Multiple fractures of the femur: Case report, literature review, and proposal for a shared algorithm of treatment

Multiple fractures of the femur, defined for the purposes of this study as the association of three or more non-contiguous fractures on the same bone segment, is an exceedingly rare condition with an unknown incidence in the literature. A limited number of studies, mainly consisting of case reports or small case series, have addressed this topic, and no shared consensus or guidelines exist on what the ideal timing and sequence of multiple fracture fixation is. The present paper reports the clinical case of a 36 years old man who sustained a blunt chest injury, a non-concussive head injury, a displaced intracapsular fracture of the left femur (AO 31B2), a left diaphyseal multifragmentary fracture (AO 32B3), a supradiacondylar fracture of the distal end of the left femur (AO 33C1.1), a Hoffa fracture of the lateral left femoral condyle (AO 33B3.2 f), and a multifragmentary fracture of the left patella with bone loss (AO 34C3) due to a vehicular high-energy trauma. The patient was surgically treated by open reduction and internal fixation according to a proposed algorithm of treatment and reported excellent clinical and radiological outcomes at 32 months follow-up. The primary aim of this study is to describe our experience in the treatment of such complex fractures, by presenting our clinical and radiological results, and to propose a treatment algorithm. The secondary aim is to provide a comprehensive review of the literature on this topic

Significance of serum Myostatin in hemodialysis patients

Background: Malnutrition and muscle wasting are common in haemodialysis (HD) patients. Their pathogenesis is complex and involves many molecules including Myostatin (Mstn), which acts as a negative regulator of skeletal muscle. The characterisation of Mstn as a biomarker of malnutrition could be useful in the prevention and management of this condition. Previous studies have reported no conclusive results on the actual relationship between serum Mstn and wasting and malnutrition. So, in this study, we evaluated Mstn profile in a cohort of regular HD patients. Methods: We performed a cross-sectional study, enrolling 37 patients undergoing bicarbonate-HD (BHD) or haemodiafiltration (HDF) at least for six months. 20 sex-matched healthy subjects comprised the control group. Mstn serum levels were evaluated by ELISA before and after HD. We collected clinical and biochemical data, evaluated insulin resistance, body composition, malnutrition [by Malnutrition Inflammation Score (MIS)] and tested muscle function (by hand-grip strength, six-minute walking test and a questionnaire on fatigue). Results: Mstn levels were not significantly different between HD patients and controls (4.7 \ub1 2.8 vs 4.5 \ub1 1.3 ng/ml). In addition, while a decrease in Mstn was observed after HD treatment, there were no differences between BHD and HDF. In whole group of HD patients Mstn was positively correlated with muscle mass (r = 0.82, p < 0.001) and inversely correlated with age (r = - 0.63, p < 0.01) and MIS (r = - 0.39, p = 0.01). No correlations were found between Mstn and insulin resistance, such as between Mstn levels and parameters of muscle strength and fatigue. In multivariate analysis, Mstn resulted inversely correlated with fat body content (\u3b2 = - 1.055, p = 0.002). Conclusions: Circulating Mstn is related to muscle mass and nutritional status in HD patients, suggesting that it may have a role in the regulation of skeletal muscle and metabolic processes. However, also considering the lack of difference of serum Mstn between healthy controls and HD patients and the absence of correlations with muscle function tests, our findings do not support the use of circulating Mstn as a biomarker of muscle wasting and malnutrition in HD

Clinical and Neurocognitive Outcome EvaluationIn locked-in Syndrome

We reported a case of Locked-in syndrome, who underwent a specific clinical and neuropsychological battery, assessing verbal memory, linguistic comprehension, perception, executive functioning..

A functional gene expression analysis in epithelial sinonasal cancer: Biology and clinical relevance behind three histological subtypes

Epithelial sinonasal cancers (SNCs) are rare diseases with overlapping morphological features and a dismal prognosis. We aimed to investigate the expression differences among the histological subtypes for discerning their molecular characteristics. We selected 47 SNCs: (i) 21 nonkeratinizing squamous cell carcinomas (NKSCCs), (ii) 13 sinonasal neuroendocrine cancers (SNECs), and (iii) 13 sinonasal undifferentiated cancers (SNUCs). Gene expression profiling was performed by DASL (cDNA-mediated annealing, selection, extension, and ligation) microarray analysis with internal validation by quantitative RT-PCR (RT-qPCR). Relevant molecular patterns were uncovered by sparse partial-least squares discriminant analysis (sPLS-DA), microenvironment cell type (xCell), CIBERSORT, and gene set enrichment (GSEA) analyses. The first two sPLS-DA components stratified samples by histological subtypes. xCell highlighted increased expression of immune components (CD8 + effector memory cells, in SNUC) and \u201cother cells\u201d: keratinocytes and neurons in NKSCC and SNEC, respectively. Pathway enrichment was observed in NKSCC (six gene sets, proliferation related), SNEC (one gene set, pancreatic \u3b2-cells), and SNUC (twenty gene sets, some of them immune-system related). Major neuroendocrine involvement was observed in all the SNEC samples. Our high-throughput analysis revealed a good diagnostic ability to differentiate NKSCC, SNEC, and SNUC, but indicated that the neuroendocrine pathway, typical and pathognomonic of SNEC is also present at lower expression levels in the other two histological subtypes. The different and specific profiles may be exploited for elucidating their biology and could help to identify prognostic and therapeutic opportunities

Clinical Study Sativex in the Management of Multiple Sclerosis-Related Spasticity: Role of the Corticospinal Modulation

Sativex is an emergent treatment option for spasticity in patients affected by multiple sclerosis (MS). This oromucosal spray, acting as a partial agonist at cannabinoid receptors, may modulate the balance between excitatory and inhibitory neurotransmitters, leading to muscle relaxation that is in turn responsible for spasticity improvement. Nevertheless, since the clinical assessment may not be sensitive enough to detect spasticity changes, other more objective tools should be tested to better define the real drug effect. The aim of our study was to investigate the role of Sativex in improving spasticity and related symptomatology in MS patients by means of an extensive neurophysiological assessment of sensory-motor circuits. To this end, 30 MS patients underwent a complete clinical and neurophysiological examination, including the following electrophysiological parameters: motor threshold, motor evoked potentials amplitude, intracortical excitability, sensory-motor integration, and H max /M max ratio. The same assessment was applied before and after one month of continuous treatment. Our data showed an increase of intracortical inhibition, a significant reduction of spinal excitability, and an improvement in spasticity and associated symptoms. Thus, we can speculate that Sativex could be effective in reducing spasticity by means of a double effect on intracortical and spinal excitability

The still under-investigated role of cognitive deficits in PML diagnosis

Background: Despite cognitive deficits frequently represent the first clinical manifestations of Progressive Multifocal Leukoencephalopathy (PML) in Natalizumab-treated MS patients, the importance of cognitive deficits in PML diagnosis is still under-investigated. The aim of the current study is to investigate the cognitive deficits at PML diagnosis in a group of Italian patients with PML. Methods: Thirty-four PML patients were included in the study. The demographic and clinical data, the lesion load and localization, and the longitudinal clinical course was compared between patients with (n = 13) and without (n = 15) cognitive deficit upon PML suspicion (the remaining six patients were asymptomatic). Clinical presentation of cognitive symptoms was described in detail. Result: After symptoms detection, the time to diagnosis resulted to be shorter for patients presenting with cognitive than for patients with non cognitive onset (p = 0.03). Within patients with cognitive onset, six patients were presenting with language and/or reading difficulties (46.15%); five patients with memory difficulties (38.4%); three patients with apraxia (23.1%); two patients with disorientation (15.3%); two patients with neglect (15.3%); one patients with object agnosia (7.7%), one patient with perseveration (7.7%) and one patient with dementia (7.7%). Frontal lesions were less frequent (p = 0.03), whereas temporal lesions were slightly more frequent (p = 0.06) in patients with cognitive deficits. The longitudinal PML course seemed to be more severe in cognitive than in non cognitive patients (F = 2.73, p = 0.03), but differences disappeared (F = 1.24, p = 0.29) when balancing for the incidence of immune reconstitution syndrome and for other treatments for PML (steroids, plasma exchange (PLEX) and other therapies (Mefloquine, Mirtazapine, Maraviroc). Conclusion: Cognitive deficits at PML onset manifest with symptoms which are absolutely rare in MS. Their appearance in MS patients should strongly suggest PML. Clinicians should be sensitive to the importance of formal neuropsychological evaluation, with particular focus on executive function, which are not easily detected without a formal assessment

Acute GVHD prophylaxis plus ATLG after myeloablative allogeneic haemopoietic peripheral blood stem-cell transplantation from HLA-identical siblings in patients with acute myeloid leukaemia in remission : final results of quality of life and long-term outcome analysis of a phase 3 randomised study

Background We previously showed that human anti-T-lymphocyte globulin (ATLG) plus ciclosporin and methotrexate given to patients with acute leukaemia in remission, having allogeneic haemopoietic stem-cell transplantation with peripheral blood stem cells from an HLA-identical sibling donor after myeloablative conditioning, significantly reduced 2-year chronic graft-versus-host disease (cGVHD) incidence and severity, without increasing disease relapse and infections, and improves cGVHD-free and relapse-free survival (cGRFS). The aim of an extended follow-up study was the assessment of long-term outcomes, which are, in this context, scarcely reported in the literature. We report unpublished data on quality of life (QoL) from the original study and the results of a follow-up extension. Methods In the original open-label study, patients with acute myeloid and lymphoblastic leukaemia in first or subsequent remission, having sibling HLA-identical allogeneic peripheral blood stem-cell transplantation, were randomly assigned (1:1) to receive ATLG plus standard GVHD prophylaxis with ciclosporin and short-term methotrexate (ATLG group) or standard GVHD prophylaxis without ATLG (non-ATLG group). Conditioning regimens were cyclophosphamide 120 mg/kg with either total body irradiation (12 Gy) or busulfan (12 . 8 mg/kg intravenously or 16 mg/kg orally), with or without etoposide (30-60 mg/kg). Randomisation was stratified according to centre and disease risk. The primary endpoint was cumulative incidence of cGVHD at 2 years. The primary and secondary endpoints, excluding QoL, have been published. QoL, assessed using European Organisation for Research and Treatment of Cancer QLQ-C30 and QLQ-HDC29 questionnaires, was an unpublished secondary endpoint, which we now report here. A follow-up extension was then done, with the primary endpoint cumulative incidence of cGVHD. Enrolment has been completed for both studies. Findings In the original study, from Dec 14, 2006, to Feb 2, 2012, 161 patients were enrolled and 155 were randomly assigned to either the ATLG group (n=83) or to the non-ATLG group (n=72). In the follow-up study, which started on Feb 7, 2017, and was completed on June 30, 2017, 61 patients were included in the ATLG group and 53 were included in the non-ATLG group. Global health status showed a more favourable time course in the ATLG group compared with the non-ATLG group (p=0 . 02; treatment by visit interaction). ATLG was descriptively superior to non-ATLG at 24 months for physical function (points estimate -14.8 [95% CI -26.4 to-3.1]; p= 0.014) and social function (-19.1 [-38.0 to -0.2]; p=0.047), gastrointestinal side-effects (8 . 8 [2.5-15.1]; p=0 . 008) and effect on family (13.5 [1.2-25.8]; p=0.032). Extended follow-up (median 5 . 9 years [IQR 1.7-7.9]) confirmed a lower 5-year cGVHD incidence (30.0% [95% CI 21.4-41.9] vs 69.1% [59.1-80.1]; analysis for entire follow-up, p Interpretation The addition of ATLG to standard GVHD prophylaxis improves the probability of surviving without disease relapse and cGVHD after myeloablative peripheral blood stem-cell transplantation from an HLA-identical sibling donor for patients with acute leukaemia in remission. Further additional benefits are better QoL and shorter immunosuppressive treatment compared with standard GVHD prophylaxis without ATLG. Therefore, in this setting, ATLG plus standard GVHD prophylaxis should be preferred over the standard GVHD prophylaxis alone. Copyright (C) 2019 Elsevier Ltd. All rights reserved.Peer reviewe

COVID-19-associated Guillain-Barré syndrome in the early pandemic experience in Lombardia (Italy)

Objective To estimate the incidence and describe clinical characteristics and outcome of GBS in COVID-19 patients (COVID19-GBS) in one of the most hit regions during the frst pandemic wave, Lombardia. Methods Adult patients admitted to 20 Neurological Units between 1/3–30/4/2020 with COVID19-GBS were included as part of a multi-center study organized by the Italian society of Hospital Neuroscience (SNO). Results Thirty-eight COVID19-GBS patients had a mean age of 60.7 years and male frequency of 86.8%. CSF albuminocytological dissociation was detected in 71.4%, and PCR for SARS-CoV-2 was negative in 19 tested patients. Based on neurophysiology, 81.8% of patients had a diagnosis of AIDP, 12.1% of AMSAN, and 6.1% of AMAN. The course was favorable in 76.3% of patients, stable in 10.5%, while 13.2% worsened, of which 3 died. The estimated occurrence rate in Lombardia ranges from 0.5 to 0.05 GBS cases per 1000 COVID-19 infections depending on whether you consider positive cases or estimated seropositive cases. When we compared GBS cases with the pre-pandemic period, we found a reduction of cases from 165 to 135 cases in the 2-month study period in Lombardia. Conclusions We detected an increased incidence of GBS in COVID-19 patients which can refect a higher risk of GBS in COVID-19 patients and a reduction of GBS events during the pandemic period possibly due to a lower spread of more common respiratory infectious diseases determined by an increased use of preventive measures

Platelets and hepatocellular cancer: Bridging the bench to the clinics

Growing interest is recently being focused on the role played by the platelets in favoring hepatocellular cancer (HCC) growth and dissemination. The present review reports in detail both the experimental and clinical evidence published on this topic. Several growth factors and angiogenic molecules specifically secreted by platelets are directly connected with tumor progression and neo-angiogenesis. Among them, we can list the platelet-derived growth factor, the vascular endothelial growth factor, the endothelial growth factor, and serotonin. Platelets are also involved in tumor spread, favoring endothelium permeabilization and tumor cells' extravasation and survival in the bloodstream. From the bench to the clinics, all of these aspects were also investigated in clinical series, showing an evident correlation between platelet count and size of HCC, tumor biological behavior, metastatic spread, and overall survival rates. Moreover, a better understanding of the mechanisms involved in the platelet-tumor axis represents a paramount aspect for optimizing both current tumor treatment and development of new therapeutic strategies against HCC