Surgical Management of Craniovertebral Junction Schwannomas: A Systematic Review

Background: Craniovertebral junction (CVJ) schwannomas are rare, with surgery and stereotactic radiosurgery (SRS) being effective yet challenging options. We systematically reviewed the literature on CVJ schwannomas. Methods: PubMed, Scopus, Web-of-Science, and Cochrane were searched following the PRISMA statement to include studies reporting CVJ schwannomas. Clinical features, management, and outcomes were analyzed. Results: We collected 353 patients from 101 included articles. Presenting symptoms were mostly neck pain (30.3%) and headache (26.3%), with most cranial neuropathies involving the XII (31.2%) and X (24.4%) nerves. Most tumors originated from C2 (30.9%) and XII (29.4%) nerves, being extracranial (45.1%) and intradural-extradural (44.2%). Erosion of C1–C2 vertebrae (37.1%), the hypoglossal canal (28.3%), and/or jugular foramen (20.1%) were noted. All tumors were operated, preferably with the retrosigmoid approach (36.5%), with the far-lateral approach (29.7%) or with the posterior approach and cervical laminectomy (26.9%), far-lateral approaches (14.2%), or suboccipital craniotomy with concurrent cervical laminectomy (14.2%). Complete tumor resection was obtained most frequently (61.5%). Adjuvant post-surgery stereotactic radiosurgery was delivered in 5.9% patients. Median follow-up was 27 months (range, 12–252). Symptom improvement was noted in 88.1% of cases, and cranial neuropathies showed improvement in 10.2%. Post-surgical complications occurred in 83 patients (23.5%), mostly dysphagia (7.4%), new cranial neuropathies (6.2%), and cerebrospinal fluid leak (5.9%). A total of 16 patients (4.5%) had tumor recurrence and 7 died (2%), with median overall survival of 2.7 months (range, 0.1–252). Conclusions: Microsurgical resection is safe and effective for CVJ schwannomas. Data on SRS efficacy and indications are still lacking, and its role deserves further evaluation.     

Bond Behavior of Steel Cords Embedded in Inorganic Mortars

This paper investigates the bond behavior of steel cords embedded in inorganic matrices. A series of pull-out tests were carried out on individual galvanized steel cords embedded in either a cementitious or lime-based mortar matrix and the corresponding bond-slip relationships were derived. The quality of bond between cord and mortar was found to be critically affected by the workability of the mortar and its ability to create adequate composite action along the entire embedment length of the cord. The more workable lime-based mortar was found to guarantee a better interaction with the steel cord, in terms of initial bond stiffness, maximum bond strength, and post-peak behavior. The experimentally derived bond–slip relationships were subsequently integrated in a 3D non-linear finite element framework and used to determine the constitutive relationship of a surface-based cohesive contact between cord and mortar. The cohesive bond behavior was used to conduct a series of parametric studies on cords embedded in a lime-based mortar and examine the stress development within specimens with cords of different embedment lengths and subjected to different loading conditions (i.e., pull-out and direct tension). The active ‘Stress Transfer Zone’ was found to be about 125 mm, while an ‘Effective Transfer Radius’ of approximately 3.5–4 mm was identified. The numerical investigation implemented in this paper enabled one to study key interaction properties of steel reinforced grouts and can assist the design of more effective strengthening solutions.     

Evaluation of the Nutritional Status of Gaucher Disease Type I Patients under Enzyme Replacement Treatment

(1) Background: Gaucher disease (GD) is a rare lysosomal storage disease. The few studies analyzing Resting Energy Expenditure (REE) in GD involved mainly untreated patients and supported a hypermetabolic condition possibly due to the associated inflammatory state. Definitive conclusions could not be drawn also because of the heterogeneity and the small size of the samples investigated. In order to expand current knowledge concerning, in particular the condition of patients under Enzyme Replacement Therapy (ERT), we evaluated the nutritional status of a relatively large sample of GD patients followed at Federico II University Hospital in Naples, Italy. (2) Methods: The study, having a cross-sectional design and involving 26 patients on ERT, included routine biochemical analyses, bioelectrical impedance analysis, indirect calorimetry, and administration of food frequency and physical activity questionnaires. The results in GD patients were compared with those from an appropriate control group. (3) Results: GD patients had normal biochemical parameters in 80% of cases, except for HDL-cholesterol, consumed a hyper-lipidic diet, and had a 60% prevalence of overweight/obesity. Body composition did not differ between patients and controls; however, measured REE was significantly lower than predicted and was reduced in comparison with the healthy controls. (4) Conclusions: This study provided novel elements to the present knowledge about REE and the nutritional status of GD patients under ERT. Its results warrant confirmation in even larger GD population samples and a more in-depth investigation of the long-term effects of treatment superimposed on the basic pathophysiological disease condition.     

Transplacental passage of Pt after treatment with the new triamine complex cis-diaminechloro-[2-(diethylamino) ethyl 4-amino-benzoate,N<Superscript>4</Superscript>]-chloride platinum (II) monohydrochloride monohydrate

Cis-diaminechloro-[2-(diethylamino) ethyl 4-amino-benzoate, N⁴]-chloride platinum (II) monohydrochloride monohydrate (DPR) is a monofunctional Pt triamine complex synthesized starting from cisplatin and procaine hydrochloride, characterized by a good antitumor activity coupled with low toxic effects and able to impair prenatal development of mice but at doses outside or just in the upper range of therapeutic doses. In the present paper the transplacental passage of DPR-derived Pt was investigated in CD1 mice on days 9, 13, 16 and 18 of pregnancy, 24 h after ip administration of 21 mg/kg DPR. For comparison, groups of mice were treated with an equivalent Pt-containing dose of cisplatin (10.7 mg/kg). Similarly to cisplatin, small amounts of Pt were detected in fetuses on day 9. From day 13 of gestation the concentration of DPR- and cisplatin-derived Pt increased up to the highest fetal concentrations detected on day 16. On day 18 the concentration of Pt decreased. Most importantly, on days 13–18 of pregnancy cisplatin-derived Pt was always significantly higher than that assayed after DPR administration. In addition, on day 13 of pregnancy Pt exposure of fetuses was significantly higher when dams were treated with cisplatin (AUC_0.5–24= 3.40 vs. 4.95 g·h/g). Finally, it is worth noting that serum decay of Pt after DPR or cisplatin administration in adult female mice was similar with AUC_0.13–2h s of 7.5 and 6.6 g·h/ml, respectively. When we determined the concentration of Pt into the main organs of fetuses from dams treated with either DPR or cisplatin on day 18 of gestation, we observed a different organ distribution. In fact, while the concentration of DPR-derived Pt was greater in the heart (1.08±0.30 vs. 0.78±0.35 g/g, p <0.10), an opposite situation was found in the kidney (0.51±0.20 vs. 0.69±0.22 g/g, p <0.05). In conclusion, our data show that DPR may pass through the placenta with an efficiency significantly lower than that of cisplatin. This finding may represent one of the possible causes of the lower embryotoxic/teratogenic effect of DPR as compared to cisplatin.     

Smart Offloading Boot System for Remote Patient Monitoring: Toward Adherence Reinforcement and Proper Physical Activity Prescription for Diabetic Foot Ulcer Patients

Background:A critical factor in healing diabetic foot ulcers is patient adherence to offloading devices. We tested a smart offloading boot (SmartBoot) combined with a smartwatch app and cloud dashboard to remotely monitor patient adherence and activity. In addition, the impact of SmartBoot on balance, gait, and user experience was investigated.Methods:Fourteen volunteers (31.6±8.7 years; 64% female) performed natural activities (eg, sitting, standing, walking) with and without the SmartBoot for approximately 30 minutes. All participants completed balance tests, 10-meter walking tests at slow, normal, and fast pace while wearing the SmartBoot, and a user experience questionnaire. The accuracy of real-time adherence reporting was assessed by comparing the SmartBoot and staff observation. Center of mass (COM) sway and step counts were measured using a validated wearable system.Results:Average sensitivity, specificity, and accuracy for adherence and non-adherence were 90.6%, 88.0%, and 89.3%, respectively. The COM sway area was significantly smaller with the SmartBoot than without the SmartBoot regardless of test condition. Step count error was 4.4% for slow waking, 36.2% for normal walking, 16.0% for fast walking. Most participants agreed that the SmartBoot is easy to use, relatively comfortable, nonintrusive, and innovative.Conclusions:To our knowledge, this is the first smart offloading system that enables remote patient monitoring and real-time adherence and activity reporting. The SmartBoot enhanced balance performance, likely due to somatosensory feedback. Questionnaire results highlight SmartBoot’s technical and clinical potential. Future studies warrant clinical validation of real-time non-adherence alerting to improve wound healing outcomes in people with diabetic foot ulcers.     

Depressive symptoms in amnesic mild cognitive impairment: an FDG-PET/CT study

IntroductionThe detection in mild cognitive impairment (MCI) of metabolic alterations suggestive of depression and/or of evolution to dementia.MethodsSixty-nine MCI patients underwent clinical and imaging evaluation including position emission tomography/computed tomography with fluorodeoxy-glucose (FDG-PET/CT).ResultsThe metabolism mean values in parietal, temporal and pre-cuneus areas were lower in subjects who evolved to dementia, and in frontal and in anterior cingulate areas in depressed subjects. Abnormal metabolism values were higher in the frontal and parietal lobes, and in the precuneus in subjects who evolved to dementia independently from depression.ConclusionsIn MCI FDG-PET/CT abnormality patterns suggest the presence of depression or the evolution to dementia.     

Selective Inhibition of Ii-dependent Antigen Presentation by Helicobacter pylori Toxin VacA

A major virulence factor in the stomach chronic infection by Helicobacter pylori is a protein toxin (VacA), which alters cell membrane trafficking of late endosomal/prelysosomal compartments. Its role in the chronic infection established by H. pylori is unknown. To test the possibility that VacA alters antigen processing taking place in prelysosomal compartments, we have used the well-established model of antigen processing and presentation consisting of tetanus toxoid–specific human (CD4⁺) T cells stimulated by autologous antigen-pulsed Epstein-Barr virus-transformed B cells. We found that VacA interferes with proteolytic processing of tetanus toxin and toxoid and specifically inhibits the Ii-dependent pathway of antigen presentation mediated by newly synthesized major histocompatibility complex (MHC) class II, while leaving unaffected the presentation pathway dependent on recycling MHC class II. The results presented here suggest that VacA may contribute to the persistence of H. pylori by interfering with protective immunity and that this toxin is a new useful tool in the study of the different pathways of antigen presentation.More than 50% of the world population is infected with Helicobacter pylori, but most infections remain asymptomatic and only 10% of infected people become sick at some point in their life (1, 2). A close correlation has been established between the prolonged infection of the human stomach mucosa by H. pylori and the development of gastritis, and gastroduodenal ulcers, and with an increased risk of developing adenocarcinomas and other gastric tumors (1–3). In fact, H. pylori has been classified as a class I cancerogenic agent, being one of the factors involved in the development of stomach cancers. This bacterium enters the mucus layer covering the stomach epithelium and colonizes the human gastric mucosa: such infection may persist for decades. Bacterial factors necessary for colonization (for review see reference 1) are the flagella, which make this bacterium highly motile, adhesins, which strongly bind the saccharide moiety of glycoproteins and glycolipids, and a powerful urease, which buffers the acid stomach environment by releasing ammonia. Biopsies from patients affected by gastroduodenal ulcers almost invariably contain H. pylori strains harboring a pathogenicity island (4), characterized by the presence of the gene encoding for the 128-kD CagA protein, the major H. pylori antigen. Such strains also produce a 145-kD precursor that is processed and released in the culture medium as a 95-kD protein toxin (VacA), whose role in H. pylori infection is unknown (5).VacA perturbs endocytosis at a prelysosomal stage in a process requiring the activity of the small GTPase Rab7 (6). This causes the formation and accumulation of compartments endowed with the vacuolar ATPase and with membrane markers both of late endosomes and lysosomes (6–8). In particular, the presence of Rab7 and lysosomal membrane glycoproteins, and the parallel absence of the cation-independent mannose 6-P receptor, allows the identification of those vesicles as an intermediate between late endosomes and lysosomes (7). A similar profile of markers is present in the compartments of APCs, where antigen proteolytic processing takes place (for review see reference 9).Here, we have considered the possibility that VacA inhibits antigen processing by interfering with late endocytic membrane trafficking by APCs. This would in turn lower the proliferation of autologous human (CD4⁺) T cells triggered by recognition of antigenic epitopes bound to MHC class II molecules exposed on APC surfaces (10). We have used the well-defined cellular system of antigen processing and presentation consisting of human tetanus toxoid (TT)– specific (CD4⁺) T cells stimulated by autologous antigen-pulsed EBV-transformed B cells (10). TT is the most used human vaccine and its proteolytic processing and presentation by human lymphoid cells in culture has been intensively investigated (10–13). By using T cell clones with different specificity, we found that VacA interferes with the generation of T cell epitopes loaded on newly synthesized MHC class II molecules (the Ii-dependent pathway of antigen presentation), leaving unaffected generation and presentation of epitopes by class II molecules that recycle through early endosomal compartments (invariant chain [Ii]–independent pathway).     

Elevated serum uric acid is associated with a greater inflammatory response and with short- and long-term mortality in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention

Background and aimsDespite elevated serum uric acid (eSUA) has been identified as independent risk factor for cardiovascular diseases, its prognostic value in the setting of ST-segment elevation myocardial infarction (STEMI) is still controversial. Although the mechanisms of this possible relationship are unsettled it has been suggested that eSUA could trigger the inflammatory response. This study sought to investigate the association between eSUA with short- and long-term mortality and with inflammatory response in patients with STEMI treated with primary percutaneous coronary intervention (pPCI).Methods and resultsBlood samples were collected on admission and at 24 and 48 h after pPCI: the inflammatory biomarkers C-reactive protein (CRP), neutrophil count and neutrophil to lymphocytes ratio (NLR) were considered. Baseline eSUA was defined as ≥6.8 mg/dl. Cumulative 30-days and 1-year mortalities were estimated using the Kaplan-Meyer analysis. Multivariable analyses were performed by Cox proportional hazard models.In the 2369 patients with STEMI considered, 30-day mortality was 5.8% among patients with eSUA and 2% among patient with normal SUA level (p < 0.001); 1-year mortality was 8.5% vs 4%, respectively (p < 0.001). At multivariable analyses eSUA was an independent predictor of 30-day mortality (HR 1.196, 95%CI 1.006–1.321, p = 0.042) and 1-year mortality (HR 1.178, 95%CI 1.052–1.320, p = 0.005). eSUA patients presented higher values in on admission CRP (p < 0.001) and in neutrophil count and NLR at 24 h (respectively, p = 0.020 and p < 0.001) and at 48 h (p = 0.018 and p < 0.001) compared to patients with normal SUA levels.ConclusionsElevated serum uric acid is associated with higher short- and long-term mortality and with a greater inflammatory response after reperfusion in patients with STEMI treated with primary PCI.     

Elevated serum uric acid is a predictor of contrast associated acute kidney injury in patient with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention

BackgroundContrast associated-acute kidney injury (CA-AKI) has been associated with adverse outcomes after ST-segment elevation myocardial infarction (STEMI). However, early markers of CA-AKI are still needed to improve risk stratification. We investigated the association between elevated serum uric acid (eSUA) and CA-AKI in patients with STEMI treated with primary percutaneous coronary intervention (pPCI).Methods and resultsSerum creatinine (Scr) was measured at admission and 24, 48 and 72 h after pPCI. CA-AKI was defined as an increase of 25% (CA-AKI 25%) or 0.5 mg/dl (CA-AKI 0.5) of Scr level above the baseline after 48 h following contrast administration. Multivariable analyses to investigate CA-AKI predictors were performed by binary logistic regression and multivariable backward logistic regression model.In the 3023 patients considered, CA-AKI was more frequent among patients with eSUA as compared with patients with normal SUA levels, considering both CA-AKI definitions (CA-AKI25%: 20.8% vs 16.2%, p < 0.012; CA-AKI 0.5: 10.1% vs 5.8%, p < 0.001). The association between eSUA and CA-AKI was confirmed at multivariable analyses (CA-AKI 25%: odd ratio 1.32, 95% CI 1.03–1.69, p = 0.027; CA-AKI 0.5: odd ratio 1.76, 95% CI 1.11–2.79, p = 0.016).ConclusionElevated serum uric acid is associated with CA-AKI after reperfusion in patients with STEMI treated with pPCI.