The Holocaust Is a Significant and Independent Risk Factor of Late-Onset Cancers: A Systematic Review of the Literature and Original Data on Jewish Israeli, Jewish Non-Israeli and Non-Jewish Non-Israeli Survivors.

BACKGROUND/AIM: Seventy-six years after Auschwitz Liberation, the Holocaust keeps on persecuting its surviving victims. As witnessed by the psychiatric and medical literature in the last decades, in fact, the Holocaust survivors (HS) appear to suffer from several Shoah-related late-onset diseases impacting their survival, such as internal illnesses and post-traumatic stress disorder (PTSD). Cancer represents a further severe pathology which seems to be connected with the Holocaust experience. Our aim was to review the existing knowledge of Holocaust-related cancer in HS in order to assess its real incidence and clinicoprognostic significance. MATERIALS AND METHODS: We systematically reviewed the literature dealing with Israeli Jewish and non-Jewish non-Israeli HS developing cancer. We also reviewed and analyzed the cancer data of noted Jewish HS not resident or having resided in Israel available as public information. RESULTS: We found 16 and 15 studies on Israeli Jews and non-Jewish non-Israeli survivors, respectively. A statistically significant association between the Holocaust and development of late-onset cancer in HS was seen in most studies with cancer adversely impacting the survival. We also selected 330 noted Jewish non-Israeli HS: genocide-related late-onset cancer resulted to be a significant and independent risk factor of poor prognosis (p<0.0001) imparting shorter survival in affected versus non-cancer subjects (57 versus 64 years, respectively, p=0.0001). CONCLUSION: Although 76 years have passed, our review shows how the Holocaust keeps on burdening its survivors. Moreover, we offered the first analysis of Jewish HS not resident or having resided in Israel in terms of genocide-related late-onset diseases focusing on cancer. Further studies on Jewish non-Israeli HS are needed in order to corroborate our findings on late-onset cancer occurring in this targeted population.

Use of a Novel Device in Reconstructive Venous Surgery: Preliminary Results.

Evaluation of the outcomes of OSES (oval-shaped external support), a novel device for external valvuloplasty of the great saphenous vein (GSV) for the conservative treatment of superficial venous insufficiency. Between 2012 and 2015, 30 patients underwent external valvuloplasty of the GSV for a total of 32 limbs. Patients were subjected to clinical and instrumental follow-up by a half-year ultrasound for a minimum of 36 months. The main endpoints were the recurrence of varicose disease, persistent or recurrent venous reflux, and venous thrombosis. Varicose recurrence was verified in six limbs on 32 (18.75%). Four limbs (12.5%) presented a recurrence of the reflux even in the absence of varicose veins. Two limbs (6.25%) underwent saphenectomy after the valvuloplasty intervention at 12 and 18 months, respectively, because of the presence of saphenofemoral reflux and varicose recurrences. No case of venous thrombosis of the saphenous trunk was observed. The external valvuloplasty of the GSV is a well-known technique that used to treat the superficial venous insufficiency. The newly introduced OSES device seems to show better midterm results, due to a better alignment of the valve flaps. In our experience, the use of this device gives better long-term results and allowed to extend the indication to patients with saphenic diameters that were considered not eligible for repair. In conclusion, although our data needs further confirmation, OSES device might represents a new interesting opportunity for reconstructive venous surgery.

Atherosclerotic plaque instability in carotid arteries: miR-200c as a promising biomarker.

Early recognition of vulnerable carotid plaques could help in identifying patients at high stroke risk, who may benefit from earlier revascularisation. Nowadays, different biomarkers of plaque instability have been unravelled, among these miRNAs are promising tools for the diagnosis and treatment of atherosclerosis. Inflammation, reactive oxygen species (ROS) and endothelial dysfunction play a key role in unstable plaques genesis. We showed that miR-200c induces endothelial dysfunction, ROS production and a positive mechanism among miR-200c and miR-33a/b, two miRNAs involved in atherosclerosis progression. The goal of the present study was to determine whether miR-200c could be an atherosclerosis biomarker. Carotid plaques of patients that underwent carotid endarterectomy (CEA) were assayed for miR-200c expression. miR-200c was up-regulated in carotid plaques (n=22) and its expression was higher in unstable (n=12) compared with stable (n=10) plaques. miR-200c positively correlated with instability biomarkers (i.e. monocyte chemoattractant protein-1, cicloxigenase-2 (COX2), interleukin 6 (IL6), metalloproteinase (MMP) 1 (MMP1), 9 (MMP9)) and miR-33a/b. Moreover, miR-200c negatively correlated with stability biomarkers (i.e. zinc finger E-box binding homoeobox 1 (ZEB1), endothelial nitric oxide (NO) synthase (eNOS), forkhead boxO1 (FOXO1) and Sirtuin1 (SIRT1)) (stable plaques = 15, unstable plaques = 15). Circulating miR-200c was up-regulated before CEA in 24 patients, correlated with miR-33a/b and decreased 1 day after CEA. Interestingly, 1 month after CEA, circulating miR-200c is low in patients with stable plaques (n=11) and increased to control levels, in patients with unstable plaques (n=13). Further studies are needed to establish whether miR-200c represents a circulating biomarker of plaque instability. Our results show that miR-200c is an atherosclerotic plaque progression biomarker and suggest that it may be clinically useful to identify patients at high embolic risk.

Peripheral Blood Mononuclear Cells Therapy for Treatment of Lower Limb Ischemia in Diabetic Patients: A Single-Center Experience.

BACKGROUND: The aim of this study is to analyze the effects of peripheral blood mononuclear cells (PBMNCs) therapy in diabetic patients with critical limb ischemia (CLI), with particular regard to its application, as adjuvant therapy in patients underwent endovascular revascularization. METHODS: Fifty diabetic patients affected by CLI were enrolled. All patients underwent PBMNCs therapy. Thirty-two patients underwent PBMNCs therapy associated with endovascular revascularization (adjuvant therapy group). In 18 patients, who were considered nonrevascularizable or underwent unsuccessful revascularization, regenerative therapy with PBMNCs was performed as the therapeutic choice (PBMNCs therapy group). RESULTS: The median follow-up period was 10 months. The baseline and end point results in adjuvant group were as follows. The mean transcutaneous partial pressure of oxygen (TcPO2) improved from 25 ± 9.2 mmHg to 45.6 ± 19.1 mmHg (P < 0.001), and visual analogue scale (VAS) score means decreased from 8.6 ± 2.1 to 3.8 ± 3.5 (P = 0.001). In PBMNCs therapy group, the mean TcPO2 improved from 16.2 ± 7.2 mmHg to 23.5 ± 8.4 mmHg (P < 0.001), and VAS score means decreased from 9 ± 1.1 to 4.1 ± 3.3 (P = 0.001). Major amputation was observed in 3 cases (9.4%), both in adjuvant therapy group and in PBMNCs therapy one (16.7%) (P = 0.6). CONCLUSIONS: The role of cellular therapy with PBMNCs is decisive in the patients that are not susceptible to revascularization. In diabetic patients with CLI and healing resistant ulcers, the adjuvant PBMNCs therapy could represent a valid therapeutic option.

Intramuscular Venous Malformations of the Upper and Lower Limbs: Indications and Outcomes of Sclerotherapy.

PURPOSE: Multiple treatment options have been described for intramuscular venous malformations (VMs) of the limbs. At the current time, there are no clear management guidelines. The aim was to evaluate efficacy and safety of sclerotherapy in this type of VMs. MATERIALS AND METHODS: This is a single-center, retrospective review of patients treated for extremity intramuscular VMs between January 2013 and June 2017. The primary outcomes were the improvement of symptoms self-assessed by questionnaires, and the reduction in VM size measured by magnetic resonance (MRI). RESULTS: Sclerotherapy was performed in 81 patients with extremity intramuscular VMs. The sclerosing agent was ethanol in 46 cases (56.8%), polidocanol in 27 cases (33.3%), a combination of both in 8 cases (9.9%). The mean follow-up was 26 months (range 3-52). Overall quality of life was improved in 62 patients (76.5%). The postoperative MRI showed a minimum change of VM size in 68 patients (83.9%). A major complication (peripheral nerve injury) was observed in 1 case (1.2% of patients, 0.5% of procedures). Minor complications occurred in 9 cases (11.1% of patients, 4.1% of procedures). CONCLUSIONS: Sclerotherapy is a low-invasive, effective and safe treatment for intramuscular VMs of the extremities. It induces a significant improvement in symptoms, also when the VM size is unchanged. LEVEL OF EVIDENCE: Level 4, Case Series.

Osteoporosis and cardiovascular diseases' cosegregation: epidemiological features.

Life expectancy in Italy is estimated to rise to 77.9 and 84.4 years in next years. Increased life expectancy is associated with a greater frailty of elderly people and an increased prevalence of chronic and degenerative illnesses such as cardiovascular diseases and osteoporosis. The impact of osteoporotic hip fractures in Italy is very similar to that of acute myocardial infarction (AMI), and there is a need for further epidemiological investigations concerning both the pathologies, as well as for a better understanding of possible mechanisms of their cosegregation. Actually, calcium metabolism is involved both in the development of osteoporosis and in the raise of cardiovascular risk. We have reviewed the most recent publications concerning epidemiological trends of both osteoporosis and acute myocardial infarction (AMI), and also the trials addressing cosegregation of these pathologies. According to the publications examined, in the Italian population (both ≥ 45 and > 65 years old), the number of hospitalizations following hip fracture and AMI are comparable. Both hip fractures and cardiovascular diseases represent in Italy a serious medical problem and a leading health cost driver, according to what has already been reported for many other Countries in the industrialized world, thus requiring a global clinical approach. Low calcium intake could represent one of the possible pathogenic paths underlining the association between hypertension and osteoporosis. Low calcium serum levels has been proved to enhance PTH and vitamin D3 production, which result in a remarkable lypogenesis performed by adypocites and switch on mechanisms leading to the raise of blood systolic pressure, the development of atherosclerotic plaques and cardiovascular events. Although many trials have suggested that bone mineral density may be included in the list of cardiovascular risk factors, more studies are needed in order to deeply investigate the causal relationships between calcium metabolism and cardiovascular diseases.