MMR vaccine in the postpartum does not expose seronegative women to untoward effects.

Contesto : Lo scopo di questo studio è stato quello di valutare se la vaccinazione rosolia immediatamente dopo il parto potrebbe esporre le donne sieronegative per effetti indesiderati specifici.Metodi : 163 donne rosolia-sieronegativi hanno ricevuto il vaccino MMR nel periodo post-partum; sono stati valutati a 1 mese a 3 mesi successivi attraverso interviste telefoniche. Come controlli, abbiamo confrontato 163 donne rosolia-sieropositivi, che potrebbe avere sintomi simili per qualsiasi motivo, nello stesso arco di tempo.Risultati : A un mese di follow-up, 161 donne nel gruppo dei casi e 162 controlli hanno risposto alla nostra intervista telefonica; alle tre mesi di follow-up, 154 casi e 159 controlli. Eruzione cutanea, faringite, artralgia, linfoadenopatia cervicale, mialgia e parestesia sono state le lamentele più frequentemente riportati in entrambi i gruppi. Una differenza statisticamente significativa nella frequenza di linfoadenopatia cervicale e rash cutaneo a un mese (p = 0.028 ep = 0.005, rispettivamente) è stata osservata tra i casi ei controlli; Tuttavia, nessuna differenza significativa è stata ancora osservata nella frequenza delle manifestazioni muscoloscheletriche acute e croniche a tre mesi.Conclusioni : Non sono sostanziali differenze sono stati segnalati tra casi e controlli per quanto riguarda la frequenza di artralgia e conseguente mialgia al MMR vaccinazione in post-partum . Postpartum rosolia la vaccinazione è sicura e consigliabile in caso di necessità per evitare la circolazione del virus e la sindrome da rosolia congenita

High prevalence of short telomeres in idiopathic porto-sinusoidal vascular disorder.

BACKGROUND Telomeres prevent damage to coding DNA as end-nucleotides are lost during mitosis. Mutations in telomere maintenance genes cause excessive telomere shortening, a condition known as short telomere syndrome (STS). One hepatic manifestation documented in STS is porto-sinusoidal vascular disorder (PSVD). METHODS As the etiology of many cases of PSVD remains unknown, this study explored the extent to which short telomeres are present in patients with idiopathic PSVD. RESULTS This monocentric cross-sectional study included patients with histologically defined idiopathic PSVD. Telomere length in 6 peripheral blood leukocyte subpopulations was assessed using fluorescent in situ hybridization and flow cytometry. Variants of telomere-related genes were identified using high-throughput exome sequencing. In total, 22 patients were included, of whom 16 (73%) had short (9/22) or very short (7/22) telomeres according to age-adjusted reference ranges. Fourteen patients (64%) had clinically significant portal hypertension. Shorter telomeres were more frequent in males (p = 0.005) and patients with concomitant interstitial lung disease (p < 0.001), chronic kidney disease (p < 0.001), and erythrocyte macrocytosis (p = 0.007). Portal hypertension (p = 0.021), low serum albumin level (p < 0.001), low platelet count (p = 0.007), and hyperbilirubinemia (p = 0.053) were also associated with shorter telomeres. Variants in known STS-related genes were identified in 4 patients with VSTel and 1 with STel. CONCLUSIONS Short and very short telomeres were highly prevalent in patients with idiopathic PSVD, with 31% presenting with variants in telomere-related genes. Telomere biology may play an important role in vascular liver disease development. Clinicians should consider measuring telomeres in any patient presenting with PSVD

Targeting lysine-specific demethylase 1 (KDM1A/LSD1) impairs colorectal cancer tumorigenesis by affecting cancer cells stemness, motility, and differentiation

: Among all cancers, colorectal cancer (CRC) is the 3rd most common and the 2nd leading cause of death worldwide. New therapeutic strategies are required to target cancer stem cells (CSCs), a subset of tumor cells highly resistant to present-day therapy and responsible for tumor relapse. CSCs display dynamic genetic and epigenetic alterations that allow quick adaptations to perturbations. Lysine-specific histone demethylase 1A (KDM1A also known as LSD1), a FAD-dependent H3K4me1/2 and H3K9me1/2 demethylase, was found to be upregulated in several tumors and associated with a poor prognosis due to its ability to maintain CSCs staminal features. Here, we explored the potential role of KDM1A targeting in CRC by characterizing the effect of KDM1A silencing in differentiated and CRC stem cells (CRC-SCs). In CRC samples, KDM1A overexpression was associated with a worse prognosis, confirming its role as an independent negative prognostic factor of CRC. Consistently, biological assays such as methylcellulose colony formation, invasion, and migration assays demonstrated a significantly decreased self-renewal potential, as well as migration and invasion potential upon KDM1A silencing. Our untargeted multi-omics approach (transcriptomic and proteomic) revealed the association of KDM1A silencing with CRC-SCs cytoskeletal and metabolism remodeling towards a differentiated phenotype, supporting the role of KDM1A in CRC cells stemness maintenance. Also, KDM1A silencing resulted in up-regulation of miR-506-3p, previously reported to play a tumor-suppressive role in CRC. Lastly, loss of KDM1A markedly reduced 53BP1 DNA repair foci, implying the involvement of KDM1A in the DNA damage response. Overall, our results indicate that KDM1A impacts CRC progression in several non-overlapping ways, and therefore it represents a promising epigenetic target to prevent tumor relapse

Association of kidney disease measures with risk of renal function worsening in patients with type 1 diabetes

Background: Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage 653 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage 653 CKD in a large cohort of patients affected by T1DM. Methods: A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage 653 CKD (eGFR &lt; 60 mL/min/1.73 m2) or eGFR reduction &gt; 30% from baseline was evaluated. Results: The mean estimated GFR was 98 \ub1 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR &lt; 90 ml/min/m2 were independent risk factors for stage 653 CKD and renal function worsening. When compared to patients with eGFR &gt; 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions: Albuminuria and eGFR reduction represent independent risk factors for incident stage 653 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening

Rôle of Prox-1 in the pathogenesis of medullary thyroid carcinoma: a histopathological and immunohistochemical study

CONTEXTE : Il a été démontré que le carcinome médullaire de la thyroïde exprime la protéine « Prospéra homeobox protein 1 » (Proxl), un facteur de transcription dont l'expression est altérée dans divers cancers humains. OBJECTIF : Tester la corrélation de l'expression de Proxl dans le carcinome médullaire de la thyroïde avec les caractéristiques clinicopathologiques et évaluer son éventuelle valeur pronostique. MATERIELS ET METHODES : Il s'agit d'une étude rétrospective menée sur une série de 32 patients atteints de carcinome médullaire de la thyroïde. La corrélation de l'expression immunohistochimique de Proxl avec la taille de la tumeur, l'indice de prolifération (Ki67), les taux sériques de calcitonine et de CEA avant la chirurgie a été évaluée pour rechercher des corrélations significatives. La différence d'expression immunohistochimique de Proxl et de Ki67 en fonction de l'intensité de la coloration immunohistochimique du CEA, de la chromogranine A et de la calcitonine a été testée en utilisant un test H de Kruskal-Wallis et une analyse de régression linéaire. La valeur pronostique de Proxl et Ki67 pour notre cohorte de patients a été évaluée par une analyse de survie de Kaplan-Meier. CONCLUSION : L'expression de Proxl dans le carcinome médullaire de la thyroïde est positivement corrélée à l'indice Ki67 de prolifération et à l'expression immunohistochimique de la chromogranine A et de la calcitonine. Cependant, la présente étude n'a pas montré de valeur pronostique de Proxl dans le carcinome médullaire de la thyroïde

Very low expression of PD-L1 in medullary thyroid carcinoma

Monoclonal antibodies that inhibit the interaction between PD1 and PD-L1 are approved for clinical use in several cancer types, and they are also in clinical trials for additional indications, including thyroid carcinomas. A few papers have reported on PD-L1 expression in thyroid carcinomas, including a recent large study by Ahn et al. in Endocrine-Related Cancer using tissue microarrays on differentiated and anaplastic thyroid carcinoma. However, the expression of PD-L1 in medullary thyroid carcinoma (MTC) has not been reported so far, even though ongoing clinical studies aim to test the effectiveness of checkpoint inhibitors in this rare histotype as well. We thus assessed PD-L1 expression in both tumor cells and tumor-infiltrating immune cells in a series of 16 MTC cases at a tertiary center. Tumor cells were positive in only one case, which had 5% positive cells. 1% and 2% of the inflammatory cells were stained in two cases. No correlation was evident between PD-L1 expression and survival in our series. Our results are indicative of near uniform absence of PD-L1 expression in MTC and its accompanying inflammatory cells; these results should be replicated on a larger scale in other centers. Definitive answers regarding the utility of PD1/PD-L1 immunophenotyping in MTC and of the use of checkpoint inhibitors in the treatment of this aggressive and rare thyroid cancer are expected from ongoing clinical trials, which should perform correlations with PD1/PD-L1 expression

Choroid Plexus Carcinoma in Adults: Literature Review and First Report of a Location into the Third Ventricle

Choroid plexus carcinoma (CPC) is a rare intraventricular neoplasm originating from choroid plexus. CPC is the most aggressive choroid plexus tumor. Almost all the CPCs are detected in children, and the preferred location is the lateral ventricle. We reviewed the literature to evaluate the state of the art concerning the management of CPC in adults and report the first case described of the extremely rare localization into the third ventricle. A 38-year-old woman presented a medical history of Parinaud syndrome and occasional facial weakness. Brain magnetic resonance imaging revealed a mass lesion in the pineal region and posterior part of the third ventricle with obstructive hydrocephalus. She underwent subtotal resection through a supracerebellar infratentorial approach. After the histopathological diagnosis of CPC, the patient underwent a second surgery with gross total resection and adjuvant radiotherapy. CPC in adults, given its extreme rarity, does not have a standardized treatment. Gross total resection should be the first step of the treatment: however, according to the literature, gross total resection is achieved only in 40-75% of cases in CPC as opposed to 95% in choroid plexus papilloma, mainly due to the difficulty in managing a highly vascularized tumor in such a deep location. Chemotherapy has not an established role and adjuvant treatment is based on radiotherapy. In the case described hereby the gross total resection associated with surgical treatment of hydrocephalus and adjuvant radiotherapy has achieved a good clinical and radiological outcome

Metamorfosi dei Lumi 6

Come muore la gloriosa “Repubblica delle Lettere” del Settecento? In che modo, al confine tra Sette e Ottocento, la comunità dei gens de lettres cede il passo alla frammentazione del sapere e della curiosità intellettuale, alle diverse modalità di scrittura che annunziano l’età moderna? A questa ricerca è dedicato il sesto volume pubblicato dal Centro Studi Interdisciplinare Metamorfosi dei Lumi dell’Università di Torino, che raccoglie il frutto della riflessione collettiva svoltasi nell’ambito del centro durante gli anni accademici 2009 e 2010. Prendendo le mosse dagli sviluppi della filosofia nel corso del Settecento, si focalizza l’attenzione su due aspetti dell’evoluzione culturale del periodo di transizione tra illuminismo e modernità: il rapporto della scienza medica con la letteratura, e il sorgere di una nuova identità dei letterati