing population - and the increased length and quality of life among the majority of Western population have introduced important changes in the organization and management of the healthcare systems. Consequently, health systems throughout the world are searching for new and effective ways to make their services more responsive to new patients and the public's health needs and demands. The idea of patient engagement - borrowed from the marketing conceptualization of consumer engagement - moves from the assumption that making patients/clients co-producers of their health can enhance their satisfaction with the healthcare system as well as their responsibility in both care and prevention by improving clinical outcomes and reducing health delivery costs. To make people aware of their health services options by supporting them in the decision-making process and to engage them in enacting preventive and healthy behaviors is vital for achieving successful health outcomes and preventing waste of resources. In this chapter, we outline a model (PHE model) that explains the patients' subjective experience with their health management process and the levers that may enact the passage from one phase of the process to the other. Based on this conceptual model of patient engagement will be proposed a tool kit of priority actions that may sustain the patient in its process of engagement.

Positive technology as a driver for health engagement.

Despite the fact that older adults are healthier than in the past, the current trend of an ageing population implies an increased risk and severity of chronic diseases. Low-resource healthcare systems face increased organizational healthcare costs, which is likely to result in an allocation of limited health resources. Healthcare organizations themselves must deal with patients' increasing need for a more active role in all the steps of the care & cure process. Technological advances may play a crucial role in sustaining people's health management in daily life, but only if it is "ecologically" designed and well-attuned to people's health needs and expectations. Healthcare is more and more called to orient innovative research approaches that recognize the crucial role of a person's engagement in health and well-being. This will enable patients to reach a higher quality of life and achieve a general psychophysical well-being. Thus, positive technological innovation can sustain people's engagement in health and invoke community empowerment, as we shall discuss in this document.

Physiological and anthropometric characteristics of junior cyclists of different specialties and performance levels.

This study analyzes the anthropometric and physiological characteristics of junior cyclists within different cycling specialties and different performance levels. One hundred and thirty-two junior riders (16.8 ± 0.6 years, 177 ± 6 cm, 66.3 ± 6.7 kg) were tested for anthropometric, aerobic and anaerobic parameters. Cyclists were classified within specialties [uphill (UH) flat terrain (FT) all terrain (AT) and sprint (SP)] and performance levels, based on a seasonal ranking [low level (LL) medium level (ML) and high level (HL)]. The results of the two-way analysis of variance showed that FT and SP have greater body dimensions than UH and AT (P<0.001). Concerning the relative aerobic parameters, AT and UH have higher values (P<0.001) than FT and SP [maximal oxygen uptake (VO(2max) ): 69.4 ± 3.6, 67.5 ± 5.0, 62.8 ± 4.5 and 61.9 ± 4.1 mL/kg/min, respectively] while absolute parameters resulted higher for FT and AT (P≤0.008). The relative power produced in the 5 s test was higher (P<0.001) for AT and SP than FT and UH (16.7 ± 1.1, 16.6 ± 0.6, 14.9 ± 1.7 and 14.4 ± 1.7 W/kg, respectively). Concerning the performance level, only the age and the aerobic parameters resulted differently within levels (VO(2max) : HL=67.3 ± 4.9, ML=65.5 ± 5.1 and LL=63.3 ± 5.2 mL/kg/min), with the highest values for HL (P≤0.007). In conclusion, juniors are specialized in the same way as professional cyclists and the aerobic characteristics are confirmed as significant in the performance level assessment.

[Avulsion of the penile skin: a conservative approach]. / Avulsione della cute peniena: un approccio conservativo.

INTRODUCTION: Skin avulsion of male genital is a rare urological emergency. Although not life-threatening such lesions are both physically and psychologically traumatic. If poorly managed in the acute setting, these injuries may result in long-term problems or permanent disabilities. METHODS: A 58 year-old male patient was admitted to the Emergency Department of our hospital with a traumatic injury of the penis, caused by a bike trauma. At the inspection, a rather complete degloving of penis and a tear in scrotal skin with no involvement of testes were observed. The skin was completely detached, out of the penis, but for a small flap at the peno-scrotal angle. After a careful cleaning, the penis was covered again with the skin attached to peno-scrotal angle through multiple circumferential sutures. RESULTS: A complete cover of the defects was obtained with one-step surgery. The patient was treated with broad spectrum of antibiotics for 1 month. No infections occurred. The patient was discharged from hospital after 5 days. After 3 months from trauma, the patient is able to achieve sexual intercourse, with normal erectile function, no painful erections and no penile recurvatum. CONCLUSIONS: Traumatic skin avulsion of penis is a rare condition; the best aesthetic and functional results depends on the choice of the proper treatment. Conservative approach in selected cases can provide good results both aesthetically and functionally.

[Transvaginal repair of neobladder vaginal fistula]. / Riparazione trans-vaginale di fistola neovescico-vaginale.

INTRODUCTION: Neobladder vaginal fistula is a known complication after cystectomy and orthotopic neobladder in women. The exact incidence is still unknown, even if in some of the largest series is reported in about 5% of female patients. We present our personal experience with a case of neobladder vaginal fistula. METHODS: A fifty-year old woman affected by T2G3 bladder cancer underwent radical cystectomy and orthotopic neobladder in December 2007. Definitive pathological examination revealed pT3aN0G3 urothelial cancer with squamous aspects. Two cycles of neoadjuvant chemotherapy were administered before cystectomy. Three weeks after cystectomy, a retrograde cystography revealed a fistula between vagina and neobladder. At first, the patient was treated conservatively, keeping the urethral catheter for two months. Cystographies, repeated every month, recorded a reduction in size of the fistula but not the complete closure. A surgical correction was planned. Preoperative cystoscopy showed the neobladder opening of the fistula on the posterior wall. Then a transvaginal approach with fistula excision and a two layer cross suture were performed. RESULTS: At the cystography performed 1 month after surgical repair no fistula was detected, and the patient was completely dry. At 3 months follow-up the patient was completely dry. CONCLUSION: The development of a neobladder-vaginal fistula is a significant, even if infrequent, complication after cystectomy. In our case, we performed a transvaginal approach without tissue interposition, with good results. Such procedure is easy and effective and, in our opinion, can be tempted as first line surgical treatment.

[Retroperitoneoscopic nephropexy]. / Nefropessi retroperitoneoscopica.

INTRODUCTION: Nephroptosis has been defined as renal descent of 5 or more cm on orthostasis. This disease is more frequent in young and slim women. The patient complains pain in upright position,that regress lying down. The therapy consists of surgical treatment. We report the case of a woman treated with retroperitoneoscopic nephropexy. METHODS: We present the case of a 25-years old woman, affected by lumbar pain in upright position for about 1 year. Ultrasound scan of the abdomen and RX-KUB did not show hydronephrosis nor stones. Both an orthopedic examination and a spinal MRI excluded bone or muscular diseases. Intravenous pyelography and diuretic isotope renography in upright position revealed a renal descent of more than 5 cm, without obstruction of upper urinary tract. The patient underwent a renal color doppler imaging, that showed reduction of right kidney resistive index in upright position. The patient underwent a right retroperitoneoscopic nephropexy. After complete dissection of the perirenal fat from the kidney, three nonabsorbable sutures were placed between the posterior renal capsule and the psoas muscle. RESULTS: No blood loss nor peri-operative complications have been observed. One month after the procedure, the patient did not complain any pain. Renal color doppler, performed one month after the nephropexy, showed a normalization of resistive index. CONCLUSIONS: Symptomatic nephroptosis is a disease that has been questioned in the past. Nowadays, the modern imaging and functional examination available allow to identify the "true"cases of symptomatic nephroptosis. The treatment with retroperitoneoscopic nephropexy is an easy and effective procedure.

Effect of exercise-induced muscle damage on endurance running performance in humans.

Exercise-induced muscle damage (EIMD) is known to decrease muscle strength and power but its effect on endurance performance is unclear. Thirty moderately trained adult runners (24 men and six women) were randomly assigned to EIMD or control. The EIMD group jumped 100 times from a 35 cm bench, while controls did not perform any muscle-damaging exercise. Before and 48 h after treatment, subjects were tested on markers of EIMD, steady-state cardiorespiratory, metabolic and perceptual responses during a constant speed submaximal run; distance ran in 30 min on a treadmill. There were significant changes in muscle soreness, creatine kinase, and knee extensors strength (P<0.01). This EIMD significantly reduced self-paced time trial performance by 4% (P<0.01) because subjects reduced running speed (P=0.02), with no change in perceived exertion (P=0.31). No significant alterations in running economy and other physiological responses to submaximal running were found. However, there was a trend (P=0.08) for increased perceived exertion, which was correlated with decreased time trial performance (P<0.01). In conclusion, EIMD has a significant impact on endurance running performance in humans, and this effect seems to be mediated by alterations in the sense of effort.

Management of 49 antebrachial and crural fractures in dogs using circular external fixators.

OBJECTIVES: To evaluate frame constructs, postoperative fracture reduction, postoperative care, complications, treatment duration and outcome of circular external fixation for management of 49 antebrachial and crural fractures in dogs. METHODS: Medical records of dogs that underwent surgery with circular external fixation were examined for fracture location, frame configuration, postoperative fracture reduction, treatment duration, complications and outcome. RESULTS: Forty-nine fractures in 48 dogs were stabilised using circular external fixation. Frame removal occurred on average 61 days after surgery (median+/-sd, 52+/-30 days). Minor complications were observed in 35 cases (71 per cent) and major complications in seven (14 per cent). Radiographic outcome at frame removal was judged as excellent in 18 cases (37 per cent), as good in 26 (53 per cent), as fair in four (8 per cent) and poor in one (2 per cent). After frame removal, one fracture was stabilised with a plate, and eight patients were lost to follow-up. Functional and cosmetic outcome at follow-up was judged as excellent in 32 cases (80 per cent), good in seven (18 per cent) and fair in one (2 per cent). CLINICAL SIGNIFICANCE: Circular external fixation can effectively treat antebrachial and crural fractures in dogs, even geometrically complex fractures. Minor complications are frequent but easily managed in most instances. Healing time is comparable to that of other external fixation methods.

Prevalence of silent myocardial ischaemia in new-onset middle-aged Type 2 diabetic patients without other cardiovascular risk factors.

AIMS: Coronary artery disease (CAD) is the leading cause of death in patients with Type 2 diabetes and is often asymptomatic. Silent myocardial ischaemia (SMI) is frequent in diabetic subjects and is responsible for a late diagnosis of CAD; its early detection is important. There are some data about the prevalence of SMI in Type 2 diabetic patients at high risk for cardiovascular disease, while no data are available in subjects at the onset of diabetes without other cardiovascular risk factors. METHODS: We screened 274 consecutive patients (mean age 64.3 +/- 8.4 years, 66% male) at the time of diagnosis of Type 2 diabetes; we enrolled 111 subjects without other cardiovascular disease risk factors (dyslipidaemia, hypertension, peripheral vascular disease, retinopathy, microalbuminuria, history of heart disease) and with normal resting electrocardiogram (ECG). Participants performed a maximal ECG exercise protocol and, if positive, underwent coronary angiography. RESULTS: The ECG exercise test was positive in 19 patients (17.1%); of those 14 (13%) had angiographic coronary disease (one with three-vessel disease, three with two vessels and 10 with one vessel involved). The positive predictive value of the exercise ECG for predicting angiographic coronary disease was 73%. CONCLUSIONS: The prevalence of SMI was 17% and angiographic coronary disease was found in 13% of middle-aged subjects with new-onset Type 2 diabetes without other cardiovascular risk factors. This prevalence is similar to that observed in studies of subjects with long duration diabetes who have additional cardiovascular risk factors.