The brain-heart connection: a multiple sclerosis relapse presenting as Takotsubo Syndrome. A case report and literature review

We hereby report a puzzling case of multiple sclerosis (MS) relapse presenting as Takotsubo syndrome (TTS). Female, 42-years old, who presented herself to the Emergency Room of University Hospital "ASST Spedali Civili" of Brescia, Italy, for a severe headache and a non-ST-segment elevation acute coronary syndrome. Coronary angiogram showed no signs of coronary atherosclerosis. Upon further neurological evaluation, a diagnosis of MS relapse, related to TTS, was made, and treatment was started accordingly. The patient was discharged after 12 days after the admission, free of symptoms, and without signs of neurological and cardiological active disease. A hallmark of TTS is its association with a preceding stressful event. It may also be connected to a wide variety of diseases, including neurological ones, such as stroke, intracranial bleeding, head trauma, migraine, and seizures. However, up to our knowledge, only few cases of MS-induced TTS were previously described. Whether it is plausible to consider TTS as an uncommon extra-neurological manifestation of MS is still debated, however all the evidence points in that direction, considering the central role of catecholamines in TTS pathogenesis. With this case report the authors hope to encourage research on this field and on the intricate topic of brain-heart connections

Performance Evaluation of Active Islanding-Detection Algorithms in Distributed-Generation Photovoltaic Systems: Two Inverters Case

Grid-connected photovoltaic (PV) inverters employ an islanding-detection functionality in order to determine the status of the electrical grid. In fact, the inverter must be stopped once the islanding operating mode is detected according to standards and grid-code limits. Diverse islanding-detection algorithms have been proposed in literature to cope with this safety requirement. Among them, active methods based on the deliberate perturbation of the inverter behavior can minimize the so-called nondetection zone, which is a range of conditions in which the inverter does not recognize that it is operating in an undesired island. In most cases, the performances of these methods have been analyzed considering a highly dispersed generation scheme, where only one distributed-generation power system is connected to the local electrical power system (EPS). However, in some studies, it has been highlighted that if two or more PV inverters are connected to the same local EPS, their anti-islanding algorithms do not behave ideally and can fail in detecting the islanding condition. However, there is no systematic study that has investigated the overall capability of different anti-islanding methods employed on several inverters connected to the same EPS to detect islanding condition. This paper is a first attempt to carry out a systematic study of the performances of the most common active detection methods in a case of two inverters connected to the same EPS. In order to evaluate the global capability of the two systems to detect islanding condition, a new performance index is introduced and applied also to the case when the two inverters employ different anti-islanding algorithms

Wavelet-based Islanding Detection in Grid-Connected PV Systems

Distributed Power Generation Systems (DPGS) based on inverters require reliable islanding detection algorithms (passive or active) in order to determine the electrical grid status and operate the grid connected inverter properly. These methods are based on the analysis of the DPGS voltage, current and power in time or frequency domain. This paper proposes a time-frequency detection algorithm based on monitoring the DPGS output power considering the influence of the PWM, the output LCL filter and of the employed current controller. Wavelet analysis is applied to obtain time localization of the islanding condition. Simulation and experimental results show the performance of the proposed detection algorithm also in comparison with existing methods

Impact of Epiretinal Membrane on Optical Coherence Tomography Tools Used for Monitoring Glaucoma

Background: Retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) measurements can be influenced by many factors including the presence of concomitant retinal diseases. The aim of this study it to assess the impact of epiretinal membrane (ERM) on RNFL and GCL assessment using optical coherence tomography (OCT). Methods: GCL, peripapillary RNFL (pRNFL), and Bruch's Membrane Opening Minimum Rim Width (BMO-MRW) thicknesses were analysed using an SD-OCT (Spectralis OCT) in eyes with idiopathic ERM and compared with a control group. Results: 161 eyes were included, 73 eyes in the control group and 88 eyes with idiopathic ERM. The pRNFL analysis revealed a statistically significant difference between the two groups in overall and temporal sector thicknesses. For GCL thickness report, the percentage of scans in which the GCL was erroneously segmented by automatic segmentation was assessed for each eye. A statistically significant difference was found in all sectors (p < 0.001), with the exception of external nasal sector. A statistically significant difference (p < 0.001) in the GCL total volume report was found in ERM group compared to the control group. For MRW at BMO analysis, there was no statistically significant difference in MRW thickness in any sector. Conclusion: In eyes with ERM, the GCL and pRNFL analysis seemed affected by the morphological retinal layers' modification. MRW-BMO did not appear to be directly affected by the presence of ERM

Risk factors for gram-negative bacterial infection of cardiovascular implantable electronic devices: Multicentre observational study (CarDINe Study)

Background: Infections of cardiovascular implantable electronic devices (CIED) are mainly due to Gram-positive bacteria (GPB). Data about Gram-negative bacteria CIED (GNB-CIED) infections are limited. This study aimed to investigate risk factors, clinical and diagnostic characteristics, and outcome of patients with GNB-CIED. Methods: A multicentre, international, retrospective, case-control-control study was performed on patients undergoing CIED implantation from 2015 to 2019 in 17 centres across Europe. For each patient diagnosed with GNB-CIED, one matching control with GPB-CIED infection and two matching controls without infection were selected. Results: A total of 236 patients were enrolled: 59 with GNB-CIED infection, 59 with GPB-CIED infection and 118 without infection. No between-group differences were found regarding clinical presentation, diagnostic and therapeutic management. A trend toward a higher rate of fluorodeoxyglucose positron emission computed tomography (FDG PET/CT) positivity was observed among patients with GNB than in those with GPB-CIED infection (85.7% vs. 66.7%; P = 0.208). Risk factors for GNB-CIED infection were Charlson Comorbidity Index Score (relative risk reduction, RRR = 1.211; P = 0.011), obesity (RRR = 5.122; P = 0.008), ventricular-pacing ventricular-sensing inhibited-response pacemaker implantation (RRR = 3.027; P = 0.006) and right subclavian vein site of implantation (RRR = 5.014; P = 0.004). At 180-day survival analysis, GNB-CIED infection was associated with increased mortality risk (HR = 1.842; P = 0.067). Conclusions: Obesity, high number of comorbidities and right subclavian vein implantation site were associated with increased risk of GNB-CIED infection. A prompt therapeutic intervention that may be guided using FDG PET/CT is suggested in patients with GNB-CIED infection, considering the poorer outcome observed in this group

Irinotecan- vs. Oxaliplatin-Based Doublets in KRASG12C-Mutated Metastatic Colorectal Cancer-A Multicentre Propensity-Score-Matched Retrospective Analysis

The sensitivity to chemotherapy of KRASG12C-mutated colorectal cancer has been investigated to verify whether the combination of chemotherapy plus a KRASG12C-inhibitor might become the standard of care in the near future. To this aim, the present retrospective study was designed to assess the performance of irinotecan vs. oxaliplatin in the first-line treatment of KRASG12C-mutated mCRC patients and provide support for first-line decision making. In this setting of patients treated with FOLFIRI or FOLFOX +/ bevacizumab, irinotecan and oxaliplatin were compared using a propensity-score-matched analysis. the survival superiority of irinotecan was demonstrated over oxaliplatin in KRASG12C-mutated patients, while no differences were observed in a control cohort of KRASG12D-mutated patients. this should be considered when investigating chemotherapy plus targeted agent combinations.background: KRAS(G12C)-mutated metastatic colorectal cancer (mCRC) has recently been recognized as a distinct druggable molecular entity; however, there are limited data on its sensitivity to standard chemotherapy. In the near future, the combination of chemotherapy plus a KRAS(G12C)inhibitor might become the standard of care; however, the optimal chemotherapy backbone is unknown. methods: a multicentre retrospective analysis was conducted including KRASG12C-mutated mCRC patients treated with first-line FOLFIRI or FOLFOX +/ bevacizumab. Both unmatched and propensity-score-matched analysis (PSMA) were conducted, with PSMA controlling for: previous adjuvant chemotherapy, ECOG PS, use of bevacizumab in first line, timing of metastasis appearance, time from diagnosis to first-line start, number of metastatic sites, presence of mucinous component, gender, and age. Subgroup analyses were also performed to investigate subgroup treatment-effect interactions. KRAS(G12D)-mutated patients were analysed as control. results: one hundred and four patients treated with irinotecan-(N = 47) or oxaliplatin-based (N = 57) chemotherapy were included. In the unmatched population, objective response rate (ORR) and median (m) progression-free and overall survival (mPFS and mOS) were comparable between the treatment arms. however, a late (>12 months) PFS advantage was observed with irinotecan (HR 0.62, p = 0.02). In the PSMA-derived cohort, a significant improvement with irinotecan vs. oxaliplatin was observed for both PFS and OS: 12- and 24-month PFS rates of 55% vs. 31% and 40% vs. 0% (HR 0.40, p = 0.01) and mOS 37.9 vs. 21.7 months (HR 0.45, p = 0.045), respectively. According to the subgroup analysis, interaction effects between the presence of lung metastases and treatment groups were found in terms of PFS (p for interaction = 0.08) and OS (p for interaction = 0.03), with a higher benefit from irinotecan in patients without lung metastases. no difference between treatment groups was observed in the KRASG12D-mutated cohort (N = 153). Conclusions: First-line irinotecan-based regimens provided better survival results in KRAS(G12C)-mutated mCRC patients and should be preferred over oxaliplatin. These findings should also be considered when investigating chemotherapy plus targeted agent combinations

Effect of resveratrol on mitochondrial function: Implications in parkin-associated familiar Parkinson's disease

Mitochondrial dysfunction and oxidative stress occur in Parkinson's disease (PD), but the molecular mechanisms controlling these events are not completely understood. Peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) is a transcriptional coactivator known as master regulator of mitochondrial functions and oxidative metabolism. Recent studies, including one from our group, have highlighted altered PGC-1α activity and transcriptional deregulation of its target genes in PD pathogenesis suggesting it as a new potential therapeutic target. Resveratrol, a natural polyphenolic compound proved to improve mitochondrial activity through the activation of several metabolic sensors resulting in PGC-1α activation. Here we have tested in vitro the effect of resveratrol treatment on primary fibroblast cultures from two patients with early-onset PD linked to different Park2 mutations. We show that resveratrol regulates energy homeostasis through activation of AMP-activated protein kinase (AMPK) and sirtuin 1 (SIRT1) and raise of mRNA expression of a number of PGC-1α's target genes resulting in enhanced mitochondrial oxidative function, likely related to a decrease of oxidative stress and to an increase of mitochondrial biogenesis. The functional impact of resveratrol treatment encompassed an increase of complex I and citrate synthase activities, basal oxygen consumption, and mitochondrial ATP production and a decrease in lactate content, thus supporting a switch from glycolytic to oxidative metabolism. Moreover, resveratrol treatment caused an enhanced macro-autophagic flux through activation of an LC3-independent pathway. Our results, obtained in early-onset PD fibroblasts, suggest that resveratrol may have potential clinical application in selected cases of PD-affected patients

Prognostic and predictive role of neutrophil/lymphocytes ratio in metastatic colorectal cancer: a retrospective analysis of the TRIBE study by GONO.

Background Neutrophil/lymphocyte ratio (NLR), defined as absolute neutrophils count divided by absolute lymphocytes count, has been reported as poor prognostic factor in several neoplastic diseases but only a few data are available about unresectable metastatic colorectal cancer (mCRC) patients (pts). The aim of our study was to evaluate the prognostic and predictive role of NLR in the TRIBE trial. Patients and methods Pts enrolled in TRIBE trial were included. TRIBE is a multicentre phase III trial randomizing unresectable and previously untreated mCRC pts to receive FOLFOXIRI or FOLFIRI plus bevacizumab. A cut-off value of 3 was adopted to discriminate pts with low (NLR < 3) versus high (NLR ≥ 3) NLR, as primary analysis. As secondary analysis, NLR was treated as an ordinal variable with three levels based on terciles distribution. Results NLR at baseline was available for 413 patients. After multiple imputation at univariate analysis, patients with high NLR had significantly shorter progression-free survival (PFS) [hazard ratio (HR) 1.27 (95% CI 1.05-1.55), P = 0.017] and overall survival (OS) [HR 1.56 (95% CI 1.25-1.95), P < 0.001] than patients with low NLR. In the multivariable model, NLR retained a significant association with OS [HR 1.44 (95% CI 1.14-1.82), P = 0.014] but not with PFS [HR 1.18 (95% CI 0.95-1.46), P = 0.375]. No interaction effect between treatment arm and NLR was evident in terms of PFS (P for interaction = 0.536) or OS (P for interaction = 0.831). Patients with low [HR 0.84 (95% CI 0.64-1.08)] and high [HR 0.73 (95% CI 0.54-0.97)] NLR achieved similar PFS benefit from the triplet and consistent results were obtained in terms of OS [HR 0.83 (95% CI 0.62-1.12) for low NLR; HR 0.82 (95% CI 0.59-1.12) for high NLR]. Conclusion This study confirmed the prognostic role of NLR in mCRC pts treated with bevacizumab plus chemotherapy in the first line, showing the worse prognosis of pts with high NLR. The advantage of the triplet is independent of NLR at baseline

Prognostic significance of KRAS mutation rate in metastatic colorectal cancer patients.

No abstract availabl

Prognostic significance of K-Ras mutation rate in metastatic colorectal cancer patients

none24noIntroduction: Activating mutations of K-Ras gene have a well-established role as predictors of resistance to anti-EGFR monoclonal antibodies in metastatic colorectal cancer (mCRC) patients. Their prognostic value is controversial, and no data regarding the prognostic value of mutation rate, defined as the percentage of mutated alleles/ tumor sample, are available. We aimed to evaluate the prognostic value of K-Ras mutation rate in a homogenous cohort of mCRC patients receiving first-line doublet plus bevacizumab. Patients and Methods: This retrospective study enrolled 397 K-Ras mutant mCRC patients from 6 Italian centers, and 263 patients were fully evaluable for our analysis. K-Ras mutation rate was assessed by pyrosequencing. Patients with less than 60% of cancer cells in tumor tissue were excluded. No patients received anti-EGFR containing anticancer therapy, at any time. Median mutation rate was 40% and was adopted as cut-off. The primary and secondary endpoints were PFS and OS respectively. Results: At univariate analysis, K-Ras mutation rate higher than 40% was significantly associated with lower PFS (7.3 vs 9.1 months; P < 0.0001) and OS (21 vs 31 months; P = 0.004). A multivariate model adjusted for age at diagnosis, site of origin of tumor tissue (primary vs metastases), referral center, number of metastatic sites, and first-line chemotherapy backbone, showed that K-Ras mutation rate remained a significant predictor of PFS and OS in the whole population. Discussion: Our data demonstrate an association between K-Ras mutation rate and prognosis in mCRC patients treated with bevacizumab-containing first-line therapy. These data deserve to be verified in an independent validation set.openVincenzi B.; Cremolini C.; Sartore-Bianchi A.; Russo A.; Mannavola F.; Perrone G.; Pantano F.; Loupakis F.; Rossini D.; Ongaro E.; Bonazzina E.; Dell'Aquila E.; Imperatori M.; Zoccoli A.; Bronte G.; Maglio G.D.; Fontanini G.; Natoli C.; Falcone A.; Santini D.; Onetti-Muda A.; Siena S.; Tonini G.; Aprile G.Vincenzi, B.; Cremolini, C.; Sartore-Bianchi, A.; Russo, A.; Mannavola, F.; Perrone, G.; Pantano, F.; Loupakis, F.; Rossini, D.; Ongaro, E.; Bonazzina, E.; Dell'Aquila, E.; Imperatori, M.; Zoccoli, A.; Bronte, G.; Maglio, G. D.; Fontanini, G.; Natoli, C.; Falcone, A.; Santini, D.; Onetti-Muda, A.; Siena, S.; Tonini, G.; Aprile, G