Anesthesia and the developing brain: a way forward for clinical research

It is now well established that many general anesthetics have a variety of effects on the developing brain in animal models. In contrast, human cohort studies show mixed evidence for any association between neurobehavioural outcome and anesthesia exposure in early childhood. In spite of large volumes of research, it remains very unclear if the animal studies have any clinical relevance; or indeed how, or if, clinical practice needs to be altered. Answering these questions is of great importance given the huge numbers of young children exposed to general anesthetics. A recent meeting in Genoa brought together researchers and clinicians to map a path forward for future clinical studies. This paper describes these discussions and conclusions. It was agreed that there is a need for large, detailed, prospective, observational studies, and for carefully designed trials. It may be impossible to design or conduct a single study to completely exclude the possibility that anesthetics can, under certain circumstances, produce long‐term neurobehavioural changes in humans; however , observational studies will improve our understanding of which children are at greatest risk, and may also suggest potential underlying etiologies, and clinical trials will provide the strongest evidence to test the effectiveness of different strategies or anesthetic regimens with respect to better neurobehavioral outcome.     

Successful interferon treatment in a patient chronically infected with hepatitis B virus carrying unusual S- (and P-) mutants in the presence of anti-HBs antibodies.

BACKGROUND: Hepatitis B virus (HBV) immune escape mutants with point mutations within the S gene may arise during the natural course of HBV infection, due to a positive selection pressure exerted by the host immune response. Mutations within the immunodominant B and T cell epitopes of hepatitis B surface antigen (HBsAg) allow the resulting S-mutants to propagate even in the presence of neutralizing anti-HBs antibodies and the HBV-specific T-cell immune response. Aim: To study the antiviral effect of Pegylated-interferon (Peg-IFN) in a patient with chronic hepatitis B carrying unusual S-(and P-) mutants in the presence of anti-HBs antibodies. PATIENTS, METHODS AND RESULTS: We report on a 43-year-old male chronically infected with a genotype A HBV strain, with cocirculation of both HBsAg and anti-HBs antibodies, who received treatment with 120 mug of Peg-IFN for 24 weeks. HBeAg seroconversion and clearance of both HBV DNA by polymerase chain reaction and HBsAg were successfully achieved. Improved histology was observed in a biopsy performed 44 weeks after Peg-IFN therapy was completed. It seems plausible that the ascribed genotype A could have contributed to the effective response to Peg-IFN, even though the treatment was provided only throughout a 24-week period. CONCLUSION: To our knowledge, this is the first report regarding the successful result obtained by using Peg-IFN as a treatment for a chronically HBV-infected patient carrying HBsAg immune escape mutants.     

Uncontrolled Web-Based Administration of Surveys on Factual Health-Related Knowledge: A Randomized Study of Untimed Versus Timed Quizzing

Background

Health knowledge and literacy are among the main determinants of health. Assessment of these issues via Web-based surveys is growing continuously. Research has suggested that approximately one-fifth of respondents submit cribbed answers, or cheat, on factual knowledge items, which may lead to measurement error. However, little is known about methods of discouraging cheating in Web-based surveys on health knowledge.

Objective

This study aimed at exploring the usefulness of imposing a survey time limit to prevent help-seeking and cheating.

Methods

On the basis of sample size estimation, 94 undergraduate students were randomly assigned in a 1:1 ratio to complete a Web-based survey on nutrition knowledge, with or without a time limit of 15 minutes (30 seconds per item); the topic of nutrition was chosen because of its particular relevance to public health. The questionnaire consisted of two parts. The first was the validated consumer-oriented nutrition knowledge scale (CoNKS) consisting of 20 true/false items; the second was an ad hoc questionnaire (AHQ) containing 10 questions that would be very difficult for people without health care qualifications to answer correctly. It therefore aimed at measuring cribbing and not nutrition knowledge. AHQ items were somewhat encyclopedic and amenable to Web searching, while CoNKS items had more complex wording, so that simple copying/pasting of a question in a search string would not produce an immediate correct answer.

Results

A total of 72 of the 94 subjects started the survey. Dropout rates were similar in both groups (11%, 4/35 and 14%, 5/37 in the untimed and timed groups, respectively). Most participants completed the survey from portable devices, such as mobile phones and tablets. To complete the survey, participants in the untimed group took a median 2.3 minutes longer than those in the timed group; the effect size was small (Cohen’s r=.29). Subjects in the untimed group scored significantly higher on CoNKS (mean difference of 1.2 points, P=.008) and the effect size was medium (Cohen’s d=0.67). By contrast, no significant between-group difference in AHQ scores was documented. Unexpectedly high AHQ scores were recorded in 23% (7/31) and 19% (6/32) untimed and timed respondents, respectively, very probably owing to “e-cheating”.

Conclusions

Cribbing answers to health knowledge items in researcher-uncontrolled conditions is likely to lead to overestimation of people’s knowledge; this should be considered during the design and implementation of Web-based surveys. Setting a time limit alone may not completely prevent cheating, as some cheats may be very fast in Web searching. More complex and contextualized wording of items and checking for the “findability” properties of items before implementing a Web-based health knowledge survey may discourage help-seeking, thus reducing measurement error. Studies with larger sample sizes and diverse populations are needed to confirm our results.     

Iliopsoas abscess in adolescents with type 1 diabetes mellitus

Iliopsoas abscesses have been reported in adult diabetic patients, but only one case has been so far reported in the pediatric diabetic literature. We report three cases of iliopsoas abscesses in three adolescents with type 1 diabetes mellitus, suggesting that an increased awareness of this condition is required for its early recognition and prompt treatment.     

The role of postoperative radiotherapy for thymomas: a multicentric retrospective evaluation from three Italian centers and review of the literature

BackgroundThymoma is a rare mediastinal neoplasia. Surgery is the backbone of the treatment, but the role of postoperative radiotherapy (PORT) remains controversial. We aimed to obtain data on survival and safety in patients treated with PORT in three different Italian institutions.MethodsWe retrospectively analyzed 183 consecutive patients who underwent surgery from 1981 to 2015. According to the Masaoka-Koga staging system, 39.3%, 32.7%, 18.6% and 9.8% patients were in stage I, II, III and IV of disease, respectively. PORT was indicated in 114 patients (62.3%), while 69 subjects underwent surgery alone. Complete resection was obtained in 68 patients who underwent PORT. Adverse events (AEs) were graded according to CTCAE v4.0. We analyzed the recent literature to describe the current reports on PORT for resected thymoma.ResultsMean follow-up was 130 months (range, 3–417 months). Overall survival (OS) at 1-, 5- and 10-year from surgery was 98.3%, 90.2% and 69.7% respectively. One-, 5- and 10-year disease specific survival (DSS) was 98.9%, 92.3% and 89.8% respectively. Disease free survival (DFS) at 1, 5 and 10 years from surgery was 96.7%, 88.3% and 82.8% respectively. Univariate analysis showed that complete resection, cell histology A-AB-B1 and stages I–II were significant predictors of better DSS and DFS. Multivariate analysis showed that sex, R0 margins and WHO histology was independent prognostic factors. Among patients treated with PORT, a trend towards better OS was evident with Masaoka stage I–II (P=0.09). Patients with R0 margins treated with PORT showed better OS and DSS (P=0.05). No differences in DSS for performance status (P=0.70), WHO histology (P=0.19), paraneoplastic syndrome (P=0.23) and surgical procedure (P=0.53) were evident. Patients treated with PORT had a higher level of acute AEs compared to surgery alone, but none of these was graded ≥3.ConclusionsOur results confirmed that patients with incompletely resected thymoma had the worst OS and DSS. High grade acute toxicity was not different between PORT and surgery alone. Other trials reported a significant benefit in OS, DSS and DFS in stage IIb–IV thymoma treated with PORT.     

COVID‐19 infection in a paucisymptomatic infant: Raising the index of suspicion in epidemic settings

Few children have been reported to have been affected by novel coronavirus disease 2019 (COVID‐19); it is unclear whether children are less likely to be infected or rather display fewer symptoms. We present the case of a 32‐day‐old boy infected by COVID‐19 that presented with an upper air way infection which resolved spontaneously and did not require any therapy. We argue that in epidemic settings children presenting with any mild symptom potentially attributable to COVID‐19 should be considered contagious until proven otherwise, and that management must be guided by clinical conditions.     

Which is the best catheter to perform atrial fibrillation ablation? A comparison between standard ThermoCool,SmartTouch, and Surround Flow catheters

Introduction

Catheter ablation (CA) is an established therapy for atrial fibrillation (AF). The SmartTouch catheter (STc) provides information about catheter tip to tissue contact force (CF). The Surround Flow catheter (SFc) provides a uniform cooling of the tip during ablation. We sought to analyze the impact of STc and SFc on CA of paroxysmal AF in terms of feasibility and acute efficacy.

Methods and results

Sixty-three patients (mean age 57.6?±?9.8 years, 53 males) with paroxysmal AF underwent pulmonary veins (PVs) antral isolation, by using standard ThermoCool catheter (TCc) in 21, STc in 21, and SFc in 21. Total procedural, fluoroscopy, and radiofrequency (RF) delivery times; percentage of persistently deconnected PVs after 30 min; and percentage of isolated PVs at the end of the procedure were measured. The use of both STc and SFc obtained a reduction of fluoroscopy time (TCc 34?±?18 min, STc 20?±?10 min, p?<?0.001; SFc 21?±?13 min, p?=?0.02 vs TCc) and RF time (TCc 41?±?13 min, STc 30?±?14 min, p?=?0.013; SFc 30?±?9 min, p?<?0.01 vs TCc). The use of STc resulted in a reduction of procedural time (TCc 181?±?53 min, STc 140?±?53 min, p?<?0.001; SFc 170?±?51 min, p?=?NS vs TCc). The percentage of isolated PVs was comparable between groups (TCc 96 % vs STc 98 % vs SFc 96 %; p?=?NS). The percentage of deconnected PVs at 30 min was lower in TCc (89 %) than in STc (95 %) and in SFc (95 %) group (p?<?0.05).

Conclusions

Both STc and SFc allowed a simplification of CA of paroxysmal AF. In addition, they reduced early PVs reconnection.

Condensed abstract

Sixty-three patients with paroxysmal AF underwent ablation by standard ThermoCool, SmartTouch, or Surround Flow catheter. Both the SmartTouch and the Surround Flow significantly reduced radiofrequency and fluoroscopy times, as well as pulmonary veins reconnection rate at 30 min. Moreover, the SmartTouch reduced overall duration of the procedure.     

A preliminary investigation of serological tools for the detection of Onchocerca lupi infection in dogs

Onchocerca lupi is a neglected filarioid causing nodular lesions associated with acute or chronic ocular disease in dogs. Despite the recent appraisal of its zoonotic potential, human cases are increasingly reported in the Old and New Worlds. Therefore, the development of accurate tools for the rapid diagnosis of O. lupi infections in dogs is becoming a priority. In this study, we conducted a preliminary investigation aimed at evaluating the usefulness of a commercially available ELISA test for the detection of O. lupi antigens in canine sera. The potential use of this tool for larger epidemiological studies of canine onchocerciasis is discussed.     

Thermotropic liquid crystals from biomacromolecules

Complexation of biomacromolecules (e.g., nucleic acids, proteins, or viruses) with surfactants containing flexible alkyl tails, followed by dehydration, is shown to be a simple generic method for the production of thermotropic liquid crystals. The anhydrous smectic phases that result exhibit biomacromolecular sublayers intercalated between aliphatic hydrocarbon sublayers at or near room temperature. Both this and low transition temperatures to other phases enable the study and application of thermotropic liquid crystal phase behavior without thermal degradation of the biomolecular components.Liquid crystals (LCs) play an important role in biology because their essential characteristic, the combination of order and mobility, is a basic requirement for self-organization and structure formation in living systems (1–3). Thus, it is not surprising that the study of LCs emerged as a scientific discipline in part from biology and from the study of myelin figures, lipids, and cell membranes (4). These and the LC phases formed from many other biomolecules, including nucleic acids (5, 6), proteins (7, 8), and viruses (9, 10), are classified as lyotropic, the general term applied to LC structures formed in water and stabilized by the distinctly biological theme of amphiphilic partitioning of hydrophilic and hydrophobic molecular components into separate domains. However, the principal thrust and achievement of the study of LCs has been in the science and application of thermotropic materials, structures, and phases in which molecules that are only weakly amphiphilic exhibit LC ordering by virtue of their steric molecular shape, flexibility, and/or weak intermolecular interactions [e.g., van der Waals and dipolar forces (11)]. These characteristics enable thermotropic LCs (TLCs) to adopt a wide variety of exotic phases and to exhibit dramatic and useful responses to external forces, including, for example, the electro-optic effects that have led to LC displays and the portable computing revolution. This general distinction between lyotropic LCs and TLCs suggests there may be interesting possibilities in the development of biomolecular or bioinspired LC systems in which the importance of amphiphilicity is reduced and the LC phases obtained are more thermotropic in nature. Such biological TLC materials are very appealing for several reasons. Most biomacromolecules were extensively characterized in aqueous environments, but in TLC phases, their solvent-free properties and functions could be investigated in a state in which no or only traces of water are present. Water exhibits a high dielectric constant and has the ability to form hydrogen bonds, greatly influencing the structure and functions of biomacromolecules or compromising electronic properties such as charge transport (12–15). Indeed, anhydrous TLC systems containing glycolipids (16–19), ferritin (20), and polylysine have been reported (21–23). However, a general approach to fabricating TLCs based on nucleic acids, polypeptides, proteins, and protein assemblies of large molecular weights such as virus particles remains elusive.Here we propose that the combination of biomaterials with suitably chosen surfactants, followed by dehydration, can be effectively applied as a simple generic scheme for producing biomacromolecular-based TLCs. We demonstrate that biological TLCs can be made from a remarkable range of biomolecules and bio-inspired molecules, including nucleic acids, polypeptides, fusion proteins, and viruses. TLC materials typically combine rigid or semirigid anisometric units, which introduce orientational anisotropy, with flexible alkyl chains, which suppress crystallization (24). In the present experiments, negatively charged biomolecules and bio-inspired molecules act as rigid parts, and cationic surfactants make up the flexible units to produce TLC phases with remarkably low LC-isotropic clearing temperatures, which is another TLC signature. Electrostatic interactions couple these rigid and flexible components into hybrid assemblies, which then order into lamellar phases of alternating rigid and flexible layers (Fig. 1) stabilized by the tendency in TLCs for rigid and flexible to spatially segregate (25).Open in a separate windowFig. 1.Proposed structures of TLCs formed by the biological building blocks complexed with surfactants, showing sketches of various lamellar phases and the corresponding phase transition temperatures (°C). The lamellar bilayer structures are made of, alternately, a sublayer of the biomacromolecules and an interdigitated sublayer of the surfactants, where the negatively charged parts of the biomolecules (e.g., phosphate groups of ssDNA and ssRNA, glutamate residues of supercharged ELPs, and N-terminal glutamate and aspartate residues of pVIII protein in phages) electrostatically interact with the cationic head groups of the surfactants. For the ssDNA–DOAB and ssRNA–DOAB smectic TLCs, the oligonucleotides are randomly orientated in the DNA (RNA) sublayers. For the ELP–DDAB complexes, in addition to the bilayer smectic phase, a modulated smectic (Sm_mod) phase is observed at lower temperature. For the phage–DOAB–DDAB lamellar structures, rodlike virus particles are embedded in a sublayer between interdigitated surfactants with additional in-plane orientational order.