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Glioblastoma multiforme (GBM) is one of the most aggressive malignancies with a high recurrence rate and poor prognosis. Theranostic, combining therapeutic and diagnostic approaches, arises as a successful strategy to improve patient outcomes through personalized medicine. Src is a non‐receptor tyrosine kinase (nRTK) whose involvement in GBM has been extensively demonstrated. Our previous research highlighted the effectiveness of the pyrazolo[3,4‐d]pyrimidine SI306 and its more soluble prodrug CMP1 as Src inhibitors both in in vitro and in vivo GBM models. In this scenario, we decided to develop a theranostic prodrug of SI306, ProSI‐DOTA(68Ga) 1, which was designed to target GBM cells after hydrolysis and follow‐up on the disease's progression and improve the therapy's outcome. First, the corresponding nonradioactive prodrug 2 was tested to evaluate its ADME profile and biological activity. It showed good metabolic stability, no inhibition of CYP3A4, suboptimal aqueous solubility, and slight gastrointestinal and blood‐brain barrier passive permeability. Compound 2 exhibited a drastic reduction of cell vitality after 72 h on two different GBM cell lines (GL261 and U87MG). Then, 2 was subjected to complexation with the radionuclide Gallium‐68 to give ProSI‐DOTA(68Ga) 1. The cellular uptake of 1 was evaluated on GBM cells, highlighting a slight but significant time‐dependent uptake. The data obtained from our preliminary studies reflect the physiochemical properties of 1. The use of an alternative route of administration, such as the intranasal route, could overcome the physiochemical limitations and enhance the pharmacokinetic properties of 1, paving the way for its future development. [ABSTRACT FROM AUTHOR]

Background: The prevalence of neurodegenerative diseases is expected to increase over the next years, therefore, new methods able to prevent and delay cognitive decline are needed. Aims: To evaluate the effectiveness of a combined treatment protocol associating a computerized cognitive training (CoRe) with anodal transcranial direct current stimulation (tDCS). Methods: In this randomized controlled trial, 33 patients in the early stage of cognitive impairment were assigned to the experimental group (CoRE + real tDCS) or control group (CoRE + sham tDCS). In each group, the intervention lasted 3 consecutive weeks (4 sessions/week). A neuropsychological assessment was administered at baseline (T0), post-intervention (T1) and 6-months later (T2). Results: The CoRE + real tDCS group only improved in working memory and attention/processing speed at both T1 and T2. It reported a stable MMSE score at T2, while the CoRE + sham tDCS group worsened. Age, mood, and T0 MMSE score resulted to play a role in predicting treatment effects. Conclusion: Combined multi-domain interventions may contribute to preventing or delaying disease progression. Trial registration: Trial registration number (ClinicalTrials.gov): NCT04118686 [ABSTRACT FROM AUTHOR]

The NOMAS is by far the most used tool to screen early oral-motor skills in newborns. Here we provide an updated review of scientific literature on the use of the Neonatal Oral Motor Assessment Scale (NOMAS) to screen early oral-motor skills in newborns. An integrative review has been carried out consistent with PRISMA guidelines and standardized qualitative appraisal. Data abstracting and synthesis were executed by two independent co-authors who solved disagreement in conference. Twenty records have been included and reviewed. The efficacy of the NOMAS in screening and identifying precocious oral-motor skills received inconsistent support. Moderate validity and low reliability emerged. Moreover, despite the NOMAS' adequately screen efficient and inefficient feeders, limited evidence emerged for predictive value of NOMAS score on feeding and psychomotor developmental trajectories during the first 2 years of age.Conclusion: The present review highlights benefits and limitations of the NOMAS. Future research is needed to develop observational and clinically-relevant tools to better identify newborns which are at lower- and higher-risk of developing less-than-optimal feeding behaviors and to guide with greater precision the diagnostic and therapeutic journey of these newborns. What is Known: • The assessment of oral-motor skills in newborns and infants is critical for early intervention • The NOMAS is the most adopted tool to assess oral-motor skills in newborns and infants What is New: • The ability of the NOMAS to target newborn at risk for feeding disorders is confirmed • Nonetheless, the capacity to predict long-term developmental outcomes is limited. [ABSTRACT FROM AUTHOR]

Objectives Recurrent varicose veins following surgery is a common, complex and costly problem in vascular surgery. Treatment for RVV is technically more difficult to perform and patient satisfaction is poorer than after primary interventions. Nevertheless, traditional vein surgery has largely been replaced by percutaneous office-based procedures, and the patients with recurrent varicose veins have not benefited from the same advantages. In this paper, we propose an endovascular laser treatment that allows reducing the invasiveness and complications in case of SFJ and SPJ reflux after ligation and stripping of the great and small saphenous vein. Methods 8 SFJ and 1 SPJ stumps were treated by endovascular laser treatment in out-patient clinic. Endovascular laser treatment was performed with a 1470 nm diode laser and a 400 µc radial slim™ fiber. Intraoperative ultrasoud was used to guide the fiber position and the delivery of tumescent anesthesia. The gravity of chronic venous disease was determined according to the CEAP classification and the severity of symptoms was scored according to the revised Venous Clinical Severity Score (VCSS). Results The average linear endovenous energy density was 237 J/cm. Patients return to daily activities after a mean of 1.9 days after. The VCSS improved drastically from a mean of 8 pre-interventional to 1 at day 30 and until one year. During the follow-up period (mean 8 months, range: 5–17 months), all the stumps except one were occluded. All patients were very satisfied or satisfied with the method. No severe complications occurred. Conclusions Office-based endovascular laser treatment of groin and popliteal recurrent varicose veins with 1470 nm diode laser and radial-slim fiber is a safe and highly effective option, with a high success rate in the early post-operative period. [ABSTRACT FROM AUTHOR]

Regarding a patient with dyspnea, the history and physical examination often lead to the correct diagnosis. In some circumstances, when more than one underlying disease is present, the diagnostic process can be more challenging. We describe an unusual case of dyspnea and persistent hypoxemia related to a hepatopulmonary syndrome in a 53-year-old patient with known heart failure and chronic liver disease. Initially managed with intravenous diuretic therapy, due to signs of lung and peripheral congestion, our patient did not improve as expected; therefore we performed more advanced studies with a chest-abdomen CT scan and a right heart catheterization. They showed, respectively, no signs of parenchymal and vasculature lung disease, a cirrhotic liver disease, splenomegaly, signs of portal hypertension, and high cardiac output with normal pulmonary vascular resistance. These results, along with the association of hypoxemia and chronic liver disease, suggested a hepatopulmonary syndrome. The diagnosis was confirmed by the demonstration of an intrapulmonary vascular dilatation with right to left shunt during a microbubble transthoracic echocardiography and a lung perfusion scan. Liver transplantation is the only successful treatment for this syndrome; however, the patient became soon unsuitable for this strategy, due to a rapid clinical deterioration. [ABSTRACT FROM AUTHOR]

Several intralesional therapeutic protocols have been proposed for the treatment of Peyronie's disease. Among all, hyaluronic acid ( HA) and verapamil have been differently tested. We aimed to evaluate the efficacy of intralesional verapamil ( ILVI) compared with intralesional HA in patients with early onset of Peyronie's disease ( PD). This is a multi-centre prospective double-arm, randomized, double-blinded study comparing ILVI vs. intralesional HA after 12-weeks. Sexually active men, older than 18 years and affected by the acute phase of PD were eligible for this study. Patients have been double-blinded randomly divided into two groups (1 : 1 ratio): Group A received intralesional treatment with Verapamil (10 mg in 5 mL of normal saline water) weekly for 12 weeks, while group B received intralesional treatment with HA (0.8% highly purified sodium salt HA 16 mg/2 mL) weekly for 12 weeks. The primary efficacy outcome was the change from the baseline to the endpoint (12 weeks after therapy) for the penile curvature (degree). The secondary outcome was the change in the plaque size and in the International Index of erectile Function ( IIEF-5) score. The difference between post- and pre-treatment plaque size was −1.36 mm ( SD ± 1.27) for Group A and −1.80 mm ( SD ± 2.47) for Group B ( p-value = NS). IIEF-5 increased of 1.46 points ( SD ± 2.18) in Group A and 1.78 ( SD ± 2.48) in Group B ( p-value ± NS). No difference in penile curvature was observed in Group A, while in Group B the penile curvature decreased of 4.60° ( SD ± 5.63) from the baseline ( p < 0.001) and vs. Group A. According to PGI-I results, we found significant difference as concerning patient global impression of improvement ( PGI-I) (4.0 vs. 2.0; p < 0.05). This prospective, double-arm, randomized, double-blinded study comparing ILVI vs. HA as intralesional therapy showed greater efficacy of HA in terms of penile curvature and PGI-I. [ABSTRACT FROM AUTHOR]

Lichen sclerosus (LS) is an inflammatory and chronic disease that causes itching, pain, dysuria, urinary retention, dyspareunia and sexual dysfunction, in both men and women. The first line pharmacological treatment is based on the use of topical steroids, which have proved their efficacy in 60-70% of cases but with a high rate of relapses in time (50-80% of the patients of both sexes). The purpose of our non-randomised prospective pilot study was to evaluate the efficacy and tolerability of a new loco regional therapy with polydeoxyribonucleotides (PDRN) in the treatment of male genital LS. PDRN is an healing and anti-dystrophic drug with anti- inflammatory effects, through the reduction of cytokine. Twenty one male patients suffering from genital LS were recruited. All the patients were submitted to treatment using loco-regional intradermal injections with PDRN. Dermatology Life Quality Index (DLQI), International Index of Erectile Function (IIEF-5) and PGI-I questionnaires were administered at baseline and at the end of treatment in order to evaluate the results of this treatment. The statistical evaluation of the data obtained with the DLQI questionnaire showed a marked improvement of the overall conditions in terms of quality of life, with an average change of scores from 15 to 4 (p < 0.0001). PGI-I questionnaire showed that 80% of the patients treated considered their post-treatment conditions as 'improved'. There was no significant change in terms of sexual function according to the IIEF questionnaire (p = 0.189). The results obtained show the excellent tolerability and the therapeutic efficacy of PDRN, with clear improvement of the local symptoms and of the quality of life. [ABSTRACT FROM AUTHOR]

Purpose: To determine the efficacy of bimanual microincision cataract surgery (B-MICS) performed by surgeons in training, evaluating clinical results, posterior capsule opacification (PCO) incidence, and clear corneal incision (CCI) architecture in a long-term follow-up and comparing results with those obtained by experienced surgeons. Patients and methods: Eighty eyes of 62 patients operated on by three surgeons in training who used B-MICS technique for the first time were included in the study (Group A). Eighty eyes of 59 patients who underwent B-MICS by three experienced surgeons were included as a control group (Group B). Best corrected visual acuity, astigmatism, corneal pachymetry, and endothelial cell count were evaluated before surgery and at 1 month and 18 months after surgery. Anterior segment optical coherence tomography images were obtained to study the morphology of CCIs. PCO incidence was evaluated using EPCO2000 software. Results: Out of 160 surgeries included in the study, mean best-corrected visual acuity improvement at 18 months was 0.343±0.246 logMAR for Group A, and 0.388±0.175 logMAR for Group B, respectively. We found no statistically significant induced astigmatism nor corneal pachymetry changes in either group, while we noticed a statistically significant endothelial cell loss postoperatively in both groups (P<0.05). In Group A, mean PCO score was 0.163±0.196, while for Group B, it was 0.057±0.132 (P=0.0025). Mean length and inclination of the CCIs for Group A and Group B were, respectively, 1,358±175 μm and 1,437±256 μm and 141.8°±6.4° and 148.7°±5.1°. As regards corneal architecture in the 320 CCIs considered, we found posterior wound retractions and endothelial gaps, respectively, 9.8% and 11.6% for Group A and 7.8% and 10.8% for Group B.Conclusion: B-MICS performed by surgeons in training is an effective surgical technique even when assessed after a long-term follow-up. PCO incidence resulted in being higher for less experienced surgeons. Corneal incisions were shorter and less angled in surgeons in training in comparison with results obtained by expert surgeons. [ABSTRACT FROM AUTHOR]

The average age of men affected by Peyronie's disease (PD) is approximately 50-55 years, but cases have been reported even in adolescence. Several studies have already investigated the presence of PD in young men, and these studies reported a PD prevalence that varies between 1.5% and 10.8%. Having noticed a greater number of young patients in our centers in recent years, we decided to carry out a retrospective study to evaluate the prevalence of PD in patients aged,40 years, as well as to investigate any possible difference in evolution based on the age of PD patients. We selected a sample of patients (n=271) with a similar time of onset of disease. We then stratified all 271 patients into two groups: group A (age <40 years [n=46]) and group B (age ≥ 40 years [n=225]). All 271 patients were evaluated for the following variables: penile plaque volume, degree of penile curvature, penile pain, and erectile function. Plaque volume was measured in cm³ by dynamic penile color Doppler sonography after administration of intracavernosal alprostadil 10 mcg. The number of younger patients was 46, accounting for 16.9% of the whole sample. Our study showed more frequent appearance and greater progression of penile curvature in younger patients. The average angle of penile curvature and average score of penile pain intensity in the younger men were significantly higher than in patients aged ≥40 years (P=0.025 and P=0.0001, respectively). In the younger patients, not only was the pain more intense (visual analog scale [VAS] of 5.2 versus 3.8), but it was also more frequently present than in patients aged ≥40 years (78.2% versus 62.2%) (P=0.042). We may conclude that since PD in young patients has a more acute onset and a greater possibility of progression, it should be treated conservatively as soon as it is diagnosed. [ABSTRACT FROM AUTHOR]

Although a growing attention is being paid to acute ischemic stroke patients, the correlation between clinical outcome and infectious events in this population has been poorly investigated. 749 ischemic stroke (mean age 71 years old, males 56 %) patients were enrolled in this prospective case-control study by 11 Italian Stroke Units. Demographic data, vascular risk factors, previous infections and post-stroke infections (PSIs) were recorded. Blood samples were collected and the enzyme-linked immunoassay was chosen to measure Chlamydia pneumoniae IgG and IgA plasma antibodies (antibody titers were classified with specific cut-off levels: IgA > 1:16 and IgG > 1:64). Early poor outcome was defined as mRS score >2 at discharge, while poor outcome at 6-month follow-up. Univariate and multivariate analyses were performed. Median NIHSS was 7, IgA and IgG antichlamydia pneumoniae seropositivities were observed in 308 (37.1 %) and 207 (23.6 %) patients, respectively. Multivariate analyses showed significant correlations between PSIs and NIHSS (RR: 1.06; 95 % CI 1.02-1.09; p < 0.001) and PSIs and IgA antichlamydia pneumoniae seropositivity (RR: 3.84; 95 % CI 2.53-5.84; p < 0.001). Significant disability was associated with baseline NIHSS (RR: 1.32; 95 % CI 1.16-1.50; p < 0.001), IgA (RR: 2.67; 95 % CI 1.06-6.70; p = 0.035) and IgG antichlamydia (RR: 5.75; 95 % CI 1.83-18.03; p = 0.003) seropositivity and atrial fibrillation (RR: 2.58; 95 % CI 1.81-3.67; p < 0.001). While previous infections were not associated with functional outcome, antichlamydia antibodies play a negative role in ischemic stroke patients. Preventive strategies may reduce the stroke burden and improve the clinical outcome. [ABSTRACT FROM AUTHOR]

Objective To evaluate the relative use of urethral dilation, urethrotomy, and urethroplasty for male stricture disease in the Veterans Affairs (VA) population and examine trends over time in this cohort. Methods A retrospective chart review was performed using the VA Informatics and Computing Infrastructure database to access the Corporate Data Warehouse. The current procedural terminology codes were used to define a cohort of all men who underwent procedures for urethral stricture disease between October 1999 and August 2013. Results A total of 92,448 procedures were performed: 50,875 urethral dilations (55.03%), 39,785 urethrotomies (43.03%), and 1788 urethroplasties (0.19%). Over the course of the study, there was a shift in the management of male stricture disease. The relative percentage of urethral dilations performed decreased in each quintile (71.27, 58.03, 45.61, 44.39, and 38.67). The relative percentage of urethrotomies increased in each quintile (27.89, 40.80, 52.18, 53.04, and 56.95) as did the relative percentage of urethroplasties performed (0.85, 1.17, 2.21, 2.57, and 4.38). A total of 80.4% of these urethroplasties were performed in locations with a residency program. Conclusion Although urethroplasty is still underused, there is a trend toward increased use of urethroplasty for male urethral stricture disease in the VA population. The majority of urethroplasties were performed at VA medical centers in locations with a residency program. We predict continued increases in utilization of urethroplasty for male urethral stricture disease as the number of fellowship-trained reconstructive urologists increases. [ABSTRACT FROM AUTHOR]

In this paper we present our endovascular LASER treatment of mixed shunts. This technique is built according the CHIVA's important principles: diastolic reflux is interrupts at its proximal origin by flush LASER obliteration while centripetal systolic reflux is preserved. In this way, the surgeon interrupts a recirculation pressure loop producing the ambulatory venous hypertension critical to the development of varicose vein symptoms. In this paper we explain how to better understand the intricate venous drainage pathophysiology of mixed shunt and the strategy to approach it using an office-based technique. With the correct strategy and the technological support it is possible to achieve a good functional and aesthetic result to prevent varicosity recurrence. [ABSTRACT FROM AUTHOR]

The article describes the case of a 62-year-old Indian man who has Stevens-Johnson syndrome secondary to tetracycline therapy. Aside from that, he also has bilateral dry eye and corneal blindness. For treatment, he underwent symblepharon release surgery with mucous membrane graft in both eyes. This case study concludes that endoscopic cyclophotocoagulation is a treatment alternative that provides good results in refractory glaucoma following osteo-odonto-keratoprosthesis surgery.

Antioxidant phytochemicals in fruits and vegetables of a vegetarian diet may account for the reduced risk of aging and stress oxidative associated diseases. In this study, a simple, rapid and accurate new bioassay for the determination of the antioxidant activity of purified or crude plant extracts and thier interactions is described, based on the fluorimetric determination of thiobarbituric acid reactive substances (TBARS) released by UV-B radiated red blood cell (RBC) ghosts. Pure resveratrol, white and red wine and pomegranate juice (PJ) were used as antioxidant source to test the biological method. TBARS production is a function of radiation time, the number of RBC ghosts in the radiated sample and the loaded antioxidant. The antioxidant activity of resveratrol was detected at a submicromolar concentration range [0.02 μg/mL-0.1 μmol/L]. The activity of red wine was almost 10 times higher than that of white wine, and PJ juice had the highest activity. Submaximal protective effects of PJ and red wine were additive. [ABSTRACT FROM AUTHOR]

Background: Platelets are frequently altered in hepatocellular carcinoma (HCC) patients. Platelet lysates (hPL) can enhance HCC cell growth and decrease apoptosis. The aims were to evaluate whether hPL can modulate the actions of Sorafenib or Regorafenib, two clinical HCC multikinase antagonists. Methods: Several human HCC cell lines were grown in the presence and absence of Sorafenib or Regorafenib, with or without hPL. Growth was measured by MTT assay, apoptosis was assessed by Annexin V and by western blot, and autophagy and MAPK growth signaling were also measured by western blot, and migration and invasion were measured by standard in vitro assays. Results: Both Sorafenib and Regorafenib-mediated inhibition of cell growth, migration and invasion were all antagonized by hPL. Drug-mediated apoptosis and decrease in phospho-ERK levels were both blocked by hPL, which also increased anti-apoptotic phospho-STAT, Bax and Bcl-xL levels. Preliminary data, obtained with epidermal growth factor (EGF) and insulin-like growth factor-I (IGF-I), included in hPL, revealed that these factors were able to antagonized Sorafenib in a proliferation assay, in particular when used in combination. Conclusions: Platelet factors can antagonize Sorafenib or Regorafenib-mediated growth inhibition and apoptosis in HCC cells. The modulation of platelet activity or numbers has the potential to enhance multikinase drug actions. [ABSTRACT FROM AUTHOR]

Background The use of botulinum toxin A (Bo NT- A) for aesthetic treatments is growing steadily, and new safety data have been reported in recently published studies. Objective To investigate the safety data on the use of the three Bo NT- A formulations approved for facial aesthetics from recent studies and to confirm their safety profiles. Methods The literature search was conducted using three online databases restricted to the timeframe from January 2000 to June 2012. Only clinical trials, randomized or open label, with safety as the primary or secondary endpoint, were included. Results Thirty-five papers were selected, with a total of subjects 8,787 studied. OnabotulinumtoxinA was used in 60.0% of the studies, abobotulinumtoxinA in 37.1%, and incobotulinumtoxinA in 2.8%. The glabella was the most investigated area (51.4%), followed by the upper face (25.7%), crow's feet (11.4%), and lower face (11.4%). Treatment-related adverse events were blepharoptosis (2.5%), brow ptosis (3.1%), and eye sensory disorders (3%) in the upper face and lip asymmetries and imbalances in the lower face (6.9%). All of these events resolved spontaneously. Conclusion The short-term safety profile of Bo NT- A in cosmetic nonsurgical procedures was confirmed for all the three commercial formulations. [ABSTRACT FROM AUTHOR]

Aim The treatment of desmoid tumours (DTs) is controversial. Anti-oestrogen therapy has frequently been used, but clear information of its efficacy is lacking. In this systematic review we have undertaken a comprehensive analysis to assess the effectiveness of anti-oestrogen therapy in terms of ability to induce partial or complete regression of DTs. Method A systematic review of articles published in English between January 1983 and December 2009 was carried out according to the RECIST criteria. A literature search was performed on electronic databases including: United States National Library of Medicine (MEDLINE-PubMed), Excerpta Medica (EMBASE), Cochrane Library and Google search engine. Two-hundred articles dealing with DTs were identified but only fourty-one were were selected as appropriate for the study. The chi-square test was used for statistical analysis. Results Data on 168 DTs treated with anti-oestrogen agents, alone or in combination with nonsteroidal anti-inflammatory drugs, were identified with an overall response rate of 51%. There was no difference in response according to the type of DTs or between different anti-oestrogen therapies. Combination with anti-inflammatory drugs did not improve the outcome. Toremifene was sometimes effective in cases resistant to tamoxifen. Response did not seem to be related to oestrogen receptor status. Conclusions Despite potential inaccuracies in the methodology, the results of the review indicate that anti-oestrogen therapy produces some effect in about one half of patients with DTs. Its indication compared with other treatments is discussed. [ABSTRACT FROM AUTHOR]

Background and Purpose: Cystine-knot miniproteins are characterized by a similar molecular structure. Some cystine-knot miniproteins display therapeutically useful biological activities, as antithrombotic agents or tumour growth inhibitors. A critical event in the progression of tumours is the formation of new blood vessels. The aim of this work was to test two tomato cystine-knot miniproteins for their effects on endothelial cell proliferation and angiogenesis in vitro.Experimental Approach: Two tomato cystine-knot miniproteins (TCMPs) were expressed and purified either as recombinant or as native proteins from tomato fruits. The Matrigel assay was used to investigate the effects of TCMPs on in vitro angiogenesis. Viability and proliferation of endothelial cells were tested. Extracellular signal-regulated kinase (ERK)1/2 phosphorylation was assayed in either HUVEC or A431 epidermal growth factor receptor (EGFR)-overexpressing cells treated with TCMPs. EGFR phosphorylation was tested in A431 cells.Key Results: Both recombinant and native TCMPs inhibited in vitro angiogenesis of HUVEC cells at concentrations of 15-100 nM. The anti-angiogenic effect of TCMPs was associated with the inhibition of ERK phosphorylation. The two miniproteins did not alter the viability and proliferation of the endothelial cells.Conclusions and Implications: The anti-angiogenetic properties of TCMPs are of potential pharmacological interest because they are common and natural components of the human diet, they possess low toxicity, they are active at submicromolar concentrations, they share a common molecular structure that can be used as a molecular platform for the design of molecules with enhanced biological activity. [ABSTRACT FROM AUTHOR]

Abstract: Background: The Italian Association for the Study of the Pancreas released a diagnostic and therapeutic algorithm for acute pancreatitis in 1999. Aim: This study focused on the analysis of the therapeutic approach for the treatment of acute pancreatitis in Italy. Patients: One thousand, one hundred and seventy-three patients were recruited: 1006 patients (85.8%) had mild acute pancreatitis (MAP) and 167 (14.2%) had the severe acute pancreatitis (SAP); 161 patients showed pancreatic necrosis at computed tomography; 121 patients (10.3%) had sequelae and 36 (3.1%) died. Results: Non-steroidal anti-inflammatory drugs and tramadol were used more frequently in patients with the MAP whereas opioids and the association schedules were used more frequently in patients with the SAP (P <0.001). Gabexate mesilate was utilised in 831 out of 1173 patients (70.8%); in particular, gabexate mesilate was used in 70.6% patients with MAP and in 73.1% of those with SAP (P =0.521). The duration of the drug administration was significantly shorter in those having MAP than in those having the SAP (P <0.001). The antibiotics most frequently used for the prophylaxis against infection from pancreatic necrosis (43.1%) were carbapenems. Only a small number of patients received enteral nutrition (4.7%). Endoscopic retrograde cholangiopancreatography was carried out in 344 of the 1173 patients (29.3%). Surgery was performed in 48 with SAP (19 had elective biliary surgery and 29 had pancreatic surgery). Conclusions: The results of this survey indicate a lack of compliance with the guidelines which regard the indications mainly for interventional endoscopy and surgery. [Copyright &y& Elsevier]

Aetiopathogenesis and therapy for Peyronie's disease are summarized below. Aetiopathogenesis: (a) Plaque fibroblasts and their products provoke an immune response; (b) there are chromosomal differences between plaques and normal albuginea; (c) plaque fibroblasts are immortalized cells; (d) plaque fibroblasts demonstrate an impaired mitochondrial activity. These patterns provoke inflammation and they compel us to regard Peyronie's disease as being more similar to keloids than to scars. Therapy: Medical therapy plays a pivotal role in the management of Peyronie's disease and should be performed prior to any surgery. Intraplaque collagenase, intraplaque verapamil, intraplaque interferon, oral acetyl-L-carnitine, oral propionyl-L-carnitine and oral colchicine have proved effective in Peyronie's disease. With the exception of collagenase, these drugs have displayed a number of activities whose final result is to improve immune response, to inhibit inflammation and to inhibit fibroblast metabolism and replication. Therefore, the primitive replicative (rather than reactive) nature of the disease is confirmed; this knowledge may be of help in the identification of new non-surgical therapies for Peyronie's disease. [ABSTRACT FROM AUTHOR]

The authors from Ferrara show that a NSAID has a role in patients who have oligoasthenospermia associated with a left-sided varicocele, although not in every case. Peyronie's disease is discussed in two papers; in the first of these, the authors make the case for histopathological diagnosis by drawing the reader's attention to the possible presence of penile epithelioid sarcoma. In the second paper, attention is drawn to the possibility of using a combination of vitamin E and colchicine in the early stages of the condition. Objective To ascertain whether a nonsteroidal anti-inflammatory drug (cinnoxicam) or surgical varicocelectomy are suitable therapies for oligoasthenospermia associated with varicocele. Patients and methods Patients who were oligoasthenospermic and had a varicocele were blindly randomized into three groups and the varicocele graded using echo-colour Doppler ultrasonography. In group 1, seven men had grade V, four grade IV and 30 grade III varicoceles; in group 2 eight had grade V, 10 grade IV and 43 grade III; in group 3 six had grade V, eight grade IV and 40 grade III. Group 1 underwent surgery, group 2 received cinnoxicam (one 30 mg suppository every 4 days for 12 months) and group 3 received a placebo (one glycerine suppository every 4 days for 12 months). Sperm was analysed at intervals to follow the response in the three groups, and any side-effects considered. Results Surgery significantly increased sperm values in men with grade III–V varicocele within 4 months, the highest values being obtained at 8 and 12 months. Cinnoxicam significantly improved sperm quality after 2 months in men with grade III varicocele, but the results were best at 4 months and stable at 12 months; stopping therapy caused a decline to the baseline values. Cinnoxicam did not change the sperm quality of men with grade IV or V varicocele. The placebo was inactive, and there were no side-effects of active treatment. Conclusions Cinnoxicam is a safe and... [ABSTRACT FROM AUTHOR]

Objective To ascertain whether oral propionyl-l-carnitine combined with intraplaque verapamil is a useful therapy for advanced or resistant Peyronie's disease. Patients and methods The combined drugs were assessed in two studies. In the first, 60 patients with advanced Peyronie's disease, diagnosed using accepted definitions, were randomized in two subgroups treated with verapamil intraplaque infiltration (10 mg weekly for 10 weeks) plus a 3-month administration of propionyl-l-carnitine (2 g/day), or verapamil infiltration plus oral tamoxifen (40 mg/day) for 3 months. In the second study, 15 patients with resistant Peyronie's disease (progression despite previous therapy) received verapamil plus propionyl-l-carnitine. The differences between subgroups or between the variables before and after therapy were compared using analysis of variance or the chi-squared test. Results In the first study, the reduction in pain was the same in both subgroups. Propionyl-l-carnitine plus verapamil significantly reduced penile curvature, plaque size, cavernosal artery end-diastolic velocity, the need for surgery and disease progression, and increased the International Index of Erectile Function score and resistivity index of the cavernosal arteries. Tamoxifen plus verapamil had none of these effects. No drug combination affected the peak systolic velocity. Patients receiving verapamil had no side-effects but those taking tamoxifen did. In the second study propionyl-l-carnitine and verapamil modified the disease patterns as in the first and no patient had side-effects. Conclusion The combination of propionyl-l-carnitine and verapamil can be considered the therapy of choice for advanced and resistant Peyronie's disease. [ABSTRACT FROM AUTHOR]

Gabexate mesilate is an antiprotease drug, which reduced the severity of pancreatitis and frequency of post-ERCP pancreatitis. In dogs gabexate inhibits sphincter of Oddi motility but no data are available in humans. The aim of this study was to verify by manometry the action of gabexate on human sphincter of Oddi motility. We enrolled 12 patients with idiopathic recurrent pancreatitis (eight males, five females, mean age 46 +/- 8 years). Standard preendoscopic sphincter of Oddi manometry was done in basal conditions and during infusion of gabexate 20 mg/min: basal pressure, amplitude and frequency of phasic contractions, and motility index (amplitude per frequency) were calculated before and after gabexate injection. Statistical analysis was performed by using Wilcoxon rank test for paired data. Six patients had a manometric diagnosis of stenosis (basal pressure greater than 40 mm Hg); six had normal findings. Phasic activity was not evaluable in five patients with stenosis. Basal pressure was unaffected by drug infusion, while gabexate caused a significant reduction of phasic activity, both in terms of frequency (4.5 +/- 1 vs 3.6 +/- 1; P < 0.05) and amplitude (157.4 +/- 44 vs 80.0 +/- 32; P < 0.05) of contractions. Motility index was reduced on average by 49%. In conclusion, this pilot study confirms, in patients with acute recurrent pancreatitis, the inhibitory action of gabexate on sphincter of Oddi motility already described in dogs. This action needs to be revaluated at therapeutic dosages. On the other hand, prophylactic use of the drug should be avoided during sphincter of Oddi manometry, in order to avoid false negative results. [ABSTRACT FROM AUTHOR]

Objective To detect whether oral acetyl-l-carnitine might be useful in the acute and early chronic phases of Peyronie's disease, compared with tamoxifen, a drug currently in use. Patients and methods The study included 48 patients with Peyronie's disease (15 acute and 33 initial chronic), randomized equally into two groups. The first group used tamoxifen 20 mg twice daily for 3 months and the second acetyl-l-carnitine 1 g twice daily for 3 months. The disease and stages were diagnosed and identified using a history, objective examination, pharmacologically induced erection, autophotography during erection, and basic and dynamic colour Doppler ultrasonography. Penile curvature, plaque size, pain and disease progression were assessed. The differences between the groups or between the variables before and after therapy were compared using analysis of variance or the chi-squared test. Results Acetyl-l-carnitine was significantly more effective than tamoxifen in reducing pain and in inhibiting disease progression. Acetyl-l-carnitine reduced penile curvature significantly, while tamoxifen did not; both drugs significantly reduced plaque size. Tamoxifen induced significantly more side-effects than acetyl-l-carnitine. Conclusions These results suggest that acetyl-l-carnitine is significantly more effective and safe than tamoxifen in the therapy of acute and early chronic Peyronie's disease. [ABSTRACT FROM AUTHOR]

Intracerebral hemorrhage (ICH) is the most serious complication of oral anticoagulant therapy (OAT), with mortality in excess of 50%. Major risk factors are advanced patient age, elevated systolic blood pressure, intensity of anticoagulation, and previous cerebral ischemia. A number of acute treatments are available, but all have significant side effects and no randomized clinical trials assessing clinical outcome have been performed. Future trials will have to address choice and dose of agent, the timing of its administration, and the risk of side effects. [ABSTRACT FROM AUTHOR]

The article focuses on a Chronic tension-type headache (CTTH) induce a pain sensation in the trapezium area. The article discusses the CTTH treatment with Quantum Molecular Resonance (QMR) therapy which helps to promote cell regeneration process through direct cell stimulation which is able to decrease local inflammatory reaction and consequently pain level. The article also discusses the prophylactic treatment for CTTH including antidepressants, muscle relaxants, drugs is used by patients.

The administration of botulinum toxin is an activity performed mostly by a specialist service for the management of a wide range of neurological conditions. For therapeutic purposes botulinum toxin type A is used, although in selected patients who develop antibodies specific for the serotype A botulinum toxin B can be used for the treatment. Hereby, we describe the organizational arrangements for the botulinum toxin treatment service at the Department of Neurology of Hospital Cardinal Massaia based in Asti. The diseases most frequently treated are movement disorders (primary and secondary focal dystonia, blepharospasm, facial emispasmo) spasticity and, more recently, chronic migraine. In particular, the latter application is one of the most promising expansions of the use of this drug in the few past years, although a larger number of patients are required to determine its efficacy and the related tolerability profile. [ABSTRACT FROM AUTHOR]

The authors discuss the advantages of diagnostic and therapeutic laparoscopy for abdominal impalement injuries (AII). They describe the use of laparoscopic surgery in treating a 13-year-old boy who sustained an AII from a ballpoint point in his pants pocket after jumping over a fence. They also explain the types of impalement injuries and some basic principles for their management.

Possible cardiac repair by adult stem cell transplantation is currently hampered by poor cell viability and delivery efficiency, uncertain differentiating fate in vivo, the needs of cx vivo cell expansion, and consequent delay in transplantation after the onset of heart attack. By the aid of magnetic resonance imaging, positron emission tomography, and immunohistochemistry, we show that injection of a hyaluronan mixed ester of butyric and retinoic acid (HBR) into infarcted rat hearts afforded substantial cardiovascular repair and recovery of myocardial performance. HBR restored cardiac [18F]fluorodeoxyglucose uptake and increased capillary density and led to the recruitment of endogenous Stro-1-positive stem cells. A terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling assay demonstrated that HBR-treated hearts exhibited a decrease in the number of apoptotic cardiomyocytes. In isolated rat cardiomyocytes and Stro-1 stem cells, HBR enhanced the transcription of vascular endothelial growth factor, hepatocyte growth factor, kdr, akt, andpim-1. HBR also increased the secretion of vascular endothelial growth factor and hepatocyte growth factor, suggesting that the mixed ester may have recruited both myocardial and Stro-1 cells also. An increase in capillarogenesis was induced in vitro with medium obtained from HBR-exposed cells. In the infarcted myocardium, HBR injection increased histone H4 acetylation significantly. Acetyl-H4 immunoreactivity increased in rat cardiomyocytes and Stro-1 cells exposed to HBR, compared with untreated cells. In conclusion, efficient cardiac regenerative therapy can be afforded by HBR without the need of stem cell transplantation or vector-mediated gene delivery. [ABSTRACT FROM AUTHOR]

Telomerase (TERT) is overexpressed in 80% to 90% of primary tumors and contributes to sustaining the transformed phenotype. The identification of several TERT epitopes in tumor cells has elevated the status of TERT as a potential universal target for selective and broad adoptive immunotherapy. TERT-specific cytotoxic T lymphocytes (CTL) have been detected in the peripheral blood of B-cell chronic lymphocytic leukemia (B-CLL) patients, but display low functional avidity, which limits their clinical utility in adoptive cell transfer approaches. To overcome this key obstacle hindering effective immunotherapy, we isolated an HLA-A2-restricted T-cell receptor (TCR) with high avidity for human TERT from vaccinated HLA-A 0201 transgenic mice. Using several relevant humanized mouse models, we demonstrate that TCR-transduced T cells were able to control human BCLL progression in vivo and limited tumor growth in several human, solid transplantable cancers. TERT-based adoptive immunotherapy selectively eliminated tumor cells, failed to trigger a self-MHC-restricted fratricide of T cells, and was associated with toxicity against mature granulocytes, but not toward human hematopoietic progenitors in humanized immune reconstituted mice. These data support the feasibility of TERT-based adoptive immunotherapy in clinical oncology, highlighting, for the first time, the possibility of utilizing a high-avidity TCR specific for human TERT. Cancer Res; 76(9); 2540-51. [ABSTRACT FROM AUTHOR]

Various models of HIV infection and evolution have been considered in the literature. This paper considers a variant of the Wodarz and Nowak mathematical model, adding “aggressiveness” as a new state variable in order to quantify the strength of the virus and its response to drugs. Although the model proposed is relatively simple, simulation results suggest that it may be useful in predicting the impact of the effectiveness of therapy on HIV dynamics. [Copyright &y& Elsevier]

The article discusses the case of a patient diagnosed with pancreaticopleural fistula (PPF). Topics discussed include the clinical presentation of the patient, pleural effusion revealed by chest radiography, and the result of thoracoabdominal computed tomography (CT). Also highlighted is the treatment of the patient with antimicrobial agents and somatostatin analogs.