Effetti della rivascolarizzazione percutanea degli arti inferiori sul profilo infiammatorio sistemico e sul rischio cardiovascolare dei pazienti affetti da claudicatio intermittens. Uno studio prospettico.

Background. L’arteriopatia obliterante degli arti inferiori (AOAI) è un’importante causa di disabilità e si associa a un elevato rischio di eventi cardiovascolari. La rivascolarizzazione endovascolare delle arterie degli arti inferiori mediante angioplastica (PTA) migliora la capacità di camminare e la qualità di vita dei pazienti affetti da AOAI e claudicatio intermittens. Nel presente studio abbiamo valutato se una rivascolarizzazione efficace delle arterie degli arti inferiori mediante PTA, oltre a migliorare i sintomi, abbia un effetto positivo anche sul rischio cardiovascolare globale dei pazienti affetti da AOAI e claudicatio intermittens. Metodi. Sono stati arruolati nello studio 479 pazienti consecutivi affetti da AOAI allo stadio II della classificazione di Fontaine, con un indice pressorio caviglia/braccio ≤0,90 e una o più stenosi >50% in almeno una delle arterie degli arti inferiori. In accordo con le raccomandazioni del Trans-Atlantic Inter Society Consensus II, 264 pazienti (55,1%) sono stati sottoposti a rivascolarizzazione percutanea mediante PTA (gruppo PTA), mentre 215 pazienti (44,9%) sono stati trattati con la sola terapia medica massimale (gruppo TM). L’incidenza di eventi cardiovascolari maggiori (morte per cause cardiovascolari, infarto del miocardio, ictus cerebrale, rivascolarizzazione coronarica o carotidea) è stata valutata prospetticamente mediante le curve di sopravvivenza di Kaplan-Meier. La regressione di Cox univariata e multivariata è stata inoltre utilizzata per calcolare il rischio di sviluppare un evento cardiovascolare durante il follow-up in relazione al tipo di trattamento. Risultati. Non vi erano differenze significative tra i due gruppi all’arruolamento, fatta eccezione per una minore capacità di marcia nel gruppo PTA. Durante un follow-up mediano di 21,0 mesi (12,0-29,0), l’incidenza di eventi cardiovascolari totali era significativamente più bassa nel gruppo PTA rispetto al gruppo TM (6,4% contro 16,3%; p=0,003), e i pazienti nel gruppo TM mostravano un rischio 4,1 volte maggiore (IC al 95% 1,22-13,57, p=0,023) di avere un evento cardiovascolare rispetto ai pazienti del gruppo PTA dopo correzione per i possibili fattori confondenti. Conclusioni. Il presente studio dimostra che la rivascolarizzazione efficace delle arterie degli arti inferiori mediante PTA nei pazienti affetti da AOAI e claudicatio intermittens, oltre a migliorare la sintomatologia, si associa ad una riduzione dell’incidenza di futuri eventi cardiovascolari maggiori

Lenalidomide, Melphalan, and Prednisone Association Is an Effective Salvage Therapy in Relapsed Plasma Cell Leukaemia

Plasma cell leukemia (PCL) is a rare and aggressive plasma cell disorder, characterized by the presence of a peripheral blood absolute plasma cell count of at least 2 × 109/l and more than 20% circulating plasma cells. The prognosis of PCL patients remains poor. Even by using autologous or allogenic transplant procedures, median survival does not exceed 3 years (Saccaro et al., 2005). Thalidomide, bortezomib and lenalidomide (Revlimid) have emerged as high active agents in the treatment of PCL (Johnston and abdalla, 2002; Musto et al., 2007; Finnegan et al., 2006). In particular, Lenalidomide is a structural analogue of thalidomide with similar but more potent biological activity; it is used as first line therapy in MM (Palumbo et al., 2007; Niesvizky et al., 2007), although information regarding its associated use with dexamethasone use as salvage therapy in PCL derives from anecdotal single case reports (Musto et al., 2008). We would like to describe a case of primary PCL with adverse cytogenetic in which excellent response was achieved with the combination of lenalidomide, melphalan, and prednisone as salvage therapy

Comment on Tay et al. A Very Low-Carbohydrate, Low–Saturated Fat Diet for Type 2 Diabetes Management: A Randomized Trial. Diabetes Care 2014;37:2909–2918

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Cushing syndrome, metabolic syndrome and inflammation: a suggested way out

Endogenous hypercortisolism is associated with an increased cardiovascular risk. Cushing Syndrome (CS) shares many clinical features with metabolic syndrome, including abdominal obesity, systemic arterial hypertension, insulin resistance, dyslipidemia, and thrombotic diatesis. Moreover, CS represents an interesting pattern of an endocrine disorder associated with chronic lowgrade inflammation which is not blunted by the resolution of hypercortisolism. The proinflammatory state that accompanies the metabolic syndrome may provide a connection between CS, inflammation and metabolic processes, which is highly deleterious for vascular functions. There is evidence that dietary patterns similar to those of the Mediterranean-style diet exert ositive effects on almost all components of the metabolic syndrome and other conditions associated with, including inflammation, insulin resistance, and endothelial dysfunction. Therefore, an intervention strategy based on lifestyle changes may play a role in patients with resolution of hypercortisolism in which the anti-inflammatory effects of cortisol are lost and cytokines levels are increased. In this setting, the Mediterranean healthy dietary pattern may represent an innovative approach in order to improve the disease course and to reduce in the long term the cardiovascular risk of people affected by C

Outcomes after non-cardiac surgery: Mortality, complications, disability, and rehospitalization

In the last 25 years, the number of patients aged ≥75 years undergoing non-cardiac surgery has greatly increased. In elderly patients, frailty is significantly associated with an increased risk of adverse events, functional decline, procedural complications, prolonged hospitalization, and mortality. The relationship between frailty and increased mortality and morbidity requires an appropriate tool of assessment to accurately quantify the patient's clinical and perioperative conditions. The preoperative evaluation of elderly patients candidate for non-cardiac surgery should include assessment of frailty, sarcopenia and malnutrition, as these are related to high surgical risk. For colon-rectal surgery as also for gastric cancer surgery, especially early gastric cancer, the introduction of laparoscopy has yielded considerable benefits in terms of short-term postsurgical outcomes, e.g. lower rate of intraprocedural bleeding and reduced length of hospital stay. Despite the progress made in preoperative assessment, surgical procedures and postoperative management, the improvement of outcomes after non-cardiac surgery in elderly patients remains a challenge and calls for future, well-designed clinical studies.</p

LL-Paraoxonase Genotype Is Associated with a More Severe Degree of Homeostasis Model Assessment IR in Healthy Subjects

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Standardization of BCR-ABL1 p210 Monitoring: From Nested to Digital PCR

The introduction of tyrosine kinase inhibitors in 2001 as a targeted anticancer therapy has significantly improved the quality of life and survival of patients with chronic myeloid leukemia. At the same time, with the introduction of tyrosine kinase inhibitors, the need for precise monitoring of the molecular response to therapy has emerged. Starting with a qualitative polymerase chain reaction, followed by the introduction of a quantitative polymerase chain reaction to determine the exact quantity of the transcript of interest-p210 BCR-ABL1, molecular monitoring in patients with chronic myeloid leukemia was internationally standardized. This enabled precise monitoring of the therapeutic response, unification of therapeutic protocols, and comparison of results between different laboratories. This review aims to summarize the steps in the diagnosis and molecular monitoring of p210 BCR-ABL1, as well as to consider the possible future application of a more sophisticated method such as digital polymerase chain reaction

Femoral Plaque Echogenicity and Cardiovascular Risk in Claudicants

OBJECTIVES: The present study was designed to verify whether the evaluation of femoral plaque echogenicity might be a useful tool for cardiovascular risk assessment in patients affected by lower extremity peripheral arterial disease. BACKGROUND: Lower extremity peripheral arterial disease is a common manifestation of atherosclerosis and is associated with a high risk of developing major cardiovascular events. Vulnerable atherosclerotic plaque plays a central role in the occurrence of acute ischemic events in different vascular territories. Furthermore, atherosclerosis is a systemic disease, and the presence of an unstable atherosclerotic plaque in a certain vascular district, characterized by low echogenicity at B-mode ultrasound, is associated to a greater prevalence of unstable plaques in other vascular beds. METHODS: Femoral plaque echogenicity of 246 claudicants with ankle/brachial index ≤0.90 was evaluated at B-mode ultrasound by visual analysis and by calculating the grayscale median (GSM) value. In these patients, the occurrence of myocardial infarction and stroke was prospectively assessed. RESULTS: Femoral GSM values and plaque types assessed by visual analysis were highly correlated by Spearman analysis (rho = 0.905, p < 0.001). During a median follow-up of 30 months, 32 patients (13%) had a major cardiovascular event. Compared with patients without events, those who experienced an event during the follow-up had a lower femoral plaque GSM value (42.9 ± 26.2 vs. 58.8 ± 19.3, p = 0.002) and a higher prevalence of hypoechoic femoral plaque at visual analysis (68.8% vs. 19.6%, p < 0.001). At Cox analysis, femoral GSM showed an inverse relationship with cardiovascular risk, even after adjustment for possible confounders (hazard ratio: 0.96, 95% confidence interval [CI]: 0.95 to 0.98, p < 0.001). Furthermore, patients with hypoechoic femoral plaques at visual analysis had a 7.24-fold increased cardiovascular risk compared with patients with hyperechoic plaques after adjustment for possible confounders (95% CI: 3.23 to 16.22, p < 0.001). CONCLUSIONS: This study demonstrates that the presence of hypoechoic atherosclerotic femoral plaques is associated with higher cardiovascular risk in lower extremity peripheral arterial disease patients

Congenital myopathy with hanging big toe due to homozygous myopalladin (MYPN) mutation

Background: Myopalladin (MYPN) is a component of the sarcomere that tethers nebulin in skeletal muscle and nebulette in cardiac muscle to alpha-actinin at the Z lines. Autosomal dominant MYPN mutations cause hypertrophic, dilated, or restrictive cardiomyopathy. Autosomal recessive MYPN mutations have been reported in only six families showing a mildly progressive nemaline or cap myopathy with cardiomyopathy in some patients. Case presentation: A consanguineous family with congenital to adult-onset muscle weakness and hanging big toe was reported. Muscle biopsy showed minimal changes with internal nuclei, type 1 fiber predominance, and ultrastructural defects of Z line. Muscle CT imaging showed marked hypodensity of the sartorius bilaterally and MRI scattered abnormal high-intensity areas in the internal tongue muscle and in the posterior cervical muscles. Cardiac involvement was demonstrated by magnetic resonance imaging and late gadolinium enhancement. Whole exome sequencing analysis identified a homozygous loss of function single nucleotide deletion in the exon 11 of the MYPN gene in two siblings. Full-length MYPN protein was undetectable on immunoblotting, and on immunofluorescence, its localization at the Z line was missed. Conclusions: This report extends the phenotypic spectrum of recessive MYPN-related myopathies showing: (1) the two patients had hanging big toe and the oldest one developed spine and hand contractures, none of these signs observed in the previously reported patients, (2) specific ultrastructural changes consisting in Z line fragmentation, but (3) no nemaline or caps on muscle pathology