Is an Impacted Morselized Graft in a Cage an Alternative for Reconstructing Segmental Diaphyseal Defects?

Large diaphyseal bone defects often are reconstructed with large structural allografts but these are prone to major complications. We therefore asked whether impacted morselized bone graft could be an alternative for a massive structural graft in reconstructing large diaphyseal bone defects. Defects in the femora of goats were reconstructed using a cage filled with firmly impacted morselized allograft or with a structural cortical autograft (n = 6 in both groups). All reconstructions were stabilized with an intramedullary nail. The goats were allowed full weightbearing. In all reconstructions, the grafts united radiographically. Mechanical torsion strength of the femur with the cage and structural cortical graft reconstructions were 66.6% and 60.3%, respectively, as compared with the contralateral femurs after 6 months. Histologically, the impacted morselized graft was replaced completely by new viable bone. In the structural graft group, a mixture of new and necrotic bone was present. Incorporation of the impacted graft into new viable bone suggests this type of reconstruction may be safer than reconstruction with a structural graft in which creeping substitution results in a mixture of viable and necrotic bone that can fracture. The data suggest that a cage filled with a loaded morselized graft could be an alternative for the massive cortical graft in reconstruction of large diaphyseal defects in an animal model

Good results with cemented total hip arthroplasty in patients between 40 and 50 years of age: 168 hips followed for 2–19 years

Background and purpose Total hip arthroplasties in young patients have lower long-term survival rates than in older patients. We evaluated the use of a unique treatment protocol in patients aged between 40 and 50 years. In all cases we used a cemented THA, and for acetabular deficiencies we also used impacted bone grafts together with a cemented cup

Early inhalant allergen sensitization at component level: an analysis in atopic Dutch children

BackgroundAllergic rhinitis is a common respiratory disease in children and sensitization to inhalant allergens plays a significant role in its development. However, limited knowledge exists regarding sensitization profiles of inhalant allergen components in atopic children, particularly in the very young individuals. Understanding these profiles could provide insights into the early development of allergic rhinitis. The objective of this cross-sectional retrospective study was to evaluate the IgE-sensitization profiles to multiple inhalant allergen components and their clinical relevance in Dutch atopic children, with specific focus on children under the age of 4 years.MethodsA total of 243 atopic children were included in the study and sensitization profiles were analyzed using multiplex microarray analysis (ISAC). Clinical information was obtained from records of a pediatric allergy outpatient clinic between 2011 and 2020. Specific IgE responses to inhalation allergen components from five allergen sources (grass pollen, tree pollen, house dust mite, cat and dog), were examined. The study encompassed children of different age groups and compared those with and without symptoms.ResultsThe results demonstrated that sensitization to inhalant allergen components was present in 92% of the cohort. Sensitization was already evident at a young age (87%), including infancy, with a rapid increase in prevalence after 1 year of age. House dust mite emerged as the most predominant sensitizing allergen in early childhood, followed by tree pollen in later years. Sensitization patterns were similar between symptomatic and asymptomatic children, although symptomatic children exhibited higher frequencies and values. The sensitization profiles in very young children were comparable to those of children across all age groups.ConclusionThese findings highlight the presence of sensitization to inhalant allergen components and the early onset of allergic rhinitis before the age of 4, including infancy, in Dutch atopic children. Notable allergen molecules in Dutch atopic children under the age of 4 years include Bet v 1, Fel d 1, Der f 1, Der p 1, Der p 10 and Phl p 4, with house dust mite sensitization being the most common among Dutch infants. Moreover, the prevalence of sensitization to inhalant allergens in this Dutch cohort surpassed that of general European populations, emphasizing the importance of early assessment and management of allergic rhinitis in young atopic children

Chronic Prednisolone Treatment Aggravates Hyperglycemia in Mice Fed a High-Fat Diet but Does Not Worsen Dietary Fat-Induced Insulin Resistance

textabstractSynthetic glucocorticoids such as prednisolone have potent antiinflammatory actions. Unfortunately, these drugs induce severe adverse effects in patients, many of which resemble features of the metabolic syndrome, such as insulin resistance. In this study, we investigated whether adverse effects of prednisolone on glucose homeostasis are aggravated in mice with compromised insulin sensitivity due to a high-fat diet by applying various methods to analyze changes in insulin sensitivity in mice. C57BL/6J micewerefed a high-fat diet for 6wkandtreated with either prednisolone (10 mg/kg · d) or vehicle for the last 7 d. Insulin sensitivity and blood glucose kinetics were analyzed with state-of-the-art stable isotope procedures in different experimental conditions. Prednisolone treatment aggravated fasting hyperglycemia and hyperinsulinemia caused by high-fat feeding, resulting in a higher homeostatic assessment model of insulin resistance. In addition, prednisolone-treated high-fat diet-fed mice appeared less insulin sensitive by detailed analysis of basal glucose kinetics. Remarkably, using hyperinsulinemic-euglycemic or hyperglycemic clamp techniques, neither hepatic nor peripheral insulin resistance was worsened in the group that was treated with prednisolone. Yet analysis of hepatic glucose metabolism revealed that prednisolone did alter glycogen balance by reducing glycogen synthase flux under hyperinsulinemic as well as hyperglycemic conditions. In addition to elevated insulin levels, prednisolone-treated mice showed a major rise in plasma leptin and fibroblast growth factor 21 levels. Our data indicate that prednisoloneinduced adverse effects on glucose metabolism in high-fat diet-fed mice do not reflect impaired insulin sensitivity but may be caused by other changes in the hormonal regulatory network controlling glucose metabolism such as fibroblast growth factor 21 and leptin. Copyrigh

Learning intrinsic excitability in medium spiny neurons

We present an unsupervised, local activation-dependent learning rule for intrinsic plasticity (IP) which affects the composition of ion channel conductances for single neurons in a use-dependent way. We use a single-compartment conductance-based model for medium spiny striatal neurons in order to show the effects of parametrization of individual ion channels on the neuronal activation function. We show that parameter changes within the physiological ranges are sufficient to create an ensemble of neurons with significantly different activation functions. We emphasize that the effects of intrinsic neuronal variability on spiking behavior require a distributed mode of synaptic input and can be eliminated by strongly correlated input. We show how variability and adaptivity in ion channel conductances can be utilized to store patterns without an additional contribution by synaptic plasticity (SP). The adaptation of the spike response may result in either "positive" or "negative" pattern learning. However, read-out of stored information depends on a distributed pattern of synaptic activity to let intrinsic variability determine spike response. We briefly discuss the implications of this conditional memory on learning and addiction.Comment: 20 pages, 8 figure

Phase II trial of natalizumab for the treatment of anti-Hu associated paraneoplastic neurological syndromes

BACKGROUND: Paraneoplastic neurological syndromes with anti-Hu antibodies (Hu-PNS) have a very poor prognosis: more than half of the patients become bedridden and median survival is less than 12 months. Several lines of evidence suggest a pathogenic T cell-mediated immune response. Therefore, we conducted a prospective open-label phase II trial with natalizumab. METHODS: Twenty Hu-PNS patients with progressive disease were treated with a maximum of three monthly natalizumab cycles (300 mg). The primary outcome measure was functional improvement, this was defined as at least one point decrease in modified Rankin Scale (mRS) score at the last treatment visit. In addition, treatment response was assessed wherein a mRS score ≤3 after treatment was defined as treatment responsive. RESULTS: The median age at onset was 67.8 years (SD 8.4) with a female predominance (n = 17, 85%). The median time from symptom onset to Hu-PNS diagnosis was 5 months (IQR 2–11). Most patients had subacute sensory neuronopathy (n = 15, 75%), with a median mRS of 4 at baseline. Thirteen patients had a tumor, all small cell lung cancer. After natalizumab treatment, two patients (10%) showed functional improvement. Of the remaining patients, 60% had a stable functional outcome, while 30% showed further deterioration. Treatment response was classified as positive in nine patients (45%). CONCLUSIONS: Natalizumab may ameliorate the disease course in Hu-PNS, but no superior effects above other reported immunosuppressive and immunomodulatory were observed. More effective treatment modalities are highly needed. TRIAL REGISTRATION: https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-000675-13/N

Brain stem encephalitis is a rare complication of COVID-19

Here, we describe the clinical phenotype of SARS-CoV-2-related CNS disease and evaluate the SARS-CoV-2 antibody index as a tool to differentiate between a direct (viral) and indirect etiology. Out of >4000 hospitalized patients with COVID-19, we included 13 patients with neurological symptoms with suspicion of neuroinflammation. On clinical grounds, eight were classified as having a possible/probable relationship between neurological symptoms and COVID-19. A clinically distinctive phenotype of brainstem and cerebellar symptoms was seen in 6/8 patients. As we found a positive SARS-CoV-2 antibody index in 3/5 patients, indicating specific intrathecal SARS-CoV-2 IgG production, a direct link with SARS-CoV-2 is likely

Treatment of knee prosthesis infections: evaluation of 15 patients over a 5-year period

Our objective was to evaluate different treatment alternatives for total knee arthroplasty (TKA) infection and to compare outcomes depending on adherence to a current treatment algorithm. All patients treated for a first episode of TKA infection between January 2000 and July 2005 were included. Patient records were reviewed and data were extracted retrospectively. Fifteen patients were followed up for a median of 25 months. The cure rate in patients with two-stage exchange of knee prosthesis was higher than in patients who had débridement without implant removal (100 vs 37%, p = 0.03). Cure rates were not different between these two surgical approaches in ten patients who were treated according to a current treatment algorithm. Success rates for treatment of TKA infections varied considerably with the treatment strategy chosen. Our results support the use of existing algorithms to select patients who are eligible for débridement with retention of the prosthesis or need two-stage exchange of knee implants

Value of EUS in Determining Curative Resectability in Reference to CT and FDG-PET: The Optimal Sequence in Preoperative Staging of Esophageal Cancer?

Background: The separate value of endoscopic ultrasonography (EUS), multidetector computed tomography (CT), and18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in the optimal sequence in staging esophageal cancer has not been investigated adequately. Methods: The staging records of 216 consecutive operable patients with esophageal cancer were reviewed blindly. Different staging strategies were analyzed, and the likelihood ratio (LR) of each module was calculated conditionally on individual patient characteristics. A logistic regression approach was used to determine the most favorable staging strategy. Results: Initial EUS results were not significantly related to the LRs of initial CT and FDG-PET results. The positive LR (LR+) of EUS-fine-needle aspiration (FNA) was 4, irrespective of CT and FDG-PET outcomes. The LR+ of FDG-PET varied from 13 (negative CT) to 6 (positive CT). The LR+ of CT ranged from 3-4 (negative FDG-PET) to 2-3 (positive FDG-PET). Age, histology, and tumor length had no significant impact on the LRs of the three diagnostic tests. Conclusions: This study argues in favor of PET/CT rather than EUS as a predictor of curative resectability in esophageal cancer. EUS does not correspond with either CT or FDG-PET. LRs of FDG-PET were substantially different between subgroups of negative and positive CT results and vice versa

Subnational climate entrepreneurship: innovative climate action in California and São Paulo

The distinct role of subnational governments such as states and provinces in addressing climate change has been increasingly acknowledged. But while most studies investigate the causes and consequences of particular governments’ actions and networking activities, this article argues that subnational governments can develop climate action as a collective entrepreneurial activity. Addressing many elements explored in this special issue, it focuses on the second question and identifies climate entrepreneurship in two subnational governments—the states of California (USA) and São Paulo (Brazil). Examining internal action, as well as interaction with local authorities, national governments and the international regime, entrepreneurial activities are identified in the invention, diffusion and evaluation of subnational climate policy in each case. The article draws from the recent scholarship on policy innovation, entrepreneurship and climate governance. It contributes to the literature by exploring entrepreneurial subnational government activity in addressing climate change and expanding the understanding of the effects of policy innovation at the subnational level