BRAF and MLH1 Analysis Algorithm for the Evaluation of Lynch Syndrome Risk in Colorectal Carcinoma Patients: Evidence-Based Data from the Analysis of 100 Consecutive Cases

settingsOrder Article Reprints Open AccessFeature PaperArticle BRAF and MLH1 Analysis Algorithm for the Evaluation of Lynch Syndrome Risk in Colorectal Carcinoma Patients: Evidence-Based Data from the Analysis of 100 Consecutive Cases by Thais Maloberti 1,2,†ORCID,Antonio De Leo 1,2,†ORCID,Viviana Sanza 2,Lidia Merlo 2,Michela Visani 1ORCID,Giorgia Acquaviva 1,Sara Coluccelli 1,2ORCID,Annalisa Altimari 2,3,Elisa Gruppioni 2,3,Stefano Zagnoni 2,3,Daniela Turchetti 4,Sara Miccoli 4,Michelangelo Fiorentino 5,6ORCID,Antonietta D’Errico 3ORCID,Dario de Biase 7,*,‡ORCID andGiovanni Tallini 1,2,‡ORCID 1 Department of Experimental, Diagnostic and Specialty Medicine, Anatomic Pathology Unit-University of Bologna Medical Center, 40138 Bologna, Italy 2 Solid Tumor Molecular Pathology Laboratory, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy 3 Department of Pathology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy 4 Unit of Medical Genetics, IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico), Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy 5 Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40138 Bologna, Italy 6 Pathology Department, Maggiore Hospital, 40133 Bologna, Italy 7 Department of Pharmacy and Biotechnology, University of Bologna, 40126 Bologna, Italy * Author to whom correspondence should be addressed. † These authors contributed equally to this work. ‡ These authors contributed equally to this work. J. Mol. Pathol. 2022, 3(3), 115-124; https://doi.org/10.3390/jmp3030011 Received: 30 March 2022 / Revised: 27 May 2022 / Accepted: 21 June 2022 / Published: 25 June 2022 (This article belongs to the Collection Feature Papers in Journal of Molecular Pathology) Download Browse Figures Versions Notes Abstract Several causes may lead to CRC, either extrinsic (sporadic forms) or genetic (hereditary forms), such as Lynch syndrome (LS). Most sporadic deficient mismatch repair (dMMR) CRC cases are characterized by the methylation of the MLH1 promoter gene and/or BRAF gene mutations. Usually, the first test performed is the mismatch repair deficiency analysis. If a tumor shows a dMMR, BRAF mutations and then the MLH1 promoter methylation status have to be assessed, according to the ACG/ASCO screening algorithm. In this study, 100 consecutive formalin-fixed and paraffin-embedded samples of dMMR CRC were analyzed for both BRAF mutations and MLH1 promoter methylation. A total of 47 (47%) samples were BRAF p.V600E mutated, while MLH1 promoter methylation was found in 77 cases (77.0%). The pipeline “BRAF-followed-by-MLH1-analysis” led to a total of 153 tests, while the sequence “MLH1-followed-by-BRAF-analysis” resulted in a total of 123 tests. This study highlights the importance of performing MLH1 analysis in LS screening of BRAF-WT specimens before addressing patients to genetic counseling. We show that MLH1 analysis performs better as a first-line test in the screening of patients with LS risk than first-line BRAF analysis. Our data indicate that analyzing MLH1 methylation as a first-line test is more cost-effective

Multi-Gene Next-Generation Sequencing Panel for Analysis of BRCA1/BRCA2 and Homologous Recombination Repair Genes Alterations Metastatic Castration-Resistant Prostate Cancer

: Despite significant therapeutic advances, metastatic CRPC (mCRPC) remains a lethal disease. Mutations in homologous recombination repair (HRR) genes are frequent in mCRPC, and tumors harboring these mutations are known to be sensitive to PARP inhibitors. The aim of this study was to verify the technical effectiveness of this panel in the analysis of mCRPC, the frequency and type of mutations in the BRCA1/BRCA2 genes, as well as in the homologous recombination repair (HRR) genes. A total of 50 mCRPC cases were analyzed using a multi-gene next-generation sequencing panel evaluating a total of 1360 amplicons in 24 HRR genes. Of the 50 cases, 23 specimens (46.0%) had an mCRPC harboring a pathogenic variant or a variant of uncertain significance (VUS), whereas in 27 mCRPCs (54.0%), no mutations were detected (wild-type tumors). BRCA2 was the most commonly mutated gene (14.0% of samples), followed by ATM (12.0%), and BRCA1 (6.0%). In conclusion, we have set up an NGS multi-gene panel that is capable of analyzing BRCA1/BRCA2 and HRR alterations in mCRPC. Moreover, our clinical algorithm is currently being used in clinical practice for the management of patients with mCRPC

"Delirium Day": A nationwide point prevalence study of delirium in older hospitalized patients using an easy standardized diagnostic tool

Background: To date, delirium prevalence in adult acute hospital populations has been estimated generally from pooled findings of single-center studies and/or among specific patient populations. Furthermore, the number of participants in these studies has not exceeded a few hundred. To overcome these limitations, we have determined, in a multicenter study, the prevalence of delirium over a single day among a large population of patients admitted to acute and rehabilitation hospital wards in Italy. Methods: This is a point prevalence study (called "Delirium Day") including 1867 older patients (aged 65 years or more) across 108 acute and 12 rehabilitation wards in Italian hospitals. Delirium was assessed on the same day in all patients using the 4AT, a validated and briefly administered tool which does not require training. We also collected data regarding motoric subtypes of delirium, functional and nutritional status, dementia, comorbidity, medications, feeding tubes, peripheral venous and urinary catheters, and physical restraints. Results: The mean sample age was 82.0 \ub1 7.5 years (58 % female). Overall, 429 patients (22.9 %) had delirium. Hypoactive was the commonest subtype (132/344 patients, 38.5 %), followed by mixed, hyperactive, and nonmotoric delirium. The prevalence was highest in Neurology (28.5 %) and Geriatrics (24.7 %), lowest in Rehabilitation (14.0 %), and intermediate in Orthopedic (20.6 %) and Internal Medicine wards (21.4 %). In a multivariable logistic regression, age (odds ratio [OR] 1.03, 95 % confidence interval [CI] 1.01-1.05), Activities of Daily Living dependence (OR 1.19, 95 % CI 1.12-1.27), dementia (OR 3.25, 95 % CI 2.41-4.38), malnutrition (OR 2.01, 95 % CI 1.29-3.14), and use of antipsychotics (OR 2.03, 95 % CI 1.45-2.82), feeding tubes (OR 2.51, 95 % CI 1.11-5.66), peripheral venous catheters (OR 1.41, 95 % CI 1.06-1.87), urinary catheters (OR 1.73, 95 % CI 1.30-2.29), and physical restraints (OR 1.84, 95 % CI 1.40-2.40) were associated with delirium. Admission to Neurology wards was also associated with delirium (OR 2.00, 95 % CI 1.29-3.14), while admission to other settings was not. Conclusions: Delirium occurred in more than one out of five patients in acute and rehabilitation hospital wards. Prevalence was highest in Neurology and lowest in Rehabilitation divisions. The "Delirium Day" project might become a useful method to assess delirium across hospital settings and a benchmarking platform for future surveys

Marco Gaiani (a cura di), Nettuno. La fontana: studio, progetto, restauro

Il volume recensito presenta gli studi e gli interventi per il restauro della cinquecentesca fontana del Nettuno a Bologna. Tra gli aspetti innovativi dell\u2019operazione, si segnala la messa a punto del sistema informativo user friendly basato su un modello digitale tridimensionale per la gestione dell\u2019intero processo, per la sua comunicazione e quale supporto per le future azioni di manutenzione programmata

Cultura del progetto e spazi commerciali nell\u2019et\ue0 del moderno \u2013 1900/1940

Primo di due contributi volti ad indagare le interrelazioni tra progettisti e committenza commerciale, il saggio considera il tema del negozio \u201cdi lusso\u201d nei primi decenni del secolo scorso. Lo scandaglio di una casistica per altro quanto mai ampia ha tra i suoi presupposti quello di riconsiderare criticamente le opinioni fin qui espresse intorno al tema, quali, ad esempio, la ricorrente affermazione che nell\u2019 \u201cet\ue0 del moderno\u201d non vi siano state particolari manifestazioni di reciproco interesse fra cultura architettonica \u201calta\u201d e committenza di spazi commerciali, cos\uec come di analizzare analogie e differenze nel ruolo svolto dallo \u201cspettacolo delle merci\u201d nell\u2019et\ue0 industriale e in quella post-industriale. In questo senso, il saggio riprende alcuni esempi riferiti al periodo 1900-1940 nei quali progettisti fra loro anche molto distanti per concezione e sensibilit\ue0 hanno fornito risposte innovative e congruenti al tema

Adalberto Libera, l'architettura come ideale

Recensendo un volume di Vieri Quilici, il testo sviluppa alcune riflessioni sull’esponente del razionalismo in bilico fra “ordine” ed “eresia”, sul suo approccio alla composizione architettonica e sulle modalità attraverso le quali riversa nella didattica il proprio metodo progettuale

Monumenti commemorativi ai caduti della \u2018Grande guerra\u2019 in Italia / Trasposizioni mitografiche e costruzione dell\u2019immaginario

Il saggio introduttivo al volume che presenta gli esiti di una ricerca finanziata dalla Presidenza del Consiglio dei Ministri propone una ricognizione sulle opere commemorative dei caduti della prima guerra mondale in Italia (monumenti, parchi delle rimembranze, \u201copere utili\u201d) riguardandole da pi\uf9 punti di vista: la disseminazione di opere, sia pure spesso di scarsa qualit\ue0 artistica, in tutto il paese come parte importante per la formazione di un\u2019identit\ue0 nazionale e l\u2019istituzione di una liturgia nazionale attorno al mito della \u201cgrande guerra\u201d; l\u2019appropriazione del culto dei caduti da parte del fascismo, che della guerra attua una vera e propria esaltazione etica, ma che negli anni 1920 non si traduce nella proposizione di nuove forme plastiche e architettoniche o di un programma estetico unitario; i cambiamenti di prospettiva che la trasfigurazione retorica della guerra operata dal regime produce negli anni 1930. La trattazione si sofferma poi su alcuni degli esempi che non si limitano ad \u201carredare\u201d lo spazio pubblico, ma vi si inseriscono quali elementi strutturanti

International Style e Razionalismo in Emilia Romagna: 1920-1940

Il numero doppio monografico della rivista costituisce uno sviluppo e una rielaborazione della tesi di laurea dell'autore, cui vanno ascritti tutti i testi ad eccezione di alcune schede biografiche dei protagonisti siglate Gi. Gr. e A.M.