Developmental milestones in type I spinal muscular atrophy

The aim of this retrospective multicentric study was to assess developmental milestones longitudinally in type I SMA infants using the Hammersmith Infant Neurological Examination. Thirty-three type I SMA infants, who classically do not achieve the ability to sit unsupported, were included in the study. Our results confirmed that all patients had a score of 0 out of a scale of 4 on items assessing sitting, rolling, crawling, standing or walking. A score of more than 0 was only achieved in three items: head control (n = 13), kicking (n = 15) and hand grasp (n = 18). In these items, the maximal score achieved was 1 out of a scale of 4, indicating only partial achievement of the milestone. Infants with symptom onset after 6 months of age had longer preservation of a score of 1 when compared to those with onset before 6 months of age. Our results suggest that even when current standards of care are applied, developmental milestones are rarely even partially achieved as part of natural history in type I SMA infants. No infants in this study achieved a major milestone such as rolling over, or sitting independently, which would therefore represent robust outcomes in future interventional trials

Content validity and clinical meaningfulness of the HFMSE in spinal muscular atrophy

© The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise statedBACKGROUND: Reports on the clinical meaningfulness of outcome measures in spinal muscular atrophy (SMA) are rare. In this two-part study, our aim was to explore patients' and caregivers' views on the clinical relevance of the Hammersmith Functional Motor Scale Expanded- (HFMSE). METHODS: First, we used focus groups including SMA patients and caregivers to explore their views on the clinical relevance of the individual activities included in the HFMSE. Then we asked caregivers to comment on the clinical relevance of possible changes of HFMSE scores over time. As functional data of individual patients were available, some of the questions were tailored according to their functional level on the HFMSE. RESULTS: Part 1: Sixty-three individuals participated in the focus groups. This included 30 caregivers, 25 patients and 8 professionals who facilitated the discussion. The caregivers provided a comparison to activities of daily living for each of the HFMSE items. Part 2: One hundred and forty-nine caregivers agreed to complete the questionnaire: in response to a general question, 72% of the caregivers would consider taking part in a clinical trial if the treatment was expected to slow down deterioration, 88% if it would stop deterioration and 97% if the treatment was expected to produce an improvement. Caregivers were informed of the first three items that their child could not achieve on the HFMSE. In response 75% indicated a willingness to take part in a clinical trial if they could achieve at least one of these abilities, 89% if they could achieve two, and 100% if they could achieve more than 2. CONCLUSIONS: Our findings support the use of the HFMSE as a key outcome measure in SMA clinical trials because the individual items and the detected changes have clear content validity and clinical meaningfulness for patients and their caregivers.Peer reviewedFinal Published versio

Significato clinico delle calcificazioni nei noduli tiroidei

Il valore predittivo delle calcificazioni tiroidee ecograficamente accertate e le loro eventuali caratteristiche suggestive di neoplasia sono state studiate in una serie di 175 pazienti operati (30 carcinomi papilliferi, 145 gozzi multinodulari). Le calcificazioni sono risultate molto più frequenti nei tumori che nei gozzi (40% vs 20,7% p<0,05), mentre le loro caratteristiche (dimensioni, numero, posizione nel nodulo e disposizione nel contesto ghiandolare) non sono risultate chiaramente differenti fra tumori e gozzi. La frequenza delle calcificazioni è stata significativamente più alta nei pazienti più anziani (età media 58,7±13,3 per i pazienti con calcificazioni v s 51,1±12,7 per i pazienti senza calcificazioni, p<0,001) e ciò potrebbe implicare che la loro insorgenza sia dipen - dente dalla durata di malattia. In conclusione, le calcificazioni possono essere un utile indicatore di rischio aumentato, da prendere in considerazione nel processo com - plessivo di “decision-making” chirurgico

Risk of Malignancy from Thyroid Nodular Disease as an Element of Clinical Management of Patients with Hashimoto's Thyroiditis.

BACKGROUND: Many studies have investigated the association between chronic lymphocytic thyroiditis (CLT) and papillary thyroid carcinoma (PTC), but clinical management of this condition has never been addressed specifically, even in recent guidelines. Surprisingly the likelihood of a nodule as being cancerous in a CLT has never been explicitly expressed in terms of relative risk. METHODS: This study was based on a retrospective analysis of 404 patients undergoing total thyroidectomy. RESULTS: Sixty-nine patients (17.1%) had histological findings of true CLT, and 36.2% had concurrent PTC versus 22.6% of patients in the non-CLT group (p < 0.05), with a tumour risk in the CLT group of ×1.6 (95% CI = 1.21-1.94, likelihood ratio = +1.63). CONCLUSIONS: Patients with CLT and a nodular condition have a ×1.6 increased risk of harbouring a PTC. Moreover, these patients develop multicentric PTC more frequently, and, as a result, total thyroidectomy should always be considered

Factors influencing the length of the incision and the operating time for total thyroidectomy

Background: The incision used for thyroid surgery has become shorter over time, from the classical 10 cm long Kocher incision to the shortest 15 mm access achieved with Minimally Invasive Video-Assisted Thyroidectomy. This rather large interval encompasses many different possible technical choices, even if we just consider open surgery. The aim of the study was to assess the correlation between incision length and operation duration with a set of biometric and clinical factors and establish a rationale for the decision on the length of incision in open surgery. Methods: Ninety-seven consecutive patients scheduled for total thyroidectomy were prospectively evaluated. All operations were performed by the same team and the surgeon decided the length of the incision according to his personal judgement. Patients who had previously undergone neck surgery were excluded. Results: The length of the incision was strongly correlated with gender, thyroid volume, neck circumference and clinical diagnosis and weakly correlated with the body mass index. Operation duration was only weakly correlated with gender and neck circumference. Multiple linear regression revealed that the set of factors assessed explained almost 60 % of the variance in incision length but only 20 % of the variance in operation duration. When patients were classified according to the distribution of their thyroid volume, cases within one standard deviation of the mean did not show a significant difference in terms of operation duration with incisions of various lengths. Conclusions: Although thyroid volume was a major factor in driving the decision with respect to the length of the incision, our study shows that it had only minor effect on the duration of the operation. Many more open thyroidectomies could therefore be safely performed with shorter incisions, especially in women. Duration of the operation is probably more closely linked to the inherent technical difficulty of each case

Increasing diagnostic accuracy for thyroid nodules by an integrated multivariate approach: a methodological study.

Objectives: Current guidelines for diagnostic management of thyroid nodules are based on a linear approach, using categorial classifications to cluster diagnostic findings and they still lead to unnecessary surgery. A diagnostic scoring system, based on clinical, cytological and ultrasound findings is described. Materials and Methods: Two groups of patients (168 and 55 pts) were used to compute a multivariate model and the discriminating threshold by ROC curves. The performance of the derived scoring system was assessed by a simulation on a third group of 60 patients, who had undergone surgery according to current guidelines. Results: The scoring system displayed a sensitivity of 100%, specificity 53.3%, positive and negative predictive values of 68.1% and 100%. According to the scoring system, 16 out of 60 operations would have been saved. Conclusions: A scoring system can take into account in a more accurate way the full informative content of the fine-grained description of diagnostic and clinical features

Un modello multivariato integrato di previsione del rischio neoplastico dei noduli della tiroide

Riassunto Obiettivo: la diagnosi di natura di un nodulo della tiroide è ancora oggi un problema non completamente risolto e spesso vengono eseguiti interventi a solo scopo di conferma istologica. Lo studio si propone di definire un modello integrato predittivo del rischio neoplastico per un nodulo tiroideo: Tale modello può essere complementare all’attuale approccio sequenziale di attività diagnostiche, governato da criteri mono-dimensionali. Materiali: sono stati raccolti i dati clinici, ecografici e citologici preoperatori di 168 pazienti consecutivi (per un totale di 197 noduli studiati), operati successivamente di tiroidectomia totale. I dati sono stati analizzati con statistica monovariata e quindi integrati in un modello statistico multivariato. Sono stati esclusi pazienti con referto citologico inadeguato (classe Th 1 secondo la British Thyroid Ass.) o con diagnosi citologica certa di neoplasia (classe Th 5). Risultati: sono risultate variabili predittive indipendenti di maggior valore la anisonucleosi, la presenza di atipie e di proliferazione follicolare nell’esame citologico; la presenza di calcificazioni interne al nodulo e l’unicità del nodulo stesso come caratteri ecografici. Conclusioni: è stato possibile integrare in un unico modello predittivo di rischio a cinque elementi i caratteri derivanti dall’ecografia e dalla citologia su FNA. Tale modello può essere la base per ottenere un sistema di punteggio da affiancare alla strategia di semplice algoritmo sequenziale raccomandata dalle linee guida attuali. Summary Objective: the diagnosis of nature of a thyroid nodule is still an unresolved problem and often patients undergo surgery just to confirm an histological diagnosis. This study is aimed to define an integrated model to predict the risk of malignancy for a thyroid nodule. This model should complement the presently preferred approach, based on a sequential diagnostic workup ruled by mono-dimensional criteria. Materials: data from clinical exam, ultrasound and cytology were collected in the preoperative period from 168 consecutive patients (for a total number of 197 considered nodules), who then underwent total thyroidectomy. Data were analysed by monovariate statistics and then integrated in a multivariate statistical model. Patients with an inadequate cytology (Th 1class, according to la British Thyroid Ass.) or with a definite cytological diagnosis of malignancy (Th 5class) were excluded. Results: anisonucleosis, the presence of atipia and follicular proliferation resulted as independent significant criteria for cytology; the presence of calcifications inside a nodule and the condition of unique nodule were the ultrasonographic most significant characters. Conclusions: it has been possible to integrate in a unique predictive model of risk with five elements the information deriving from ultrasound and cytology. This model can be the starting point to obtain a scoring system to improve the strategy of simple sequential algorithm recommended by the present guidelines. Introduzione La diagnosi di natura di un nodulo della tiroide è ancora oggi un problema non completamente risolto e poiché, nonostante l’alta prevalenza dei noduli della tiroide, solo in una piccola percentuale di casi essi sono maligni, spesso vengono eseguiti interventi a solo scopo di conferma istologica. Le più recenti linee guida (1, 2, 3) raccomandano un flusso sequenziale di attività diagnostiche, governato da criteri mono-dimensionali (anamnesi-esame obiettivo ecografia FNA) e non sembrano esistere in letteratura tentativi di costruire sistemi di punteggio di rischio, specie per quella tipologia di noduli tiroidei con caratteristiche ecografie sospette o con citologia di tipo “lesione follicolare”. Lo scopo dello studio è quello di confermare il valore diagnostico di alcune delle caratteristiche della citologia e dell’ecografia citate in letteratura come predittive di malignità (4, 5, 6) e integrarle in un unico modello statistico multivariato predittivo del rischio di neoplastico

Unusual posterior reversible encephalopathy syndrome in a case of influenza A/H1N1 infection

Central nervous system involvement is an uncommon though potentially a severe complication during influenza infection; the pathogenic mechanisms of the neurological syndromes described in humans are largely unknown. We describe a case of a 51-year-old man who presented with fever and behavioral changes but no focal neurological deficits. The next day, the condition rapidly evolved into a severe neurological syndrome with recurrent focal motor seizures with secondary generalization. At the brain MRI, FLAIR disclosed a slight area of increased signal in the left mesial frontal cortex extending to the frontopolar area and insula. At DWI, a mild hyperintensity was evident in the mesial-frontopolar cortex, with normal ADC values. MR perfusion was indicative of severe hypoperfusion. Fungal, bacterial and viral cultures in CSF, blood and urine were negative. The nasopharyngeal swab PCR was positive for the H1N1-influenza A virus. The patient was thus treated and by day five the neurological examination results had returned to normal. A follow-up MRI, performed two weeks later, only revealed a residual slight hyperintensity in the left medial frontal cortex. The onset of a rapidly evolving encephalopathy syndrome, its close association with a MRI brain pattern of acute vasogenic edema and favorable outcome support a diagnosis of PRES during influenza A infection. However, the topographic characteristics of the cerebral lesion seem to define a PRES with an atypical pattern. (C) 2012 Elsevier B.V. All rights reserved