Cancer Related Anemia: An Integrated Multitarget Approach and Lifestyle Interventions

Cancer is often accompanied by worsening of the patient’s iron profile, and the resulting anemia could be a factor that negatively impacts antineoplastic treatment efficacy and patient survival. The first line of therapy is usually based on oral or intravenous iron supplementation; however, many patients remain anemic and do not respond. The key might lie in the pathogenesis of the anemia itself. Cancer-related anemia (CRA) is characterized by a decreased circulating serum iron concentration and transferrin saturation despite ample iron stores, pointing to a more complex problem related to iron homeostatic regulation and additional factors such as chronic inflammatory status. This review explores our current understanding of iron homeostasis in cancer, shedding light on the modulatory role of hepcidin in intestinal iron absorption, iron recycling, mobilization from liver deposits, and inducible regulators by infections and inflammation. The underlying relationship between CRA and systemic low-grade inflammation will be discussed, and an integrated multitarget approach based on nutrition and exercise to improve iron utilization by reducing low-grade inflammation, modulating the immune response, and supporting antioxidant mechanisms will also be proposed. Indeed, a Mediterranean-based diet, nutritional supplements and exercise are suggested as potential individualized strategies and as a complementary approach to conventional CRA therapy.     

Adaptation of eye and hand movements to target displacements of different size

Previous work has documented that the direction of eye and hand movements can be adaptively modified using the double-step paradigm. Here we report that both motor systems adapt not only to small direction steps (5° gaze angle) but also to large ones (28° gaze angle). However, the magnitude of adaptation did not increase with step size, and the relative magnitude of adaptation therefore decreased from 67% with small steps to 15% with large steps. This decreasing efficiency of adaptation may reflect the participation of directionally selective neural circuits in double-step adaptation.     

5‐S‐cysteinyldopamine neurotoxicity: Influence on the expression of α‐synuclein and ERp57 in cellular and animal models of Parkinson's disease

Parkinson's disease (PD) is a progressive neurodegenerative disorder whose etiology is still unclear in spite of extensive investigations. It has been hypothesized that 5‐S‐cysteinyldopamine (CysDA), a catechol‐thioether metabolite of dopamine (DA), could be an endogenous parkinsonian neurotoxin. To gain further insight into its role in the neurodegenerative process, both CD1 mice and SH‐SY5Y neuroblastoma cells were treated with CysDA, and the data were compared with those obtained by the use of 6‐hydroxydopamine, a well‐known parkinsonian mimetic. Intrastriatal injection of CysDA in CD1 mice caused a long‐lasting depletion of DA, providing evidence of in vivo neurotoxicity of CysDA. Both in mice and in SH‐SY5Y cells, CysDA treatment induced extensive oxidative stress, as evidenced by protein carbonylation and glutathione depletion, and affected the expression of two proteins, α‐synuclein (α‐Syn) and ERp57, whose levels are modulated by oxidative insult. Real‐time PCR experiments support these findings, indicating an upregulation of both ERp57 and α‐Syn expression. α‐Syn aggregation was also found to be modulated by CysDA treatment. The present work provides a solid background sustaining the hypothesis that CysDA is involved in parkinsonian neurodegeneration by inducing extensive oxidative stress and protein aggregation. © 2013 Wiley Periodicals, Inc.     

Bioabsorbable Calcaneo-Stop Implant for the Treatment of Flexible Flatfoot: A Retrospective Cohort Study at a Minimum Follow-Up of 4 Years

Arthroereisis of the subtalar joint is a common surgical technique in Europe for the management of flexible flatfoot in the pediatric population. In most cases, it is performed using a calcaneo-stop metallic screw. Despite the good clinical results, screw removal is always advised after 2 to 3 years. The use of a bioabsorbable screw might overcome the need for a second operation to remove a nonabsorbable device. We report the results of a biodegradable calcaneo-stop screw at a minimum of 4 years of follow-up. Eighty-eight procedures were performed on 44 children. All patients were clinically and radiologically evaluated preoperatively and at a minimum 4-year follow-up period. Patient satisfaction and plantar collapse using Viladot's classification were recorded. Meary's talus–first metatarsal angle and talocalcaneal angle were measured on radiographs preoperatively and at the last follow-up visit. The presence of the device at the last follow-up examination was assessed by magnetic resonance imaging. The mean follow-up duration was 56 months. Of the 44 patients, 33 (75%) reported excellent clinical outcomes, 9 (20.5%) good outcomes, and 2 (4.5%) poor. Foot print improvement was registered for all patients. The mean Meary's talus–first metatarsal angle had improved from 160.6° ± 7.7° preoperatively to 170.6° ± 6.5° at the last follow-up visit (p < .001). The talocalcaneal angle had decreased from 39.9° ± 5.2° preoperatively to 29.4° ± 4° at the last follow-up examination (p < .001). At the 4-year follow-up point, the implant could be seen to have almost completely biodegraded on magnetic resonance imaging. Two screw breakages occurred. The bioabsorbable calcaneo-stop screw seems to be an effective solution for flexible flatfoot in pediatric patients. Also, owing to its biodegradable composition, the need of a second operation for implant removal will not always be necessary.     

Leukopenia, Hypoxemia, and Complement Activation During a Single Hemoperfusion

White blood cell count, acid-base balance, PO2, and complement function in five uremic patients undergoing a single hemoperfusion employing activated charcoal coated with methacrylate were studied. After 20 min on hemoperfusion, a marked leukopenia [ranging from 6,080 +/- 526 to 3,740 +/- 1,124 (p less than 0.02)] and hypoxemia [ranging from 106 +/- 13.8 to 80.2 +/- 11.9 mm Hg (p less than 0.02)] were observed. At the same time, total hemolytic complement decreased from 135 +/- 15.7 to 123 +/- 14.7 U/ml (p less than 0.001) and alternative pathway activity from 38.1 +/- 5.1 to 33.1 +/- 6.7 U/ml (p less than 0.005). C3 and B cleavage fragments were detected in the samples tested, thus demonstrating the activation of the complement alternative pathway. After 60 min, the different parameters tended to increase but did not reach the baseline levels. A direct correlation between the degree of leukopenia and the reduction of PO2 throughout the hemoperfusion period was found. pH PCO2, and HCO-3 did not change throughout the hemoperfusion period. The results demonstrate that complement activation, leukopenia, and hypoxemia occur during hemoperfusion.     

Duplex ultrasound evaluation of cavernosal peak systolic velocity and waveform acceleration in the penile flaccid state: clinical significance in the assessment of the arterial supply in patients with erectile dysfunction

The aim of this paper was to establish if duplex ultrasound parameters obtained for assessment of the patency of cavernosal arteries in the penile flaccid state can give sufficient clinical information without the use of intracavernosal injection of vasodilatory drugs. We assessed mean cavernosal peak systolic velocity (PSV) in the penile flaccid state (basal PSV), and after PGE1 injection (dynamic PSV) in 339 unselected patients with erectile dysfunction. In 55 of these patients the waveform acceleration in the flaccid state was also assessed. The results of the study can be summarized as follows: (1) a significant relationship was found between basal and dynamic PSV in the 339 patients (r=0.477; p < 0.0001); (2) a basal PSV >12.5 cm/sec was predictive of a dynamic PSV >/=30 cm/sec in 129/139 (92.8%) of the patients, whereas in patients with a basal PSV or <30 cm/sec could be found; and (3) an acceleration >1 m/sec2 in the flaccid state was coupled to a dynamic PSV >30 cm/sec in 43/46 (93.5%) of the patients independent of the basal PSV. In conclusion, these results suggest that the combined duplex ultrasound assessment of PSV and waveform acceleration in the penile flaccid state can predict arterial dynamic inflow in the majority (51/55; 92.7%) of patients with erectile dysfunction, with less time and expense and less discomfort for the patient.     

Long-term survival after cardiac retransplantation: a twenty-year single-center experience

OBJECTIVE: To identify risk factors for survival after cardiac retransplantation and compare the survival after retransplantation with that after primary cardiac transplantation. METHODS: A retrospective analysis of 952 patients undergoing cardiac transplantation for the treatment of end-stage heart disease at a single center between 1977 and October 1997. Of these, 43 patients (4.5%) underwent cardiac retransplantation for cardiac failure resulting from transplant-related coronary artery disease, rejection, and early graft failure. RESULTS: No significant difference in actuarial patient survival was found by Kaplan-Meier analysis at 1, 2, and 5 years between patients undergoing primary transplantation and those undergoing retransplantation 76%, 71%, and 60% versus 66%, 66%, and 51%, respectively (P =.2). Multivariable analysis identified a shorter interval between transplants and an initial diagnosis of ischemic cardiomyopathy as significant risk factors for death after retransplantation (P =.04 and.03, respectively). Since 1993, when our criteria for patient selection for retransplantation were revised on the basis of earlier experience to exclude patients with allograft dysfunction as a result of primary graft failure and those with intractable acute rejection occurring less than 6 months after transplantation, the survival has been significantly better (<1993 = 45%, 45%, and 33% versus >/=1993 = 94%, 94%, and 94% at 1, 2, and 4 years, respectively, P =.003). CONCLUSION: The long-term outcome of cardiac retransplantation is comparable with that of primary transplantation, especially in patients with transplant-related coronary artery disease. Patient characteristics and other preoperative variables should assist in the rational application of retransplantation to ensure optimal use of donor organs.