Retrospective study of consecutive rib fracture patients treated by open reduction internal fixation in a single major trauma centre, UK.

INTRODUCTION: Rib fractures are a common presentation in both patients presenting with high impact poly-trauma and as a result of low energy falls in the elderly. This injury can lead to various complications including prolonged hospital admission, pneumonia, need for ventilation and in admission to intensive care unit. There is much controversy around the management of this injury in the literature, with favourable outcomes for patients treated non-operatively as well as surgically. METHODS: We collated a database for all rib fracture fixations between 2014 and 2019 that took place at the major trauma centre in Liverpool. The decision to undergo surgical fixation was after discussion with multidisciplinary team at trauma meeting. Following British Orthopaedic Association Standards for Trauma and Orthopaedics (BOASTs), these injuries should ideally be operated on within 48 h. RESULTS: Overall, a total of 220 patients were included in the study (143 male and 77 female). 142 (64%) patients were operated on within 48 h of admission. A total of 101 (45%) patients required admission to ITU. Those in the early surgical fixation group had a statistically significant decrease in their hospital length of stay (12.8 days compared to 15.5 days, p=<0.001). Mean length of ITU stay was shorter in the early surgical group with no statistical significance (p = 0.1). Those patients that required mechanical ventilation in turn stayed in hospital for a longer period compared to those who did not (p=<0.001). There is no statistical difference in survival between the 2 patient groups (p = 0.3). DISCUSSION: To our knowledge, this is the largest data set published in the rib fracture fixation cohort. Our results agree with previous studies which have demonstrated that those who undergo ORIF tend require fewer days of hospital stay, less ventilatory support and overall have better outcomes in terms of pain when compared to those treated non-operatively. Our study adds that patients who receive treatment within 48-hours as per BOAST guidelines have better outcomes, specifically reducing hospital length of stay by nearly 4 days (p = 0.014). CONCLUSION: Early surgical fixation of rib fractures leads to significantly favoured outcomes.

Assessing Neurofilaments as Biomarkers of Neuroprotection in Progressive Multiple Sclerosis: From the MS-STAT Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: Improved biomarkers of neuroprotective treatment are needed in progressive multiple sclerosis (PMS) to facilitate more efficient phase 2 trial design. The MS-STAT randomized controlled trial supported the neuroprotective potential of high-dose simvastatin in secondary progressive MS (SPMS). Here, we analyze serum from the MS-STAT trial to assess the extent to which neurofilament light (NfL) and neurofilament heavy (NfH), both promising biomarkers of neuroaxonal injury, may act as biomarkers of simvastatin treatment in SPMS. METHODS: The MS-STAT trial randomized patients to 80 mg simvastatin or placebo. Serum was analyzed for NfL and NfH using Simoa technology. We used linear mixed models to investigate the treatment effects of simvastatin compared with placebo on NfL and NfH. Additional models examined the relationships between neurofilaments and MRI and clinical measures of disease severity. RESULTS: A total of 140 patients with SPMS were included. There was no evidence for a simvastatin treatment effect on NfL or NfH: compared with placebo, NfL was 1.2% lower (95% CI 10.6% lower to 9.2% higher; p = 0.820) and NfH was 0.4% lower (95% CI 18.4% lower to 21.6% higher; p = 0.969) in the simvastatin treatment group. Secondary analyses suggested that higher NfL was associated with greater subsequent whole brain atrophy, higher T2 lesion volume, and more new/enlarging T2 lesions in the previous 12 months, as well as greater physical disability. There were no significant associations between NfH and MRI or clinical variables. DISCUSSION: We found no evidence of a simvastatin treatment effect on serum neurofilaments. While confirmation of the neuroprotective benefits of simvastatin is awaited from the ongoing phase 3 study (NCT03387670), our results suggest that treatments capable of slowing the rate of whole brain atrophy in SPMS, such as simvastatin, may act via mechanisms largely independent of neuroaxonal injury, as quantified by NfL. This has important implications for the design of future phase 2 clinical trials in PMS. TRIAL REGISTRATION INFORMATION: MS-STAT: NCT00647348. CLASSIFICATION OF EVIDENCE: This study provides class I evidence that simvastatin treatment does not have a large impact on either serum NfL or NfH, as quantified in this study, in SPMS.

Dexamethasone treatment may mitigate adverse effects of vitamin D deficiency in hospitalized Covid-19 patients.

AIMS: We have previously demonstrated that vitamin D deficiency might be associated with worse outcomes in hospitalized Covid-19 patients. The aim of our study was to explore this relationship with dexamethasone therapy. METHODS: We prospectively studied two cohorts of hospitalized Covid-19 patients between March and April and between September and December 2020 (n = 192). Patients were tested for serum 25-hydroxyvitamin D (25-OH-D) levels during admission. The first cohort not treated with dexamethasone (n = 107) was divided into vitamin D deficient (25-OH-D ≤ 30 nmol/L) (n = 47) and replete subgroups (25-OH-D > 30 nmol/L) (n = 60). The second cohort treated with dexamethasone (n = 85) was similarly divided into deficient (25-OH-D ≤ 30 nmol/L) (n = 27) and replete subgroups (25-OH-D > 30 nmol/L) (n = 58). Primary outcome was in-hospital mortality and secondary outcomes were elevation in markers of cytokine storm and ventilatory requirement. RESULTS: No mortality difference was identified between cohorts and subgroups. The "no dexamethasone" cohort 25-OH-D deplete subgroup recorded significantly higher peak D-Dimer levels (1874 vs. 1233 µgFEU/L) (p = 0.0309), CRP (177 vs. 107.5) (p = 0.0055), and ventilatory support requirement (25.5% vs. 6.67%) (p = 0.007) compared to the replete subgroup. Among the 25-OH-D deplete subgroup higher peak neutrophil counts, peak CRP, peak LDH, peak ferritin, and lower trough lymphocyte counts were observed, without statistical significance. In the "dexamethasone" cohort, there was no apparent association between 25-OH-D deficiency and markers of cytokine storm or ventilatory requirement. CONCLUSION: Vitamin D deficiency is associated with elevated markers of cytokine storm and higher ventilatory requirements in hospitalized Covid-19 patients. Dexamethasone treatment appears to mitigate adverse effects of vitamin D deficiency.