In Situ Photo-crosslinkable Hyaluronic Acid/Gelatin Hydrogel for Local Nitric Oxide Delivery.

An increasing number of studies have shown that the local release of nitric oxide (NO) from hydrogels stimulates tissue regeneration by modulating cell proliferation, angiogenesis, and inflammation. The potential biomedical uses of NO-releasing hydrogels can be expanded by enabling their application in a fluid state, followed by controlled gelation triggered by an external factor. In this study, we engineered a hydrogel composed of methacrylated hyaluronic acid (HAGMA) and thiolated gelatin (GELSH) with the capacity for in situ photo-cross-linking, coupled with localized NO release. To ensure a gradual and sustained NO release, we charged the hydrogels with poly(l-lactic-co-glycolic acid) (PLGA) nanoparticles functionalized with S-nitrosoglutathione (GSNO), safeguarding SNO group integrity during photo-cross-linking. The formation of thiol-ene bonds via the reaction between GELSH's thiol groups and HAGMA's vinyl groups substantially accelerated gelation (by a factor of 6) and increased the elastic modulus of hydrated hydrogels (by 1.9-2.4 times). HAGMA/GELSH hydrogels consistently released NO over a 14 day duration, with the release of NO depending on the hydrogels' equilibrium swelling degree, determined by the GELSH-to-HAGMA ratio. Biocompatibility assessments confirmed the suitability of these hydrogels for biological applications as they display low cytotoxicity and stimulated fibroblast adhesion and proliferation. In conclusion, in situ photo-cross-linkable HAGMA/GELSH hydrogels, loaded with PLGA-GSNO nanoparticles, present a promising avenue for achieving localized and sustained NO delivery in tissue regeneration applications.

Photocurable Nitric Oxide-Releasing Copolyester for the 3D Printing of Bioresorbable Vascular Stents.

The design of bioresorbable vascular stents (BVS) capable of releasing nitric oxide (NO) at the implant site may enable BVS to mimic the antiplatelet, antiproliferative, and pro-endothelial actions of NO, overcoming complications of BVS such as late thrombosis and restenosis. In this study, the fabrication of BVS composed of methacrylated poly(dodecanediol citrate-co-dodecanediol S-nitroso-mercaptosuccinate) (mP(DC-co-DMSNO)), a novel elastomeric, bioabsorbable, and photocurable copolyester, containing covalently bound S-nitrosothiol groups in the carbon backbone of the polymer, is reported. The mP(DC-co-DMSNO) stents are manufactured via photoinduced 3D printing and allow deployment via a self-expansion process from a balloon catheter. After deployment, hydration of the stents triggers the release of NO, which is maintained during the slow hydrolysis of the polymer. Real-time NO release measurements show that by varying the copolyester composition and the strut geometry of the mP(DC-co-DMSNO) stents, it is possible to modulate their NO release rate in the range of 30-52 pmol min-1 cm-2 . Preliminary biological assays in cell culture show that endothelial cells adhere to the surface of the stents and that NO release favors their endothelization. Thus, mP(DC-co-DMSNO) may emerge as a new platform for the fabrication of advanced BVS.

Determinants and prognostic value of in-hospital infection in patients waiting for permanent pacemaker implantation.

BACKGROUND: In-hospital delays in permanent cardiac pacemaker (PPM) implantation are common and may result in in-hospital infection among patients waiting for PPM implantation (pre-PPM-HI). This study investigated the predictors and prognostic impact of these events. METHODS: We retrospectively evaluated 905 consecutive patients (68.2 ± 16.0 years; 54% males) who underwent PPM implantation. Clinical characteristics, pre-PPM-HI and 30-day mortality were recorded and a risk score for pre-PPM-HI was generated using multivariable logistic regression coefficients. RESULTS: Eigthy-nine patients (10% of the sample) developed pre-PPM-HI. Multivariable logistic regression analysis identified urinary catheter use, complete atrioventricular block, implantation of temporary pacemaker and diabetes mellitus as independent predictors of pre-PPM-HI. The generated score (range 0-10.1) played a better role in predicting pre-PPM-HI than individual factors, yielding an area under the curve [95%CI] of 0.754 [0.705-0.803]. Patients with score ≥ 7.5 had 18-fold greater risk of developing pre-PPM-HI than those with score < 2.5. Furthermore, multivariable Cox-regression analysis showed that patients who developed pre-PPM-HI had greater 30-day mortality after PPM implantation (hazard ratio [95%CI] = 2.90 [1.18-7.16], p = 0.021) compared with their counterparts. CONCLUSIONS: This study reveals that pre-PPM-HI is an independent predictor of early mortality after PPM implantation. In addition, a clinical score developed from simple clinical variables accurately identified patients at high risk of pre-PPM-HI. In scenarios where delays in PPM implantation are unavoidable, such as reference hospitals with high demand, the use of this tool can potentially help in the hierarchy of patients and in the reduction of this adverse event.

Left Ventricular Concentric Geometric Patterns Are Associated With Worse Prognosis Among Patients With Type-A Aortic Dissection.

Background This study compared left ventricular (LV) characteristics between patients with type-A and type-B aortic dissection (AD) and evaluated the ability of LV remodeling phenotypes (hypertrophy, concentricity, or geometric patterns) to predict mortality in both AD types. Methods and Results We evaluated 236 patients with type A and 120 patients with type B who had echocardiograms within 60 days before or after AD diagnosis (median [25th, 75th percentiles] time difference between echocardiogram and AD diagnosis=1 [0, 6] days) from 3 centers. Patients were stratified according to LV phenotypes, and early (90-day) and late (1-year) mortality after AD diagnosis were assessed. In adjusted logistic regression analysis, patients with type A had higher and lower odds of concentric and eccentric hypertrophy (odds ratio [OR], 2.56; 95% CI, 1.50-4.36; P<0.001; and OR, 0.55; 95% CI, 0.31-0.97; P=0.039, respectively) than those with type B. Results of multivariable Cox-regression analysis showed that LV remodeling phenotypes were not related to mortality in patients with type B. By contrast, LV concentricity was associated with greater early and late mortality (hazard ratio [HR], 2.22; 95% CI, 1.24-3.96; P=0.007 and HR, 2.06; 95% CI, 1.20-3.54; P=0.009, respectively) in type A. In further analysis considering normal LV geometry as reference, LV concentric remodeling and concentric hypertrophy were associated with early mortality (HR, 7.78; 95% CI, 2.35-25.78; P<0.001 and HR, 4.38; 95% CI, 1.47-13.11; P=0.008, respectively), whereas concentric remodeling was associated with late mortality (HR, 5.40; 95% CI, 1.91-15.26; P<0.001) among patients with type A. Assessment of LV geometric patterns and concentricity provided incremental prognostic value in predicting early and late mortality beyond clinical variables in patients with type A based on net reclassification improvement and integrated discrimination improvement. Conclusions LV geometric patterns derived from LV concentricity were associated with greater mortality among patients with type A and may be markers of adverse prognosis in this population.

Impact of Hypertension History and Blood Pressure at Presentation on Cardiac Remodeling and Mortality in Aortic Dissection.

OBJECTIVE: This study compared clinical, echocardiographic, and prognostic characteristics among patients with aortic dissection (AD) with (HypHist) and without (No-HypHist) hypertension history and evaluated the association of blood pressure (BP) at presentation with 1-year mortality, left ventricular (LV) remodeling and renal dysfunction. METHODS: We investigated clinical and echocardiographic characteristics and 1-year mortality among 367 patients with AD (81% HypHist, 66% Type-A) from three Brazilian centers. RESULTS: Patients with No-HypHist were more likely to have Marfan syndrome, bicuspid aortic valve, to undergo surgical therapy, were less likely to have LV hypertrophy and concentricity, and had similar mortality compared with HypHist patients. Adjusted restricted cubic spline analysis showed that systolic BP (SBP) and diastolic BP (DBP) at presentation had a J-curve association with mortality among patients with No-HypHist, but did not associate with death among patients with HypHist (p for interaction = 0.001 for SBP and = 0.022 for DBP). Conversely, the association between SBP at presentation and mortality was influenced by previous use of antihypertensive medications in the HypHist group (p for interaction = 0.002). Results of multivariable logistic regression analysis comprising the whole sample showed direct associations of SBP and DBP at presentation with LV hypertrophy (p = 0.009) and LV concentricity (p = 0.015), respectively, and an inverse association between pulse pressure at presentation and estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 (p = 0.008). CONCLUSION: Combined information on BP at presentation, previous diagnosis of hypertension, and use of antihypertensive medications might be useful to predict mortality risk and to estimate extra-aortic end-organ damage among patients with AD.

Botryosphaeran, a (1 → 3)(1 → 6)-ß-D-glucan, reduces tumor development and cachexia syndrome in obese male rats by increasing insulin sensitivity and FOXO3a activity.

Obesity is an important risk factor in tumor development. Botryosphaeran, a (1 â†’ 3)(1 â†’ 6)-ß-D-glucan, produced by the fungus Botryosphaeria rhodina (MAMB-05), is a high molecular mass, water-soluble exopolysaccharide. It consists of a main chain of (1 â†’ 3)-linked ß-d-glucose units, with a degree of branching of ~22% at carbon-6 with glucose and gentiobiose residues linked through ß-(1 â†’ 6)-bonds, and presents a triple helix conformation. Botryosphaeran presents anticlastogenic, antiproliferative, pro-apoptotic and anti-obesogenic activities. This study evaluated the effects of botryosphaeran on tumor development in obesity and analyzed its mechanism of action. Obesity was induced in male Wistar rats by a high-fat/high-sugar diet. After 9 weeks, rats were divided into two groups: Obese Tumor (OT) and Obese Tumor Botryosphaeran (OTB), and inoculated with 1 × 107 Walker-256 tumor cells, and treatment with botryosphaeran (30 mg/kg b.w./day via gavage for 15 days) commenced. On the 11th week, biological parameters, tumor development, metabolic profile, erythrogram and protein expression were evaluated. Botryosphaeran significantly reduced tumor growth, body-weight loss and cachexia. Furthermore, botryosphaeran decreased mesenteric fat and insulin resistance, corrected macrocytic anemia, and increased Forkhead transcription factor-3a (FOXO3a) activity. Our study demonstrated the potential role of botryosphaeran in the management of cancer in tumor-bearing obese rats by increasing insulin sensitivity and FOXO3a activity.

Tumor development in rats and cancer cachexia are reduced by treatment with botryosphaeran by increasing apoptosis and improving the metabolic profile.

AIMS: Cancer is a multifactorial disease characterized by an uncontrolled growth of cells that can lead to cachexia-anorexia syndrome. Botryosphaeran, a fungal (1 â†’ 3)(1 â†’ 6)-ß-D-glucan produced by Botryosphaeria rhodina MAMB-05, has presented antimutagenic, antiproliferative, pro-apoptotic, hypoglycemic and hypocholesterolemic effects. This study evaluated the effects of botryosphaeran (30 mg/kg b.w./day) on tumor development and cachexia syndrome in Walker-256 tumor-bearing rats, and also the metabolic and hematological profiles of these animals. MATERIALS AND METHODS: Male Wistar rats were divided into 3 groups: control (C), control tumor (CT) and control tumor botryosphaeran (CTB). On the first day, 1 × 107 Walker-256 tumor cells were inoculated subcutaneously into the right flank of the CT and CTB rats, and concomitantly treatment with botryosphaeran (30 mg/kg b.w./day) started. After the 15th day of treatment, biological parameters, tumor development, cachexia, glucose and lipid profiles, hemogram and protein expression were analyzed. KEY FINDINGS: Botryosphaeran significantly reduced tumor development (p = 0.0024) and cancer cachexia, modulated the levels of glucose, triglycerides and HDL-cholesterol, and corrected macrocytic anemia. Botryosphaeran also increased significantly the bax expression in the tumor tissue (p = 0.038) demonstrating that this (1 â†’ 3)(1 â†’ 6)-ß-D-glucan is increasing the apoptosis of tumor cells. p53, p27, bcl-2, caspase-3 and Forkhead transcription factor 3a (FOXO3a) protein expression were similar among the groups. SIGNIFICANCE: This study demonstrated that botryosphaeran was effective in decreasing tumor development and cachexia by direct and indirect mechanisms increasing apoptosis and improving the metabolic and hematological profiles.

Preparation of Organic Nitrates from Aryldiazoacetates and Fe(NO3)3·9H2O.

A thermal protocol is reported for the formal insertion of nitric acid into aryldiazoacetates using Fe(NO3)3·9H2O. This strategy is mild and high yielding and allows the preparation of a large variety of members of an unprecedented family of organic nitrates. The nitrate group can be also readily transformed into other functional groups and heterocyclic moieties and can possibly allow new biological explorations of untapped potential associated with their NO-releasing ability.

Orbital Compartment Syndrome After Frontotemporal Craniotomy: Case Report and Review of Literature.

INTRODUCTION: Orbital compartment syndrome (OCS) is a rare condition characterized by increased intraorbital pressure and hypoperfusion of critical neural structures. It is usually associated with external ophthalmoplegia. We report a case of postoperative OCS following a frontotemporal craniotomy and review pertinent literature. CASE DESCRIPTION: A 3-year-old female patient presented with a 3-year history of refractory epilepsy and diagnosis of right frontobasal cortical dysplasia. She underwent an elective frontotemporal craniotomy to allow resection of dysplastic cortex. The intraoperative period was uneventful. Postoperatively, following removal of operating fields, we noticed proptosis and right periorbital swelling. A diagnosis of orbital compartment syndrome was made. At the pediatric intensive care unit, the patient underwent an emergency right lateral canthotomy with wide inferior and superior cantholysis. Nowadays she is in the fourth month of postoperative follow-up. There is still slight and almost indistinguishable exophthalmos, but her extrinsic eye movement ranges and reaction to light are normal. DISCUSSION: OCS is a rare ophthalmologic emergency characterized by an acute rise in orbital pressure and may result in complete irreversible blindness if not rapidly treated. The frontotemporal or "pterional" craniotomy exposure requires a myocutaneous flap to be retracted anteriorly and inferiorly near the orbit. There may be orbital compression due to this flap leading to potential harmful complications. Attention to factors such as direct ocular pressure from skin flaps, congestion from head positioning, and adequate intraoperative eye protection may reduce the risk or allow faster management.

Performance of the fixed pressure valve with antisiphon device SPHERA® in the treatment of normal pressure hydrocephalus and prevention of overdrainage / Efeito da válvula de pressão fixa com antisifão SPHERA®no tratamento da hidrocefalia de pressão normal e prevenção de hiperdrenagem

ABSTRACT Normal pressure hydrocephalus (NPH) is characterized by the triad of gait apraxia, dementia and urinary incontinence associated with ventriculomegaly and normal pressure of cerebrospinal fluid. Treatment is accomplished through the implantation of a ventricular shunt (VPS), however some complications are still frequent, like overdrainage due to siphon effect. This study analyses the performance of a valve with anti-siphon device (SPHERA®) in the treatment of patients with NPH and compares it with another group of patients with NPH who underwent the same procedure without anti-siphon mechanism (PS Medical® valve). 30 patients were consecutively enrolled in two groups with 15 patients each and followed clinically and radiologically for 1 year. Patients submitted to VPS with SPHERA® valve had the same clinical improvement as patients submitted to VPS with PS Medical®. However, complications and symptomatology due to overdrainage were significantly lower in SPHERA® group, suggesting it as a safe tool to treat NPH.

RESUMO A hidrocefalia de pressão normal (HPN) é caracterizada pela tríade de sintomas de apraxia de marcha, demência e incontinência urinária. O tratamento padrão é realizado através de implantação de derivação ventricular, porém várias complicações são frequentes, como a hiperdrenagem secundária ao efeito sifão. Este estudo avaliou o resultado da válvula SPHERA® no tratamento desses pacientes em comparação com um grupo controle (PS Medical®). 30 pacientes foram consecutivamente alocados em dois grupos de 15 e seguidos por 1 ano. Pacientes com a válvula SPHERA® tiveram o mesmo grau de melhora clínica em comparação ao grupo controle, no entanto as complicações diagnósticadas e sintomatologia secundária à hiperdrenagem foi significativamente inferior no grupo da válvula SPHERA® group, sugerindo-a como uma ferramenta segura e aplicável.

Intradural calcifying pseudoneoplasm of the neuraxis presenting as a cauda equina syndrome.

BACKGROUND: Calcifying nonneoplastic pseudoneoplasms of the neuraxis (CAPNON) have been reported in 59 cases in literature, however, they rarely involve the spinal cord. Owing to the advances in immunohistochemical markers, their structure and origin are better understood now. CASE REPORT: We present the case of a 72-year-old female who had longstanding history of low back pain that exacerbated 20 days prior to the presentation to the emergency room with a frank cauda equina syndrome. The lumbar computed tomography scan showed a hyperdense lesion, suggestive of calcified tumor, whereas the magnetic resonance imaging revealed a hypointense lesion on theT1 and T2-weighted images, without contrast enhancement or edema on fluid-attenuated inversion recovery. She underwent an emergent L2-L4 laminectomy and L3-L4 discectomy with resection of L2 intradural tumor, following which she regained normal function. CONCLUSION: A 72-year-old female presented with a cauda equina syndrome attributed to an L2 intradural CAPNON. Following gross total resection, the patient was neurologically intact.

Performance of the fixed pressure valve with antisiphon device SPHERA® in the treatment of normal pressure hydrocephalus and prevention of overdrainage.

Normal pressure hydrocephalus (NPH) is characterized by the triad of gait apraxia, dementia and urinary incontinence associated with ventriculomegaly and normal pressure of cerebrospinal fluid. Treatment is accomplished through the implantation of a ventricular shunt (VPS), however some complications are still frequent, like overdrainage due to siphon effect. This study analyses the performance of a valve with anti-siphon device (SPHERA®) in the treatment of patients with NPH and compares it with another group of patients with NPH who underwent the same procedure without anti-siphon mechanism (PS Medical® valve). 30 patients were consecutively enrolled in two groups with 15 patients each and followed clinically and radiologically for 1 year. Patients submitted to VPS with SPHERA® valve had the same clinical improvement as patients submitted to VPS with PS Medical®. However, complications and symptomatology due to overdrainage were significantly lower in SPHERA® group, suggesting it as a safe tool to treat NPH.

Psychiatric symptoms are present in most of the patients with idiopathic normal pressure hydrocephalus.

Normal pressure hydrocephalus (NPH) is characterized by gait disturbance, dementia and/or urinary incontinence associated with dilation of ventricular system with normal opening cerebrospinal fluid pressure. Wide scientifical evidence confirms association between NPH and psychiatric symptoms. We selected 35 patients with idiopathic normal pressure hydrocephalus from January 2010 to January 2012 in a Brazilian tertiary hospital and performed a formal psychiatric evaluation to identify psychiatric disorders. Psychiatric disorders were present in 71% of these patients, especially anxiety, depression and psychotic syndromes. NPH patients may develop symptoms with frontal dominance, such as personality changes, anxiety, depression, psychotic syndromes, obsessive compulsive disorder, Othello syndrome; shoplifting and mania. Unusual appearances of NPH symptoms may hinder early diagnosis and consequently proper treatment.

Psychiatric symptoms are present in most of the patients with idiopathic normal pressure hydrocephalus / Sintomas psiquiátricos são encontrados na maioria dos pacientes com hidrocefalia de pressão normal idiopática

Normal pressure hydrocephalus (NPH) is characterized by gait disturbance, dementia and/or urinary incontinence associated with dilation of ventricular system with normal opening cerebrospinal fluid pressure. Wide scientifical evidence confirms association between NPH and psychiatric symptoms. We selected 35 patients with idiopathic normal pressure hydrocephalus from January 2010 to January 2012 in a Brazilian tertiary hospital and performed a formal psychiatric evaluation to identify psychiatric disorders. Psychiatric disorders were present in 71% of these patients, especially anxiety, depression and psychotic syndromes. NPH patients may develop symptoms with frontal dominance, such as personality changes, anxiety, depression, psychotic syndromes, obsessive compulsive disorder, Othello syndrome; shoplifting and mania. Unusual appearances of NPH symptoms may hinder early diagnosis and consequently proper treatment.

A hidrocefalia de pressão normal (HPN) é caracterizada por distúrbios da marcha, demência e/ou incontinência urinária associada com dilatação do sistema ventricular e pressão de abertura do líquido cefalorraquidiano normal. Evidências científicas confirmam associação entre HPN e sintomas psiquiátricos. Foram selecionados 35 pacientes com hidrocefalia de pressão normal idiopática, de janeiro de 2010 a janeiro de 2012 em um hospital terciário brasileiro e realizada uma avaliação psiquiátrica formal para identificar transtornos psiquiátricos. Transtornos psiquiátricos foram detectados em 71% dos pacientes, principalmente depressão, ansiedade e síndromes psicóticas. Pacientes com HPN podem desenvolver sintomas com predomínio frontal, tais como mudanças de personalidade, ansiedade, depressão, síndromes psicóticas, transtorno obsessivo compulsivo, síndrome de Otelo, furtos e mania. Sintomas incomuns de HPN podem dificultar o diagnóstico precoce e o tratamento adequado.

Neuroendoscopic assessment of choroid plexus coagulation to release ventricular catheter: note on the seldinger technique.

Shunting is fundamental in neurosurgical practice and a large number of patients experience shunt dysfunction throughout life. The Seldinger technique seems to be a valuable tool in the management of dysfunctions and consists of coagulating the choroid plexus before shunt removal. We report the unique case of a neuroendoscopic view of choroid plexus coagulation by the Seldinger technique in a 7-year-old child with shunt dysfunction submitted to endoscopic third ventriculostomy and previous shunt removal. We reinforce the security and efficacy of the Seldinger technique with a direct neuroendoscopic view of the coagulation process.