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Spinal muscular atrophy (SMA) type 1 is a severe infantile autosomal-recessive neuromuscular disorder caused by a survival motor neuron 1 gene (SMN1) mutation and characterized by progressive muscle weakness. Without supportive care, SMA type 1 is rapidly fatal. The antisense oligonucleotide nusinersen has recently improved the natural course of this disease. Here, we investigated, with a functional proteomic approach, cerebrospinal fluid (CSF) protein profiles from SMA type 1 patients who underwent nusinersen administration to clarify the biochemical response to the treatment and to monitor disease progression based on therapy. Six months after starting treatment (12 mg/5 mL × four doses of loading regimen administered at days 0, 14, 28, and 63), we observed a generalized reversion trend of the CSF protein pattern from our patient cohort to that of control donors. Notably, a marked up-regulation of apolipoprotein A1 and apolipoprotein E and a consistent variation in transthyretin proteoform occurrence were detected. Since these multifunctional proteins are critically active in biomolecular processes aberrant in SMA, i.e., synaptogenesis and neurite growth, neuronal survival and plasticity, inflammation, and oxidative stress control, their nusinersen induced modulation may support SMN improved-expression effects. Hence, these lipoproteins and transthyretin could represent valuable biomarkers to assess patient responsiveness and disease progression.

Nusinersen is the first approved drug to treat spinal muscular atrophy (SMA). Its periodic intrathecal delivery may cause psychological burden in infants and in their parents. We report our experience during expanded access program (EAP) for type 1 SMA in a single Italian center. Because of the occurrence of stress emotional states, anxious reactions and fear before, during, and after lumbar puncture (LP), a specific psychological intervention was implemented based on regulation of emotions, anticipatory expectations, and post-event attributions. Activities included the use of fairy tales, distraction, music play through listening preferred cartoon themes in the youngest children, and contextual games and solution of fun riddle quizzes in the oldest ones. State anxiety greatly reduced in children and their parents. Treatment of psychological aspects should therefore become an integral part of health care in SMA infants and children during Nusinersen treatment.

ObjectiveTo report cross-sectional clinical findings in a large cohort of patients affected by type 1 spinal muscular atrophy.MethodsWe included 122 patients, of age ranging between 3 months and 22 years, 1 month. More than 70% (85/122) were older than 2 years and 25% (31/122) older than 10 years. Patients were classified according to the severity of phenotype and to the number of SMN2 copies.ResultsPatients with the more common and the most severe phenotype older than 2 years were, with few exceptions, on noninvasive ventilation and, with increasing age, more often had tracheostomy or >16-hour ventilation and a gastrostomy inserted. In contrast, 25 of the 28 patients with the mildest phenotype older than 2 years had no need for tracheostomy or other ventilatory or nutritional support. In patients older than 2 years, the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders scores were generally lower compared to those found in younger patients and showed distinct levels of functional abilities according to the severity of the phenotype. Similar findings were also observed on the Hammersmith Infant Neurological Examination.ConclusionsOur findings confirm that, after the age of 2 years, patients with type 1 spinal muscular atrophy generally survive only if they have gastrostomy and tracheostomy or noninvasive ventilation >16 hours and have low scores on the functional scales. More variability, however, can be expected in those with the mildest phenotype, who achieve head control. These data provide important baseline information at the time treatments are becoming available.

Summary Introduction Post-neurosurgical nosocomial meningitis has become an important subgroup of bacterial meningitis in the hospital setting. The increase in meningitis caused by multidrug-resistant (MDR) Acinetobacter baumannii has resulted in a significant reduction in available treatment options. Case report and literature review We report the case of a 36-year-old man with a complex craniofacial trauma, who developed a nosocomial meningitis due to MDR A. baumannii that was cured by intrathecal colistin. The case is contextualized among all the published cases of Acinetobacter meningitis treated with topical colistin found through a MEDLINE search of the literature. To date, including the present case, eight reported cases of Acinetobacter meningitis have been treated with colistin administered by an intrathecal route and 24 by an intraventricular route. The daily dose of colistin used ranged from 1.6mg every 24h to 20mg every 24h in adult patients. The median time necessary to obtain cerebrospinal fluid sterilization was 4.1 days, and treatment was always successful even if in two cases Acinetobacter meningitis relapsed. Toxicity probably or possibly related to the topical administration of colistin was noted in five out of the 32 patients. Conclusions Topical colistin can be an effective and safe treatment for MDR Acinetobacter meningitis.

Cardiac surgery performed with cardiopulmonary bypass (CPB) may be complicated by hypotension due to low systemic vascular resistance (SVR). Often in those cases, hypotension is resistant to pressor catecholamines. We report six cases of norepinephrine-resistant postcardiotomy hypotension, treated by terlipressin (TP), a potent vasopressor agent. Between May 2007 and May 2008, we treated six patients with TP administration (1 mg bolus) for post CPB refractory vasodilatory hypotension. Analyzed parameters were: mean arterial pressure (m-AP), SVR, cardiac output index (CI), mean pulmonary pressure (m-PP), and lactate, at baseline (before TP bolus) and 3 h after injection. Before TP bolus, the average m-AP was 53.32+/-8.86 mmHg, the CI was 3.45+/-0.24 l/min/m(2), the SVR was 650+/-62.03 dyne*s/cm(5) and the arterial lactate level was 4.6+/-0.95 mmol/l. Three hours after the TP bolus, the m-AP increased to 81.83+/-9.71 mmHg (P=0.002), the CI decreased to 2.88+/-0.14 l/min/m(2) (P=0.002), the SVR increased to 1154+/-116 dyne*s/cm(5) (P=0.002), and arterial lactates decreased to 3.13+/-0.78 mmol/l (P=0.015), without significant modification of m-PP and CVP. We treated postoperative refractory low SVR hypotension by TP administration in bolus. Exogenous administration of TP normalized SVR and increased the systemic arterial pressure with a minimum effect on pulmonary pressure. Subsequently, the effect on systemic blood pressure enhanced urine output. No major collateral effects were observed. The administration of TP in bolus may result as a useful alternative for treating refractory low SVR hypotension post CPB.

Hepatobiliary scintigraphy (HBS) was performed in a patient in whom pyogenic liver abscess developed approximately 1 month after he underwent an interventional radiology procedure to relieve obstructive jaundice caused by an ampullary tumor. HBS, apart from detecting the abscess cavity as a cold space-occupying lesion, well demonstrated biliary flow impairment and dilatation of bile ducts, the communication between the abscess cavity and the biliary tree, and the presence of a bile leak. All these findings were disclosed by a single imaging procedure and appeared to be useful for patient management.