Effects of bulk tank milk, waste milk, and pasteurized waste milk on the nutrient utilization, gastrointestinal tract development, and antimicrobial resistance to Escherichia coli in pre-weaned dairy calves.

This study aimed to assess the impact of bulk tank milk (BTM), waste milk (WM), and pasteurized waste milk (PWM) on nutrient digestibility, ruminal and cecal fermentation, gastrointestinal tract (GIT) development, and antimicrobial resistance of fecal Escherichia coli from dairy calves at 2 periods (30 and 60 d of age). Calves were grouped according to body weight, serum protein levels, and breed composition. Three treatments were included: BTM (n = 21), WM from cows under antibiotic treatment (n = 21), and PWM (waste milk submitted to high-temperature, short-time pasteurization; n = 21). A total of 63 calves were used, of which: 18 animals (n = 6 per treatment) evaluated in the period of 4 - 30 d and 45 (n = 15 per treatment) from 4 - 60 d. During the experimental period, a daily intake of 6 L of milk was divided into 2 equal meals, with ad libitum access to water and starter. Milk and feed intakes were recorded daily. Apparent total-tract digestibility and nitrogen balance were conducted from 25 to 29 d of age (n = 6) and from 53 to 57 d of age (n = 15). Animals were euthanized at 30 ± 1 and 60 ± 1 d of age for the assessment of ruminal and cecal fermentation and GIT development. Antimicrobial susceptibility testing was conducted at 1, 30, and 60 d of age (n = 15/treatment). Statistical analysis utilized a linear mixed-effects model for continuous outcomes and generalized linear models for single measurements (R software). Treatments WM and PWM had lower rumen pH, higher ruminal acetate concentration, larger reticulorumen and liver, and a higher prevalence of fecal-resistant E. coli compared with BTM at both 30 and 60 d. Up to 60 d, both BTM and WM treatments exhibited higher digestibility of ether extract and gross energy compared with the PWM, whereas WM and PWM treatments showed increased nitrogen intake and retention compared with the BTM. These findings suggest that pasteurization of waste milk negatively affects nutrient digestibility and calf performance, while also impacting rumen development. Additionally, the use of milk containing antibiotic residue leads to the selection of resistant E. coli in the GIT over time.

Dissemination of UTC(NIST) over 20 km of commercial optical fiber with active phase stabilization.

We demonstrate the transfer of a cesium frequency standard steered to UTC(NIST) over 20 km of dark telecom optical fiber. Our dissemination scheme uses an active stabilization technique with a phase-locked voltage-controlled oscillator. Out-of-loop characterization of the optical fiber link performance is done with dual-fiber and single-fiber transfer schemes. We observe a fractional frequency instability of 1.5 × 10-12 and 2 × 10-15 at averaging intervals of 1 s and 105 s, respectively, for the link. Both schemes are sufficient to transfer the cesium clock reference without degrading the signal, with nearly an order of magnitude lower fractional frequency instability than the cesium clocks over all time scales. The simplicity of the two-fiber technique may be useful in future long-distance applications where higher stability requirements are not paramount, as it avoids technical complications involved with the single-fiber scheme.

Aligning quality of life and guidelines for off-label psychotropic drugs in adults with intellectual disabilities and challenging behaviour.

Introduction: Adults with intellectual disabilities have an increased vulnerability to mental health problems and challenging behaviour. In addition to psychotherapeutic or psychoeducational methods, off-label pharmacotherapy, is a commonly used treatment modality. Objective: The aim of this study was to establish evidence-based guideline recommendations for the responsible prescription of off-label psychotropic drugs, in relation to Quality of Life (QoL). Method: A list of guidelines was selected, and principles were established based on international literature, guideline review and expert evaluation. The Delphi method was used to achieve consensus about guideline recommendations among a 58-member international multidisciplinary expert Delphi panel. Thirty-three statements were rated on a 5-point Likert-scale, ranging from totally disagree to totally agree, in consecutive Delphi rounds. When at least 70% of the participants agreed (score equal or higher than 4), a statement was accepted . Statements without a consensus were adjusted between consecutive Delphi rounds based on feedback from the Delphi panel. Results: Consensus was reached on 4 general:the importance of non-pharmaceutical treatments, comprehensive diagnostics and multidisciplinary treatment. Consensus was reached in 4 rounds on 29 statements. No consensus was reached on 4 statements concerning: freedom-restricting measures, the treatment plan, the evaluation of the treatment plan, and the informed consent. Conclusion: The study led to recommendations and principles for the responsible prescription - aligned with the QoL perspective - of off-label psychotropic drugs for adults with intellectual disabilities and challenging behaviour. Extensive discussion is needed regarding the issues on which there was no consensus to furthering the ongoing development of this guideline.

Paracetamol and Ibuprofen Removal from Aqueous Phase Using a Ceramic-Derived Activated Carbon.

Emerging pollutants, including pharmaceuticals and personal care products, have been detected in surface and groundwaters. The adsorption of paracetamol and ibuprofen, two widespread drugs, has been studied in aqueous medium, using a ceramic-derived carbon (CeDC) and a commercial activated carbon (CoAC). CeDC yielded a BET surface area of 895 m2 g-1, a bimodal pore size distribution (13.2 and 35 nm) and a total pore volume of 1.99 cm3 g-1. CoAC had an approximate surface area of 1000 m2 g-1, a homogeneous pore size distribution and a total pore volume of 0.42 cm3 g-1. Kinetic and equilibrium tests were carried out in batch systems to study the materials' sorption performances. The intraparticle diffusion model best fitted the experimental kinetic data. The maximum ibuprofen sorption capacities were 120 mg g-1 and 133 mg g-1 for CoAC and CeDC, respectively, whereas no major differences on the maximum paracetamol sorption capacities (qm) were observed among the sorbents (150-159 mg g-1). Therefore, CeDC, synthesized easily from a ceramic composite, improved time and sorption capacity of paracetamol and ibuprofen compared to the commercial activated carbon, indicating the potential of the developed carbon as an emerging pollutant sorbent material.

Collateral presence and extent do not predict myocardial viability and ischemia in chronic total occlusions: A stress-CMR study.

BACKGROUND: Well-developed collaterals are assumed as a marker of viability and ischemia in chronic total occlusions (CTO). We aim to correlate viability and ischemia with collateral presence and extent in CTO patients by cardiac magnetic resonance (CMR). METHODS: Multicentre study of 150 CTO patients undergoing stress-CMR, including adenosine if normal systolic function, high-dose-dobutamine for patients with akinetic/>2 hypokinetic segments and EF ≥35%, otherwise low-dose-dobutamine (LDD); all patients underwent late gadolinium enhancement (LGE) imaging. Viability was defined as mean LGE transmurality ≤50% for adenosine, as functional improvement for dobutamine-stress-test, ischemia as ≥1.5 segments with perfusion defects outside the scar zone. RESULTS: Rentrop 3/CC 2 defined well-developed (WD, n = 74) vs poorly-developed collaterals (PD, n = 76). Viability was equally prevalent in WD vs PD: normo-functional myocardium with ≤50% LGE in 52% vs 58% segments, p = 0.76, functional improvement by LDD in 48% vs 52%, p = 0.12. Segments with none, 1-25%,26-50%,51-75% LGE showed viability by LDD in 90%,84%,81%,61% of cases, whilst in 12% if 76-100% LGE (p < 0.01). There was no difference in WD vs PD for ischemia presence (74% vs 75%, p = 0.99) and extent (2.7 vs 2.8 segments, p = 0.77). CONCLUSIONS: In a large cohort of CTO patients, presence and extent of collaterals did not predict viability and ischemia by stress-CMR. Scar extent up to 75% LGE was still associated with viability, whereas ischemia was undetectable in 25% of patients, suggesting that the assessment of CTO patients with CMR would lead to a more comprehensive evaluation of viability and ischemia to guide revascularization.

Further Introduction of DNA Methylation (DNAm) Arrays in Regular Diagnostics.

Methylation tests have been used for decades in regular DNA diagnostics focusing primarily on Imprinting disorders or specific loci annotated to specific disease associated gene promotors. With the introduction of DNA methylation (DNAm) arrays such as the Illumina Infinium HumanMethylation450 Beadchip array or the Illumina Infinium Methylation EPIC Beadchip array (850 k), it has become feasible to study the epigenome in a timely and cost-effective way. This has led to new insights regarding the complexity of well-studied imprinting disorders such as the Beckwith Wiedemann syndrome, but it has also led to the introduction of tests such as EpiSign, implemented as a diagnostic test in which a single array experiment can be compared to databases with known episignatures of multiple genetic disorders, especially neurodevelopmental disorders. The successful use of such DNAm tests is rapidly expanding. More and more disorders are found to be associated with discrete episignatures which enables fast and definite diagnoses, as we have shown. The first examples of environmentally induced clinical disorders characterized by discrete aberrant DNAm are discussed underlining the broad application of DNAm testing in regular diagnostics. Here we discuss exemplary findings in our laboratory covering this broad range of applications and we discuss further use of DNAm tests in the near future.

Reduction in unplanned hospitalizations associated with a physician focused intervention to reduce potentially inappropriate medication use among older adults: a population-based cohort study.

BACKGROUND: A multimodal general practitioner-focused intervention in the Local Health Authority (LHA) of Parma, Italy, substantially reduced the prevalence of potentially inappropriate medication (PIM) use among older adults. Our objective was to estimate changes in hospitalization rates associated with the Parma LHA quality improvement initiative that reduced PIM use. METHODS: This population-based longitudinal cohort study was conducted among older residents (> 65 years) using the Parma LHA administrative healthcare database. Crude and adjusted unplanned hospitalization rates were estimated in 3 periods (pre-intervention: 2005-2008, intervention: 2009-2010, post-intervention: 2011-2014). Multivariable negative binomial models estimated trends in quarterly hospitalization rates among individuals at risk during each period using a piecewise linear spline for time, adjusted for time-dependent and time-fixed covariates. RESULTS: The pre-intervention, intervention, and post-intervention periods included 117,061, 107,347, and 121,871 older adults and had crude hospitalization rates of 146.2 (95% CI: 142.2-150.3), 146.8 (95% CI: 143.6-150.0), and 140.8 (95% CI: 136.9-144.7) per 1000 persons per year, respectively. The adjusted pre-intervention hospitalization rate was declining by 0.7% per quarter (IRR = 0.993; 95% CI: 0.991-0.995). The hospitalization rate declined more than twice as fast during the intervention period (1.8% per quarter, IRR = 0.982; 95% CI: 0.979-0.985) and was nearly constant post-intervention (IRR: 0.999; 95% CI: 0.997-1.001). Contrasting model predictions for the intervention period (Q1 2009 to Q4 2010), the intervention was associated with 1481 avoided hospitalizations. CONCLUSION: In a large population of older adults, a multimodal general practitioner-focused intervention to decrease PIM use was associated with a decline in the unplanned hospitalization rate. Such interventions to reduce high risk medication use among older adults warrant consideration by health systems seeking to improve health outcomes and reduce high-cost acute care utilization.

Epstein-Barr virus recruits PDL1-positive cells at the microenvironment in pediatric Hodgkin lymphoma.

BACKGROUND: Classic Hodgkin lymphoma (cHL) is a lymphoid malignancy in which the microenvironment, where the neoplastic cells are immersed, contributes to the lymphomagenesis process. Epstein-Barr virus (EBV) presence also influences cHL microenvironment composition and contributes to pathogenesis. An increase in PDL1 expression in tumor cells and at the microenvironment was demonstrated in adult cHL. Therefore, our aim was to assess PD1/PDL1 pathway and EBV influence on this pathway in pediatric cHL, given that in Argentina, our group proved a higher incidence of EBV-associated pediatric lymphoma in children. METHODS: For that purpose, EBV presence was assessed by in situ hybridization, whereas PD1 and PDL1 expressions were studied by immunohistochemistry. PDL1 genetic alterations were analyzed by FISH, and survival was evaluated for PD1 and PDL1 expressions. RESULTS: EBV presence demonstrated no influence neither on PD1 expression at the microenvironment nor on PDL1 expression at HRS tumor cells. Unexpectedly, only 38% pediatric cHL displayed PDL1 genetic alterations by FISH, and no difference was observed regarding EBV presence. However, in EBV-related cHL cases, a higher number of PDL1 + cells were detected at the microenvironment. CONCLUSION: Even though a high cytotoxic environment was previously described in EBV-related pediatric cHL, it might be counterbalanced by an immunoregulatory micro-environmental PDL1 + niche. This regulation may render a cytotoxic milieu that unsuccessfully try to eliminate EBV + Hodgkin Reed Sternberg tumor cells in pediatric patients.

Installing oncofertility programs for common cancers in limited resource settings (Repro-Can-OPEN Study): An extrapolation during the global crisis of Coronavirus (COVID-19) pandemic.

PURPOSE: The state of limited resource settings that Coronavirus (COVID-19) pandemic has created globally should be taken seriously into account especially in healthcare sector. In oncofertility, patients should receive their fertility preservation treatments urgently even in limited resource settings before initiation of anticancer therapy. Therefore, it is very crucial to learn more about oncofertility practice in limited resource settings such as in developing countries that suffer often from shortage of healthcare services provided to young patients with cancer. METHODS: As an extrapolation during the global crisis of COVID-19 pandemic, we surveyed oncofertility centers from 14 developing countries (Egypt, Tunisia, Brazil, Peru, Panama, Mexico, Colombia, Guatemala, Argentina, Chile, Nigeria, South Africa, Saudi Arabia, and India). Survey questionnaire included questions on the availability and degree of utilization of fertility preservation options in case of childhood cancer, breast cancer, and blood cancer. RESULTS: All surveyed centers responded to all questions. Responses and their calculated oncofertility scores showed different domestic standards for oncofertility practice in case of childhood cancer, breast cancer, and blood cancer in the developing countries under limited resource settings. CONCLUSIONS: Medical practice in limited resource settings has become a critical topic especially after the global crisis of COVID-19 pandemic. Understanding the resources necessary to provide oncofertility treatments is important until the current COVID-19 pandemic resolves. Lessons learned will be valuable to future potential worldwide disruptions due to infectious diseases or other global crises.

PICC-PORT: Valid indication to placement in patient with results of extensive skin burns of the neck and chest in oncology. The first case in the scientific literature.

INTRODUCTION: The management of patients with advanced gastric cancer requires a stable venous access required at different stages of disease (treatment phase, palliative phase). Totally implantable central venous access in the arm, named PICC-PORT, is used in a patient with results of extensive skin burns of the neck, chest and right arm and surgical outcomes of multiple skin grafts of chest. The described clinical case is the first event in the scientific literature. PRESENTATION OF CASE: We report a case of a patient with results of extensive skin burns of the neck, chest and right arm and surgical outcomes of multiple skin grafts of chest that must perform chemotherapy with a port. In this patient, due to the difficulty of implanting a door in the cervico-thoracic district, we opt for the totally subcutaneous implantation of the vascular device (PICC-PORT 5 Fr) in the left arm. DISCUSSION: In this patient for the difficulty of implanting a port in the cervico-thoracic district, we opt for the totally subcutaneous implantation of the vascular device (PICC-PORT) in the arm. The PICC-PORT is positioned with the same technique as the PICC (ultrasound-guided vein puncture, with modified Seldinger technique and tip location with ECG technique); presents all the functional and aesthetic advantages of a totally subcutaneous device.The case described is the first case in the scientific literature. CONCLUSION: In Europe in recent years for the availability of the vascular device of small dimensions and materials increasingly compatible, the "PICC-PORT" is positioned in the veins of the arm with ultrasound-guidance without complications such as pneumothorax, arterial puncture, hematoma of the neck, Pinch-off syndrome, such as the clinical case presented with extensive scars on the chest and neck. Thoracic devices (chest port, tunnel venous catheter) are not indicated in thickened and inelastic skins, due to the high risk of dehiscence of the surgical wound.

M1-like macrophage polarization prevails in young children with classic Hodgkin Lymphoma from Argentina.

The microenvironment in classical Hodgkin lymphoma (cHL) comprises a mixture of different types of cells, which are responsible for lymphoma pathogenesis and progression. Even though microenvironment composition in adult cHL has been largely studied, only few groups studied pediatric cHL, in which both Epstein Barr virus (EBV) infection and age may display a role in their pathogenesis. Furthermore, our group described that EBV is significantly associated with cHL in Argentina in patients under the age of 10 years old. For that reason, our aim was to describe the microenvironment composition in 46 pediatric cHL patients. M1-like polarization status prevailed in the whole series independently of EBV association. On the other hand, in children older than 10 years, a tolerogenic environment illustrated by higher FOXP3 expression was proved, accompanied by a macrophage polarization status towards M2. In contrast, in children younger than 10 years, M1-like was prevalent, along with an increase in cytotoxic GrB+ cells. This study supports the notion that pediatric cHL exhibits a particular tumor microenvironment composition.

Distal biceps tendon rupture: advantages and drawbacks of the anatomical reinsertion with a modified double incision approach.

BACKGROUND: Distal biceps tendon rupture occurs more often in middle-aged male population, involving the dominant arm. In this retrospective study, it's been described the occurrence of the most frequent adverse events and the clinical outcomes of patients undergoing surgical repair of distal biceps tendon rupture with the modified Morrey's double-incision approach, to determine better indications for patients with acute tendon injury. METHODS: Sixty-three patients with acute distal biceps tendon rupture treated with a modified double-incision technique between 2003 and 2015 were retrospectively evaluated at a mean 24 months of follow-up. Clinical evaluation including range of motion (ROM) and isometric strength recovery compared to the healthy contralateral side assessment, together with documentation of nerve injury, was performed. Patients were asked to answer DASH, OES and MEPS scores. RESULTS: The ROM recovery showed excellent results compared to the healthy contralateral side. The reported major complications included: one case of proximal radio-ulnar synostosis, 3 cases of posterior interosseous nerve (PIN) palsy and one case of a-traumatic tendon re-rupture. Concerning minor complications, intermittent pain, ROM deficiency < 30° in flexion/extension and pronation/supination, isometric flexion strength deficiency < 30% and isometric supination strength deficiency < 60%, lateral antebrachial cutaneous nerve (LACBN) injury, were observed. The average DASH score was 8.5; the average OES was 41.5 and the MEPS was 96.3. CONCLUSION: The Morrey modified double-incision technique finds its indication in young and active patients if performed within 2 weeks from injury. If performed by experienced surgeons, the advantages can exceed the drawbacks of possible complications.

Cardiac magnetic resonance for ischaemia and viability detection. Guiding patient selection to revascularization in coronary chronic total occlusions: The CARISMA_CTO study design.

BACKGROUND: It is debated whether percutaneous revascularization (PCI) of total coronary chronic occlusion (CTO) is superior to optimal medical therapy (OMT) in improving symptoms, left ventricular (LV) function and major adverse cardiac/cerebrovascular events (MACCE). Furthermore, CTO-PCI is a challenging technique, with lower success rate than in other settings. A systematic analysis of baseline LV function, infarction extent and ischaemic burden to predict response to revascularization has never been performed. PURPOSES: To establish a CMR protocol to identify patients (pts) who can benefit most from CTO-PCI. Myocardial viability/ischaemia retains high biological plausibility as predictors of response to revascularization. Therefore, baseline viability (necrotic tissue extent, response to inotropic stimulation) and ischaemia (perfusion defect, wall motion abnormality during stress) will be studied as potential predictors of mechanical LV segmental improvement and ischaemic burden reduction in CTO territory (primary endpoint), LV remodelling and global function, Seattle Angina Questionnaire, and MACCE improvement (secondary endpoints) in the follow-up. METHODS: Pts with CTO suitable for PCI undergo stress-CMR for viability/ischaemia assessment. Pts with normal LV function undergo adenosine, those with moderately-reduced ejection fraction (EF) and wall motion abnormalities high-dose dobutamine, pts with EF <35% low-dose dobutamine. All pts undergo late gadolinium enhancement and repeat the same scan at 12 ±â€¯3 months, regardless of PCI success or decision for OMT. CONCLUSIONS: A multi-parameter CMR protocol tailored on pts characteristics to study viability/ischaemia could help in identifying responders in terms of LV function, ischaemic burden and clinical outcome among pts suitable for CTO-PCI, improving selection of best candidates to percutaneous revascularization.

Dermoscopy and reflectance confocal microscopy for monitoring the treatment of actinic cheilitis with ingenol mebutate gel: Report of three cases.

Actinic cheilitis (AC) can precede the development of squamous cell carcinoma (SCC) of the lip, a location with higher risk of invasiveness and metastasis. Herein, we reported the use of ingenol mebutate (IngMeb) 0.015% gel on three consecutive days to treat three patients suffering from AC. All the three patients achieved complete clearance of AC with rapid clinical effect, favorable safety profile, good patient's compliance related to short time of applications, and few local skin reactions. So IngMeb is an attractive new therapy for AC. Moreover, the present case report adds further evidence to the usefulness of dermoscopy and Reflectance confocal microscopy (RCM) in the assessment and monitoring of treatment outcome.

How confident are physicians in deprescribing for the elderly and what barriers prevent deprescribing?

WHAT IS KNOWN AND OBJECTIVE: Deprescribing is the process of discontinuing or reducing the dosage of medications that are no longer appropriate or aligned with goals of care, which is paramount in elderly patients with multiple comorbidities and polypharmacy. The objective of this study was to assess the perceptions of primary care physicians on deprescribing for elderly patients and potential barriers to deprescribing that physicians experience in the Local Health Authority (LHA) of Parma, Emilia-Romagna, Italy. METHODS: One hundred and sixty physicians (57% of the total number of primary care physicians in Parma) attended an educational session related to deprescribing and were asked to anonymously complete a paper survey. Participants were asked to assess their level of agreement on nine questions about their perception of deprescribing and potential factors affecting the deprescribing process using a seven-point Likert-type scale. A correlation coefficient was calculated to assess the association between physicians' confidence in deprescribing and attitudes or barriers associated with deprescribing. RESULTS AND DISCUSSION: Many physicians (72%) reported general confidence in their ability to deprescribe. Most respondents (78%) reported they were comfortable deprescribing preventive medications, yet only half (53%) were comfortable deprescribing guideline-recommended therapies. Lack of evidence on discontinuing preventive medicines and concern about withdrawal side effects were reported to impede deprescribing by more than one-third of physicians. When medications were initially prescribed by another physician, 40% of physicians reported hesitance in deprescribing them. About half of physicians (45%) did not feel comfortable deprescribing when patients/caregivers believed that continuation of the medication was needed. Lack of time and difficulty engaging patients/caregivers in the deprescribing process were cited as barriers by about one in four physicians. There was no strong correlation between physicians' confidence and attitudes or barriers associated with deprescribing. WHAT IS NEW AND CONCLUSION: The study results show that physicians believe they are generally comfortable with deprescribing, although there are still several factors that hamper their ability to engage in the process. An improved understanding of physicians' views on deprescribing may help guide further research, and policies to help patients remain healthy while streamlining their medication regimen.

Tracking actinic keratosis of face and scalp treated with 0.015% ingenol mebutate to identify clinical and dermoscopic predictors of treatment response.

BACKGROUND: Ingenol mebutate (IngMeb) 0.015% gel is an approved field treatment option for non-hyperkeratotic non-hypertrophic actinic keratosis (AK) of face and scalp. Efficacy of IngMeb has been assessed only on a clinical ground, in the majority of studies. Dermoscopy is a pivotal tool for the diagnosis of AK, while its role in evaluating the response to non-surgical therapies for AK has not been fully defined. OBJECTIVES: Our study aims to determine whether some dermoscopic features of AK of the face and scalp areas may independently predict the response to IngMeb therapy. METHODS: Clinical and dermoscopic responses, 1 month after 0.015% IngMeb therapy, were retrospectively evaluated using a per-patient and per-lesion approach. Safety was evaluated through local skin reaction composite score calculation. Demographic, clinical and dermoscopic factors were then evaluated via univariate and multivariate logistic regression analysis to assess independent predictors of response. RESULTS: Fifty-five patients with 245 AKs were enrolled. Clinically, per-patient response evaluation identified 25 (45.4%) poor/partial and 30 (54.5%) complete responders, corresponding on a per-lesion approach to 66 (26.9%) and 179 (73.1%) AKs, respectively. Dermoscopy reclassified 14 patients in the per-patient and 48 AKs in the per-lesion analysis from complete to poor/partial responders. Multivariate logistic regression analysis showed that AKs dermoscopically characterized by red pseudonetwork and located on the face were independently associated with a complete dermoscopic response to 0.015% IngMeb therapy, while microerosions were negative predictors. CONCLUSION: Specific dermoscopic features of AK may predict the response to 0.015% IngMeb therapy, together with the location on the face.

Low-dose aspirin for primary prevention of cardiovascular events in patients with diabetes: Benefit or risk?

Primary prevention aims to avert the onset of cardiovascular disease (CVD) by targeting its natural causes and risk factors; secondary prevention includes strategies and therapies that address preclinical or clinical evidence of CVD progression. The value of aspirin for primary CVD prevention is controversial because of increased bleeding, which may offset the overall modest benefits in patients with no overt CVD. In contrast, the benefits of aspirin for secondary prevention have been repeatedly and convincingly demonstrated to outweigh the risk of bleeding. Diabetes mellitus is a strong risk factor for cardiovascular events, and has been associated with an increased risk of both first and recurrent atherothrombotic events. Therefore, prevention of CVD, the major cause of mortality in patients with diabetes, is one of the most important therapeutic goals. Although the benefit of low-dose aspirin for secondary prevention of CVD is well established, its role for primary prevention remains inconclusive and controversial in diabetes patients. The benefit of aspirin for patients with CVD clearly exceeds the risk of bleeding, and even though a modest benefit has also been demonstrated in primary prevention, the trade-off for aspirin initiation against the increased risk of intracranial and gastrointestinal bleeding is more uncertain. Thus, aspirin for primary CVD prevention should be highly individualized, based on a benefit-risk ratio assessment for the given patient. In conclusion, the mere presence of diabetes is apparently not enough for aspirin to confer a benefit that clearly outweighs the risk of bleeding, and further evidence to the contrary is now needed.