Convexal subarachnoid hemorrhage and acute ischemic stroke: a border zone matter?

Background Convexal subarachnoid hemorrhage (c-SAH) is an infrequent condition with variable causes. c-SAH concomitant to acute ischemic stroke (AIS) is even less frequent, and the relationship between the two conditions remains unclear. Methods Between January 2016 and January 2018, we treated four patients who were referred to our stroke unit with ischemic stroke and concomitant nontraumatic c-SAH. The patients underwent an extensive diagnostic workup, including digital subtraction angiography (DSA). Results All four patients developed acute focal neurological symptoms with restricted MRI diffusion in congruent areas. In three of the patients, infarcts were in a border zone between the main cerebral arteries and c-SAH was nearby. The fourth patient showed a small cortical infarct, and c-SAH was in a border zone territory of the contralateral hemisphere. An embolic source was discovered or strongly suspected in all cases. One patient was treated with intravenous thrombolysis, but this treatment was not related to c-SAH. None of the four patients showed microbleeds or further cortical siderosis, thus excluding cerebral amyloid angiopathy. In addition, DSA did not show signs of vasculitis, reversible cerebral vasoconstriction syndrome, or intracranial arterial dissection. Conclusions We proposed the embolism or hemodynamic changes of the border zone arterioles as a unifying pathogenetic hypothesis of coexisting c-SAH and AIS

Erdheim-Chester disease: A systematic review.

Erdheim-Chester disease (ECD) is a rare form of non-Langerhans-cell histiocytosis, associated in more than 50% of cases to BRAF(V600E) mutations in early multipotent myelomonocytic precursors or in tissue-resident histiocytes. It encompasses a spectrum of disorders ranging from asymptomatic bone lesions to multisystemic, life-threatening variants. We reviewed all published reports of histologically-confirmed ECD and explored clinical, radiological, prognostic and therapeutic characteristics in a population of 448 patients, including a unique patient from our Department. To find a clinically relevant signature defining differentiated prognostic profiles, the patients' disease features were compared in relation to their CNS involvement that occurred in 56% of the entire population. Diabetes insipidus, visual disturbances, pyramidal and extra-pyramidal syndromes were the most recurrent neurological signs, whereas concomitant pituitary involvement, retro-orbital masses and axial lesions in the presence of symmetric bilateral osteosclerosis of long bones depicted the typical ECD clinical picture. Patients with CNS infiltration showed a lower occurrence of heart involvement and a higher incidence of bone, skin, retro-peritoneal, lung, aortic and renal infiltration. No difference in the therapeutic algorithm was found after stratification for CNS involvement. A better understanding of the disease pathogenesis, including BRAF deregulation, in keeping with improved prognostic criteria, will provide novel suggestions for the management of ECD

Cortical thinning and clinical heterogeneity in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) has heterogeneous clinical features that could be translated into specific patterns of brain atrophy. In the current study we have evaluated the relationship between different clinical expressions of classical ALS and measurements of brain cortical thickness. Cortical thickness analysis was conducted from 3D-MRI using FreeSurfer software in 29 ALS patients and 20 healthy controls. We explored three clinical traits of the disease, subdividing the patients into two groups for each of them: the bulbar or spinal onset, the higher or lower upper motor neuron burden, the faster or slower disease progression. We used both a whole brain vertex-wise analysis and a ROI analysis on primary motor areas. ALS patients showed cortical thinning in bilateral precentral gyrus, bilateral middle frontal gyrus, right superior temporal gyrus and right occipital cortex. ALS patients with higher upper motor neuron burden showed a significant cortical thinning in the right precentral gyrus and in other frontal extra-motor areas, compared to healthy controls. ALS patients with spinal onset showed a significant cortical thinning in the right precentral gyrus and paracentral lobule, compared to healthy controls. ALS patients with faster progressive disease showed a significant cortical thinning in widespread bilateral frontal and temporal areas, including the bilateral precentral gyrus, compared to healthy controls. Focusing on the primary motor areas, the ROI analysis revealed that the mean cortical thickness values were significantly reduced in ALS patients with higher upper motor neuron burden, spinal onset and faster disease progression related to healthy controls. In conclusion, the thickness of primary motor cortex could be a useful surrogate marker of upper motor neuron involvement in ALS; also our results suggest that cortical thinning in motor and non motor areas seem to reflect the clinical heterogeneity of the disease. © 2013 Mezzapesa et al

Early magnesium reduction in advanced colorectal cancer patients treated with cetuximab plus irinotecan as predictive factor of efficacy and outcome

Introduction: Magnesium plays a role in a large number of cellular metabolic reactions. Cetuximab is able to induce hypomagnesemia by interfering with magnesium (Mg2+) transport in the kidney.We designed this trial to investigate if Mg2+ serum level modifications may be related with clinical response andoutcome in advancedcolorectal cancer patients during treatment with cetuximab plus irinotecan. Experimental Design: Sixty-eight heavily pretreatedmetastatic colorectal cancer patients were evaluatedfor Mg2+ serum levels at the following time points: before; 6 hours; and1, 7, 14, 21, 50, and92 days after the start of treatment. Results: Basal Mg2+ median levels were significantly decreased just 7 days after the first anticancer infusion and progressively decreased from the 7th day onward, reaching the highest significance at the last time point (P < 0.0001).Twenty-five patients showeda reduction in median Mg2+ circulating levels of at least 20% within the 3rdweek after the first infusion. Patients with this reduction showed a response rate of 64.0% versus 25.6% in the nonreduced Mg2+ group. The median time to progression was 6.0 versus 3.6 months in the reduced Mg2+ group andin that without reduction, respectively (P < 0.0001). Overall survival was longer in patients with Mg2+ reduction than in those without (10.7 versus 8.9 months). Conclusions: Our results confirm that cetuximab treatment may induce a reduction of Mg2+ circulating levels andoffer the first evidence that Mg2+ reduction may represent a new predictive factor of efficacy in advanced colorectal cancer patients treated with cetuximab plus irinoteca

High-dose-rate Brachytherapy as Adjuvant Local rEirradiation for Salvage Treatment of Recurrent breAst cancer (BALESTRA): a retrospective mono-institutional study

Purpose: To evaluate clinical results of catheter-based interstitial high-dose-rate (HDR) brachytherapy (BT) as adjuvant treatment in previously irradiated recurrent breast cancer. Material and methods: Between January 2011 and September 2015, 31 consecutive patients with histologically confirmed recurrent breast cancer after conservative surgery and conventional whole breast radiotherapy, were retreated with a second conservative surgical resection and reirradiated with adjuvant interstitial HDR-BT. None of the brachytherapy implant was performed during the quadrantectomy procedure. A dose of 34 Gy in 10 fractions, 2 fractions per day, with a minimal interval of 6 hours was delivered. Results: At the time of the implant, the median age of patients was 59.7 years (range, 39.3-74.9 years). The median time from first treatment until BT for local recurrence was 11.9 years (range, 2.5-27.8 years). The median interval between salvage surgery and BT was 3.6 months (range, 1-8.2 months). No acute epidermitis or soft tissue side effects higher than grade 2 were recorded, with good cosmetic results in all patients. Most of the patients presented grade 1-2 late side effects. Only one patient developed grade 3 liponecrosis. After a median follow-up of 73.7 months (range, 28.8-102.4 months), the overall survival and cancer specific survival were 87.1% and 90.3%, respectively; 5-year local control and 5-year progression-free survival rate were 90.3% and 83.9%, respectively. Conclusions: Our preliminary analysis showed that HDR-BT is a feasible treatment for partial breast reirradiation offering very low complications rate and fast procedure. Higher patients' cohort is warranted in order to define the role of this treatment modality in the breast conservative management of local recurrence

The DEMO magnet system – Status and future challenges

We present the pre-concept design of the European DEMO Magnet System, which has successfully passed the DEMO plant-level gate review in 2020. The main design input parameters originate from the so-called DEMO 2018 baseline, which was produced using the PROCESS systems code. It defines a major and minor radius of 9.1 m and 2.9 m, respectively, an on-axis magnetic field of 5.3 T resulting in a peak field on the toroidal field (TF) conductor of 12.0 T. Four variants, all based on low-temperature superconductors (LTS), have been designed for the 16 TF coils. Two of these concepts were selected to be further pursued during the Concept Design Phase (CDP): the first having many similarities to the ITER TF coil concept and the second being the most innovative one, based on react-and-wind (RW) Nb3Sn technology and winding the coils in layers. Two variants for the five Central Solenoid (CS) modules have been investigated: an LTS-only concept resembling to the ITER CS and a hybrid configuration, in which the innermost layers are made of high-temperature superconductors (HTS), which allows either to increase the magnetic flux or to reduce the outer radius of the CS coil. Issues related to fatigue lifetime which emerged in mechanical analyses will be addressed further in the CDP. Both variants proposed for the six poloidal field coils present a lower level of risk for future development. All magnet and conductor design studies included thermal-hydraulic and mechanical analyses, and were accompanied by experimental tests on both LTS and HTS prototype samples (i.e. DC and AC measurements, stability tests, quench evolution etc.). In addition, magnet structures and auxiliary systems, e.g. cryogenics and feeders, were designed at pre-concept level. Important lessons learnt during this first phase of the project were fed into the planning of the CDP. Key aspects to be addressed concern the demonstration and validation of critical technologies (e.g. industrial manufacturing of RW Nb3Sn and HTS long conductors, insulation of penetrations and joints), as well as the detailed design of the overall Magnet System and mechanical structures

Population genetic structure, antibiotic resistance, capsule switching and evolution of invasive pneumococci before conjugate vaccination in Malawi

INTRODUCTION: Pneumococcal infections cause a high death toll in Sub Saharan Africa (SSA) but the recently rolled out pneumococcal conjugate vaccines (PCV) will reduce the disease burden. To better understand the population impact of these vaccines, comprehensive analysis of large collections of pneumococcal isolates sampled prior to vaccination is required. Here we present a population genomic study of the invasive pneumococcal isolates sampled before the implementation of PCV13 in Malawi. MATERIALS AND METHODS: We retrospectively sampled and whole genome sequenced 585 invasive isolates from 2004 to 2010. We determine the pneumococcal population genetic structure and assessed serotype prevalence, antibiotic resistance rates, and the occurrence of serotype switching. RESULTS: Population structure analysis revealed 22 genetically distinct sequence clusters (SCs), which consisted of closely related isolates. Serotype 1 (ST217), a vaccine-associated serotype in clade SC2, showed highest prevalence (19.3%), and was associated with the highest MDR rate (81.9%) followed by serotype 12F, a non-vaccine serotype in clade SC10 with an MDR rate of 57.9%. Prevalence of serotypes was stable prior to vaccination although there was an increase in the PMEN19 clone, serotype 5 ST289, in clade SC1 in 2010 suggesting a potential undetected local outbreak. Coalescent analysis revealed recent emergence of the SCs and there was evidence of natural capsule switching in the absence of vaccine induced selection pressure. Furthermore, majority of the highly prevalent capsule-switched isolates were associated with acquisition of vaccine-targeted capsules. CONCLUSIONS: This study provides descriptions of capsule-switched serotypes and serotypes with potential to cause serotype replacement post-vaccination such as 12F. Continued surveillance is critical to monitor these serotypes and antibiotic resistance in order to design better infection prevention and control measures such as inclusion of emerging replacement serotypes in future conjugate vaccines

DNA Sequence Profiles of the Colorectal Cancer Critical Gene Set KRAS-BRAF-PIK3CA-PTEN-TP53 Related to Age at Disease Onset

The incidence of colorectal cancer (CRC) increases with age and early onset indicates an increased likelihood for genetic predisposition for this disease. The somatic genetics of tumor development in relation to patient age remains mostly unknown. We have examined the mutation status of five known cancer critical genes in relation to age at diagnosis, and compared the genomic complexity of tumors from young patients without known CRC syndromes with those from elderly patients. Among 181 CRC patients, stratified by microsatellite instability status, DNA sequence changes were identified in KRAS (32%), BRAF (16%), PIK3CA (4%), PTEN (14%) and TP53 (51%). In patients younger than 50 years (n = 45), PIK3CA mutations were not observed and TP53 mutations were more frequent than in the older age groups. The total gene mutation index was lowest in tumors from the youngest patients. In contrast, the genome complexity, assessed as copy number aberrations, was highest in tumors from the youngest patients. A comparable number of tumors from young (<50 years) and old patients (>70 years) was quadruple negative for the four predictive gene markers (KRAS-BRAF-PIK3CA-PTEN); however, 16% of young versus only 1% of the old patients had tumor mutations in PTEN/PIK3CA exclusively. This implies that mutation testing for prediction of EGFR treatment response may be restricted to KRAS and BRAF in elderly (>70 years) patients. Distinct genetic differences found in tumors from young and elderly patients, whom are comparable for known clinical and pathological variables, indicate that young patients have a different genetic risk profile for CRC development than older patients