Wronger than wrong: Graded mapping of the errors of an avatar in the performance monitoring system of the onlooker.

EEG studies show that observing errors in one's own or others' actions triggers specific electro-cortical signatures in the onlooker's brain, but whether the brain error-monitoring system operates according to graded or discrete rules is still largely unknown. To explore this issue, we combined immersive virtual reality with EEG recording in participants who observed an avatar reaching-to-grasp a glass from a first-person perspective. The avatar could perform correct or erroneous actions. Erroneous grasps were defined as small or large depending on the magnitude of the trajectory deviation from the to-be-grasped glass. Results show that electro-cortical indices of error detection (indexed by ERN and mid-frontal theta oscillations), but not those of error awareness (indexed by error-Positivity), were gradually modulated by the magnitude of the observed errors. Moreover, the phase connectivity analysis revealed that enhancement of mid-frontal theta phase synchronization paralleled the magnitude of the observed error. Thus, theta oscillations represent an electro-cortical index of the degree of control exerted by mid-frontal regions whose activation depends on how much an observed action outcome results maladaptive for the onlooker. Our study provides novel neurophysiological evidence that the error monitoring system maps observed errors of different magnitude according to fine-grain, graded rather than all-or-none rules.

Mere observation of body discontinuity affects perceived ownership and vicarious agency over a virtual hand.

The mental representation of one's body typically implies the continuity of its parts. Here, we used immersive virtual reality to explore whether mere observation of visual discontinuity between the hand and limb of an avatar could influence a person's sense of ownership of the virtual body (feeling of ownership, FO) and being the agent of its actions (vicarious agency, VA). In experiment 1, we tested whether placing different amounts of visual discontinuity between a virtual hand and limb differently modulate the perceived FO and VA. Participants passively observed from a first-person perspective four different versions of a virtual limb: (1) a full limb; a hand detached from the proximal part of the limb because of deletion of (2) the wrist; (3) the wrist and forearm; (4) and the wrist, forearm and elbow. After observing the static or moving virtual limb, participants reported their feeling of ownership (FO) and vicarious agency (VA) over the hand. We found that even a small visual discontinuity between the virtual hand and arm significantly decreased participants' FO over the hand during observation of the static limb. Moreover, in the same condition, we found that passive observation of the avatar's actions induced a decrease in both FO and VA. We replicated the same results in a second study (experiment 2) where we investigated the modulation of FO and VA by comparing the visual body discontinuity with a condition in which the virtual limb was partially occluded. Our data show that mere observation of limb discontinuity can change a person's ownership and agency over a virtual body observed from a first-person perspective, even in the absence of any multisensory stimulation of the real body. These results shed new light on the role of body visual continuity in modulating self-awareness and agency in immersive virtual reality.

Electrochemotherapy as palliative treatment in patients with recurrent and/or metastatic head and neck tumours: features analysis for an early determination of the partial responsive patients.

OBJECTIVE: The aim of this study was to identify features mainly involved in determining the partial response (PR) to the Electrochemotherapy (ECT) in patients with recurrent and/or metastatic head and neck (H&N) tumor; the identified features were also used in a decision chart in order to provide the clinician with a support tool in deciding further therapies. PATIENTS AND METHODS: 131 patients (186 treatment sessions) with recurrent and/or metastatic H&N neoplasm were subjected to ECT. Treatment response was evaluated based on Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1 two months after the ECT. The grade of bleeding and pain before, at the end and one week after ECT treatment were evaluated. Univariate and multivariate analysis were performed to identify features involved in determining the patient PR. RESULTS: In the context of the univariate analysis, tumor size significantly influenced the response to ECT, with higher PR rate of 58.3%: 28 among 48 patients with lesion size ≤ 3 centimeters (p-value < 0.001 at Chi-square test). Pain and bleeding pre-treatment were positively correlated to PR (p-value < 0.001 at Chi-square test). A difference in the current flowing in the tissue during treatment was also observed in partially responsive patients, where the median current value (6.6 A) was higher than that achieved in patients that did not show PR (3.3 A). In the context of the multivariate analysis, the best performances are achieved with the BART method (accuracy of 84%). The main clinical factors to predict the partial response, among investigated features, that have shown to be considered were the pain value felt before performing the treatment and the median current delivered during the ECT treatment. A decision-making support tool to predict the patient prognosis in terms of response rate could be represented by the decision tree obtained with CART algorithm, where a pain pre-treatment more than 5 and a median delivered current not less than 2.8 A led to the prediction a partial responsive patient with an accuracy of 75%. CONCLUSIONS: The study confirmed that ECT is an interesting antitumoral therapy in advanced chemo- and radio-refractory H&N neoplasms, able to reduce frequent symptoms and to improve the quality of life. Pain pre-treatment and delivered current are the most important variables when predicting the partial response of patients.

Triptans: low utilization and high turnover in the general population.

Studies performed in selected populations have shown a poor utilization of triptans for migraine. Our study was aimed at establishing patterns of triptans utilization in a large community using the pharmaceutical prescriptions database of two consecutive years in a regional Health Authority in Italy. About 0.5% of the population observed received triptans prescriptions in a year, but > 50% of the cases received only one prescription. On the other hand, 46% of triptan users did not receive a triptan prescription in the following year (past users): in 80% of cases, patients received only 1-2 triptan packages. The evaluation of the discontinued triptan type has shown percentages varying between 30 and 70%. The percentage of triptan users who received a triptan prescription for the first time in the successive year of study (new users) was 52%. These findings together highlight a high turnover in triptans utilization. Less than 15% of subjects received more than one triptan product in the 2 years. In conclusion, we observed a low percentage of triptan users and a low rate of utilization, associated with a high percentage of discontinuation and new utilization (high turnover), without any substantial increase in triptans utilization during the years. All these data probably do not support optimal satisfaction with triptan therapy.

Transoral robotic surgery of parapharyngeal space tumours: a series of four cases.

Tumours arising from the parapharyngeal space (PPS) represent less than 1% of all head and neck tumours. Salivary gland tumours account for 40-50% of PPS lesions and are located in the pre-styloid parapharyngeal space. Pleomorphic adenomas represent 80-90% of salivary tumours in the PPS. Recently, transoral robotic surgery (TORS) has become common in head and neck surgery as a minimally invasive procedure. Four cases of benign PPS tumour treated with TORS are presented here. Preoperative diagnosis was conducted by fine needle aspiration biopsy and magnetic resonance imaging, and the results were used to plan the correct surgical approach. One case required a change of approach to conventional transoral blunt dissection. Patients required pain control and reported dysphagia symptoms for a period of weeks, but no nasogastric tube was needed at any time. This case series indicates that TORS is a safe surgical procedure for the excision of benign tumours of the PPS in selected cases.

Electrocortical signatures of detecting errors in the actions of others: An EEG study in pianists, non-pianist musicians and musically naïve people.

Detecting others' action errors plays a critical role in social life. Studies indicate that executing action errors and observing other's errors activate a specific cerebral system specialized for performance monitoring and detecting mismatches between an internal model of the action and the executed/observed one. Such a system may be particularly important for highly skilled performance. By recording electro-encephalographic (EEG) activity in expert pianists, non-pianist musicians and musically naïve individuals while they observed correct or incorrect mute piano sequences, we explored the link between sensorimotor expertise, the ability to detect another's erroneous action (indexed by positivity error, Pe) and action simulation (indexed by mu frequency suppression). Superior error detection in pianists was paralleled by a larger Pe, hinting at the selective activation of the parietal error-monitoring system in visuo-motor experts. Moreover, only in pianists did action observation induce left lateralized mu suppression in the 10-12 Hz band, reflecting somatotopic sensorimotor simulation. A mediation analysis showed that mu suppression and performance (indexed by d') were mediated by Pe amplitude, indicating that the higher the simulation, the higher the sensitivity to errors for large Pe amplitude. This study shows that specific electrocortical indices link motor simulation and detection of errors in the actions of others.

Platelet rich plasma in the treatment of bisphosphonate-related osteonecrosis of the jaw: personal experience and review of the literature.

Bisphosphonates (BPs) are a class of synthetic drugs commonly used to treat bone metastasis and various bone diseases that cause osseous fragility (such as osteoporosis). Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a common complication in patients who received BPs, especially intravenously. Recently, osteonecrosis of the jaw (ONJ) caused by chemotherapeutic not belonging to BPs drug class has been reported. For this reason, it has been proposed recently to rename BRONJ in antiresorptive agents related osteonecrosis of the jaw (ARONJ), to include a wider spectrum of drugs that may cause osteonecrosis of the jaw. The most debated topic about ARONJ/BRONJ is therapy. The most adequate procedure is far from being standardized and prevention seems to play a pivotal role. In our study, we considered 72 patients with BRONJ with nonsurgical therapy, surgical therapy, and surgical therapy with platelet rich plasma (PRP) gel to evaluate its therapeutic effect in promoting ONJ wounds healing. Good results showed by PRP in improving wound healing give away to case-control randomized studies that could give definitive evidence of its effectiveness.

Status of level IIb lymph nodes of the neck in squamous cell carcinoma of the oral tongue in patients who underwent modified radical neck dissection and lymph node sentinel biopsy.

Status of lymph nodes of level IIb was examined to identify the incidence of nodal metastasis and the lymphatic drainage in squamous cell carcinoma of the oral tongue in patients undergoing modified radical neck dissection (MRND) and sentinel node biopsy (SNB). Overall, 72 patients were divided into two groups; 38 patients (Group A) of any T and N+ or T3-T4- N0 stage underwent MRND. The surgical specimens were sent to the Pathology Department, divided into specific levels (I, IIa, IIb, III, IV, V) and labelled. The remaining 34 patients (Group B) T1-T2 -N0 stage were submitted to SNB. The histological examination of the specimens of the two groups was performed by staining with haematoxylin and eosin several sections from each node at different levels and then using a molecular marker such as cytokeratin and Epithelial Membrane Antigen (EMA). In Group A: In N0 there were no occult metastases at level IIb; in N+ neck, 8 cases (33.3%) showed metastasis at level IIb (P = 0.04). Metastases at level IIb were observed only in combination with other levels (P = 0.03). In Group B, direct lymphatic drainage was found in 2 patients (5.9%) at level IIb. There were no occult metastases at level IIb. Out of the 54 sentinel nodes harvested, 4 lymph nodes (7.4%) were found to be metastatic; these 4 sentinel nodes were found respectively in 4 patients, 1 at level III, 3 at level II a with an occult metastasis rate of 11.7%. In conclusion, SNB has prospected a new concept of lymphatic drainage that is variable and individual. SNB has demonstrated that direct lymphatic drainage is possible to level II b. In our experience with early cancer of the tongue (T1-T2 NO ), SNB aided with lympho-scintigraphy seems to be a good technique for staging the neck with minimal morbidity.

New approaches in parotid gland surgery.

Various skin incision for access to the parotid region are described by different authors, which differ in extension and localization of the scar. Therefore after parotidectomy, patients are often left with a retromandibular and cervical depression. Maintaining normal facial contour may be difficult in parotidectomy defects, but a good symmetry can and should be achieved when reconstructing the parotid region with a specific approach. The authors show their experience in parotid gland surgery using a new skin incision to improve the aesthetic and functional results and three different techniques the reconstruction of the parotid region.

Patterns of triptans use: a study based on the records of a community pharmaceutical department.

Studies performed in selected populations show that the use of triptans for migraine is low. Our study was aimed at establishing patterns of triptan utilization in a large community using the drug prescription database of a regional Health Authority in Italy. In a population of 224,065 residents, 0.55% received at least one prescription of triptans in 1 year: 77.9% were female and 22.1% male. Oral dosage forms accounted for 94% of prescriptions. About 60% of patients received a single prescription (containing one or two packages) of one triptan in 1 year. Age distribution showed that 7% of patients were aged > 65 years. They received 14% of packages, prevalently sumatriptan and zolmitriptan (the two triptans with the longest commercialization in Italy); 5.7% of patients received 40% of packages. Moreover, 3.2% of triptans users received > 120 dosage units in the year in the form of tablets (>10 single doses/month), and were potential triptan abusers. Our data indicate suboptimal treatment of migraine patients and also incorrect treatment of some patients (potential triptans abusers, the elderly).

ERP and fMRI correlates of endogenous and exogenous focusing of visual-spatial attention.

The aim of this study was to investigate the neural correlates of the functional distinction underlying attentional mechanisms of endogenous-sustained and exogenous-transient spatial selection. We recorded event related potentials (ERPs) and used functional magnetic resonance imaging (fMRI) in separate experiments while subjects performed a simple reaction time (RT) to the same visual stimulus displayed to one of several field locations. Endogenous-sustained or exogenous-transient focusing of attention onto target location were obtained by presenting the stimulus in blocks of same-point vs. randomised-point trials, respectively. Same-point stimuli yielded overall faster RT than randomised stimuli, indicating a facilitating effect of endogenous-sustained spatial attention on the perceptual processing of the impending stimulus. Moreover, same-point vs. randomised presentations revealed significant increases in the fMRI signal in the bilateral lingual and fusiform gyri as well as in the right calcarine sulcus, in conjunction with a larger amplitude of the posterior P1 component of ERPs, but no modulation of the amplitude of the N1 component. Rather, a larger amplitude of N1 was found in the reverse contrast, randomised minus same-point trials, which revealed increases in the fMRI signal along the posterior left superior frontal sulcus and bilaterally in the superior precuneus. These findings indicate that N1 indexes exogenous orienting of attention and is likely to represent the activity of frontal and parietal components of the attention network involved in eliciting attention changes. In contrast, the effects of those changes, resulting in a modulation of activation in visual occipital areas, are indexed by P1.

Isometric torque of the quadriceps femoris after concentric, eccentric and isometric training.

Twenty-seven normal, healthy women participated in this study, which investigated three methods of increasing the isometric strength of the quadriceps femoris through a six-week training program. Three experimental exercise groups were formed: A, eccentric, B, concentric, and C, isometric. The peak isometric torque of the quadriceps femoris was determined on the Cybex II Isokinetic Dynamometer before and after training. A total of 18 exercise sessions per subject were held. A two-way ANOVA with repeated measures revealed that while all three experimental groups significantly increased in isometric strength, no one method of training was superior. No interaction occurred in the population between the effects of pre- and posttraining scores and the type of training. The relationship between the experimental design and knee joint biomechanics may have precluded significant differences in strength gain among the experimental groups.

Outpatient therapeutic ERCP: a series of 262 consecutive cases.

BACKGROUND: Because of possible complications, it has been common practice to admit most if not all patients undergoing therapeutic ERCP. Therefore, little descriptive data exist on the safety of outpatient therapeutic ERCP. METHODS: We assessed 262 consecutive ERCPs in 209 patients undergoing outpatient therapeutic ERCP over a 5-year period, with particular attention to the development of complications. All outpatient endoscopic sphincterotomies and stent placements performed over a 5-year period were prospectively entered into an ongoing data base that was used for the analysis. In addition, hospital and office records for all patients were retrospectively reviewed, including a 30 to 45 day follow-up in a private office setting. RESULTS: Suspected or documented choledocholithiasis was the most common indication for ERCP and was present in 132 (50%), followed by malignant obstruction in 77 (29%), type I sphincter of Oddi dysfunction (on the basis of symptoms, liver test abnormalities, and bile duct dilatation) in 36 (14%), chronic pancreatitis in 10 (3.8%), HIV cholangiopathy in 4 (1.5%), and other conditions in 3 (1.1%). Overall, 181 patients (69%) underwent a sphincterotomy. The 30-day post-ERCP complication rate was 5.7% (95% CI: 3.2% to 9.3%), occurring in 15 of 262 cases. Complications necessitating hospitalization developed in 9 of the 262 ERCPs for a rate of 3.4% (95% CI: 1.6% to 6.4%). The mean duration of hospital stay among patients admitted for a complication was 2.7 +/- 1.8 days (range, 1 to 7 days). All patients were discharged without permanent sequelae. No 30-day procedure-related fatalities were reported. CONCLUSION: In this selected series of 262 consecutive cases, endoscopic sphincterotomy and stent placement were safely performed in an ambulatory setting. Prior to recommending a generalized change in existing practice, however, this finding requires validation with larger series of cases, including the performance of other outpatient therapeutic ERCP techniques.

Predictors of post-ERCP complications in patients with suspected choledocholithiasis.

BACKGROUND AND STUDY AIMS: Determinants of complications after endoscopic retrograde cholangiopancreatography (ERCP) have not yet been completely characterized. PATIENTS AND METHODS: Data were collected from an endoscopic database. Univariate analysis and multivariate logistic regression analysis were used to generate the best model of independent predictors of post-ERCP pancreatitis. RESULTS: The database included 1239 ERCP examinations carried out to investigate suspected choledocholithiasis over a five-year period. From these, 45 patients who developed post-ERCP complications were compared to a random sample of 486 patients who had undergone an uncomplicated ERCP for suspected choledocholithiasis. Univariate analysis demonstrated significant differences between the two patient groups for the following factors: age, using a cut-off point of 59 years (27% vs. 51%, P = 0.002), pancreatic channel opacification (73% vs. 58%, P = 0.05), and absence of common bile duct stones (41% vs. 24%, P = 0.03). Using multivariate logistic regression, the best model for predicting post-ERCP pancreatitis in patients undergoing sphincterotomy included age under 59 years (P = 0.04), and absence of a common bile duct stone (P = 0.004). The model yielded probabilities of developing post-sphincterotomy pancreatitis that ranged from 2.8% if no predictor was present, to 27% when both predictors were present. Among patients in whom a sphincterotomy was not performed, the only significant independent predictor found was pancreatic channel opacification (P = 0.05). CONCLUSION: Age under 59 years, pancreatic channel opacification, and an absence of common bile duct stones at ERCP are all independent predictors of post-ERCP pancreatitis.

Postcholecystectomy biliary leaks in the laparoscopic era: risk factors, presentation, and management. McGill Gallstone Treatment Group.

BACKGROUND: The management of bile leaks has evolved in the laparoscopic era. This study characterizes risk factors for their developmental and their clinical course and management. METHODS: Data on a cohort of patients who developed bile leaks after cholecystectomy in the laparoscopic era were gathered prospectively and retrospectively from an ongoing surgical database and following a review of hospital charts. RESULTS: Sixty-four patients (mean age 56 +/- 17.1 years, 72% women) were included over a 5-year study period. The incidence of leaks was 1.1% among patients entered in a laparoscopic cholecystectomy database. Intraoperative complications were encountered in 36%. Rates of intraoperative complication and conversion to open surgery were greater among patients who developed leaks (5.2% vs 0.6% and 33% vs 6.3%, respectively, p < 0.00001). Patients presented 5.3 +/- 4.2 days following surgery with abdominal pain (89%), fever (74%), and tenderness (81%). Ultrasound diagnosed a suspected leak in 73%, which ERCP showed as originating from the cystic duct stump in 77%. Biliary obstruction was noted in 20 (31%) patients (14 with stones). Treatments included percutaneous (13%), endoscopic (28%), primary or secondary operative procedures (14%), or a combination thereof (45%). CONCLUSION: A complication at laparoscopic cholecystectomy increases the likelihood of a subsequent bile leak. Most patients present early with a patent cystic duct stump in the absence of biliary obstruction. Endoscopic therapy is successful in the majority of cases, but otherwise percutaneous or operative procedures may be needed.

Role of ERCP in the diagnosis of intraductal papillary mucinous neoplasms.

Mucinous cystic neoplasms of the pancreas may present in a "ductectatic" form, which parallels a distinct clinical presentation. We describe six patients with this entity termed mucinous ductal ectasia, or intraductal papillary mucinous neoplasm. All six patients presented with typical clinical and endoscopic findings and subsequently, almost all were found to have mucinous ductal cystadenocarcinomas. The endoscopic and pancreatographic findings associated with an intraductal papillary mucinous neoplasm are characteristic, unique, and yield a high diagnostic accuracy. It is important to recognize these features of intraductal papillary mucinous neoplasm since the tumor has a lower malignant potential than adenocarcinoma of the pancreas, and surgical resection is curative in many cases.

Primary mediastinal large B-cell lymphoma with sclerosis: a clinical study of 89 patients treated with MACOP-B chemotherapy and radiation therapy.

BACKGROUND AND OBJECTIVES: Primary mediastinal large B-cell lymphoma (PMLBCL) with sclerosis has recently been recognized as a specific clinical and pathologic entity for which the best therapeutic approach seems to be a combination of chemotherapy and radiotherapy. DESIGN AND METHODS: Between 1989 and 1998, 89 previously untreated patients with PMLBCL with sclerosis were treated with a combination of a third-generation chemotherapy regimen (MACOP-B) and mediastinal radiation therapy. The response evaluations were examined after chemotherapy and at the end of radiotherapy. RESULTS: Twenty-three (26%) patients achieved a complete response (CR) and 59 (66%) obtained a partial response (PR) after the MACOP-B regimen. After radiation therapy, 55/59 (93%) of the patients in PR achieved CR. The CR rate at the end of the treatment was 88% (78/89). Only 7 (8%) patients were non-responders. Among the 78 patients who obtained a CR there were 7 (9%) relapses in a median follow-up of 5 months (all relapses occurred within 9 months); the other 71 patients are currently in continuous CR with a median follow-upof 45 months (range, 4-110 months). Projected overall survival was 86% at 9 years; the relapse-free survival curve of the 78 patients who achieved CR was 91% at 9 years. INTERPRETATION AND CONCLUSIONS: In patients with PMLBCL with sclerosis, combined modality treatment using the MACOP-B chemotherapy regimen and radiation therapy induces a good remission rate with the patients having a greater than 90% chance of surviving disease-free at 9 years. Radiotherapy often plays a pivotal role in obtaining CR status.

Randomized trial of 8-week versus 12-week VNCOP-B plus G-CSF regimens as front-line treatment in elderly aggressive non-Hodgkin's lymphoma patients.

BACKGROUND: Among the third-generation chemotherapy regimens specifically adapted in the last decade for elderly aggressive non-Hodgkin's lymphoma (NHL) patients, we designed an 8-week cyclophosphamide, mitoxantrone, vincristine, etoposide, bleomycin and prednisone (VNCOP-B) plus granulocyte colony-stimulating factor (G-CSF) regimen which, in a national multicenter trial, induced good complete response (CR) and relapse-free survival rates with only moderate toxic effects. Here we report a prospective, multicenter, randomized trial comparing the efficacy and toxicity of 8- and 12-week regimens of VNCOP-B plus G-CSF. PATIENTS AND METHODS: From February 1996 to June 2001, 306 consecutive previously untreated stage II-IV aggressive NHL patients > or =60 years of age were enrolled from 12 Italian cooperative institutions. Of the 297 evaluable patients, 149 and 148 received 8- and 12-week regimens, respectively, of VNCOP-B. RESULTS: The CR rates were 63% and 56% in the 8- and 12-week groups; at a median of 32 months (range 3-62 months), relapse-free survival rates were 59% and 55%, respectively. Hematological and non-hematological toxicities were similar in both treatment groups. CONCLUSIONS: Our data show that extending induction treatment with the VNCOP-B plus G-CSF regimen from 8 to 12 weeks does not raise the CR rate or provide a more durable remission.