Lacosamide in monotherapy in BTRE (brain tumor-related epilepsy): results from an Italian multicenter retrospective study.

PURPOSE: Lacosamide (LCM) is a third-generation anti-seizure medication (ASM) approved for focal onset epilepsy in patients aged ≥ 4.378 Previous studies have reported an efficacy of LCM as add-on treatment in brain tumor-related epilepsy (BTRE). To date, there are no studies in the literature focusing on lacosamide used in monotherapy to treat BTRE. In our retrospective study we investigated efficacy and tolerability of LCM in monotherapy in a multicenter national cohort of primary brain tumor patients. METHODS: We collected from 12 Italian Centers 132 patients with primary brain tumors who were treated with LCM in monotherapy. For each patient we evaluated seizure freedom at 3 and 6 months (primary endpoints), side effects and drop-out rate (secondary endpoints). RESULTS: Overall, LCM led to seizure freedom in 64.4% of patients at 3 months and 55% at 6 months. Patients who used two or more ASMs before LCM had a worse seizure control than patients in monotherapy with LCM as first choice. In 14 patients, we observed seizure control despite tumor progression on magnetic resonance (MRI). Multivariate analysis showed that gross-total resection at diagnosis was significantly associated with higher seizure freedom rate at 6 months. Side effects were mainly mild (grade 1-2 according to CTCAE classification) and drop-out rate was low (1.5%). Main side effects were dizziness and somnolence. CONCLUSIONS: This is the first study showing a good efficacy and tolerability of LCM when used in monotherapy in BTRE. Further prospective studies are needed to confirm these preliminary data, investigating also quality of life and neurocognitive functions.

Expanding the spectrum of SOX1-antibodies in neuropathy: the coexistence of anti-SOX1 and Guillain-Barré syndrome-a case report.

BACKGROUND AND AIMS: Antibodies against SOX1 (or anti-glial nuclear antibody, AGNA) are partially characterized onconeural antibodies, firstly described in association with small cell lung cancer (SCLC). Lambert-Eaton myasthenic syndrome is the most frequent paraneoplastic syndrome (PNS) found in patients with anti-SOX1-antibody positivity. Other associations are chronic axonal polyneuropathy, paraneoplastic limbic encephalitis, and paraneoplastic cerebellar degeneration. METHODS: We describe a case of Guillain-Barré syndrome (GBS) with classical demyelinating phenotype associated with a positivity for anti-SOX1-antibodies. RESULTS: A therapy with intravenous immunoglobulin led to progressive clinical improvement. After 12 months, clinical and neurophysiological pictures showed complete recovery. A thorough paraneoplastic screening was negative for underlying tumors. CONCLUSIONS: This is the first case of GBS associated with anti-SOX1-antibodies described in literature. Although the concept of paraneoplastic GBS is controversial, different cases have been reported and GBS is considered a non-classical paraneoplastic syndrome. Our case expands the anti-SOX1-antibody clinical spectrum with relevant implications for the clinical practice.

fMRI-Based Effective Connectivity in Surgical Remediable Epilepsies: A Pilot Study.

Simultaneous EEG-fMRI can contribute to identify the epileptogenic zone (EZ) in focal epilepsies. However, fMRI maps related to Interictal Epileptiform Discharges (IED) commonly show multiple regions of signal change rather than focal ones. Dynamic causal modeling (DCM) can estimate effective connectivity, i.e. the causal effects exerted by one brain region over another, based on fMRI data. Here, we employed DCM on fMRI data in 10 focal epilepsy patients with multiple IED-related regions of BOLD signal change, to test whether this approach can help the localization process of EZ. For each subject, a family of competing deterministic, plausible DCM models were constructed using IED as autonomous input at each node, one at time. The DCM findings were compared to the presurgical evaluation results and classified as: "Concordant" if the node identified by DCM matches the presumed focus, "Discordant" if the node is distant from the presumed focus, or "Inconclusive" (no statistically significant result). Furthermore, patients who subsequently underwent intracranial EEG recordings or surgery were considered as having an independent validation of DCM results. The effective connectivity focus identified using DCM was Concordant in 7 patients, Discordant in two cases and Inconclusive in one. In four of the 6 patients operated, the DCM findings were validated. Notably, the two Discordant and Invalidated results were found in patients with poor surgical outcome. Our findings provide preliminary evidence to support the applicability of DCM on fMRI data to investigate the epileptic networks in focal epilepsy and, particularly, to identify the EZ in complex cases.

Management of odonto-stomatological emergencies during the COVID-19 alarm state in dental clinics in the Autonomous Community of Madrid (CAM), Spain: An observational study.

BACKGROUND: Odontology practice has been severely compromised by the pandemic caused by COVID-19 and Spain is one of the countries with higher incidence. Our aim with this study is to find out the number of cases and type of odonto-stomatological emergencies (OSE) treated in four dental clinics of the Madrid capital area and region (CAM) in the period covered between March 17th and 4th of May. MATERIAL AND METHODS: We search the cases in the demographic/epidemiological databases of the CAM regional government and the Illustrious Official College of Dentists and Stomatologists of the First Region (Madrid). RESULTS: We found that the most prevalent pathology was acute apical periodontitis whereas odontogenic abscess showed the lowest frequency. Prosthetic-orthodontic OSE represented 14% of cases. CONCLUSIONS: In this period of time, the most prevalent pathology acute apical periodontitis, odontogenic abscess reported the lowest frequency and prosthetic-orthodontic treatments were the third in number of cases. Most of OSE were resolved, without referring the patient to a hospital emergency department.

Control and estimation of anaerobic digestion processes using hydrogen and volatile fatty acids measurements.

The anaerobic digestion (AD) technology is widely used in the treatment of waste and wastewater. To ensure the treatment efficiency and to increase the production of biogas, which can be reused as a renewable energy source, a good understanding of the process and tight control are needed. This paper presents an estimation and control scheme, which can be successfully used in the operation of the AD process. The process is simulated by the ADM1 model, the most complex and detailed model developed so far to characterize AD. The controller and the observer, which provides estimates of the unmeasurable variables needed in the computation of the control law, are designed based on a simplified model developed in a previous work. Since it has been shown that hydrogen concentration is an accurate and fast indicator of process stability, it was chosen as controlled variable. Aside from the hydrogen concentration, the only measurement employed by the proposed control structure is the volatile fatty acids concentration. Simulation results prove the effectiveness of the proposed control structure.

Prognostic significance of proteinuria in stroke patients treated with intravenous thrombolysis.

BACKGROUND AND PURPOSE: Proteinuria and estimated glomerular filtration rate (eGFR) are indicators of renal function. Whether proteinuria better predicts outcome than eGFR in stroke patients treated with intravenous thrombolysis (IVT) remains to be determined. METHODS: In this explorative multicenter IVT register based study, the presence of urine dipstick proteinuria (yes/no), reduced eGFR (<60 ml/min/1.73 m2 ) and the coexistence of both with regard to (i) poor 3-month outcome (modified Rankin Scale score 3-6), (ii) death within 3 months and (iii) symptomatic intracranial hemorrhage (ECASS-II criteria) were compared. Unadjusted and adjusted odds ratios (ORs) with 95% confidence intervals were calculated. RESULTS: Amongst 3398 patients, 881 (26.1%) had proteinuria and 623 (18.3%) reduced eGFR. Proteinuria [ORadjusted 1.65 (1.37-2.00) and ORadjusted 1.52 (1.24-1.88)] and reduced eGFR [ORadjusted 1.26 (1.01-1.57) and ORadjusted 1.34 (1.06-1.69)] were independently associated with poor functional outcome and death, respectively. After adding both renal markers to the models, proteinuria [ORadjusted+eGFR 1.59 (1.31-1.93)] still predicted poor outcome whilst reduced eGFR [ORadjusted+proteinuria 1.20 (0.96-1.50)] did not. Proteinuria was associated with symptomatic intracranial hemorrhage [ORadjusted 1.54 (1.09-2.17)] but not reduced eGFR [ORadjusted 0.96 (0.63-1.62)]. In 234 (6.9%) patients, proteinuria and reduced eGFR were coexistent. Such patients were at the highest risk of poor outcome [ORadjusted 2.16 (1.54-3.03)] and death [ORadjusted 2.55 (1.69-3.84)]. CONCLUSION: Proteinuria and reduced eGFR were each independently associated with poor outcome and death but the statistically strongest association appeared for proteinuria. Patients with coexistent proteinuria and reduced eGFR were at the highest risk of poor outcome and death.

Impact of body mass index on outcome in stroke patients treated with intravenous thrombolysis.

BACKGROUND AND PURPOSE: The impact of body mass index (BMI) on outcome in stroke patients treated with intravenous thrombolysis (IVT) was investigated. METHODS: In a multicentre IVT-register-based observational study, BMI with (i) poor 3-month outcome (i.e. modified Rankin Scale scores 3-6), (ii) death and (iii) symptomatic intracranial haemorrhage (sICH) based on criteria of the ECASS II trial was compared. BMI was used as a continuous and categorical variable distinguishing normal weight (reference group 18.5-24.9 kg/m2 ) from underweight (<18.5 kg/m2 ), overweight (25-29.9 kg/m2 ) and obese (≥30 kg/m2 ) patients. Univariable and multivariable regression analyses with adjustments for age and stroke severity were done and odds ratios with 95% confidence intervals [OR (95% CI)] were calculated. RESULTS: Of 1798 patients, 730 (40.6%) were normal weight, 55 (3.1%) were underweight, 717 (39.9%) overweight and 295 (16.4%) obese. Poor outcome occurred in 38.1% of normal weight patients and did not differ significantly from underweight (45.5%), overweight (36.1%) and obese (32.5%) patients. The same was true for death (9.5% vs. 14.5%, 9.6% and 7.5%) and sICH (3.9% vs. 5.5%, 4.3%, 2.7%). Neither in univariable nor in multivariable analyses did the risks of poor outcome, death or sICH differ significantly between BMI groups. BMI as a continuous variable was not associated with poor outcome, death or sICH in unadjusted [OR (95% CI) 0.99 (0.97-1.01), 0.98 (0.95-1.02), 0.98 (0.94-1.04)] or adjusted analyses [OR (95% CI) 1.01 (0.98-1.03), 0.99 (0.95-1.05), 1.01 (0.97-1.05)], respectively. CONCLUSION: In this largest study to date, investigating the impact of BMI in IVT-treated stroke patients, BMI had no prognostic meaning with regard to 3-month functional outcome, death or occurrence of sICH.

Typical values of z-resolution for different Digital Breast Tomosynthesis systems evaluated in a multicenter study.

PURPOSE: The aim of the present study, conducted by a working group of the Italian Association of Medical Physics (AIFM), was to define typical z-resolution values for different digital breast tomosynthesis (DBT) models to be used as a reference for quality control (QC). Currently, there are no typical values published in internationally agreed QC protocols. METHODS: To characterize the z-resolution of the DBT models, the full width at half maximum (FWHM) of the artifact spread function (ASF), a technical parameter that quantifies the signal intensity of a detail along reconstructed planes, was analyzed. Five different commercial phantoms, CIRS Model 011, CIRS Model 015, Modular DBT phantom, Pixmam 3-D, and Tomophan, were evaluated on reconstructed DBT images and 82 DBT systems (6 vendors, 9 models) in use at 39 centers in Italy were involved. RESULTS: The ASF was found to be dependent on the detail size, the DBT angular acquisition range, the reconstruction algorithm and applied image processing. In particular, a progressively greater signal spread was observed as the detail size increased and the acquisition angle decreased. However, a clear correlation between signal spread and angular range width was not observed due to the different signal reconstruction and image processing strategies implemented in the algorithms developed by the vendors studied. CONCLUSIONS: The analysis led to the identification of typical z-resolution values for different DBT model-phantom configurations that could be used as a reference during a QC program.

New onset status epilepticus in influenza associated encephalopathy: The presenting manifestation of genetic generalized epilepsy.

We hereby present a case of a young woman with no history of seizures or epilepsy who experienced a de novo generalized Non Convulsive Status Epilepticus (NCSE) followed by encephalopathy lasting for several days during influenza B infection. Influenza can have a broad spectrum of presentation ranging from an uncomplicated illness to many serious conditions as is the case of influenza associated encephalitis/encephalopathy (IAE). In this context however, it is possible to observe seizures and/or status epilepticus as the presenting manifestation of a genetic generalized epilepsy.

A radio ridge connecting two galaxy clusters in a filament of the cosmic web.

Galaxy clusters are the most massive gravitationally bound structures in the Universe. They grow by accreting smaller structures in a merging process that produces shocks and turbulence in the intracluster gas. We observed a ridge of radio emission connecting the merging galaxy clusters Abell 0399 and Abell 0401 with the Low-Frequency Array (LOFAR) telescope network at 140 megahertz. This emission requires a population of relativistic electrons and a magnetic field located in a filament between the two galaxy clusters. We performed simulations to show that a volume-filling distribution of weak shocks may reaccelerate a preexisting population of relativistic particles, producing emission at radio wavelengths that illuminates the magnetic ridge.

Suppression of tumorigenesis by the breast cancer cell line MCF-7 following transfer of a normal human chromosome 11.

Breast cancer development is associated with several genetic abnormalities. Loss of heterozygosity in the short arm of chromosome 11 has been observed in 30% of tumors. We found homozygosity at five chromosome 11 polymorphic loci in genomic DNA of the MCF-7 breast carcinoma cell line, suggesting a possible loss of one chromosome 11. We have studied the transformed and tumorigenic phenotypes of MCF-7 cells following introduction of a normal human chromosome 11 via microcell fusion. MCF-7/H11 cell hybrids, containing chromosome 11, showed in vitro characteristics similar to the parental cell line. However, tumorigenicity in athymic mice was completely suppressed. Since tumor formation by MCF-7 cells is estrogen dependent, we have analysed the expression of the estrogen receptor and of the estrogen-activated gene pS2. No difference was detected between the parental MCF-7 cells and the derived chromosome 11 cell hybrids, indicating that the mechanism of MCF-7 tumor suppression by chromosome 11-associated functions does not directly involve the estrogen/estrogen receptor molecular pathway.

[Prevalence and determinants of low back pain in hospital workers]. / Prevalenza e fattori determinanti delle lombalgie tra i dipendenti dell'ospedale di Terni.

This study evaluated the prevalence and determinants of low back pain (LBP) in Terni hospital workers. Each ward sister completed a questionnaire about potential determinants of LBP associated with physical loads. Moreover, a trained ward sister administered a questionnaire about the characteristics of low back pain to 512 subjects. In the previous year the prevalence of LBP was 58.8%. It was more common in subjects under 45 years of age. >3 LBP episodes annually were more frequent in operating rooms and medical wards. LBP lasted >1 week in 29% of females and in 23% of males. LBP caused change of duties or time off work in 11% of females and in 8% of males.

Comparison between single saturating dose ligand binding assay and enzyme immunoassay for low-salt extractable oestrogen and progesterone receptors in breast cancer: a multicentre study.

An excellent correlation between ligand binding assay (LBA) and enzyme immunoassay (EIA) for both oestrogen (ER) and progesterone (PR) receptors has been reported. Nevertheless, considering that the clinical value of any discrepancy between LBA and EIA probably varies with the receptor level, we undertook a collaborative study in which a single saturating dose (SSD) LBA and EIA were compared in different ER and PR dose ranges. The values of ER measured by EIA were higher in tumours with low or intermediate receptor content, causing a misclassification of ER status in 9% of cases (ER+: 77.5%, EIA, 68.8% SSD). In the case of ER, EIA values tended to be higher than SSD in all centres. For PR, EIA and SSD were generally more comparable (PR+: 66.0% EIA, 72.0% SSD, discordance rate 6%), with EIA showing, however, different trends in different centres. PR concentration was not significantly different in ER SSD-/EIA+ and in ER SSD+/EIA+ cases, suggesting that EIA detects at least in part integer ER. We conclude that although EIA may be a reliable methodological alternative to SSD, the two methods are not interchangeable until effective cut-off levels for clinical decisions are assessed for EIA.

Plasminogen activator system in serum and amniotic fluid of euploid and aneuploid pregnancies.

OBJECTIVE: To compare euploid and aneuploid pregnancies with respect to maternal serum and amniotic fluid (AF) levels of the components of the plasminogen system. METHODS: The study population consisted of 123 single pregnancies at the 17th gestational week, 16 with minor chromosomal abnormalities, 15 aneuploid, and 92 euploid. RESULTS: Both groups with chromosomal abnormalities had significantly higher serum levels of urokinase plasminogen activator and its complexed form with its type-1 inhibitor compared with euploid pregnancies. In AF, tissue plasminogen activator was significantly lower in the aneuploid than the euploid group, whereas type-1 inhibitor of plasminogen activator was significantly higher in the cases with minor chromosomal abnormalities compared with euploid. At cutoff levels set at 100% sensitivity, the complexed form of urokinase plasminogen activator with its type-1 inhibitor had the strongest specificity (66.3%); after logarithmic transformation, its serum level was 7.53 times higher in aneuploidies than euploidies. CONCLUSION: Aneuploid pregnancies appear to be accompanied by abnormalities of the plasminogen activation system, which could lead to impaired placental perfusion and thus to abortion, fetal death, and fetal growth restriction.

Estrogen and progesterone measurement and its quality control in breast cancer: a reappraisal.

This article illustrates the two main methods for routine measurement of cytoplasmic estrogen receptor status in neoplastic biopsy. The first is the Dextran Coated Charcoal Technique (D.C.C. Assay) which is still the method of choice in the majority of clinical laboratories for its simplicity, reproducibility and low cost. The second is a more advanced technique based on the specific binding, enzymatically displayed, of commercially available antiestrogen monoclonal antibodies (Enzyme Immuno Assay - ABBOTT). The sui generis characteristics of endocrine sensitivity assessment on tumor tissues and the importance of decision-making connected with the assay justify rigorous quality assurance schemes. The quality control design proposed by the Italian Committee concerned the evaluation of several lyophilized preparations with scalar receptor content; this permits the identification through linear regression analysis of systematic and non-systematic errors. The Italian Committee has currently connected 50 labs from most regions of the country.

Immunometric assays of ras and c-erbB-2/neu overexpression in breast cancer: a pilot study.

The expression of the ras and c-erbB2 oncoproteins (p21 and p185, respectively), together with estrogen receptor (ER) and progesterone receptor (PgR) determination, has been retrospectively analyzed in 68 primary breast carcinomas and in 19 normal breast tissue samples. The aims of this study were: a) to explore the association between ras and c-erbB2 expression; b) to evaluate the relationship between ras and c-erbB2 expression and both steroid receptor status and the classical clinical and pathological parameters; and c) to compare two different methods for p185 determination. p185 and p21 were measured by enzyme immunoassay (EIA); p185 was also determined by Western blotting (WB); ER and PgR were assayed by radioligand binding assay. The highest value of p185 in benign breast lesions was used as the threshold to distinguish between positive and negative samples. With this threshold the c-erbB2 oncoprotein was overexpressed in 41.2% (with EIA) and in 50% (with WB) of cancer samples. The concordance rate between the two methods was 79.4. No significant association was found between p21 and p185 levels either in cancer or in normal breast tissue samples. Increasing levels of tumor p21 were associated with a shorter time to recurrence and overall survival. Increasing levels of p185 were associated with a significantly shorter time to recurrence (p185 EIA: p = 0.04, p185 WB: p = 0.029) and overall survival (p185 EIA: p = 0.04, p185 WB: p = 0.029).

Relationship between cytosol TPS, TPA and cell proliferation.

The serological tumor marker tissue polypeptide antigen (TPA) and the more recently identified tissue-specific polypeptide antigen (TPS) have been reported to be indicators of the proliferation rate of the tumor. In the present investigation we compared the cytosol level of the two markers with the proliferative activity of the tumor measured using the 3H-thymidine labelling index. The preliminary results presented here show that higher TLI is associated with lower cytosol levels of both TPA and TPS. TPA and TPS in the cytosol were significantly associated. These findings are in agreement with the previously demonstrated association between high TPA cytosol levels and better prognosis in breast cancer. Further studies are ongoing in order to: 1. confirm these findings in a larger patient series; 2. investigate any possible prognostic indication provided by TPS; 3. evaluate any possible biological meaning of the negative association between TPA/TPS and TLI in the cytosol of breast cancer.

Relationship between teat tissue immune defences and intramammary infections.

The teat is the main entrance for pathogens into the mammary gland. It also acts as a sensory, motor and primary defence organ. This latter function is important in preventing intramammary infections while efficiency in preventing new infections is determined by teat tissue integrity. Machine milking may evoke mechanical and circulatory impairment in teat tissues. These local metabolic disorders may decrease the efficiency of the local immune defence mechanisms. Teat tissue changes can be estimated by measuring teat thickness before and after milking. Experimental and field studies showed a high correlation between changes in thickness and infection risk. Teats with > 5% change in thickness have significantly increased teat duct colonisation rates and intramammary infection rates. The link between changes in teat thickness and infections should be found in changes in local immune defences and measurable changes in cytological and biochemical immune factors are expected. Indeed, the application of experimental milking conditions (i.e. no pulsation milking and positive pressure milking) showed to have a significant influence on some non specific immune factors in teat secretion. Positive pressure milking increases PMNs content and decreases macrophages content of teat secretion. Some enzymes such as NAGase and lysozyme were decreased by positive pressure milking, the concentration of the same enzymes were higher after no pulsation milking. A better knowledge on the interaction between the teat apex immune defense mechanisms and the machine milking process is necessary to reduce the new infection rate of the bovine mammary gland.

Characterization of laboratory working standard for quality control of immunometric and radiometric estrogen receptor assays. Clinical evaluation on breast cancer biopsies. Italian Committee for Hormone Receptor Assays Standardization.

The objective of the study was to characterize a low-cost and reliable working standard material for quality control of estrogen receptor (ER) determination with dextran-coated charcoal (DCC) and enzyme immunoassay (EIA) methods. Human fibromatous uterine lyophilized cytosol demonstrated good characteristics of stability and applicability for this purpose. Eleven laboratories participated in the intralaboratory and interlaboratory quality control study, and they achieved slightly higher coefficients of variation for ER-EIA (interlaboratory, 37.7%; intralaboratory, 22.9%) than for ER-DCC (interlaboratory, 24.2%; intralaboratory, 15.7%). There was an excellent correlation between ER results with ER-EIA and ER-DCC for 268 breast cancer biopsies. Quality assurance for ER assays using DCC techniques and immunometric methods with monoclonal antibodies (ER-EIA) can be set up with this available material of human origin to satisfy the characteristics of both techniques and the species specificity of monoclonal antibodies.

Hormone receptors and breast cancer: correlations with clinical and histologic features.

The possible relationships between hormone receptor status and several clinical (age, gynecologic history, clinical stage) and morphologic aspects (histologic grade, vascular invasion, lymphocytic infiltration, necrosis, fibrosis, elastosis and lymph node metastasis) were evaluated. A highly significant correlation between estrogen receptor levels, patient age, menses regularity and postmenopausal status was found. The histologic features most significantly related to tumor receptor status were histologic grade, lymphocytic infiltrate, necrosis and elastosis. Since these same histologic aspects appear to influence prognosis in breast cancer, the prognostic significance attributed to tumor receptor levels is substantiated. Therefore the importance of this assay is confirmed, not only for its diagnostic and therapeutic purposes, but also for its prognostic value.