Predicting intraoperative feasibility of combined TES-mMEP and cSSEP monitoring during scoliosis surgery based on preoperative neurophysiological assessment

Background contextCombined monitoring of muscle motor evoked potentials elicited by transcranial electric stimulation (TES-mMEP) and cortical somatosensory evoked potentials (cSSEPs) is safe and effective for spinal cord monitoring during scoliosis surgery. However, TES-mMEP/cSSEP is not always feasible. Predictors of feasibility would help to plan the monitoring strategy.PurposeTo identify predictors of the feasibility of TES-mMEP/cSSEP during scoliosis surgery.Study design/settingProspective cohort study in a clinical neurophysiology unit and pediatric orthopedic department of a French university hospital.Patient sampleA total of 103 children aged 2 to 19 years scheduled for scoliosis surgery.Outcome measuresFeasibility rate of intraoperative TES-mMEP/cSSEP monitoring.MethodsAll patients underwent a preoperative neurological evaluation and preoperative mMEP and cSSEP recordings at both legs. For each factor associated with feasibility, we computed sensitivity, specificity, positive predictive value (PPV), and negative predictive value. A decision tree was designed.ResultsPresence of any of the following factors was associated with 100% feasibility, 100% specificity, and 100% PPV: idiopathic scoliosis, normal preoperative neurological findings, and normal preoperative mMEP and cSSEP recordings. Feasibility was 0% in the eight patients with no recordable mMEPs or cSSEPs during preoperative testing. A decision tree involving three screening steps can be used to identify patients in whom intraoperative TES-mMEP/cSSEP is feasible.ConclusionsPreoperative neurological and neurophysiological assessments are helpful for identifying patients who can be successfully monitored by TES-mMEP/cSSEP during scoliosis surgery.     

In vitro analysis of flufenamic acid activity against Candida albicans biofilms

In a recent high-throughput screen against specific Candida albicans drug targets, several compounds that exhibited non-specific antifungal activity were identified, including the non-steroidal anti-inflammatory drug flufenamic acid (FFA). This study sought to determine the effect of different doses of FFA, alone or in combination with fixed concentrations of the standard antifungal agents amphotericin B (AmB), caspofungin (CAS) or fluconazole (FLU), for the prevention and treatment of C. albicans biofilms. Biofilms were formed in a 96-well microplate followed by evaluation of antifungal activity using the XTT assay. FFA concentrations of ≥512 mg/L demonstrated >80% prevention of biofilm formation. FFA concentrations of 1024 mg/L demonstrated >85% reduction of mature biofilms. When FFA (≥8 mg/L) was used in combination with FLU (32 mg/L), antifungal activity increased to 99% for the prevention of biofilm formation. Similarly, when a FFA concentration of ≥8 mg/L was used in combination with either AmB (0.25 mg/L) or CAS (0.125 mg/L), antifungal activity also increased up to 99% for the prevention of biofilm formation. The inhibitory effect of FFA on C. albicans biofilms has not been reported previously, therefore these findings suggest that FFA in combination with traditional antifungals might be useful for the treatment and prevention of C. albicans biofilms.     

Supramolecular gels of poly-α-cyclodextrin and PEO-based copolymers for controlled drug release

The aim of this work was to prepare syringeable supramolecular gels of α-cyclodextrin-polymer (poly-αCD) with various poly(ethylene oxide) (PEO)-based copolymers, which can be suitable to form depots for controlled drug release. A series of water-soluble poly-αCDs was synthesized from αCD by crosslinking with epichlorohydrin in alkaline medium. The chemical composition of the polymers was characterized by NMR (αCD content > 53%) and the molecular weight was evaluated using static light scattering (SLS). Supramolecular assemblies occurred by mixing poly-αCD (20–40% w/v) with a PEO-based polymer (i.e., PEG, Pluronic® F127 or Tetronic® 908) (10–15% w/v). Phase separation was observed and the αCD content in each phase was determined by means of the phenol–sulfuric acid colorimetric method. Formation of poly-αCD/PEO-based polymer 3D-supramolecular complexes was confirmed by diffusion-ordered NMR spectroscopy (DOSY) and X-ray diffractometry. The supramolecular assemblies showed good cytocompatibility against SAOS-2 cells and in the HET-CAM test. The supramolecular gels were able to sustain the release of vancomycin for at least 5 days at 37 °C, more efficiently than dispersions of each polymer component in separate. These results open new possibilities in the design of novel controlled delivery systems for the treatment of bone infections.     

Toxicological effects of the sunscreen UV filter,benzophenone-2, on planulae and in vitro cells of the coral,Stylophora pistillata

Benzophenone-2 (BP-2) is an additive to personal-care products and commercial solutions that protects against the damaging effects of ultraviolet light. BP-2 is an “emerging contaminant of concern” that is often released as a pollutant through municipal and boat/ship wastewater discharges and landfill leachates, as well as through residential septic fields and unmanaged cesspits. Although BP-2 may be a contaminant on coral reefs, its environmental toxicity to reefs is unknown. This poses a potential management issue, since BP-2 is a known endocrine disruptor as well as a weak genotoxicant. We examined the effects of BP-2 on the larval form (planula) of the coral, Stylophora pistillata, as well as its toxicity to in vitro coral cells. BP-2 is a photo-toxicant; adverse effects are exacerbated in the light versus in darkness. Whether in darkness or light, BP-2 induced coral planulae to transform from a motile planktonic state to a deformed, sessile condition. Planulae exhibited an increasing rate of coral bleaching in response to increasing concentrations of BP-2. BP-2 is a genotoxicant to corals, exhibiting a strong positive relationship between DNA-AP lesions and increasing BP-2 concentrations. BP-2 exposure in the light induced extensive necrosis in both the epidermis and gastrodermis. In contrast, BP-2 exposure in darkness induced autophagy and autophagic cell death. The LC₅₀ of BP-2 in the light for an 8 and 24 h exposure was 120 and 165 parts per billion (ppb), respectively. The LC₅₀s for BP-2 in darkness for the same time points were 144 and 548 ppb. Deformity EC20 levels (24 h) were 246 parts per trillion in the light and 9.6 ppb in darkness.     

Iron Deficiency Is Associated With Impaired Biventricular Reserve and Reduced Exercise Capacity in Patients With Unexplained Dyspnea

BackgroundIron deficiency (ID) is frequent and associated with diminished exercise capacity in heart failure (HF), but its contribution to unexplained dyspnea without a HF diagnosis at rest remains unclear.Methods and ResultsConsecutive patients with unexplained dyspnea and normal echocardiography and pulmonary function tests at rest underwent prospective standardized cardiopulmonary exercise testing with echocardiography in a tertiary care dyspnea clinic. ID was defined as ferritin of <300 µg/L and a transferrin saturation of <20% and its impact on peak oxygen uptake (peakVO₂), biventricular response to exercise, and peripheral oxygen extraction was assessed. Of 272 patients who underwent cardiopulmonary exercise testing with echocardiography, 63 (23%) had ID. For a similar respiratory exchange ratio, patients with ID had lower peakVO₂ (14.6 ± 7.6 mL/kg/minvs 17.8 ± 8.8 mL/kg/min; P = .009) and maximal workload (89 ± 50 watt vs 108 ± 56 watt P = .047), even after adjustment for the presence of anemia. At rest, patients with ID had a similar left ventricular and right ventricular (RV) contractile function. During exercise, patients with ID had lower cardiac output reserve (P < .05) and depressed RV function by tricuspid s' (P = .004), tricuspid annular plane systolic excursion (P = .034), and RV end-systolic pressure-area ratio (P = .038), with more RV–pulmonary artery uncoupling measured by tricuspid annular plane systolic excursion/systolic pulmonary arterial pressure ratio (P = .023). RV end-systolic pressure-area ratio change from rest to peak exercise, as a load-insensitive metric of RV contractility, was lower in patients with ID (2.09 ± 0.72 mm Hg/cm² vs 2.58 ± 1.14 mm Hg/cm²; P < .001). ID was associated with impaired peripheral oxygen extraction (peakVO₂/peak cardiac output; P = .036). Cardiopulmonary exercise testing with echocardiography resulted in a diagnosis of HF with preserved ejection fraction in 71 patients (26%) based on an exercise E/e' ratio of >14, with equal distribution in patients with (28.6%) or without ID (25.4%, P = .611). None of these findings were influenced in a sensitivity analysis adjusted for a final diagnosis of HFpEF as etiology for the unexplained dyspnea.ConclusionsIn patients with unexplained dyspnea without clear HF at rest, ID is common and associated with decreased exercise capacity, diminished biventricular contractile reserve, and decreased peripheral oxygen extraction.