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In recent years, whey proteins (WP) have attracted increasing attention in health and disease for their bioactive functions. The aim of this study was to evaluate the benefit of WP isolate (WPI) supplementation in addition to nutritional counseling in malnourished advanced cancer patients undergoing chemotherapy (CT). In a single‐center, randomized, pragmatic, and parallel‐group controlled trial (http://www.ClinicalTrials.gov: NCT02065726), 166 malnourished advanced cancer patients with mixed tumor entities candidate to or undergoing CT were randomly assigned to receive nutritional counseling with (N = 82) or without (N = 84) WPI supplementation (20 g/d) for 3 months. The primary endpoint was the change in phase angle (PhA). Secondary endpoints included changes in standardized PhA (SPA), fat‐free mass index (FFMI), body weight, muscle strength, and CT toxicity (CTCAE 4.0 events). In patients with the primary endpoint assessed (modified intention‐to‐treat population), counseling plus WPI (N = 66) resulted in improved PhA compared to nutritional counseling alone (N = 69): mean difference, 0.48° (95% CI, 0.05 to 0.90) (P = .027). WPI supplementation also resulted in improved SPA (P = .021), FFMI (P = .041), body weight (P = .023), muscle strength (P, Whey proteins (WP) have attracted increasing attention in health and disease for their bioactive functions. In malnourished advanced cancer patients undergoing chemotherapy (CT) and receiving nutritional counseling, a 3‐month supplementation with WP resulted in improved body composition, muscle strength, and reduced CT toxicity.

Background & aims: To investigate the association between the parameters used in nutritional screening assessment (body mass index [BMI], unintentional weight loss [WL] and reduced food intake) and clinical outcomes in non-critically ill, hospitalized coronavirus disease 2019 (COVID-19) patients. Methods: This was a prospective multicenter real-life study carried out during the first pandemic wave in 11 Italian Hospitals. In total, 1391 patients were included. The primary end-point was a composite of in-hospital mortality or admission to ICU, whichever came first. The key secondary end-point was in-hospital mortality. Results: Multivariable models were based on 1183 patients with complete data. Reduced self-reported food intake before hospitalization and/or expected by physicians in the next days since admission was found to have a negative prognostic impact for both the primary and secondary end-point (P < .001 for both). No association with BMI and WL was observed. Other predictors of outcomes were age and presence of multiple comorbidities. A significant interaction between obesity and multi-morbidity (≥2) was detected. Obesity was found to be a risk factor for composite end-point (HR = 1.36 [95%CI, 1.03–1.80]; P = .031) and a protective factor against in-hospital mortality (HR = 0.32 [95%CI, 0.20–0.51]; P < .001) in patients with and without multiple comorbidities, respectively. Secondary analysis (patients, N = 829), further adjusted for high C-reactive protein (>21 mg/dL) and LDH (>430 mU/mL) levels yielded consistent findings. Conclusions: Reduced self-reported food intake before hospitalization and/or expected by physicians in the next days since admission was associated with negative clinical outcomes in non-critically ill, hospitalized COVID-19 patients. This simple and easily obtainable parameter may be useful to identify patients at highest risk of poor prognosis, who may benefit from prompt nutritional support. The presence of comorbidities could be the key factor, which may determine the protective or harmful role of a high body mass index in COVID-19.

Background Acute hematogenous osteomyelitis (AHOM) is an insidious infection of the bone that more frequently affects young males. The etiology, mainly bacterial, is often related to the patient’s age, but it is frequently missed, owing to the low sensitivity of microbiological cultures. Thus, the evaluation of inflammatory biomarkers and imaging usually guide the diagnosis and follow-up of the infection. The antibiotic treatment of uncomplicated AHOM, on the other hand, heavily relies upon the clinician experience, given the current lack of national guidelines for the management of this infection. Methods A systematic review of the studies on the empirical treatment of uncomplicated AHOM in children published in English or Italian between January 1, 2009, and March 31, 2020, indexed on Pubmed or Embase search engines, was carried out. All guidelines and studies reporting on non-bacterial or complicated or post-traumatic osteomyelitis affecting newborns or children older than 18 years or with comorbidities were excluded from the review. All other works were included in this study. Results Out of 4576 articles, 53 were included in the study. Data on different topics was gathered and outlined: bone penetration of antibiotics; choice of intravenous antibiotic therapy according to the isolated or suspected pathogen; choice of oral antibiotic therapy; length of treatment and switch to oral therapy; surgical treatment. Conclusions The therapeutic management of osteomyelitis is still object of controversy. This study reports the first Italian consensus on the management of uncomplicated AHOM in children of pediatric osteomyelitis, based on expert opinions and a vast literature review.

Background & Aims Great interest has been raised by the possible protective role of vitamin D in coronavirus disease 2019 (COVID-19), but objective data on 25(OH)vitamin D deficiency in hospitalized COVID-19 patients are not conclusive. The aim of this study was to determine the prevalence of 25(OH)vitamin D deficiency in COVID-19 patients admitted to an Italian referral hospital and explore its association with clinical outcomes and the markers of disease severity. Methods In this single-center cohort study, 129 consecutive adult COVID-19 patients hospitalized in an Italian referral center were enrolled from March to April 2020. 25(OH)Vitamin D serum levels were assessed 48 hours since hospital admission and categorized into: normal (≥30 ng/mL), insufficient (

Background: Malnutrition is common in cancer patients, particularly in those affected by gastrointestinal malignancies, and negatively affects treatment tolerance, survival, functional status, and quality of life (QoL). Nutritional support, including supplemental parenteral nutrition (SPN), has been recommended at the earliest opportunity in malnourished cancer patients. The limited available evidence on the efficacy of SPN in gastrointestinal cancer patients is positive, particularly with regards to QoL, body composition, and energy intake, but the evidence on survival is still scanty. Furthermore, studies regarding the early administration of SPN in combination with nutritional counseling from the beginning of first-line chemotherapy (CT) are lacking. We hypothesize that early systematic SPN in combination with nutritional counseling (NC), compared with NC alone, can benefit patients with previously untreated metastatic gastric cancer at nutritional risk undergoing first-line CT. Methods: The aim of this pragmatic, multicenter, randomized (1:1), parallel-group, open-label, controlled clinical trial is to evaluate the efficacy in terms of survival, weight maintenance, body composition, QoL and feasibility of cancer therapy of early systematic SNP. This is in combination with NC, compared with NC alone, in treatment-naïve metastatic gastric cancer patients at nutritional risk undergoing first-line CT. Discussion: Malnutrition in oncology remains an overlooked problem. Although the importance of SPN in gastrointestinal cancer patients has been acknowledged, no studies have yet evaluated the efficacy of early SPN in metastatic gastric patients undergoing CT. The present study, which guarantees the early provision of nutritional assessment and support to all the enrolled patients in accordance with the recent guidelines and recommendations, could represent one of the first proofs of the clinical effectiveness of early intensive nutritional support in cancer patients undergoing CT. This study could stimulate further large randomized trials in different cancer types, potentially resulting in the improvement of supportive care quality. Trial registration: This study is registered on ClinicalTrials.gov: NCT03949907.

Objective To report the early and mid-term outcomes following open surgical conversion (OSC) after failed endovascular aortic repair (EVAR) using data from a multicentric registry. Methods A retrospective study was carried out on consecutive patients undergoing OSC after failed EVAR at eight tertiary vascular units from the same geographic area in the North-East of Italy, from April 2005 to November 2019. Study endpoints included early and follow-up outcomes. Results A total of 144 consecutive patients were included in the study. Endoleaks were the most common indication for OSC (50.7%), with endograft infection (24.6%) and occlusion (21.9%) being the second most prevalent causes. The overall rate of 30-day all-cause mortality was 13.9% (n = 20); 32 patients (22.2%) experienced at least one major complication. Mean length of stay was 13 ± 12.7 days. On multivariate logistic regression, age (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.01-1-19; P = .02), renal clamping time (OR, 1.07; 95% CI, 1.02-1.13; P = .01), and suprarenal/celiac clamping (OR, 6.66; 95% CI, 1.81-27.1; P = .005) were identified as independent predictors of perioperative major complications. Age was the only factor associated with perioperative mortality at 30 days. Renal clamping time >25 minutes had sensitivity of 65% and specificity of 70% in predicting the occurring of major adverse events (area under the curve, 0.72; 95% CI, 0.61-0.82). At 5 years, estimated survival was significantly lower for patients treated due to aortic rupture/dissection (28%; 95% CI, 13%-61%), compared with patients in whom the indication for treatment was endoleak (54%; 95% CI, 40%-73%), infection (53%; 95% CI, 30%-94%), or thrombosis (82%; 95% CI, 62%-100%; P = .0019). Five-year survival rates were significantly lower in patients who received emergent treatment (28%; 95% CI, 14%-55%) as compared with those who were treated in an urgent (67%; 95% CI, 48%-93%) or elective setting (57%; 95% CI, 43%-76%; P = .00026). Subjects who received suprarenal/celiac (54%; 95% CI, 36%-82%) or suprarenal (46%; 95% CI, 34%-62%) aortic cross-clamping had lower survival rates at 5 years than those whose aortic-cross clamp site was infrarenal (76%; 95% CI, 59%-97%; P = .041). Using multivariate Cox proportional hazard, older age and emergency setting were independently associated with higher risk for overall 5-year mortality. Conclusions OSC after failed EVAR was associated with relatively high rates of early morbidity and mortality, particularly for emergency setting surgery. Endoleaks with secondary sac expansion were the main indication for OSC, and suprarenal aortic cross-clamping was frequently required. Endograft infection and emergent treatment remained associated with poorer short- and long-term survival.

Epidermal Growth Factor Receptor (EGFR) inhibition leads to the production of reactive oxygen metabolites causing skin inflammatory reactions. Anti-EGFR therapies are frequently associated with skin toxicities which often cause treatment delay and impairment to patient quality of life. Lycopene is a compound in the carotenoid group with an extreme antioxidant action which accumulates in the skin due to its hydrophobic structure. In a pilot study, we describe lactolycopene effectiveness in reducing skin toxicity and protecting tissues from oxidative stress in patients treated with panitumumab. Despite the limited number of patients, we show an absolute reduction of skin grade 2–3 toxicity in 41% of patients and 46% of panitumumab cumulative cycles in the experimental group versus placebo; lactolycopene administration was able to abolish malondialdehyde (MDA) production, a biomarker used to measure lipid peroxidation in the organism, and replenish antioxidant consumption in the course of anti-EGFR therapy. Trial registration: Clinicaltrials.gov NCT 03,167,268 (Pasto trial).

Objective: Pediatric autoimmune neuropsychiatric disorder associated with Streptococcus pyogenes infection (PANDAS) and pediatric acute-onset neuropsychiatric syndrome (PANS) are emerging ...

Background and purpose The presence of a continuum between physiological deja vu (DV) and epileptic DV is still not known as well as epidemiological data in the Italian population. The aim was to identify the epidemiological distribution of DV in Italy, and secondly to look for specific features of DV able to discriminate between epileptic and non-epileptic DV. Methods In all, 1000 individuals, 543 healthy controls (C) (313 women; age 40 ± 15 years) and 457 patients with epilepsy (E) (260 women; age 39 ± 14 years), were prospectively recruited from 10 outpatient neurological clinics throughout Italy. All populations were screened using the Italian Inventory for Deja Vu Experiences Assessment (I-IDEA) test and E and pairwise C underwent a comprehensive epilepsy interview. Results Of E, 69% stated that they experienced 'recognition' and 13.2% reported that this feeling occurred from a few times a month to at least weekly (versus 7.7% of the control group). Furthermore, a greater percentage of E (6.8% vs. 2.2%) reported that from a few times a month to at least weekly they felt that it seemed as though everything around was not real. In E, the feeling of recognition raised fright (22.3% vs. 13.2%) and a sense of oppression (19.4% vs. 9.4%). A fifth of E felt recognition during epileptic seizures. Conclusion Only E regardless of aetiology firmly answered that they had the feeling of recognition during an epileptic seizure; thus question 14 of the I-IDEA test part 2 discriminated E from C. Paranormal activity, remembering dreams and travel frequency were mostly correlated to DV in E suggesting that the visual-memory network might be involved in epileptic DV.

Background: Nutritional support, including nutritional counseling and oral nutritional supplements (ONSs), has been recommended at the earliest opportunity in head and neck (H&N) cancer patients. The limited available evidence on the efficacy of immunonutrition during chemoradiotherapy (CT-RT) in H&N cancer patients is positive with regard to some secondary endpoints, but is still scanty, particularly with regard to toxicity and treatment tolerance. We hypothesize that early systematic provision of ONSs with a high-protein–high-calorie mixture containing immunonutrients (Impact) compared to standard high-calorie–high-protein nutritional blends, in addition to nutritional counseling, may be beneficial to patients with H&N cancer during CT-RT. Hence, we designed the present study to evaluate the efficacy, in terms of treatment tolerance, toxicity and response, body weight, body composition, protein-calorie intake, quality of life (QoL), fatigue, muscle strength and immunological profile of the early systematic provision of ONSs enriched in immunonutrients compared to isonitrogenous standard blends, in H&N cancer patients undergoing CT-RT. Methods: This is a pragmatic, bicentric, randomized (1:1), parallel-group, open label, controlled, pilot clinical trial. Discussion: Many efforts are still to be taken to improve the efficacy of nutritional support in oncology. Immunonutrition represents a promising approach also in H&N cancer patients, but the evidence on its efficacy in improving clinical outcomes during CT-RT is still inconclusive. The present pilot study, which guarantees the early provision of nutritional assessment and support to all the enrolled patients in accordance with the recent guidelines and recommendations, could represent one of the first proofs of the clinical effectiveness of early oral immunonutrition in cancer patients undergoing CT-RT and could stimulate further large randomized trials, potentially resulting in the improvement of supportive care quality. Trial registration: This study is registered on ClinicalTrials.gov Identifier: NCT04611113.

Background The recent technological evolution has also allowed for the treatment of juxtarenal aortic aneurysm (JAA) with an endovascular technique, but short- and long-term results must be compared with the results of open treatment, which is the gold standard. In this study, we analyzed the short- and long-term results of open surgical treatment (open repair) in patients with JAA in our series. Methods From January 2006 to December 2016, 155 patients were treated for JAA with open repair; the data were analyzed retrospectively. The mean age was 71.17 years (standard deviation [SD] 7.1), and mean size of aneurysm was 6.15 cm (SD 1.1). The ASA classes 2, 3, and 4 were 20%, 74% and 6%, respectively. Follow-up included clinical visit and abdominal aorta Duplex scan after 1 and 6 months and annually. The mean follow-up interval was 48.6 (SD 32.4) months. Results The mean surgical time was 256 min (SD 69), the mean stay in the intensive care unit was 1.6 days (SD 1.2), and the mean total hospital stay was 10.2 days (SD 4.3). Aortic cross-clamping was usually suprarenal (110, 71%); in 39 (25%), the aortic clamping was between the renal arteries, and 6 patients (4%) required a supraceliac cross-clamping. The mean renal ischemia time due to aortic clamping was 17 min (SD 3.5). In 32 patients (21%), the left renal vein was sectioned for performing proximal aortic anastomosis and then reconstructed. Twelve patients (8%) required a renal revascularization, and in 49 patients (32%), an hypogastric bypass was performed. The 30-day mortality rate was 0.6%, and only 1 patient died in the postoperative due to intestinal infarction. The postoperative morbidities occurred in 15 cases (10%). Six patients had dehiscence of the laparotomy without the involvement of the muscle, 4 patients had an asymptomatic small increase of the troponin, and in 3 patients, there was an increase in creatinine >1.8 mg/dL. No dialysis was performed. Two patients had peripheral embolism in the lower limbs. Twenty-six patients (15%) died in the follow-up, but causes have never been related to aortic disease. Conclusions Open repair of JAA is still safe, effective, and durable also in the long-term period and even in patients with multiple cardiovascular risk factors.

Here we review the development of tivantinib, a selective oral inhibitor of c-MET. The initially identified dose and schedule for clinical use was 360 mg twice daily. Biological considerations and early results suggested its activity against hepatocellular carcinoma after progression on sorafenib. The results of randomized Phase II study in this setting have already been reported; while in the overall population, the risk of progression was reduced by 36% (HR: 0.64; 90% CI: 0.43-0.94; p = 0.04), in the pre-defined MET-high population median overall survival (7.2 vs 3.8 months; p = 0.01), median time to progression (2.7 vs 1.4 months; p = 0.03) as well as disease control rate (50 vs 20%), were increased by tivantinib. During study conduction, tivantinib dose was amended to 240 mg twice daily, due to a high incidence of neutropenia, without losing clinical efficacy. Presently, a global Phase III trial is being conducted.

Since its early development, the vascular endothelial growth factors (VEGFRs) inhibitor pazopanib showed both activity and tolerability in patients with metastatic RCC (mRCC) (Hurwitz et al., 2009), results which were subsequently confirmed in the following studies. A phase II study was at first designed as a randomized discontinuation study, but lately revised to an open-label study based on week 12 response rate (RR) of 38% in the first 60 patients. Thus, the primary end-point was changed from progressive disease rate at 16 weeks post-randomization to RR (Hutson et al., 2010). Overall RR was 35%, median duration of response was 68 weeks, and median progression-free survival (PFS) was 52 weeks (Hutson et al., 2010). Pazopanib was registered based on a global randomized, placebo-controlled, phase III trial. Of the 435 patients enrolled, 233 (54%) were treatment-naive, while 202 (46%) were pre-treated with cytokines. Pazopanib significantly prolonged PFS in overall study population [median PFS: 9.2 vs. 4.2 months, hazard ratio (HR): 0.46, 95% CI: 0.34–0.62, p < 0.0001], in the cytokine-pretreated subpopulation, as well as in the treatment-naive subpopulation (median PFS: 11.1 vs. 2.8 months, HR: 0.40, 95% CI: 0.27–0.60, p < 0.0001), compared to placebo (Sternberg et al., 2010). Furthermore, the objective response rate (ORR) was 30% with pazopanib with a median duration of response longer than 1 year. None clinically important difference in quality of life for pazopanib vs. placebo was observed in the safety analysis (Sternberg et al., 2010). More recently, the phase III COMPARZ study directly compared pazopanib with sunitinib in a non-inferiority study (Escudier et al., 2014). Pazopanib was non-inferior to sunitinib in terms of PFS (HR: 1.05, 95% CI: 0.90–1.22—predefined upper bound of the 95% CI < 1.25), and similar in OS (HR: 0.91, 95% CI: 0.76–1.08; Motzer et al., 2013); ORR was higher for pazopanib, as compared to sunitinib (31 vs. 25%, p = 0.03; Motzer et al., 2013). In terms of safety, pazopanib-treated patients experienced less fatigue, fewer side effects, including soreness of hand/foot and mouth/throat, and were more satisfied with treatment than those who received sunitinib (Motzer et al., 2013; Table ​Table1).1). Less fatigue and better overall quality of life were the most common reasons that justified the preference of pazopanib vs. sunitinib (70 vs. 22%, p < 0.01) in the PISCES study, a cross-over, double blind trial which specifically assessed the innovative endpoint of patients' preference (Escudier et al., 2014). Table 1 Comparison of baseline characteristics, clinical outcomes and adverse events in pivotal studies.

Over the past decade metastatic renal cell carcinoma (RCC) treatment landscape has dramatically evolved from the era of cytokines-based immunotherapy (which benefited very few patients, at the expenses of high toxicities) to the present era of targeted agents and novel immunotherapeutics, greatly improving the prognosis of our patients. Areas covered: Here we have reviewed the present status of the medical treatment of metastatic RCC. To do this, we interrogated the Medline database, as well as the proceedings of the main Oncological and Urological conferences for the relevant trials coducted so far. Expert opinion: Despite all the advances made in these relatively few years, further improvements are needed, since none of the available agents proved able to cure even a sigle metastatic RCC patient. In particular, advances are awaited from the results of ongoing trial of combinations of different immune checkpoint inhibitors and of immune checkpoint inhibitors with anti-VEGF/VEGFRs agents. Furthermore, a better understanding of the molecular escape pathways used by the tumor to overcome VEGFR blockade or immune activation will hopefully bring soon to the clinic more active, tailored treatments, to be used in second line and beyond.

A questionnaire survey was undertaken to assess the impact of a nationwide educational campaign about epilepsy on the knowledge and attitudes toward the disease among Italian primary school teachers. Five hundred and eighty-two teachers participated. All interviewees were aware of the existence of epilepsy, and most of them had direct experience with the disease. Answers about frequency, causes, outcome, and response to treatments were variable and not correlated with age, residency, and years of experience. Teachers had positive attitudes toward epilepsy, except for the idea that driving and sports can be safe for people with epilepsy. Epilepsy and its treatment were considered a source of learning disability and social disadvantages. Several teachers declared themselves being unable to help a child having seizures. Calling an ambulance was a frequent action. Knowledge and attitudes toward epilepsy are improved compared with those reported in our previous studies. Although this may be a positive reflection of the increasing knowledge and the greater availability of information on epilepsy, there are still areas of uncertainty and incorrect behaviors.

In reply: We thank Drs Salturk and Esquinas for their interest and comments on our paper entitled “CPAP devices for emergency prehospital use: a bench study.”[1][1] We absolutely agree with them that this study only represents a technical basis for clinical studies, which are necessary to make

e16081 Background: Sunitinib is a 1st-line standard of care in mRCC. Lack of cross-resistance to sequential VEGF-targeting drugs and the possibility of a successful rechallenge with Sunitinib have been postulated. Whether mRCC patients (pts) could benefit from rechallenge with Sunitinib after progressing on 1st-line Sunitinib and 2nd-line Everolimus was the aim of this phase II study Methods: 39 mRCCpts were prospectively treated with Sunitinib (50 mg/daily, 4:2); main inclusion criteria were: histologically proven RCC with clear cell component, previous 1st-line Sunitinib with a Disease Control Rate lasting at least 10 months, 2nd-line Everolimus, and written informed consent. The primary end-point of this study was 6-months progression-free survival (PFS). A Simon’s 2-stage design was used; after testing Sunitinib on 12 pts in the first stage, the trial would have been terminated if 5 or fewer had a PFS of less than 6 months. Otherwise, the trial would have proceeded to the second stage, enrolling a total of 38 pts. If the total number of pts free of progression at 6 months would have been less than or equal to 18, Sunitinib would have been rejected Results: As a whole, 39 pts (30 males, 9 females) were enrolled. The study quickly moved from the first stage to its completion and ultimately succeeded; indeed, 6-months PFS was 60%, median PFS being 8.6 months (average: 9.59, range: 0.7-24.6 months). In terms of safety no unexpected toxicities were observed. Tx-related grade 3-4 AEs observed in ≥5% of the pts were: hand-foot skin reaction, fatigue, nausea, hypertriglyceridemia, hypophosphatemia, hypocalcemia, hyperglycemia, and neutropenia. One case each of myocardial infarction, atrial flutter and spontaneous pneumothorax were also reported, but resolved Conclusions: Despite an ineluctable time-lead-bias, median PFS on Sunitinib rechallenge was high (8.6 months), clearly showing that many pts may become sensitive again to VEGFRs-inhibition. Although many agents are presently available from 2nd-line on, in countries where treatment options are still limited, Sunitinib rechallenge could still represent a reasonable treatment option. EudraCT number: 2012-000473-23. Clinical trial information: 2012-000473-23.

NT2 cells are a transfectable human embryonal carcinoma cell line, that can be differentiated into postmitotic neuron-like cells (NT2N cells), and transplanted into rodent brains. Differentiation requires a 5-week-long treatment with retinoic acid prior to transplantation. Here, we show that this step can be omitted, and that undifferentiated NT2 cells migrate over long distances and differentiate into both neuron- and oligodendrocyte-like cell types upon grafting into brains of immunocompetent newborn mice. Grafted cells can be traced by fluorogold, with no evidence for tumor formation. Our approach provides an experimental model system which allows the immunohistological and biochemical study of neuronal and glial differentiation of human cells in vivo, and which may be suitable as an in vivo model for pharmacological studies.

We report a case of epithelioid angiosarcoma of the abdominal aortic wall after endovascular treatment for abdominal aortic aneurysm (EVAR). A 60-year-old male, treated 7 years before with EVAR, presented with abdominal back pain, general fatigue, and fever. It was assumed to be a graft infection with periaortic tissue compatible with an inflammatory reaction. The endograft was therefore completely removed and a Dacron silver aorto-bisiliac graft was implanted. After a few days the patient worsened, the angio-computed tomography scan showed a progressive increase of the periaortic mass and numerous small nodules in the abdomen were also detected. The patient was again brought to surgery, an axillo-bifemoral bypass was performed, and the aorto-bisiliac graft was removed but the patient died after surgery. The histological examination showed an aortic epithelioid angiosarcoma with peritoneal metastasis.

Levofloxacin is a third generation fluorinated quinolone ntibiotic with a broad spectrum of antibacterial activity. It s generally well tolerated, with a very low rate of clinially important neurological adverse events. Fluoroquinolonessociated neurotoxicity may manifest as seizures, delirium or ncephalopathy. Here we describe the first case of levofloxacinnduced NCSE in a woman without history of neurological iseases.

Collagen VI is a survival factor for skeletal muscle produced by endomysial cells and localized in connective tissue around muscle fibers. Mutations of its genes (COL6A1, COL6A2 and COL6A3) cause two muscular disorders, Bethlem myopathy and Ullrich disease. Expression of Collagen VI is highly dynamic during development, suggesting that developmental and homeostatic cues of the muscle microenvironment are relevant to confine its expression in this tissue. In face of the large body of work highlighting the relevance for human diseases of the adhesion of muscle cells with their surrounding extracellular matrix, remarkably little is known on how myogenic cells control gene expression in the connective tissue cells that produce such matrix. By expressing promoter-lacZ constructs in transgenic mice, we identify a Col6a1 gene enhancer region that is necessary for activation of transcription in connective tissue cells associated with skeletal muscle. By means of a lacZ transgenic mouse line crossed in metD/D mutant background, in which muscles of limb buds fail to form, we provide evidence that the presence of cells of the myogenic lineage is needed for enhancer activation in mesenchymal cells. Accordingly, lack of myogenic cells in limb buds of metD/D mice reduces Collagen VI deposition in connective tissue. The Col6a1 enhancer characterized here is conserved in mammals and may be relevant in some cases of heritable diseases of Collagen VI.

Alzheimer's disease (AD) is characterized histopathologically by beta-amyloid-containing plaques, neurofibrillary tangles (NFT), reduced synaptic density, and neuronal loss in selected brain areas. Plaques consist of aggregates of a small peptide termed Abeta which is derived by proteolysis of the larger amyloid precursor protein APP, whereas NFT are composed of hyperphosphorylated forms of the microtubule-associated protein tau. Tau pathology in the presence of scant or no beta-amyloid plaques characterizes additional neurodegenerative disorders collectively called tauopathies. In the course of plaque and NFT formation, the major proteinaceous components of these lesions undergo post-translational modifications. In the case of tau, these include phosphorylation of mainly serine and threonine, but also tyrosine residues. In addition, tau is subject to ubiquitination, nitration, truncation, prolyl isomerization, association with heparan sulfate proteoglycan, glycosylation, glycation and modification by advanced glycation end-products (AGEs). This review aims to provide insight into the complexity of tau modifications in human tauopathies such as AD and frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17). Selected aspects of the post-translational modification of tau have been reproduced in transgenic animal models. Most of this work has been done in mice, but insight has also been gained from studies in the sea lamprey, the nematode C. elegans and Drosophila. Attempts have been made to link specific post-translational modifications with tau aggregation and nerve cell dysfunction.

Mutations in the coding and intronic regions of the tau gene cause frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). Some of these mutations lead to an overproduction of tau isoforms with four microtubule-binding repeats, followed by the development of fibrillary lesions and selective cell death. In order to analyze the development of these neurofibrillary lesions in transgenic mice, the longest four-repeat human brain tau isoform was expressed under control of two different neuron-specific promoters. In a first model, utilizing the human Thyl promoter, transgenic tau was hyperphosphorylated and abnormally localized to cell bodies and dendrites. In a second model, which made use of a human Thy1.2 expression vector, transgenic expression levels were much higher, and an additional phenotype was observed: Large numbers of pathologically enlarged axons containing neurofilament- and tau-immunoreactive spheroids were present, especially in spinal cord. Signs of Wallerian degeneration and neurogenic muscle atrophy were observed. Behaviorally, transgenic mice showed signs of muscle weakness. Our data show that overexpression of human four-repeat tau in itself is sufficient to lead to nerve cell dysfunction and amyotrophy. We have now extended our initial studies by introducing exonic mutations including G2t 2V and PS01L into the tau gene in order to achieve a more advanced FTDP-17 associated phenotype.

OBJETIVO: Os hematomas de mama sao comuns apos traumatismo, cirurgias ou contusoes. Raramente sao espontâneos, podendo ocorrer em pacientes com doenca hematologica ou outras doencas associadas a disturbios da coagulacao sanguinea. MATERIAL E METODOS: Os autores relatam o caso de paciente feminina, 48 anos, com diagnostico e acompanhamento de Hemoglobinuria paroxistica noturna ha 27 anos, submetida a mamografia por apresentar em consulta de rotina nodulo palpavel em quadrante superior interno (QSI ) da mama direita, movel e indolor. RESULTADOS: A mamografia evidenciou nodulo heterogeneo, de 35 mm, em QSI da mama direita, de contorno parcialmente delimitado, sem microcalcificacoes, que correlacionado com a historia clinica, sugeria o diagnostico de hematoma. O controle evolutivo com mamografia e ecografia, apos 45 dias mostrou substancial regressao da lesao e novo exame apos 60 dias foi normal. Decorridos 75 dias do primeiro episodio, a paciente apresentou outro nodulo, agora associado a hematoma cutâneo, em quadrante superior externo da mesma mama, interpretado como novo hematoma. O controle clinico apos dois meses do segundo episodio foi normal. CONCLUSOES: A hipotese de hematoma deve ser considerada no diagnostico diferencial de nodulo mamario, com ou sem historia de trauma ou doenca sistemica associada.

11598 Background: Malnutrition is frequent in cancer pts, particularly in advanced disease, which requires appropriate multidisciplinary interventions. We evaluated the benefit of whey protein isolate (WPI) supplementation in addition to nutritional counseling in malnourished cancer pts undergoing chemotherapy (CT). Methods: In a single-center, randomized, pragmatic, parallel-group controlled trial (ClinicalTrials.gov: NCT02065726), 166 malnourished advanced cancer pts undergoing CT were randomly assigned to receive nutritional counseling with (N=82) or without (N=84) WPI supplementation (20 grams/daily) for 3 months. Primary endpoint was the change in phase angle (PhA). Secondary endpoints included changes in standardized PhA (SPA), fat-free mass index (FFMI), body weight, muscle strength, quality of life and CT toxicity. Results: In pts with the primary endpoint assessed (modified intention-to-treat population), counseling plus WPI (N=66) resulted in improved PhA compared to nutritional counseling alone (N=69): mean difference, 0.48° [95%CI, 0.05 to 0.90] (P=0.027). Imputation of missing outcomes yielded consistent findings. WPI supplementation resulted also in improved SPA (P=0.021), FFMI (P=0.041), body weight (P=0.023), muscle strength (P