Nusinersen treatment and cerebrospinal fluid neurofilaments: An explorative study on Spinal Muscular Atrophy type 3 patients.

The antisense oligonucleotide Nusinersen has been recently licensed to treat spinal muscular atrophy (SMA). Since SMA type 3 is characterized by variable phenotype and milder progression, biomarkers of early treatment response are urgently needed. We investigated the cerebrospinal fluid (CSF) concentration of neurofilaments in SMA type 3 patients treated with Nusinersen as a potential biomarker of treatment efficacy. The concentration of phosphorylated neurofilaments heavy chain (pNfH) and light chain (NfL) in the CSF of SMA type 3 patients was evaluated before and after six months since the first Nusinersen administration, performed with commercially available enzyme-linked immunosorbent assay (ELISA) kits. Clinical evaluation of SMA patients was performed with standardized motor function scales. Baseline neurofilament levels in patients were comparable to controls, but significantly decreased after six months of treatment, while motor functions were only marginally ameliorated. No significant correlation was observed between the change in motor functions and that of neurofilaments over time. The reduction of neurofilament levels suggests a possible early biochemical effect of treatment on axonal degeneration, which may precede changes in motor performance. Our study mandates further investigations to assess neurofilaments as a marker of treatment response.

Respiratory failure in infants due to spinal muscular atrophy with respiratory distress type 1.

BACKGROUND: Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is a rare autosomal recessive neuromuscular disease of unknown prevalence characterized by degeneration of anterior horn alpha-motoneurons and manifesting in the first 6months of life as life-threatening irreversible diaphragmatic paralysis associated with progressive symmetrical muscular weakness (distal lower limbs mainly involved), muscle atrophy, and peripheral sensory neuropathy. SETTING: Pediatric intensive care unit of tertiary care hospital. PATIENTS: We present two new cases of SMARD1 and report two new mutations in the gene IGHMBP2 which encodes immunoglobulin mu-binding protein 2 on chromosome 11q13. CONCLUSIONS: SMARD1 is a poor-prognosis disease that should be considered when acute respiratory insufficiency, of suspected neuromuscular or unclear cause, develops during the first 6months of life. Diaphragmatic paralysis, manifesting as dyspnea and paradoxical respiration, is the most prominent presenting sign and diaphragmatic motility should be investigated early by fluoroscopy or ultrasound. Electromyography and nerve conduction studies revealing peripheral motor and sensory neuropathy then suggest the diagnosis which should be confirmed by genetic analysis.

Lung-deflating ability of rib cage and abdominal muscles in rabbits.

Anesthetized, apneic, mechanically ventilated rabbits were placed into a tilting plethysmograph that a rubber diaphragm, tightly fitting the animal's body just below the xiphoid process, separated into a rib cage and abdominal chamber. Expired volumes (DeltaV) and abdominal pressure changes (DeltaPab) were assessed in supine and upright posture during maximal rib cage (RCC) and/or abdominal compression (ABC) by pressurizing either or both chambers, and during maximal stimulations of abdominal muscles (ABS). With RCC, DeltaV supine and upright amounted to 16+/-4.9 (mean+/-S.D.) and 20.9+/-7% of the vital capacity in supine posture (VCs) and to 75.8+/-14.5 and 44.8+/-13.9% of the expiratory reserve volume (ERV) in corresponding posture, DeltaPab being negligible. With ABC, DeltaV was 13.7+/-2 and 38.9+/-7.3% VCs and 68.4+/-14.8 and 84.4+/-10.5% ERV, respectively. Both DeltaV and DeltaPab were similar with ABC and ABS, independent of posture. If this applies also to RCC and expiratory rib cage muscle contraction, maximal expiratory effects of the latter (a) are larger in upright than supine posture; (b) contribute to ERV more in supine than upright posture; and (c) are similar to those caused by ABS in supine, but substantially smaller in upright posture.

Partial liberalization of visiting policies and ICU staff: a before-and-after study.

PURPOSE: To investigate possible psychological distress among staff after partial liberalization of visiting policies in intensive care units (ICUs). METHODS: We surveyed eight Italian ICUs planning to increase daily visiting to at least 8 h. Participants completed the Maslach-Jackson Burnout Inventory and the State-Trait Anxiety Inventory before policy change (T0), after 6 months (T1) and 12 months (T2). At T0 and T2, their opinions on the new policy were solicited. Analyses were adjusted for main known confounders (age, gender, centre, educational and marital status, experience in ICU, baseline level of burnout or anxiety, and mortality rate). RESULTS: Baseline response rate was 89 % (230/258); 198 subjects (77 %) responded at T0 and T2, whereas 184 (71 %) participated in all three phases. High burnout levels were identified in 34.5 % of participants at T0 and 42.6 % at T2 (adjusted p = 0.001). All three phases showed a predominance of high burnout among nurses (adjusted p = 0.002). State and trait anxiety scores remained stable (adjusted p = 0.100 and 0.288, respectively). Most participants viewed the change positively at T0 (doctors 81.7 %; nurses 67.7 %) and T2 (doctors 87.0 %; nurses 62.7 %). At T2, 129 participants made comments (180 positive, 136 negative). Subjects with high burnout were more likely to comment negatively (p = 0.011). CONCLUSIONS: Partial liberalization of ICU visiting policies was associated over the course of a year with a small but significant increase in staff members' burnout levels. Nonetheless, doctors and nurses viewed the policy positively, maintaining this opinion after 1 year. Negative views were strongly correlated with burnout.

Ventilator-associated pneumonia in an Italian pediatric intensive care unit: a prospective study.

BACKGROUND: This study was undertaken to determine the prevalence, risk factors and outcomes associated with ventilator-associated pneumonia (VAP) in a European pediatric intensive care unit (PICU). METHODS: A total of 451 children who had been mechanically ventilated in the PICU for ≥ 48 hours during a 3-year period were enrolled in this prospective study. RESULTS: In comparison with children without VAP, 30 children (6.6%) who developed VAP had a longer PICU stay (P=0.0001) and hospital stay (P=0.0001), and a higher mortality rate (P=0.04). Logistic regression analysis showed that the need for re-intubation (P=0.0001), the presence of tracheostomy (P=0.04), and enteral feeding (P=0.02) were independent risk factors for VAP. CONCLUSIONS: A relevant proportion of intubated children develop VAP, which is closely related to invasive procedures. As VAP is associated with increased medical costs and death, multicenter studies are urgently needed to improve the therapeutic approach to VAP and VAP prevention.

Noninvasive continuous positive airway pressure in acute respiratory failure: helmet versus facial mask.

OBJECTIVE: Noninvasive continuous positive airway pressure (nCPAP) is applied through different interfaces to treat mild acute respiratory failure (ARF) in infants. Recently a new pediatric helmet was introduced in clinical practice to deliver nCPAP. The objective of this study was to compare the feasibility of the delivery of nCPAP by the pediatric helmet with delivery by a conventional facial mask in infants with ARF. PATIENTS AND METHODS: We conducted a single-center physiologic, randomized, controlled study with a crossover design on 20 consecutive infants with ARF. All patients received nCPAP by helmet and facial mask in random order for 90 minutes. In infants in both trials, nCPAP treatment was preceded by periods of unassisted spontaneous breathing through a Venturi mask. The primary end point was the feasibility of nCPAP administered with the 2 interfaces (helmet and facial mask). Feasibility was evaluated by the number of trial failures defined as the occurrence of 1 of the following: intolerance to the interface; persistent air leak; gas-exchange derangement; or major adverse events. nCPAP application time, number of patients who required sedation, and the type of complications with each interface were also recorded. The secondary end point was gas-exchange improvement. RESULTS: Feasibility of nCPAP delivery was enhanced by the helmet compared with the mask, as indicated by a lower number of trial failures (P < .001), less patient intolerance (P < .001), longer application time (P < .001), and reduced need for patient sedation (P < .001). For both delivery methods, no major patient complications occurred. CONCLUSIONS: The results of this current study revealed that the helmet is a feasible alternative to the facial mask for delivery of nCPAP to infants with mild ARF.