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Demand for nipple- and skin- sparing mastectomy (NSM/SSM) with immediate breast reconstruction (BR) has increased at the same time as indications for post-mastectomy radiation therapy (PMRT) have broadened. The aim of the Oncoplastic Breast Consortium initiative was to address relevant questions arising with this clinically challenging scenario. A large global panel of oncologic, oncoplastic and reconstructive breast surgeons, patient advocates and radiation oncologists developed recommendations for clinical practice in an iterative process based on the principles of Delphi methodology. The panel agreed that surgical technique for NSM/SSM should not be formally modified when PMRT is planned with preference for autologous over implant-based BR due to lower risk of long-term complications and support for immediate and delayed-immediate reconstructive approaches. Nevertheless, it was strongly believed that PMRT is not an absolute contraindication for implant-based or other types of BR, but no specific recommendations regarding implant positioning, use of mesh or timing were made due to absence of high-quality evidence. The panel endorsed use of patient-reported outcomes in clinical practice. It was acknowledged that the shape and size of reconstructed breasts can hinder radiotherapy planning and attention to details of PMRT techniques is important in determining aesthetic outcomes after immediate BR. The panel endorsed the need for prospective, ideally randomised phase III studies and for surgical and radiation oncology teams to work together for determination of optimal sequencing and techniques for PMRT for each patient in the context of BR • Autologous breast reconstruction is increasingly preferred over implants in the setting of radiation therapy. • Use of patient-reported outcomes is endorsed. • Shape and size of reconstructed breasts can hinder radiotherapy planning. • There is a need for randomised phase III trials. [ABSTRACT FROM AUTHOR]

The American College of Surgeons Oncology Group (ACOSOG) Z0011 trial demonstrated that in clinically node-negative women undergoing breast-conserving therapy (BCT) and found to have metastases to 1 or 2 sentinel nodes, sentinel lymph node biopsy (SLNB) alone resulted in rates of local control, disease-free survival, and overall survival equivalent to those seen after axillary lymph node dissection (ALND), but with significantly lower morbidity. Application of the Z0011 guidelines resulted in fewer ALNDs without affecting locoregional recurrence or survival. Changes in practice inevitably affect health care costs. The current study investigated the actual impact of applying the Z0011 guidelines to eligible patients and determined the costs of care at a single institution. We compared axillary nodal management and cost data in breast cancer patients who met the Z0011 criteria and were treated with BCT and SLNB. Patients were allocated into two mutually exclusive cohorts based on the date of surgery: pre-Z0011 (June 2013 to December 2015) and post-Z0011 (June 2016 to December 2018). Of 3912 patients, 433 (23%) and 357 (17.6%) patients in the pre- and post-Z0011 era had positive lymph nodes. ALND decreased from 15.3% to 1.57% in the post-Z0011 era. The mean overall cost of SLNB in the pre-Z0011 cohort was €1312 per patient, while that for SLNB with completion ALND was €2613. Intraoperative frozen section (FS) use decreased from 100% to 12%. Omitting the FS decreased mean costs from €247 to €176. The mean total cost in the pre-Z0011 cohort was €1807 per patient, while in the post-Z0011 cohort it was €1498. The application of Z0011 resulted in an overall mean cost savings of €309 for each patient. Application of the Z0011 criteria to patients undergoing BCT at our institution results in more than half a million Euro cost savings. [ABSTRACT FROM AUTHOR]

On October 15th, 2020, the first Surgical National Consensus Conference on neoadjuvant chemotherapy (NACT) was promoted by the Italian Association of Breast Surgeons (ANISC). The Consensus Conference was entirely held online due to anti-Covid-19 restrictions and after an introductory four lectures held by national and international experts in the field, a total of nine questions were presented and a digital "real-time" voting system was obtained. A consensus was reached if 75% or more of all panelists agreed on a given question. A total of 202 physicians, from 76 different Italian Breast Centers homogeneously distributed throughout the Italian country, participated to the Conference. Most participants were surgeons (75%). Consensus was reached for seven out of the nine considered topics, including management of margins and lymph nodes at surgery, and there was good correspondence between the 32 "Expert Panelists" and the "Participants" to the Conference. Consensus was not achieved regarding the indications to NACT for high-grade luminal-like breast tumors, and the need to perform an axillary lymph node dissection in case of micrometastases in the sentinel lymph node after NACT. NACT is a topic of major interest among surgeons, and there is need to develop shared guidelines. While a Consensus was obtained for most issues presented at this Conference, controversies still exist regarding indications to NACT in luminal B-like tumors and management of lymph node micrometastases. There is need for clinical studies and analysis of large databases to improve our knowledge on this subject. • Neo-adjuvant chemotherapy (NACT) has been increasingly used in the last two decades, initially with the aim to downstage a locally advanced breast cancer (BC) allowing breast conservative surgery instead of a mastectomy, and to test tumor's chemosensitivity "in vivo". •Although in the last few years, other rationales have been suggested to broaden its indications, several controversial issues on this topic still persists. •The first Surgical National Consensus Conference on Neoadjuvant Chemotherapy was promoted with the aim to discuss controversial issues and to obtain a "picture of a the current national approach. •While a Consensus was obtained for most issues presented at this Conference, controversies exist regarding indications to NACT in luminal B-like tumors and management of lymph node micrometastases. •There is need for clinical studies and analysis of large databases to improve our knowledge on this subject. [ABSTRACT FROM AUTHOR]

Piacenza is the closest city to the first coronavirus disease 2019 (COVID-19) cluster in Italy and has the highest national COVID-19 death rates per population. The objective of this study is to present characteristics and outcomes of patients admitted to medical departments of the Hospital of Piacenza during the first wave of the epidemic. A total of 218 patients with confirmed or suspect COVID-19 and severe pneumonia were included from February 21st to May 15th, 2020. Routinely-collected clinical and laboratory data were retrospectively retrieved from electronic medical files. A Cox proportional-hazards model was fit to assess the association of treatment and other variables with death. Median age of patients was 68 years; 150 patients (69%) had comorbidities, mainly hypertension (107, 49%). Overall, 185 (85%) patients had acute respiratory distress syndrome (ARDS) on admission, including 103 (47%) with moderate or severe ARDS. Chest computed tomography scan showed bilateral disease in 201 (98%) and extensive lung involvement in 79 (50%) patients. Most patients received antiviral treatment (187, 86%) and corticosteroids (134, 61%). All patients received respiratory support and 64 (29%) were admitted to intensive care unit. As of June 30th, 100 patients (46%) died, 109 patients (50%) were discharged, and 9 patients (4%) were still hospitalized. In multivariable Cox analysis, age above 65 years, having more than one comorbidity, severe ARDS, low platelet counts, and high LDH levels at admission were associated with mortality, while having diarrhea at admission was associated with survival. The use of antivirals or corticosteroids was not associated with survival. Overall case fatality rates were high and associated with comorbidities, extensive lung involvement, ARDS at admission, and advanced age. The use of antivirals was not associated with increased survival. [ABSTRACT FROM AUTHOR]

Background Patent foramen ovale (PFO) is present in as many as 25% of the general population and is considered an irrelevant condition in healthy subjects. Here, we sought to determine an association between an asymptomatic PFO at baseline and postoperative short-term adverse events in patients undergoing major pulmonary resection for lung cancer. In addition, we evaluated for the rate of PFO after pulmonary resections. Methods This prospective, observational study assessed patients by transcranial Doppler with contrast at baseline and discharge. To confirm interatrial shunting, patients with positive transcranial Doppler at baseline also underwent contrast transthoracic echocardiography. Multivariate logistic regression models were adopted to investigate for independent factors that could have been associated with complications. Backward stepwise procedure was used for model selection. Results Median age was 67.7 ± 9.2 years (range, 36 to 86), and 67% were men. Overall, 18 patients underwent pneumonectomy, 11 bilobectomy, and 118 lobectomy; 54% underwent right-sided procedure and 46%, left-sided. One perioperative death was recorded, and 34 patients had one or more cardiopulmonary complications. At baseline, PFO was positive in 25% (37 of 147) and negative in 75% (110 of 147); of the latter, 11% were positive at discharge. Detection of PFO at baseline, on multivariate analysis, was significantly associated with a risk of postoperative complications (odds ratio 2.5; 95% confidence interval: 1.1 to 5.8). Specifically, we observed a significant association between atrial fibrillation and positive PFO at baseline (odds ratio 3.5; 95% confidence interval: 1.4 to 9.0). Conclusions Preoperative asymptomatic PFO was independently associated with postoperative adverse events. Moreover, 11% of patients who had negative transcranial Doppler studies at baseline had asymptomatic PFOs at discharge. Larger prospective studies are needed to further investigate for a prognostic impact of PFO in thoracic surgery. [ABSTRACT FROM AUTHOR]

Abstract Background The burden of Crohn's disease (CD) and ulcerative colitis (UC) has never been estimated in the Republic of San Marino, the third smallest nation of the world. Aims To assess the occurrence and clinical features of CD and UC in San Marino during the last 35 years. Methods We retrospectively evaluated the prevalence, incidence, and main clinical aspects of CD and UC from 1980 to 2014, crossing data from various sources. Results Prevalence rates (per 100,000) on December 31, were 241 for CD (263 in males and 220 in females) and 311 for UC (370 in males and 255 in females). The specific incidence of UC steadily increased from 4.6 (95% CI: 1.5–10.6) in 1980–1984 to 12.4 (95% CI: 7.6–19.1) in 2010–2014; CD incidence showed a higher proportional increase, from 1.8 (95% CI: 0.2–6.6) in 1980–1984 to 17.9 (95% CI: 12.0–25.7) in 2010–2014. The main clinical features of CD and UC (activity and location at diagnosis, extra-intestinal manifestations, disease progression overtime, therapies, and hospitalizations) were analyzed. Conclusions This study provides the first epidemiological report on CD and UC in San Marino, showing specific traits and overall higher prevalence and incidence rates than previously reported in neighbor Areas. [ABSTRACT FROM AUTHOR]

Abstract Marine pollution, overrepresented by plastic, is a growing concern worldwide. However, there is little knowledge on occurrence and detrimental impacts of marine debris in cetaceans. To partially fill in this gap of knowledge, we aimed to investigate the occurrence and pathologies associated with foreign bodies (FBs) in a large cohort of cetaceans (n = 465) stranded in the Canary Islands. The Canary Islands shelter the greatest cetacean biodiversity in Europe, with up to 30 different species, of which nine are regularly present year around. We found at least one ingested FB in 36 out of 465 (7.74%) studied cetaceans, involving 15 different species, including eight out of the nine (80%) cetacean species present year-round in the Canary Islands. Risso's dolphin was the species most affected, followed by sperm whale, beaked whale and mysticetes. Plastic FB were the most common item found (80.56%). FB was directly associated with death in 13/36 (36.11%) animals. Poor body condition and deep diving behavior were found to be risk factors for FB ingestion, whereas the adult age was a protective factor. To the authors knowledge this is the first study that use statistical analysis to investigate risk and protective factors for FB ingestion. This study also provides insights of the potential impact caused by ingested FBs on the animal's health and mortality. This knowledge is critical to better understand and assess the impact of FB in cetaceans setting the scientific basis for prospective impact monitoring and future conservation policies. Graphical abstract Image 1 Highlights • Foreign bodies were found in 7.7% (36/465) studied cetaceans in the Canary Islands in a 16 year period. • Severe digestive disease (impactions and gastrointestinal perforations) caused the death of 13 animals (2.8%,13/465). • Plastic was the most common item found (80.6%). • Poor body condition and deep diving behavior were risk factors for foreign body ingestion. • Adult age was a protective factor for foreign body ingestion. This manuscript contributes to increase the current understanding of the epidemiology and pathology of foreign bodies in cetaceans and provides a scientific foundation for conservation policies. [ABSTRACT FROM AUTHOR]

Hair shed by domestic cats is a potentially useful source of forensic evidence. Analysable hair DNA is predominantly mitochondrial, but the recent domestication history of cats means that mtDNA diversity is low. A 402-bp control region segment is usually sequenced, defining only a small number of distinct haplotypes in populations. Previously, we used a long-amplicon approach to sequence whole mitogenomes in a sample of blood DNAs from 119 UK cats, greatly increasing observed diversity and reducing random match probabilities. To exploit this variation for forensic analysis, we here describe a multiplex system that amplifies the cat mitogenome in 60 overlapping amplicons of mean length 360 bp, followed by Nanopore sequencing. Variants detected in multiplex sequence data from unrooted hair completely mirror those from long-amplicon data from blood from the same individuals. However, applying the multiplex to matched blood DNA reveals additional sequence variants which derive from the major feline nuclear mitochondrial insertion sequence (numt), which covers 7.9 kb of the 17-kb mitogenome and exists in multiple tandem copies. We use long-amplicon Nanopore sequencing to investigate numt variation in a set of cats, together with an analysis of published genome sequences, and show that numt arrays are variable in both structure and sequence, thus providing a potential source of uncertainty when nuclear DNA predominates in a sample. Forensic application of the multiplex was demonstrated by matching hairs from a cat with skeletal remains from its putative mother, both of which shared a globally common haplotype at the control region. The random match probability in this case with the CR 402-bp segment was 0.21 and this decreased to 0.03 when considering the whole mitogenome. The developed multiplex and sequencing approach, when applied to cat hair where nuclear DNA is scarce, can provide a reliable and highly discriminating source of forensic genetic evidence from a single hair. The confounding effect of numt co-amplification in degraded samples where mixed sequences are observed can be mitigated by variant phasing, and by comparison with numt sequence diversity data, such as those presented here. • Cat mitogenomes sequenced using Nanopore technology from 60 overlapping amplicons. • Hair DNA gives true mtDNA sequence, but some numt variants co-detected from blood. • Major tandemly repeated cat numt is polymorphic, contributing further variability. • Useful in cat hair analysis; we provide mitigation for numt variants in blood DNA. • In a test case random match probability improves 7-fold compared to control region. [ABSTRACT FROM AUTHOR]

DNA variation in 402 bp of the mitochondrial control region flanked by repeat sequences RS2 and RS3 was evaluated by Sanger sequencing in 152 English domestic cats, in order to determine the significance of matching DNA sequences between hairs found with a victim’s body and the suspect’s pet cat. Whilst 95% of English cats possessed one of the twelve globally widespread mitotypes, four new variants were observed, the most common of which (2% frequency) was shared with the evidential samples. No significant difference in mitotype frequency was seen between 32 individuals from the locality of the crime and 120 additional cats from the rest of England, suggesting a lack of local population structure. However, significant differences were observed in comparison with frequencies in other countries, including the closely neighbouring Netherlands, highlighting the importance of appropriate genetic databases when determining the evidential significance of mitochondrial DNA evidence. [ABSTRACT FROM AUTHOR]

• The OPBC and EUBREAST ranked 51 important questions in axillary management. • Guidelines should be developed for axillary imaging and de-escalation of surgery. • Research was recommended for de-escalation of radiotherapy. • Management of residual nodal disease after surgery remains unclear. The aims of this Oncoplastic Breast Consortium and European Breast Cancer Research Association of Surgical Trialists initiative were to identify uncertainties and controversies in axillary management of early breast cancer and to recommend appropriate strategies to address them. By use of Delphi methods, 15 questions were prioritized by more than 250 breast surgeons, patient advocates and radiation oncologists from 60 countries. Subsequently, a global virtual consensus panel considered available data, ongoing studies and resource utilization. It agreed that research should no longer be prioritized for standardization of axillary imaging, de-escalation of axillary surgery in node-positive cancer and risk evaluation of modern surgery and radiotherapy. Instead, expert consensus recommendations for clinical practice should be based on current evidence and updated once results from ongoing studies become available. Research on de-escalation of radiotherapy and identification of the most relevant endpoints in axillary management should encompass a meta-analysis to identify knowledge gaps, followed by a Delphi process to prioritize and a consensus conference to refine recommendations for specific trial designs. Finally, treatment of residual nodal disease after surgery was recommended to be assessed in a prospective register. [ABSTRACT FROM AUTHOR]

Background We previously devised and reported on an innovative surgical technique of robotic nipple-sparing mastectomy and immediate robotic breast reconstruction. Here we describe the outcome of the first 29 such consecutive procedures performed on breast cancer patients to assess feasibility, reproducibility and safety. Methods The following morbidity factors were tested: operation time, conversion rate to open technique, length of hospitalization, registration of complications for 1 year postoperatively and their characterization as either minor, major, or multiple, depending on clinical severity and treatment required. Results The total duration of the final robotic surgeries of our series was around 3 h, showing a very rapid learning curve. The conversion rate due to technical problems was 2 of the 29 procedures (6,9%). No major complications, including hematoma, seroma, skin or nipple-areola injury or necrosis or infection were observed for any case. Two patients had a small degree of blistering from internal electrocautery in the breast skin flap, both of which resolved in one week without any specific therapy. No systemic complications were observed. Conclusion The low conversion rate to open surgery, the rapid learning curve and the low rate of post-operative complications observed in this preliminary series lead us to endorse a prospective study aimed at evaluating patient satisfaction. [ABSTRACT FROM AUTHOR]

Summary A uterine prolapse associated with a leiomyoma (fibroid) was observed in a live-stranded Atlantic spotted dolphin ( Stenella frontalis ). A 7 cm segment of the reproductive tract including the cervix, uterine neck and caudal uterine body had intussuscepted and prolapsed into the cranial vaginal vault. In the leading edge of the intussuscepted/prolapsed uterine wall was a 6 × 3 × 3.5 cm leiomyoma expanding the myometrium. The leiomyoma and prolapse were associated with necrotizing exposure endometritis. This is the first report of a uterine prolapse associated with a leiomyoma in a cetacean. This lesion was believed to be the underlying cause of the live stranding. [ABSTRACT FROM AUTHOR]

Since chronic hepatitis C has mostly become curable, issues concerning choice and allocation of treatment are of major concern. We assessed the foremost ethical issues in hepatitis C virus therapy with 1st generation protease inhibitors using the personalist ethical framework within the health technology assessment methodology. Our aim was to identify values at stake/in conflict and to support both the physicians’ choices in hepatitis C therapy and social (macro-) allocation decision-making. The ethical assessment indicates that: (1) safety/effectiveness profile of treatment is guaranteed if its use is restricted to the patients subgroups who may benefit from it; (2) patients should be carefully informed, particularly on treatment deferral, and widespread information on these therapies should be implemented; (3) since treatment was proven to be cost-effective, its use is acceptable respecting resource macro-allocation. Concerning individual (micro-) location criteria: (a) criteria for eligibility to treatment should be clearly identified and updated periodically; (b) information on criteria for eligibility/deferral to treatment for specific patients’ subgroups should be made widely known. Interferon-based regimens will disappear from use within the next year, with the introduction of highly effective/tolerable combination regimens of direct-acting antivirals, thus profoundly changing social choices. Nonetheless, our model could support future ethical assessment since the evaluation pertaining ethical domains remains generally applicable. [ABSTRACT FROM AUTHOR]

Summary This report describes the gross, microscopical and immunohistochemical features of a high-grade astrocytoma (glioblastoma multiforme) in an adult male Atlantic spotted dolphin ( Stenella frontalis ). On necropsy examination, a 5 × 2.5 × 2 cm, poorly demarcated, red, friable and locally expansile mass effaced the thalamus and the left periventricular region and extended to the left lateral ventricle of the brain. Microscopically, the mass consisted of haphazardly arranged bundles and rows of interweaving polygonal to spindle-shaped cells. These often palisaded along serpentine foci of necrosis and were surrounded by prominent vessels. Immunohistochemically, the neoplastic cells expressed glial fibrillary acidic protein, but not vimentin, S100 protein, neuron-specific enolase or neurofilament protein. A diagnosis of high-grade astrocytoma was made and this represents the first description of a glioma in a cetacean species. [ABSTRACT FROM AUTHOR]

Abstract: Status dystonicus (SD) is a medical emergency weighed by a relevant morbidity and mortality. It mainly affects patients with primary or secondary dystonia and is often triggered by events such as fever, infections, exposure medications or their abrupt cessation. We report on three patients presenting with SD. Two of them were affected by a static encephalopathy and the other one by a neurodegenerative disorder such as megalencephalic leukoencephalopathy with subcortical cysts (MLC). To our knowledge this is the first patient affected by MLC presenting with SD. All our patients underwent continuous infusion of midazolam, in association with pimozide and trihexyphenidyl, which led to complete resolution of muscular spasms in two patients. In the other one a complete cessation of dystonic spasms was obtained after intrathecal baclofen. From a therapeutic point of view there are no evidence-based management guidelines in SD. The approach is empiric and based on very limited anecdotal reports. On the basis of our observations and an extensive review of the literature we delineated a possible therapeutic strategy of SD in children. [Copyright &y& Elsevier]

A total of 482 LBC patients were genetically tested in search for constitutional CDH1 mutations and 16 (3.2%) novel germline CDH1 variants were identified. Although the mutation frequency of CDH1 is significantly lower than that of BRCA1/2, genetic testing for germline CDH1 mutations is not indicated for HBOC patients with pathogenic BRCA1/2 variations but could be recommended for those without. [Extracted from the article]

The article discusses research on the oncological safety and technical outcomes after nipple areola skin-sparing mastectomy (NASSM) and skin-sparing mastectomy (SSM). It references a study by H. J. Kim and colleagues published in a 2010 issue of "Annals of Surgery." The researchers found out that 9.6% of the NASSM patients developed complete nipple areola necrosis, while the 5-year disease-free survival rates were 89% for NASSM and 87.2% for SSM.

The article discusses research on the effectiveness and safety of endoscopic nipple-sparing mastectomy (E-NSM) for treating breast cancer. It references a study by N. Sakamoto and colleagues published in a 2009 issue of "Annals of Surgical Oncology." The researchers reported that nipple coring was performed in patients with bloody nipple discharge and suspicious extension near the nipple. They said that the rate of nipple necrosis in E-NSM with nipple coring was higher than those without because of a technical problem.

Tamoxifen is a candidate drug for prevention of breast cancer, although findings from trials have not been consistent. In our extended follow-up (median 81·2 months, IQR 66·0–87·2) of the Italian Tamoxifen Trial, this drug did not significantly protect against breast cancer in women at usual or slightly reduced risk of the disease (p=0·215). Use of hormone replacement therapy increased risk of breast cancer, and users of such treatment who were randomly allocated to tamoxifen had a rate of breast cancer that was close to that of never-users. So far, no woman has died from breast cancer in this study. Decisions about introduction of tamoxifen to reduce risk of breast cancer remain important and open questions. [Copyright &y& Elsevier]

Skin-sparing (SSM) and nipple-sparing (NSM) mastectomies are relatively new conservative surgical approaches to breast cancer. In SSM most of the breast skin is conserved to create a pocket that facilitates immediate breast reconstruction with implant or autologous graft to achieve a quality cosmetic outcome. NSM is closely similar except that the nipple-areola complex (NAC) is also conserved. Meta-analyses indicate that outcomes for SSM and NSM do not differ from those for non-conservative mastectomies. Recurrence rates in the NAC after NSM are acceptably low (0–3.7%). Other studies indicate that NSM is associated with high patient satisfaction and good psychological adjustment. Indications are carcinoma or DCIS that require mastectomy (including after neoadjuvant chemotherapy). NSM is also suitable for women undergoing risk-reducing bilateral mastectomy. Tumor not less than 2 cm from the NAC is recommended, but may be less important than no evidence of nipple involvement on mandatory intraoperative nipple margin assessment. A positive margin is an absolute contraindication for nipple preservation. Other contraindications are microcalcifications close to the subareolar region and a positive nipple discharge. Complication rates are similar to those for other types of post-mastectomy reconstructions. The main complication of NSM is NAC necrosis, however as surgeon experience matures, frequency declines. Factors associated with complications are voluminous breast, ptosis, smoking, obesity, and radiotherapy. Since the access incision is small, breast tissue may be left behind, so only experienced breast surgeons should do these operations in close collaboration with the plastic surgeon. For breast cancer patients requiring mastectomy, NSM should be the option of choice. [ABSTRACT FROM AUTHOR]

Background: Wearing-off (WO) is one of the main problems in levodopa-treated patients. An increased dopamine turnover might play a relevant role in WO pathogenesis. Objective: To investigate the modulation of treatment of a COMT-inhibitor in wearing-off Parkinson’s disease (PD) patients regarding cortical motor area activities with f-MRI, we prospectively studied nine PD patients with WO, before and during treatment with entacapone. Methods: Nine right-handed PD patients, and 10 age and sex-matched controls were included. Main inclusion criteria were disease duration >5years, WO and l-Dopa therapy. f-MRI was used to study BOLD signal changes associated with hand movements. A 1.5T MR system (Signa LX,GEMS) with epibold sequence (TR/TE 3s/40ms) and activation map sequences (TR/TE 500/20) was used. For right side, a finger tapping was separately performed, during seven activation blocks interleaved with seven rest periods. In PD-group f-MRI was acquired at baseline and after entacapone introduction. Statistical analysis were performed using SPM2 software. Results: The patient group showed a significant response to the COMT-inhibitor. The ON time, based on home diary, significantly improved (hours in OFF: baseline 8.5; last visit at 1month 6.4; p <0.01). The hand movements differed compared with controls numbers of execution/time: 26+2.1/min (PD) vs 40+4.4c/min (controls). In baseline condition, compared to controls, bilateral M1 areas showed activations with a main BOLD signal increase in the area contralateral to finger tapping (p <0.001). Moreover, in premotor areas both contralateral PMC and SMA showed an increase in activation with respect to controls. During entacapone therapy, regarding finger tapping of the right hand, the activation of the contralateral M1 was detected but less evident than at baseline (cluster volume: 406 vs 1462; p <0.001), where ipsilateral M1 did not show any difference. In premotor areas both contralateral PMC (cluster volume: 100 vs 50; p <0.001) and SMA showed a reduction in activation (cluster volume: 147 vs 54; p <0.001). Unlike baseline condition, ipsilateral PMC showed a significant activation (cluster volume: 65 vs no activation). Conclusions: Our preliminary findings suggest that, in PD patients, wearing-off is associated with the hyperactivation of the primary and secondary motor areas and that entacapone is able to reverse this hyperactivity. [Copyright &y& Elsevier]

Abstract: Leukoencephalopathy with brain stem and spinal cord involvement and high lactate (LBSL) is a recently identified leukoencephalopathy, first described by Van der Knaap in 2003. To date 24 cases have been described. Distinctive features were as follows. First, brain MRI showed white matter abnormalities and involvement of brain stem structures. Second, sparing of the u-fibers was an invariant, distinctive feature of the syndrome. Third, whenever evaluated, spinal cord was always involved. Fourth, brain [1H]-MR spectroscopy failed to show a lactate peak in all cases. In our little child, the diagnosis was confirmed by genetic analysis but unlike previous report both the u-fibers and globus pallidus were involved; spectroscopic data were more consistent with hypomyelination than demyelination. Our findings add to the phenotype variability of this novel disease. [Copyright &y& Elsevier]