Late-onset of immunodysregulation, polyendocrinopathy, enteropathy, x-linked syndrome (IPEX) with intractable diarrhea

The syndrome of immune dysregulation, polyendocrinopathy, enteropathy, X linked (IPEX) is a rare disorder caused by mutations in the FOXP3 gene. Diarrhea, diabetes and dermatitis are the hallmark of the disease, with a typical onset within the first months of life. We describe the case of a twelve-year old male affected by a very late-onset IPEX with intractable enteropathy, which markedly improved after starting Sirolimus as second-line treatment. This case suggests that IPEX should always be considered in the differential diagnosis of watery intractable diarrhea, despite its unusual onset

Prevalence of hypospadias in Italy according to severity, gestational age and birthweight: an epidemiological study

<p>Abstract</p> <p>Background</p> <p>Hypospadias is a congenital displacement of the urethral meatus in male newborns, being either an isolated defect at birth or a sign of sexual development disorders. The aim of this study was to assess the prevalence rate of hypospadias in different Districts of Italy, in order to make a comparison with other countries all over the world.</p> <p>Methods</p> <p>We reviewed all the newborns file records (years 2001–2004) in 15 Italian Hospitals.</p> <p>Results</p> <p>We found an overall hypospadias prevalence rate of 3.066 ± 0.99 per 1000 live births (82.48% mild hypospadias, 17.52% moderate-severe). In newborns Small for Gestational Age (birthweight < 10^thpercentile) of any gestational age the prevalence rate of hypospadias was 6.25 per 1000 live births. Performing multivariate logistic regression analysis for different degrees of hypospadias according to severity, being born SGA remained the only risk factor for moderate-severe hypospadias (p = 0.00898) but not for mild forms (p > 0.1).</p> <p>Conclusion</p> <p>In our sample the prevalence of hypospadias results as high as reported in previous European and American studies (3–4 per 1000 live births). Pathogenesis of isolated hypospadias is multifactorial (genetic, endocrine and environmental factors): however, the prevalence rate of hypospadias is higher in infants born small for gestational age than in newborns with normal birth weight.</p

Increase of Parkin and ATG5 plasmatic levels following perinatal hypoxic‐ischemic encephalopathy

Brain injury at birth is an important cause of neurological and behavioral disorders. Hypoxic‐ischemic encephalopathy (HIE) is a critical cerebral event occurring acutely or chronically at birth with high mortality and morbidity in newborns. Therapeutic strategies for the prevention of brain damage are still unknown, and the only medical intervention for newborns with moderate‐to‐severe HIE is therapeutic hypothermia (TH). Although the neurological outcome depends on the severity of the initial insult, emerging evidence suggests that infants with mild HIE who are not treated with TH have an increased risk for neurodevelopmental impairment; in the current clinical setting, there are no specific or validated biomarkers that can be used to both correlate the severity of the hypoxic insult at birth and monitor the trend in the insult over time. The aim of this work was to examine the presence of autophagic and mitophagic proteins in bodily fluids, to increase knowledge of what, early at birth, can inform therapeutic strategies in the first hours of life. This is a prospective multicentric study carried out from April 2019 to April 2020 in eight third‐level neonatal intensive care units. All participants have been subjected to the plasma levels quantification of both Parkin (a protein involved in mitophagy) and ATG5 (involved in autophagy). These findings show that Parkin and ATG5 levels are related to hypoxic‐ischemic insult and are reliable also at birth. These observations suggest a great potential diagnostic value for Parkin evaluation in the first 6 h of life

Listening comprehension in profoundly deaf children with cochlear implants: the role of auditory perception and foundational linguistic and cognitive skills

Purpose: The aim of the study was to investigate the listening comprehension (LC) skills in deaf and hard of hearing children (DHH) using cochlear implants (CI). Besides, personal and audiological variables that could influence the levels of competence reached were analyzed. Methods: Thirty-four children using CI were enrolled. LC skills were assessed through the standardized Italian test "Comprensione Orale-Test e Trattamento" (CO-TT). A univariate analysis was conducted to compare LC with gender, listening mode (unilateral or bilateral), maternal level of education and family income. A bivariate analysis was performed to search possible connections between children's performances and their individual characteristics, audiological conditions, and language levels. Finally, a multivariate analysis was performed using a stepwise hierarchical linear regression model which included all variables whose p value resulted ≤ 0.05. Results: Twenty-one children using CI (61.8%) showed adequate performances in terms of chronological age, while 13 (38.2%) showed difficulties in LC. Maternal level of education, age at diagnosis and non-verbal cognitive level accounted for 43% of the observed variance. Auditory attention skills explained an additional 15% of variance. Morphosyntactic comprehension added a further 12% of variance. Conclusion: CI can really help many DHH children to reach adequate LC skills, but in some cases difficulties remain. Factors influencing LC need to be early investigated and considered when planning an appropriate rehabilitative intervention

Neoadjuvant radiotherapy dose escalation for locally advanced rectal cancers in the new era of radiotherapy: A review of literature

BACKGROUND The standard treatment of locally advanced rectal cancers (LARC) consists on neoadjuvant chemoradiotherapy followed by total mesorectal excision. Different data in literature showed a benefit on tumor downstaging and pathological complete response (pCR) rate using radiotherapy dose escalation, however there is shortage of studies regarding dose escalation using the innovative techniques for LARC (T3-4 or N1-2). AIM To analyze the role of neoadjuvant radiotherapy dose escalation for LARC using innovative radiotherapy techniques. METHODS In December 2020, we conducted a comprehensive literature search of the following electronic databases: PubMed, Web of Science, Scopus and Cochrane library. The limit period of research included articles published from January 2009 to December 2020. Screening by title and abstract was carried out to identify only studies using radiation doses equivalent dose 2 Gy fraction (EQD2) ≥ 54 Gy and Volumetric Modulated Arc Therapy (VMAT), intensity-modulated radiotherapy or image-guided radiotherapy (IGRT) techniques. The authors’ searches generated a total of 2287 results and, according to PRISMA Group (2009) screening process, 21 publications fulfil selection criteria and were included for the review. RESULTS The main radiotherapy technique used consisted in VMAT and IGRT modality. The mainly dose prescription was 55 Gy to high risk volume and 45 Gy as prophylactic volume in 25 fractions given with simultaneous integrated boosts technique (42.85%). The mean pCR was 28.2% with no correlation between dose prescribed and response rates (P value ≥ 0.5). The R0 margins and sphincter preservation rates were 98.88% and 76.03%, respectively. After a mean follow-up of 35 months local control was 92.29%. G3 or higher toxicity was 11.06% with no correlation between dose prescription and toxicities. Patients receiving EQD2 dose &gt; 58.9 Gy and BED &gt; 70.7 Gy had higher surgical complications rates compared to other group (P value = 0.047). CONCLUSION Dose escalation neoadjuvant radiotherapy using innovative techniques is safe for LARC achieving higher rates of pCR. EQD2 doses &gt; 58.9 Gy is associated with higher rate of surgical complications

Padiglione Piacenza. Expo Milano 2015 - EartHand Project

Expo Milano 2015 ‘eartHand Project’ Il progetto del Padiglione ‘eartHand’, costruito all’interno del grande spazio EXPO 2015, nasce dalla collaborazione tra il Politecnico di Milano Campus Piacenza (Coordinamento del progetto: Guya Bertelli; crediti a pag. 207 del volume), l’Ordine degli Architetti di Piacenza (Coordinamento: Beppe Baracchi) e la Società Piacenza EXPO, con l’obiettivo di rappresentare la città di Piacenza all’interno dell’evento: ‘Nutrire il Pianeta’. La volontà del progetto, risultato vincitore di un Concorso interno che ha visto la partecipazione di Quattro Gruppi di Architetti e collaboratori, è stata quella di mettere in evidenza l’identità del territorio nelle diverse specificità: dal patrimonio storico-culturale e paesaggistico alle eccellenze eno-gastronomiche, dalle grandi innovazioni della scienza e della tecnica alle persone che hanno portato questo territorio a essere, già storicamente, un crocevia importante di storia, cultura e popoli. Di qui la ragione della proposta, che identifica in una ‘Zolla di terra sospesa l’elemento principale capace di riassumere tutti i significati, nelle sue diverse accezioni: produzione di materia prima, trasformazione a cura dell’uomo, ricchezza proveniente dai vari processi, sedimentazione e stratificazione storica. Il titolo stesso dichiara la volontà di legare indissolubilmente due elementi: earth, la terra, l’elemento materico primigenio e generatore; hand, la mano, simbolo dell’uomo e della sua energia in grado di plasmarla. EartHand si presenta così come la grande metafora piacentina: una zolla di terra estratta dal suolo, sollevata nell’aria e trasformata in icona da trasportare nel contesto di Expo Milano 2015. Il rivestimento interno del caleidoscopio contenuto nella zolla, è stato pensato da una tecnologia avanzata in pannellature lisce, luminose e interattive. Il padiglione è stato costruito all’incrocio tra ‘cardo e decumano’ dell’impianto EXPO, definendo la così detta ‘piazzetta Piacenza’, luogo di incontro e presentazione di iniziative internazionali durante tutto il periodo dell’evento.Expo Milano 2015: 'EartHand Project' The eartHand Pavillon project originates from the collaboration between the Milan Polytechnic Campus Piacenza (Coordination of the project: Guya Bertelli; credits at pag. 2017 of the Volume), the Order of Architects of Piacenza (Coordination: Beppe Baracchi) and the Piacenza EXPO Society, with the aim of representing the city of Piacenza in the EXPO 2015 event: 'Feeding the Planet'. The will was to highlight the identity of the territory in the different specificities: from the historical-cultural heritage to the eno-gastronomic excellences, from the great innovations of science and technology to the people who brought this territory to be, already historically, an important crossroads of history, culture and peoples. Hence the reason for the project, which identifies in a 'Zolla di terra sospesa the main element able to summarize all the meanings, in its different meanings: production of raw material, transformation by man, wealth coming from the various processes, sedimentation and historical stratification. The title itself declares the desire to indissolubly link two elements: earth, the earth, the primitive and generating material element; hand, the hand, symbol of man and his energy capable of shaping it. EartHand infact presents itself as the great Piacenza metaphor: a clod of earth extracted from the ground, raised in the air and transformed into an icon to be transported in the context of Expo Milano 2015. The internal coating of the kaleidoscope contained in the plate was conceived by an advanced technology in smooth, bright and interactive panels. The Pavillon was built inside the crossroad formed by ‘Cardus and Decumanus’ of the EXPO site, creating the new ‘Piacenza little square’, a place for meetings and other international initiatives

Comparison of three validated PD-L1 immunohistochemical assays in urothelial carcinoma of the bladder: interchangeability and issues related to patient selection

Different programmed cell death-ligand 1 (PD-L1) assays and scoring algorithms are being used in the evaluation of PD-L1 expression for the selection of patients for immunotherapy in specific settings of advanced urothelial carcinoma (UC). In this paper, we sought to investigate three approved assays (Ventana SP142 and SP263, and Dako 22C3) in UC with emphasis on implications for patient selection for atezolizumab/pembrolizumab as the first line of treatment. Tumors from 124 patients with invasive UC of the bladder were analyzed using tissue microarrays (TMA). Serial sections were stained with SP263 and SP142 on Ventana Benchmark Ultra and with 22C3 on Dako Autostainer Link 48. Stains were evaluated independently by two observers and scored using the combined positive score (CPS) and tumor infiltrating immune cells (IC) algorithms. Differences in proportions (DP), overall percent agreement (OPA), positive percent agreement (PPA), negative percent agreement (NPA), and Cohen kappa were calculated for all comparable cases. Good overall concordance in analytic performance was observed for 22C3 and SP263 with both scoring algorithms; specifically, the highest OPA was observed between 22C3 and SP263 (89.6%) when using CPS. On the other hand, SP142 consistently showed lower positivity rates with high differences in proportions (DP) compared with 22C3 and SP263 with both CPS and IC, and with a low PPA, especially when using the CPS algorithm. In conclusion, 22C3 and SP263 assays show comparable analytical performance while SP142 shows divergent staining results, with important implications for the selection of patients for both pembrolizumab and atezolizumab

Reduced mortality in COVID-19 patients treated with colchicine: Results from a retrospective, observational study.

ObjectivesEffective treatments for coronavirus disease 2019 (COVID-19) are urgently needed. We hypothesized that colchicine, by counteracting proinflammatory pathways implicated in the uncontrolled inflammatory response of COVID-19 patients, reduces pulmonary complications, and improves survival.MethodsThis retrospective study included 71 consecutive COVID-19 patients (hospitalized with pneumonia on CT scan or outpatients) who received colchicine and compared with 70 control patients who did not receive colchicine in two serial time periods at the same institution. We used inverse probability of treatment propensity-score weighting to examine differences in mortality, clinical improvement (using a 7-point ordinary scale), and inflammatory markers between the two groups.ResultsAmongst the 141 COVID-19 patients (118 [83.7%] hospitalized), 70 (50%) received colchicine. The 21-day crude cumulative mortality was 7.5% in the colchicine group and 28.5% in the control group (P = 0.006; adjusted hazard ratio: 0.24 [95%CI: 0.09 to 0.67]); 21-day clinical improvement occurred in 40.0% of the patients on colchicine and in 26.6% of control patients (adjusted relative improvement rate: 1.80 [95%CI: 1.00 to 3.22]). The strong association between the use of colchicine and reduced mortality was further supported by the diverging linear trends of percent daily change in lymphocyte count (P = 0.018), neutrophil-to-lymphocyte ratio (P = 0.003), and in C-reactive protein levels (P = 0.009). Colchicine was stopped because of transient side effects (diarrhea or skin rashes) in 7% of patients.ConclusionIn this retrospective cohort study colchicine was associated with reduced mortality and accelerated recovery in COVID-19 patients. This support the rationale for current larger randomized controlled trials testing the safety/efficacy profile of colchicine in COVID-19 patients