Sclerotherapy with 3% polidocanol foam to treat second-degree haemorrhoidal disease: Three-year follow-up of a multicentre, single arm, IDEAL phase 2b trial.

BACKGROUND: Sclerotherapy with 3% polidocanol foam is becoming increasingly popular for the treatment of symptomatic I-II or III degree haemorrhoidal disease (HD). However, there are no studies that have reported a follow-up of more than 1 year. The purpose of this study was to analyse the long-term outcomes of sclerotherapy with 3% polidocanol foam in the treatment of II-degree HD. METHODS: This was an open label, single-arm, phase 2b trial conducted in 10 tertiary referral centres for HD. A total of 183 patients with II-degree HD, aged between 18 and 75 years with symptomatic HD according to the Goligher classification and unresponsive to medical treatment, were included in the study and underwent sclerotherapy with 3% polidocanol foam. The efficacy was evaluated in terms of bleeding score, haemorrhoidal disease symptom score (HDSS) and short health scale for HD (SHS-HD) score. Successful treatment was defined as the complete absence of bleeding episodes after 7 days (T1) according to the bleeding score. RESULTS: The overall success rate ranged from 95.6% (175/183) at 1 year to 90.2% (165/183) after the final 3 year follow-up. The recurrence rate, based on the primary outcome, ranged from 12% (15/125) to 28% (35/125). The greatest increase in recurrence (15) was recorded between 12 and 18 months of follow-up, then another five between 18 and 24 months. Both the HDSS and the SHS score remained statistically significant (p < 0.001) from a median preoperative value of 11 (10-13) and 18 (15-20) to 0 (0-2) and 4 (0-4), respectively. Symptom-free (HDSS = 0) patients, excluding patients converted to surgery, increased from 55.5% (101/182) at 1 year to 65.1% at 3 years (110/169). There were no intraoperative complications in redo-sclerotherapy nor additional adverse events (AEs) compared to the first 12 months. CONCLUSIONS: Sclerotherapy with 3% polidocanol foam is gradually establishing itself in the treatment of bleeding HD due to its repeatability, safety, convenience in terms of direct and indirect costs with the absence of discomfort for the patient as well as AEs rather than an excellent overall success rate.

Endoscopic Pilonidal Sinus Treatment: A Tertiary Care Academic Center Experience.

Background: Pilonidal disease (PD) represents one of the most common proctological diseases in young adults. Although several approaches to treating PD have been described, there is still a lack of agreement on which is the best. The aim of this study was to evaluate the long-term efficacy of endoscopic pilonidal sinus treatment (EPSiT) at a tertiary care academic center. Methods: Between June 2017 and January 2021, a total of 32 patients [12 women (37.5%) and 20 men (62.5%)] with a mean age of 29.22 ± 12.98 years were treated with EPSiT. Pre- and post-operative symptoms were assessed with a score of 0-5. Success was defined as the absence of any subjective symptoms, as well as by complete post-operative wound healing. Results: Most of the patients had a midline external opening (17/32; 53.1%), with a mean number of external openings of 2.41 (1-4) ± 1.04. The median post-operative pain score was 0, and the mean follow-up period was 22 (4-42) ± 11.49 months. The time to wound healing was reduced in patients with one opening (28.14 ± 4.06 days) compared to patients with two or more openings (33.64 ± 7.3 days) (p = 0.067). The mean operative time was longer in patients who subsequently had a recurrence (41.75 ± 6.24 vs. 34.18 ± 6.24 min; p = 0.031). The overall success rate was 87.5% (28/32), and the mean time to recurrence was 3.25 (2-5) ± 1.26 months. Conclusions: EPSiT represents a viable option for the treatment of PD. More evidence and a longer follow-up period are needed to validate the results.

Anatomo-functional outcomes of the laparoscopic Frykman-Goldberg procedure for rectal prolapse in a tertiary referral centre.

Rectal prolapse is a common disorder that represents a burden for patients due to the associated symptoms that may include both incontinence and constipation. Currently, a huge variation in techniques exist. The aim of this study was to evaluate the anatomo-functional results of the laparoscopic Frykman-Goldberg procedure (LFGP) for the treatment of both internal (IRP) and complete rectal prolapse (CRP). Between July 2004 and October 2019, 45 patients with IRP and CRP underwent a LFGP. The Cleveland Clinic Constipation Score (CCCS), Obstructed Defecation Syndrome Score (ODSS) and Vaizey Score (VS) were assessed preoperatively, 3 months before the procedure, 12 months after the procedures and at the final follow-up visit. The patients' mean age was 51.4 ± 17.9 (15-93) years, and the mean follow-up was 9.24 ± 4.57 (1.6-16.3) years. The VS, CCCS and ODSS significantly improved (p = 0.008; p < 0.001; p < 0.001) from median preoperative values of 3, 20 and 18 to 2, 6 and 5, respectively. Furthermore, the improvements in scores during follow-up remained constant and significant over time when considering the two groups separately (time effect for ODSS p < 0.001, for VS p = 0.026, for CCCS p < 0.001) and when the patients were divided by age (< 40, 41-60 and > 60; p < 0.001). The overall complication rate was 8.9% (4/45), and no intraoperative complications or anastomotic leakage occurred. Conversion to the open approach was not necessary in any case. The overall success rate was 97.7%, and only one recurrence in the IRP group occurred after 14 months. LRGP can be considered a safe, effective and long-lasting procedure in young patients with IRP or CRP, a history of ODS and a redundant sigmoid colon.

Short-Term Results of Sclerotherapy with 3% Polidocanol Foam for Symptomatic Second- and Third-Degree Hemorrhoidal Disease.

BACKGROUND: Hemorrhoidal disease (HD) is defined as the symptomatic enlargement and/or distal displacement of anal cushions and is one of the most common proctological diseases. Sclerotherapy (ST) with 3% polidocanol foam induces an inflammatory reaction with sclerosis of the submucosal tissue and consequent suspension of the hemorrhoidal tissue. The aim of this study was to evaluate the short-term effectiveness and safety of ST with 3% polidocanol foam for the treatment of symptomatic second- and third-degree HD. METHODS: A total of 66 patients with symptomatic second- and third-degree HD underwent a single ST session between March 2017 and July 2018. A visual analog scale score was used to assess post-operative pain and patient satisfaction. The symptoms severity and anal continence were investigated through the Hemorrhoid Severity Score (HSS) and Vaizey score, respectively, at baseline, at 4 weeks and after 1 year. RESULTS: Fifty-seven out of 66 patients were male (86.3%), and the mean age was 52 (29-75; SD ± 12) years. The mean operative time was 4.5 (2-6; SD ± 1.23) minutes. No intraoperative complications and no drug-related side effects occurred. The overall success rate was 78.8% (52/66 patients) after a single ST session and 86% after two ST sessions (57/66 patients). The mean treatment effect, obtained comparing preoperative and 12 months symptom scores in each patient, showed a median change of 8 (p < 0.001). All patients resumed their normal daily activities the day after the procedures. CONCLUSIONS: ST with 3% polidocanol foam is a safe, cost-effective and repeatable conservative treatment.

Use of an Aortic Valve Replacement Simulation Model to Understand Hospital Costs and Resource Utilization Associated With Rapid-deployment Valves.

PURPOSE: Aortic stenosis (AS) is the most common cause of adult valvular heart disease. In the past decade, minimally invasive surgery (MIS) to treat AS has gained popularity, especially if performed in combination with rapid deployment valves (RDVs), which shorten cross-clamp time (XCT). This study examines specific outcomes and related costs of aortic valve replacement (AVR) before and after the introduction of RDVs. METHODS: We used the AVR simulator, an economic model developed to correlate cost and resource utilization associated with the adoption of RDVs, to compare 2 scenarios: (1) a current scenario based on standard AVR practices and (2) a proposed scenario based on increasing use of RDVs and an MIS approach. Both scenarios involved 3 subgroups of patients treated with (1) conventional AVR, (2) MIS, and (3) AVR combined with a coronary artery bypass graft. The current scenario (status quo) involved patients treated with traditional biological valves, and the proposed scenario involved patients who underwent implantation with an RDV. The AVR simulator was fed with real-world input data to estimate complication rates and resource consumption in the proposed scenario. Real-world input data for this analysis were obtained from patients diagnosed with a symptomatic heart valve disease between 2015 and 2018, at Clinica-San-Gaudenzio, Novara, Italy. Lastly, the AVR simulator estimated hospital savings by comparing the 2 scenarios. FINDINGS: A total of 132 patients underwent implantation with a traditional biological valve, and 107 were treated with a commercial valve system. The RDV was associated with an increase of 52% of patients undergoing MIS, which generated a 6.1-h reduction of XCT and a total savings of €6695. RDVs also reduced intensive care unit (ICU) and hospital ward length of stay (LOS), leading to savings of €677 and €595 per patient, respectively. Mortality and blood transfusions also improved. The savings for the hospital (related to shorter XCT, hospital ward LOS, and ICU LOS) amounted to €144.111. Our findings were consistent with data gathered from our real-word setting, and results of a sensitivity analysis indicate that our findings were robust across different possible situations. IMPLICATIONS: Switching to RDVs and MIS procedures for AVRs was associated with a reduction of costs related to XCT, hospital ward LOS, and ICU LOS. Hospitals can upload literature- and experience-based clinical and cost values to the AVR simulator to estimate a hospital's performance with the introduction of RDVs compared with standard biological valves. This study was not randomized, so more extensive studies could confirm our results in the future.

Altemeier's procedure for complete rectal prolapse; outcome and function in 43 consecutive female patients.

BACKGROUND: The aim of this retrospective study was to evaluate morbidity, mortality, postoperative function and recurrences in patients treated by Altemeier's rectosigmoidectomy for complete rectal prolapse in a referral center for pelvic floor functional disorders. METHODS: Peri-operative data on 43 consecutive female patients were reviewed. At follow-up any change in pelvic floor function and recurrences were determined. Thirty four patients were assessed at a median interval of 49 (2-135) months, six being deceased for reason not related to the prolapse and three lost to follow-up. RESULTS: Post-operative complications at 30 days occurred in 18 patients (38%). Major complication occurred in only one patient that was pneumonia with lung failure. Major complications were not related to the ASA score, BMI or age [average age 76.4]. There was no post-operative mortality at 30 days. At long-term follow-up functional results demonstrate a statistically significant decrease in the Obstructive Defecation Syndrome (ODS) score, but no statistically significant changes in the Vaizey score, the International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF) score and the urinary retention score. ODS score decreased with respect to levatorplasty and the change was statistically significant instead of Vaizey score in which were not. At the same follow-up there were 12 (35%) cases of recurrence with an estimated risk at 48 months of 40%. There were no statistically significant differences between patients with and without recurrence regarding age (p = 0.188), BMI (p = 0.864), ASA score (p = 0.433), previously repaired prolapse (p = 0.398), previous hysterectomy (p = 0.705), length of resected bowel (p = 0.126), and levatorplasty (p = 0.304). Patient satisfaction showed a mean of 8.8 and 6.4 respectively in patients without and with recurrences (p = 0.012). CONCLUSIONS: Altemeier's procedure had in our series low complications rate and no mortality. It offered improved evacuation in constipated patients while didn't improve fecal and urinary continence. Recurrence of prolapse was 40% at four years.

The role of Geriatric screening tool (G8) in predicting side effect in older patients during therapy with aromatase inhibitor.

BACKGROUND: Endocrine therapy is the main treatment in hormonosensitive breast cancer; the most frequent side effects are arthralgia, osteoporosis, depression, dyslipidemia and hypertension. G8 is a simple test developed to identify older patients who could benefit from a comprehensive geriatric assessment (CGA). The aim of this study is to evaluate the possible role of G8 in predicting side effects from treatment with aromatase inhibitor in women ≥65 years old. MATHERIAL AND METHOD: Women ≥65 years old affected by breast cancer about to start a therapy with an aromatase inhibitor, in the adjuvant setting, were evaluated with the G8 tool. Patients were classified as "fit" with G8 score > 14 or "vulnerable" with G8 score ≤ 14; they then started treatment and clinical-instrumentalfollow-up. RESULTS: From April 2016 to February 2018, 50 consecutive patients were screened. Median age was 75.1 (range 65-86). G8 identified 30 patients (60%) as "fit" (score > 14) and 20 (40%) as "vulnerable" (score ≤ 14). The grade of concordance between G8 score and the appearance/absence of adverse events were statistically significant (41/50 patients, 82%, p = 0.0002); sensitivity resulted in 78% and specificity was 81%; positive predictive value was 70% and negative predictive value was 87%. The most frequent adverse event was arthromyalgia. CONCLUSION: The G8 screening tool has a potential role in predicting side effects during a treatment with aromatase inhibitor. G8 could be very useful in everyday clinical practice for this population.

Symptomatic pile tailored procedure. A new perspective for hemorrhoidal disease treatment.

AIM: Aim of the present paper was to evaluate the role of tailored different single pile treatment in the clinical outcome of hemorrhoids. MATERIAL OF STUDY: The surgical strategy considered to treat only pathological piles with different procedure according to each pathological Goligher's degree, presence of fibrous, inelastic redundant internal pile(F) and presence of external pathological pile (external pile congestion or subversion of dental line (E) and skin tag not tolerated from the patient (S)). We treated with Hemorrhoidopexy second and third degree pile without F or ES; with Hemorrhoidopexy and excision of external component every second and third degree pile with E or S and with complete semi-closed pile excision all third degree with F and IV degree piles. The number of post operative days of self administered analgesics was the primary end point and short/long term post operative complications, hospital stay, re-admission and recurrence were secondary end points. RESULTS: 157 patients were treated. No differences were noted in term of time of discharge between hemorrhoidopexy and complete or external excision. The painkiller assumption increases with the number of treated pile (r= 0.227, p=0.006). We observed 10.2% early complications (48h) all secondary to urinary retention and 7% late complications (2-15days) within only one reoperation for bleeding. After mean follow up of 16 months no patients required further treatments for hemorrhoids. DISCUSSIONS: A tailored approach showed to be effective in terms of short and long term complications and moreover to relapse. CONCLUSIONS: Single pile tailored treatment showed good results. KEY WORDS: Excision, Hemorrhoids, Hemorrhoidectomy, Hemorrhoidopexy, Pain, Tailored.

Safe Reentry for False Aneurysm Operations in High-Risk Patients.

BACKGROUND: In the absence of a standardized safe surgical reentry strategy for high-risk patients with large or anterior postoperative aortic false aneurysm (PAFA), we aimed to describe an effective and safe approach for such patients. METHODS: We prospectively analyzed patients treated for PAFA between 2006 and 2015. According to the preoperative computed tomography scan examination, patients were divided into two groups according to the anatomy and extension of PAFA: in group A, high-risk PAFA (diameter ≥3 cm) developed in the anterior mediastinum; in group B, low-risk PAFA (diameter <3 cm) was situated posteriorly. For group A, a safe surgical strategy, including continuous cerebral, visceral, and coronary perfusion was adopted before resternotomy; group B patients underwent conventional surgery. RESULTS: We treated 27 patients (safe reentry, n = 13; standard approach, n = 14). Mean age was 60 years (range, 29 to 80); 17 patients were male. Mean interval between the first operation and the last procedure was 4.3 years. Overall 30-day mortality rate was 7.4% (1 patient in each group). No aorta-related mortality was observed at 1 and 5 years in either group. The Kaplan-Meier overall survival estimates at 1 and 5 years were, respectively, 92.3% ± 7.4% and 73.4% ± 13.4% in group A, and 92.9% ± 6.9% and 72.2% ± 13.9% in group B (log rank test, p = 0.830). Freedom from reoperation for recurrent aortic disease was 100% at 1 year and 88% at 5 years. CONCLUSIONS: The safe reentry technique with continuous cerebral, visceral, and coronary perfusion for high-risk patients resulted in early and midterm outcomes similar to those observed for low-risk patients undergoing conventional surgery.

Long-Term Contrast Echocardiography and Clinical Follow-Up after Percutaneous Closure of Patent Foramen Ovale Using Two Different Atrial Septal Occluder Devices.

INTRODUCTION: Percutaneous patent foramen ovale (PFO) closure by means of a septal occluder device (SOD) is a well-known therapeutic strategy for the secondary prevention of paradoxical embolic neurological events. The aim of this study was to provide long-term echocardiographic and clinical follow-up data on patients who had undergone percutaneous PFO closure with 2 different SOD. METHODS: We selected 2 groups of patients treated with 2 different SOD: Group A: 52 patients with an Amplatzer(®) PFO Occluder and Group B: 49 patients with a Figulla Flex(®) device. All patients underwent follow-up Bubble Test Transthoracic Echocardiography (BTTE) and clinical examination. The results were compared with those recently reported in a group of patients with similar characteristics, but that had been treated conservatively, which acted as a control group. RESULTS: The mean follow-up after PFO closure was 53 months. The Amplatzer(®) PFO Occluder and the Figulla Flex were used in 52 (51.5%) and 49 (48.5%) of patients, respectively. We found no significant difference in the rate of effective PFO closure between the devices: Amplatzer 91.4%, Figulla 93.9% (P = 0.71). One patient (1.0%) suffered a recurrent neurologic event. BTTE was positive (BTTE+) in 8 patients (8%), 5 with an Amplatzer, and 3 with a Figulla device (P = 0.516). Only 1 patient with BTTE+ had a recurrent TIA (12.5%). No significant relationship was found between device dimensions and BTTE+ (P = 0.062). In the control group (163 patients), the recurrence of neurologic events was 9.2% (15 events), that was significantly higher in respect to the patients who had undergone percutaneous closure of the PFO. CONCLUSIONS: Percutaneous PFO closure was associated with a remarkably low risk of recurrent embolic neurological events, and no long-term device-related major complications. No statistically significant difference emerged between the 2 different SODs regarding BTTE positivity. Long-term follow-up showed that the recurrence of neurological events has been significantly higher in the group treated in a conservative way.

Low-Dose Paclitaxel Reduces S100A4 Nuclear Import to Inhibit Invasion and Hematogenous Metastasis of Cholangiocarcinoma.

Nuclear expression of the calcium-binding protein S100A4 is a biomarker of increased invasiveness in cholangiocarcinoma, a primary liver cancer with scarce treatment opportunities and dismal prognosis. In this study, we provide evidence that targeting S100A4 nuclear import by low-dose paclitaxel, a microtubule-stabilizing agent, inhibits cholangiocarcinoma invasiveness and metastatic spread. Administration of low-dose paclitaxel to established (EGI-1) and primary (CCA-TV3) cholangiocarcinoma cell lines expressing nuclear S100A4 triggered a marked reduction in nuclear expression of S100A4 without modifying its cytoplasmic levels, an effect associated with a significant decrease in cell migration and invasiveness. While low-dose paclitaxel did not affect cellular proliferation, apoptosis, or cytoskeletal integrity, it significantly reduced SUMOylation of S100A4, a critical posttranslational modification that directs its trafficking to the nucleus. This effect of low-dose paclitaxel was reproduced by ginkolic acid, a specific SUMOylation inhibitor. Downregulation of nuclear S100A4 by low-dose paclitaxel was associated with a strong reduction in RhoA and Cdc42 GTPase activity, MT1-MMP expression, and MMP-9 secretion. In an SCID mouse xenograft model, low-dose metronomic paclitaxel treatment decreased lung dissemination of EGI-1 cells without significantly affecting their local tumor growth. In the tumor mass, nuclear S100A4 expression by cholangiocarcinoma cells was significantly reduced, whereas rates of proliferation and apoptosis were unchanged. Overall, our findings highlight nuclear S100A4 as a candidate therapeutic target in cholangiocarcinoma and establish a mechanistic rationale for the use of low-dose paclitaxel in blocking metastatic progression of cholangiocarcinoma. Cancer Res; 76(16); 4775-84. ©2016 AACR.

Human Cardiac Progenitor Spheroids Exhibit Enhanced Engraftment Potential.

A major obstacle to an effective myocardium stem cell therapy has always been the delivery and survival of implanted stem cells in the heart. Better engraftment can be achieved if cells are administered as cell aggregates, which maintain their extra-cellular matrix (ECM). We have generated spheroid aggregates in less than 24 h by seeding human cardiac progenitor cells (hCPCs) onto methylcellulose hydrogel-coated microwells. Cells within spheroids maintained the expression of stemness/mesenchymal and ECM markers, growth factors and their cognate receptors, cardiac commitment factors, and metalloproteases, as detected by immunofluorescence, q-RT-PCR and immunoarray, and expressed a higher, but regulated, telomerase activity. Compared to cells in monolayers, 3D spheroids secreted also bFGF and showed MMP2 activity. When spheroids were seeded on culture plates, the cells quickly migrated, displaying an increased wound healing ability with or without pharmacological modulation, and reached confluence at a higher rate than cells from conventional monolayers. When spheroids were injected in the heart wall of healthy mice, some cells migrated from the spheroids, engrafted, and remained detectable for at least 1 week after transplantation, while, when the same amount of cells was injected as suspension, no cells were detectable three days after injection. Cells from spheroids displayed the same engraftment capability when they were injected in cardiotoxin-injured myocardium. Our study shows that spherical in vivo ready-to-implant scaffold-less aggregates of hCPCs able to engraft also in the hostile environment of an injured myocardium can be produced with an economic, easy and fast protocol.

Jugular Vein Insufficiency and Choroidal Neovascularization in Moderate Myopia: A New Unknown Factor of Additional Risk?

To date, choroidal blood flow reduction in highly myopic eyes appears to be related to the development of choroidal neovascularization secondary to local reduction of arterial flow. Instead, no evidence of choroidal neovascularization was found in subjects with low or moderate myopia. The authors' aim has been to encourage new studies regarding the potential role of chronic retinal venous congestion in the pathogenesis of choroidal neovascularization. In December 2011, a 54-year-old woman with moderate bilateral myopia had a sudden block upon swallowing while she was eating. Subsequently (January 2013) metamorphopsia in the left eye revealed macular degeneration with choroidal neovascularization. The related echo-color Doppler study of the neck veins, performed in November 2014, showed an atypical left jugular insufficiency associated with homolateral hypertension of the superior ophthalmic veins. This singular case highlights the necessity to further investigate the potential role of chronic alterations of intra- and extracranial venous drainage in the disruption of choroidal flow in myopic patients.

Automated carbon dioxide digital angiography for lower-limb arterial disease evaluation: safety assessment and comparison with standard iodinated contrast media angiography.

INTRODUCTION: Carbon dioxide (CO2) has been validated as a contrast agent in a large series of studies. A particular advantages of CO2 over iodinated contrast medium (ICM) is the absence of nephrotoxicity and allergic reactions. One of the limitations of CO2 angiography is the difficulty of CO2 manual injection due to its compressibility. The manual gas injection does not permit optimal control of the gas output. Development of an automated CO2 injector has overcome these problems. AIM: This study compares the feasibility, safety, and diagnostic accuracy of automated CO2 digital subtraction angiography (DSA) in comparison with ICM-DSA in the evaluation of critical limb ischemic (CLI) patients. METHODS: We performed DSA with both CO2 and ICM on 40 consecutive CLI patients and directly compared the two techniques. Sixteen females and 24 males participated in the study (mean age, 71.7 years). We assessed the diagnostic accuracy of CO2 in identifying arterial stenosis in the lower limb, with ICM-DSA used as the gold standard. RESULTS: The overall diagnostic accuracy of CO2-DSA was 96.9% (sensitivity, 99.0%; specificity, 96.1%; positive predictive value, 91.1%; negative predictive value, 99.6%). Tolerable minor symptoms occurred in 3 patients. No allergic reactions or significant decline in renal function were observed in patients receiving the CO2 injection. CONCLUSION: Carbon dioxide DSA is a valuable and safe alternative to traditional ICM-DSA for evaluating CLI patients. This modality should be considered as the standard choice for CLI patients undergoing angiographic evaluation who are known to have renal insufficiency or contrast allergy.

Venous Hemodynamic Insufficiency Severity Score variation after endovascular treatment of chronic cerebrospinal venous insufficiency.

INTRODUCTION: Chronic cerebrospinal venous insufficiency (CCSVI) is a vascular condition characterized by anomalies of the internal jugular veins (IJVs) and/or azygos veins with disturbed flow and formation of collateral venous channels. The presence of CCSVI has been associated with multiple sclerosis (MS). Percutaneous venous angioplasty (PVA) has been proposed to improve extracranial outflow; however, a non-invasive, post-procedural follow-up outcome measure has not been established. AIM OF THE STUDY: To evaluate the short-term hemodynamic follow-up of CCSVI after PVA using color Doppler ultrasound (CDU) and to investigate whether hemodynamic variation correlated with clinical variation. MATERIALS AND METHODS: Forty-five patients affected by MS with confirmed CCSVI underwent IJVs PVA. Venous hemodynamic (VH) parameters indicative of CCSVI and the Venous Hemodynamic Insufficiency Severity Score (VHISS) were evaluated by CDU at baseline and 3 months post-PVA. Concurrently, the MS-related disability status (EDSS) was evaluated. RESULTS: The VH parameters and VHISS 3 months after IJVs PVA significantly decreased: the VH parameters -32.1% and the VHISS -33.8% (p < 0.001). The EDSS score 3 months after IJVs PVA was significantly lower than the baseline (-5.5%, p < 0.001). Using the median value of the VHISS variation as the cut-off, we were able to identify two groups of patients: responders, group A; and non-responders, group B. The EDSS score variation at 3 months was 0.310 in group A and 0.275 in group B (p = 0.746). CONCLUSIONS: CCSVI endovascular treatment can induce an improvement in VH parameters and the VHISS. The neurological disability score (EDSS) also improved after PVA; however, there was no correlation to the VHISS variation after PVA, MS type and duration.

The prognostic role of troponin I elevation after elective percutaneous coronary intervention.

OBJECTIVES: To assess the prognostic role of isolated troponin I (TnI) elevation after elective percutaneous coronary intervention (PCI) in patients with stable coronary artery disease. BACKGROUND: The prognostic role of minor troponin elevation after PCI is controversial. METHODS: A total of 1532 consecutive patients who underwent elective PCI were included. Follow-up data were obtained for 1432 of 1532 (93.4%) patients. The events taken into account in the follow-up included total mortality, cardiac death, hospitalization for acute myocardial infarction and/or unstable angina. RESULTS: The following variables were identified as predictive of major adverse cardiac events (MACE) by univariate analysis: age 75 years at least (P = 0.012), ejection fraction less than 50% (P = 0.001), prior myocardial infarction (P = 0.031) and TnI 1.0 ng/ml at least after PCI (P = 0.04). The Cox-regression model identified the TnI elevation after PCI, the older age and the ejection fraction as independent predictors of MACE during follow-up (TnI: P = 0.042; older age: P = 0.001; ejection fraction: P = 0.003). In a subgroup of patients with preserved ejection fraction, the incidence of MACE was significantly higher in those with TnI of at least 1.0 ng/ml at least than in the ones with TnI less than 1.0 ng/ml, with the highest incidence among the older cohort. The multivariate analysis confirmed the TnI elevation 1.0 ng/ml at least after PCI and the older age as predictors of MACE. CONCLUSION: This study documented that in clinically stable patients, minor TnI elevations after elective PCI are independent predictors of MACE during follow-up, as are older age and reduced ejection fraction. Additionally, TnI elevation was a predictor of MACE during follow-up in a subset of patients with preserved ejection fraction. The combination of TnI elevation and older age confers the highest risk of MACE.

Activity of a three-drug combination including cisplatin (CLOVER regimen) for poorly differentiated neuroendocrine carcinoma.

BACKGROUND/AIM: No standard treatment has been established for poorly-differentiated neuroendocrine carcinomas (PDNEC). The aim of this study is to evaluate the response to the combination of three drugs. MATERIAL AND METHODS: We reviewed 21 PDNEC patients treated from 2008 to 2013 in two Institutions. Five patients were initially treated with epirubicin, fluorouracil and temozolomide. Because of toxicity, the regimen was modified into cisplatin, capecitabine and dacarbazine (scheme B-CLOVER regimen). RESULTS: Primary tumor site was: pancreas 7 (33%), lung 5 (24%), colon-rectum 5 (24%), unknown 3 (14%) and stomach 1 (5%). The response rate was 24% (0 complete response, 24% partial responses, 38% stable disease, 9% progression and 19% unassessable). The global overall survival (OS) is 13 months (range=1-29) and progression-free survival (PFS) was 6 months (range=1-11). CONCLUSION: The combination chemotherapy of cisplatinum, capecitabine and dacarbazine is feasible and should be considered as an option for PDNEC.

Monophasic and biphasic electrical stimulation induces a precardiac differentiation in progenitor cells isolated from human heart.

Electrical stimulation (ES) of cells has been shown to induce a variety of responses, such as cytoskeleton rearrangements, migration, proliferation, and differentiation. In this study, we have investigated whether monophasic and biphasic pulsed ES could exert any effect on the proliferation and differentiation of human cardiac progenitor cells (hCPCs) isolated from human heart fragments. Cells were cultured under continuous exposure to monophasic or biphasic ES with fixed cycles for 1 or 3 days. Results indicate that neither stimulation protocol affected cell viability, while the cell shape became more elongated and reoriented more perpendicular to the electric field direction. Moreover, the biphasic ES clearly induced the upregulation of early cardiac transcription factors, MEF2D, GATA-4, and Nkx2.5, as well as the de novo expression of the late cardiac sarcomeric proteins, troponin T, cardiac alpha actinin, and SERCA 2a. Both treatments increased the expression of connexin 43 and its relocation to the cell membrane, but biphasic ES was faster and more effective. Finally, when hCPCs were exposed to both monophasic and biphasic ES, they expressed de novo the mRNA of the voltage-dependent calcium channel Cav 3.1(α1G) subunit, which is peculiar of the developing heart. Taken together, these results show that ES alone is able to set the conditions for early differentiation of adult hCPCs toward a cardiac phenotype.

Cross-sectional area variations of internal jugular veins during supine head rotation in multiple sclerosis patients with chronic cerebrospinal venous insufficiency: a prospective diagnostic controlled study with duplex ultrasound investigation.

BACKGROUND: Normally, chronic cerebrospinal venous insufficiency (CCSVI) has been studied using echo-colour Doppler (ECD). Subjects are examined in the supine and sitting positions, in accordance with a static protocol without rotation of the head. A dynamic approach, to assess venous sizes with different degrees of head rotation, has only been performed to improve jugular venous catheterisation. These echographic studies have suggested that head rotation to the contralateral side increases the cross-sectional area (CSA) of the internal jugular veins (IJVs) in supine subjects. Our goal was to evaluate the behaviour of CSA of the IJVs during supine head rotation in multiple sclerosis (MS) patients with CCSVI, compared to healthy controls (HCs). METHODS: The IJVs of 313 MS patients with CCSVI (male 43.8%, male/female 137/176; mean age 45 years old, range 19-77 years) and 298 HCs, matched by gender (male 43.6%, male/female 130/168) and age (mean age 46 years old, range 20-79 years), were compared using ECD. Their CSAs were evaluated with the subjects seated in a tiltable chair, first in the supine position at the level of the cricoid cartilage, with the head in a neutral position, and then after contralateral rotation to 90° from midline. RESULTS: Significant differences between the jugular CSAs before and after head rotation were observed only in the MS patients for the IJVs with wall collapse (F[6,1215] = 6414.57, p < 0.001), showing on longitudinal scans a typical "hourglass" aspect that we defined as "miopragic". No significant difference was found in the distribution of these miopragic veins with regard to MS duration. There was a strong association between the CCSVI scores and the complexity of jugular morphological types (Χ2 [9, N = 313] = 75.183, p < 0.001). Wall miopragia was mainly observed in MS patients with SP (59.3%) and PP (70.0%) clinical forms, compared to RR (48.3%) forms (p = 0.015). CONCLUSION: A dynamic ECD approach allowed us to detect IJVs with a significant increase in their CSAs during head rotation, but only in MS subjects. This feature, most likely the expression of congenital wall miopragia, could be secondary to dysregulation of collagen synthesis, but further histochemical studies will be needed to confirm this hypothesis.