Plasma Inflammatory Cytokines Are Elevated in ALS

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease which leads to death in a median time of 2–3 years. Inflammation has been claimed important to the ALS pathogenesis, but its role is still not well-characterized. In the present study, a panel of five cytokines (IL-2, IL-6, IL-10, IFN-gamma, and TNF-alpha)measured in plasma has been investigated in ALS. These biomarkers of inflammation were measured in a population-based cohort of 79 patients with ALS and 79 age- and sex-matched healthy controls using the Bio-Plex technology (Bio-Rad). All the five cytokines were significantly increased in plasma samples of patients compared with controls (p < 0.0001), with IL-6 having the highest median concentration (10.11 pg/ml) in the ALS group. Furthermore, IL-6 was the plasma cytokine with the highest discrimination ability between patients and controls according to the receiver operating characteristic analysis (area under the curve = 0.93). At a cut-off point of 5.71 pg/ml, it was able to classify patients and controls with 91% of sensitivity and 87% of specificity. In the ALS group, plasma IL-6 concentration correlated with demographic (age: rs = 0.25, p = 0.025) and clinical (revised ALS Functional Rating Scale at evaluation: rs = −0.32, p = 0.007; Manual Muscle Testing: rs =−0.33, p=0.004; progression: rs=0.29, p=0.0395) parameters. In line with previous studies, our results confirm that inflammatory cytokines are elevated in ALS, supporting a possible role of inflammation in disease mechanism and progression. However, the precise role of inflammation in ALS needs to be further investigated on larger samples and with more mechanistic studies

Telemedicine for Delivery of Care in Frontotemporal Lobar Degeneration during COVID-19 Pandemic: Results from Southern Italy

Background: The COVID-19 pandemic is changing clinical practice in neurology, after the governments decided the introduction of social distancing and interruption of medical non-emergency services in many countries. Teleneurology is an effective tool for the remote evaluation of patients but its adoption for frontotemporal lobar dementia (FTD) is in a preliminary stage. Objective: We evaluated multidisciplinary assessment of patients with FTD using telehealth during the COVID-19 pandemic. Methods: All patients received a diagnosis of FTD during 2018-2019 according to international criteria. A structured questionnaire and Clinical Dementia Rating Scale (CDR)-FTD were used by the neurologist with patients and/or caregivers. Index symptoms of COVID-19 infection were searched. Results: Twenty-eight clinical interviews were completed with caregivers and four with both patients/caregivers. Most patients and caregivers were satisfied with the neurological interview and expressed their willingness to continue to be included in remote evaluation programs (90%). Fifty percent of patients experienced significant worsening of clinical picture and quality of life since the start of social distancing. The CDR-FTD scale revealed a significant worsening of behavior (p = 0.01) and language functions (p = 0.009), compared to the last in-person evaluation at the center. One patient presented index symptoms of COVID-19 infection and was confirmed to be positive for COVID-19 with pharyngeal swab. Conclusion: The study was conducted in Italy, one of the countries hit particularly hard by the COVID-19 pandemic, with interruption of all non-emergency medical services. Our study indicates that telemedicine is a valid tool to triage patients with FTD to increase practice outreach and efficiency

Incidence of Syndromes Associated With Frontotemporal Lobar Degeneration in 9 European Countries

Importance Diagnostic incidence data for syndromes associated with frontotemporal lobar degeneration (FTLD) in multinational studies are urgent in light of upcoming therapeutic approaches.Objective To assess the incidence of FTLD across Europe.Design, Setting, and Participants The Frontotemporal Dementia Incidence European Research Study (FRONTIERS) was a retrospective cohort study conducted from June 1, 2018, to May 31, 2019, using a population-based registry from 13 tertiary FTLD research clinics from the UK, the Netherlands, Finland, Sweden, Spain, Bulgaria, Serbia, Germany, and Italy and including all new FTLD-associated cases during the study period, with a combined catchment population of 11 023 643 person-years. Included patients fulfilled criteria for the behavioral variant of frontotemporal dementia (BVFTD), the nonfluent variant or semantic variant of primary progressive aphasia (PPA), unspecified PPA, progressive supranuclear palsy, corticobasal syndrome, or frontotemporal dementia with amyotrophic lateral sclerosis (FTD-ALS). Data were analyzed from July 19 to December 7, 2021.Main Outcomes and Measures Random-intercept Poisson models were used to obtain estimates of the European FTLD incidence rate accounting for geographic heterogeneity.Results Based on 267 identified cases (mean [SD] patient age, 66.70 [9.02] years; 156 males [58.43%]), the estimated annual incidence rate for FTLD in Europe was 2.36 cases per 100 000 person-years (95% CI, 1.59-3.51 cases per 100 000 person-years). There was a progressive increase in FTLD incidence across age, reaching its peak at the age of 71 years, with 13.09 cases per 100 000 person-years (95% CI, 8.46-18.93 cases per 100 000 person-years) among men and 7.88 cases per 100 000 person-years (95% CI, 5.39-11.60 cases per 100 000 person-years) among women. Overall, the incidence was higher among men (2.84 cases per 100 000 person-years; 95% CI, 1.88-4.27 cases per 100 000 person-years) than among women (1.91 cases per 100 000 person-years; 95% CI, 1.26-2.91 cases per 100 000 person-years). BVFTD was the most common phenotype (107 cases [40.07%]), followed by PPA (76 [28.46%]) and extrapyramidal phenotypes (69 [25.84%]). FTD-ALS was the rarest phenotype (15 cases [5.62%]). A total of 95 patients with FTLD (35.58%) had a family history of dementia. The estimated number of new FTLD cases per year in Europe was 12 057.Conclusions and Relevance The findings suggest that FTLD-associated syndromes are more common than previously recognized, and diagnosis should be considered at any age. Improved knowledge of FTLD incidence may contribute to appropriate health and social care planning and in the design of future clinical trials.Peer reviewe

Inflammatory response in serrated precursor lesions of the colon classified according to WHO entities, clinical parameters and phenotype-genotype correlation.

Studies on traditional serrated adenoma (TSA) and sessile serrated adenoma with dysplasia (SSA-D) are rare due to the low frequency of these lesions, which are well defined by the latest WHO classification. However, introducing new morphological criteria such as intra-epithelial lymphocytes (IELs) might facilitate colorectal polyp diagnoses. Additionally, the phenotype-genotype correlation needs to be updated as the terminology has repeatedly changed. This study analysed 516 polyps, consisting of 118 classical adenomas (CAD), 116 hyperplastic polyps (HPP), 179 SSAs, 41 SSA-Ds, and 62 TSAs. The lesions were analysed in relation to the patients' clinical parameters including gender, age, localisation, and size. The inflammatory background of the polyps was quantified and BRAF and KRAS mutations as well as MLH1 and CDKN2A promoter methylation were assessed. In multivariate analyses, an increase in IELs was an independent and robust new criterion for the diagnosis of SSA-D (p < 0.001). Superficial erosions and acute neutrophil granulocytes led to reactive changes potentially resembling dysplasia. KRAS and BRAF mutations were associated with CAD/TSA and HPP/SSA, respectively. However, almost half of TSAs had a BRAF mutation and were KRAS wild type. CDKN2A seems to precede MLH1 hyper-methylation within the serrated carcinogenesis model. The genotyping of WHO-based entities - and especially SSA - has sharpened in comparison to previously published data. TSAs can be sub-grouped according to their mutation status. Of note, the higher number of IELs in SSA-D reflects their close relationship to colorectal cancers with micro-satellite instability. Therefore, IELs might represent a new diagnostic tool for SSA-D

This Sounds Like That

Le reti neurali sono ormai utilizzate in qualsiasi ambito e in differenti modi, con l’obiettivo di semplificare compiti di classificazione e di completare steps che possano facilitare i professionisti di vari settori. Quello che però molto spesso non va incontro all’utente è la mancata spiegazione della classificazione, dovuta in primis alla non linearità dei modelli adottati. Per questo motivo la maggior parte delle reti neurali viene trattata come “black box”. Se nel passato l’obiettivo era più mirato ad ottenere prestazioni elevate basandosi sulle metriche restituite dai vari classificatori, oggi si cerca di andare oltre e costruire sistemi quanto più user-friendly possibile, quindi interpretabili. Relativamente alla spiegazione, quando ci troviamo di fronte a compiti di classificazione di immagini, spesso illustriamo il nostro ragionamento sezionando l’immagine e sottolineando gli aspetti prototipici di una classe o dell’altra. Le prove raccolte per ciascuna di queste ci aiutano a prendere la nostra decisione finale. In questo lavoro, viene studiata un’architettura di deep learning – ProtoPNet – che ragiona in modo simile: la rete seziona l’immagine trovando le parti prototipiche e combina le prove dei prototipi per effettuare la classificazione finale. Il modello ragiona quindi in modo qualitativa- mente simile al modo in cui gli esperti spiegano come risolvere compiti di classificazione del suono. Il lavoro di tesi è però incentrato sulla “Sound-Recognition”, ovvero la capacità delle reti di simulare il procedimento umano di elaborazione dei dati partendo da una registrazione di suoni e trasformandoli in informazioni utili. L’obiettivo è quello di adattare l’architettura ProtoPNet al caso di segnali audio. In questo caso, gli audio vengono trasformati in spettrogrammi con il fine di ricercare prototipi “sonori” all’interno dell’audio, i quali caratterizzano le classi. La classificazione sarà quindi incentrata sì sui risultati delle solite metriche utilizzate, ma soprattutto sull’interpretabilità dei risultati. Abbiamo dimostrato l’efficacia del metodo sviluppato su datasets differenti in lunghezza e complessità del segnale

Laparoscopic treatment of sigmoid colon intussusception by large malignant tumor. Case report

L’intussuscezione intestinale è un’evenienza rara negli adulti, più comune in età pediatrica. Le sedi ileale e ileo-ciecale sono più frequenti rispetto alla sede colica. Riportiamo il caso di un paziente affetto da intussuscezione da carcinoma del sigma. La TC addominale pre-operatoria dimostrava la presenza di intussuscezione colo-colica a livello della lesione tumorale con dilatazione del colon a monte. Il paziente è stato sottoposto in urgenza a emicolectomia sinistra laparoscopica. Si è proceduto a estrazione del pezzo operatorio tramite incisione di Pfannenstiel di 10 cm. Il trattamento laparoscopico è risultato sicuro poiché la dilatazione a monte era di grado moderato. Nel caso di intussuscezione colica da carcinoma l’approccio laparoscopico può essere condotto in sicurezza secondo criteri oncologici se è stata posta preoperatoriamente una corretta diagnosi