Nerve fibre organisation in the human optic nerve and chiasm: what do we really know?

A recent anatomical study of the human optic chiasm cast doubt on the widespread assumption that nerve fibres travelling in the human optic nerve and chiasm are arranged retinotopically. Accordingly, a scoping literature review was performed to determine what is known about the nerve fibre arrangement in these structures. Meta-analysis suggested that the average number of fibres in each optic nerve was 1.023 million with an inter-individual range of approximately 50% of the mean. Loss of nerve fibres with age (approximately 3,400 fibres/year) could not account for this variability. The review suggested that there might be a retinotopic arrangement of nerve fibres in the orbital portion of the optic nerve but that this arrangement is most likely to be lost posteriorly with a more random distribution of nerve fibres at the chiasm. Limited studies have looked at nerve fibre arrangement in the chiasm. In summary, the chiasm is more 'H-shaped' than 'X-shaped': nerve fibre crossings occur paracentrally with nerves in the centre of the chiasm travelling coronally and in parallel. There is interaction between crossed and uncrossed fibres which are widely distributed. The review supports the non-existence of Wilbrand's knee. Considerable further work is required to provide more precise anatomical information, but this review suggests that the assumed preservation of retinotopy in the human optic nerve and chiasm is probably not correct.

Union and Complication Rates After Total Wrist Arthrodesis: A Systematic Review and Meta-Analysis.

PURPOSE: Total wrist arthrodesis (TWA) has been performed using various techniques. We aimed to provide pooled prevalence estimates of union and complications of TWA by technique. A secondary aim was to provide estimates of union and complication rates by treatment of the carpometacarpal joint (CMCJ) in TWA using plates. Given the widespread adoption of wrist arthrodesis plates (WAP), we hypothesized that these implants would result in higher union and lower complication rates. We also hypothesized that TWA with CMCJ arthrodesis would improve these outcomes. METHODS: Online databases including PubMed, Medline, Embase, and Cochrane were searched. Studies reporting union and/or complication rates of 10 or more TWA performed with a similar technique (analyzed as bone graft only, bone graft with minimal fixation, intramedullary, augmented intramedullary, plate, WAP, and other) were included. Studies with fewer than 10 TWA, studies reporting TWA where union or complications could not be analyzed separately, and studies without union and complication rates were excluded. Data extraction was performed independently by two English-speaking reviewers with a translator where required. Pooled prevalence estimates were made using a random-effects meta-analysis model and presented as a percent prevalence with 95% confidence and prediction intervals. RESULTS: One hundred and thirty-six studies with a total of 3,517 patients and 3,969 TWA were analyzed. No differences in union and complication prevalence were observed between TWA techniques and in TWA with different treatments of the CMCJ using plates and WAP. CONCLUSION: Using meta-analysis, we found no difference in union and complication prevalence between TWA techniques and TWA with different treatments of the CMCJ with plates and WAP. It must be acknowledged that this research included low-quality studies with high heterogeneity, and confidence in the precision of the estimates is low. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic IV.

What's old is best again Is anterior plating best for fixation of type-C pelvic fractures? A systematic review and meta-analysis.

BACKGROUND: Type-C pelvic fractures are a rare but potentially fatal injury that often leads to poor outcomes, despite surgical fixation. Many fixation methods are used but the optimal method remains contentious, with failure and complications common. This study compared outcomes for each fixation method. METHODS: A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A search of studies which reported on outcomes after surgically treated type-C pelvic fractures was undertaken. Data retrieved included fixation method, length of follow up, surgical revision, and complications rates (hardware breakage, post-operative outcomes, screw mal-positioning, screw loosening, loss of reduction and infection). Study quality was assessed using the Methodological Index for Non-Randomised Studies (MINORS). Pooled revision, outcome and complication rates were calculated using a quality-adjusted model in MetaXL 5.3. RESULTS: Fifty-two studies met the inclusion criteria representing 1567 patients and 7 fixation methods. The meta-analyses demonstrated high rates of 'less-than-good' outcomes for most fixation methods, with a higher rate for bilateral injuries (overall 23%; unilateral 21% v bilateral 41%). The mean pooled rate for surgical revision rate was 4%, hardware breakage 3%, screw mal-positioning 2%, screw loosening 3%, loss of reduction 5% and infection 4%. Each fixation method had different performance profiles; however, anterior plating outperformed all other fixation methods for patient outcomes, with a 'less-than-good' rate of just 7% vs the pooled mean of 23% and demonstrated at or below pooled mean rates for all complications except revision which was 5%. CONCLUSIONS: Post-operative outcomes for surgically treated type-C pelvic fractures revealed a 'less-than-good' pooled outcome rate of 23% and a revision rate of 4%. Anterior plates outperformed most other systems particularly for patient reported outcomes. Pooled revision, patient-reported outcome and complication rates for type-C pelvic fractures have not previously been reported and these data provide a benchmark for practice and future research.

Salvage Therapy with Sofosbuvir/Velpatasvir/Voxilaprevir in DAA-experienced Patients: Results from a Prospective Canadian Registry.

BACKGROUND: Despite the current highly effective therapies with direct-acting antiviral agents (DAAs), some patients with chronic hepatitis C virus (HCV) infection still do not achieve sustained virological response (SVR) and require retreatment. Sofosbuvir/velpatasvir/voxilaprevir (SVV) is recommended as the first-line retreatment option for most patients. The aim of this study was to evaluate the efficacy of SVV as salvage therapy after at least one course of DAA. METHODS: Data were collected on all HCV-infected patients who failed DAAs and were prescribed SVV from a prospective Canadian registry (CANUHC) including 17 sites across Canada. Factors associated with failure to achieve SVR with SVV therapy and the utility of RAS testing and ribavirin use were evaluated. RESULTS: A total of 128 patients received SVV after non-SVR with DAA treatment: 80% male, median age 57.5 (31-86), 44% cirrhotic, and 17 patients post liver transplant. First line regimens included: sofosbuvir/velpatasvir (27.3%), sofosbuvir/ledipasvir (26.5%), grazoprevir/elbasvir (12.5%), other (33.5%). Ribavirin was added to SVV in 26 patients due to past sofosbuvir/velpatasvir use (n = 8), complex resistance associated substitution profiles (n = 16) and/or cirrhosis (n = 9). Overall SVR rate was 96% (123/128). Of 35 patients who previously failed sofosbuvir/velpatasvir, 31 (88.5%) achieved SVR compared to 92 of 93 (99%) among those receiving any other regimen (P = .01). CONCLUSIONS: Similar to reports from phase 3 clinical trials, SVV proved highly effective as salvage therapy for patients who failed a previous DAA therapy. Those who failed SVV had at least 2 of the following factors: genotype 3, presence of cirrhosis, past liver transplantation, past exposure to sofosbuvir/velpatasvir and/or complex resistance profiles.

Peginterferon lambda for the treatment of outpatients with COVID-19: a phase 2, placebo-controlled randomised trial.

BACKGROUND: To date, only monoclonal antibodies have been shown to be effective for outpatients with COVID-19. Interferon lambda-1 is a type III interferon involved in innate antiviral responses with activity against respiratory pathogens. We aimed to investigate the safety and efficacy of peginterferon lambda in the treatment of outpatients with mild-to-moderate COVID-19. METHODS: In this double-blind, placebo-controlled trial, outpatients with laboratory-confirmed COVID-19 were randomly assigned to a single subcutaneous injection of peginterferon lambda 180 µg or placebo within 7 days of symptom onset or first positive swab if asymptomatic. Participants were randomly assigned (1:1) using a computer-generated randomisation list created with a randomisation schedule in blocks of four. At the time of administration, study nurses received a sealed opaque envelope with the treatment allocation number. The primary endpoint was the proportion of patients who were negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA on day 7 after the injection, analysed by a χ2 test following an intention-to-treat principle. Prespecified analysis of the primary endpoint, adjusted for baseline viral load, using bivariate logistic regression was done. The trial is now complete. This trial is registered with ClinicalTrials.gov, NCT04354259. FINDINGS: Between May 18, and Sept 4, 2020, we recruited 30 patients per group. The decline in SARS-CoV-2 RNA was greater in those treated with peginterferon lambda than placebo from day 3 onwards, with a difference of 2·42 log copies per mL at day 7 (p=0·0041). By day 7, 24 (80%) participants in the peginterferon lambda group had an undetectable viral load, compared with 19 (63%) in the placebo group (p=0·15). After controlling for baseline viral load, patients in the peginterferon lambda group were more likely to have undetectable virus by day 7 than were those in the placebo group (odds ratio [OR] 4·12 [95% CI 1·15-16·73; p=0·029). Of those with baseline viral load above 106 copies per mL, 15 (79%) of 19 patients in the peginterferon lambda group had undetectable virus on day 7, compared with six (38%) of 16 in the placebo group (OR 6·25 [95% CI 1·49-31·06]; p=0·012). Peginterferon lambda was well tolerated, and adverse events were similar between groups with mild and transient aminotransferase, concentration increases more frequently observed in the peginterferon lambda group. Two individuals met the threshold of grade 3 increase, one in each group, and no other grade 3 or 4 laboratory adverse events were reported. INTERPRETATION: Peginterferon lambda accelerated viral decline in outpatients with COVID-19, increasing the proportion of patients with viral clearance by day 7, particularly in those with high baseline viral load. Peginterferon lambda has potential to prevent clinical deterioration and shorten duration of viral shedding. FUNDING: The Toronto COVID-19 Action Initiative, University of Toronto, and the Ontario First COVID-19 Rapid Research Fund, Toronto General & Western Hospital Foundation.

On Particle Size Distributions in Catalytic Chain Transfer Emulsion Polymerization: Chain-Extension and the Use of Derived Macromonomers as Reactive Surfactants in Emulsion Polymerization.

Catalytic chain transfer emulsion polymerization (CCTP) and subsequent chain extension via reversible addition-fragmentation chain transfer (RAFT) were used to synthesize amphiphilic macromonomers (MM), in the form of polymer latexes. The macromonomers consisted of two blocks whose first was a random copolymer of methacrylic acid and methyl methacrylate, at 35:65 mol:mol, while the second block was n-butyl methacrylate P[(MAA-co-MMA)-block-PBMA]. The block copolymer colloids were disintegrated and micellized upon addition of ammonia. The resulting nanosized polymer dispersions were used as reactive surfactants in the emulsion polymerization of n-butyl methacrylate. For this, a dual stage slow-fast monomer feed profile was used. The final polymer latexes were in the sub-100 nm range for the particle diameter at 30% w/w total polymer content. The emphasis of the work is to discuss and find an explanation for the observed particle size distributions in the three consecutive emulsion polymerization steps. The particle size distribution of the ω-unsaturated macromonomer latex synthesized by CCTP emulsion polymerization was found to be much broader than expected. This discrepancy is attributed to an extended particle nucleation period. The chain extension step in the macromonomer latex preparation showed considerable secondary nucleation. The presence of water-soluble macromonomer species from the CCTP emulsion polymerization step assured that control of chain growth persisted. The use of the amphiphilic macromonomers as reactive surfactants in the form of a nanosized aggregate seed dispersion showed that the average particle diameter could be tuned and that the molecular weight distributions could be regulated, when monomer starved conditions were used in the emulsion polymerizations.

Introducing Porosity in Colloidal Biocoatings to Increase Bacterial Viability.

A biocoating confines nongrowing, metabolically active bacteria within a synthetic colloidal polymer (i.e., latex) film. Bacteria encapsulated inside biocoatings can perform useful functions, such as a biocatalyst in wastewater treatment. A biocoating needs to have a high permeability to allow a high rate of mass transfer for rehydration and the transport of both nutrients and metabolic products. It therefore requires an interconnected porous structure. Tuning the porosity architecture is a challenge. Here, we exploited rigid tubular nanoclays (halloysite) and nontoxic latex particles (with a relatively high glass transition temperature) as the colloidal "building blocks" to tailor the porosity inside biocoatings containing Escherichia coli bacteria as a model organism. Electron microscope images revealed inefficient packing of the rigid nanotubes and proved the existence of nanovoids along the halloysite/polymer interfaces. Single-cell observations using confocal laser scanning microscopy provided evidence for metabolic activity of the E. coli within the biocoatings through the expression of a yellow fluorescent protein. A custom-built apparatus was used to measure the permeability of a fluorescein sodium salt in the biocoatings. Whereas there was no measurable permeability in a coating made from only latex particles, the permeability coefficient of the composite biocoatings increased with increasing halloysite content up to a value of 1 × 10-4 m h-1. The effects of this increase in permeability was demonstrated through a specially developed resazurin reduction assay. Bacteria encapsulated in halloysite composite biocoatings had statistically significant higher metabolic activities in comparison to bacteria encapsulated in a nonoptimized coating made from latex particles alone.

To Finish the Cut or Not.

We retrospectively evaluated the management of patients with unrecognized glanular hypospadias and a completed (group 1) or aborted (group 2) neonatal circumcision. The rate and type of subsequent surgeries performed were analyzed. Penile curvature, urinary stream deviation, and their impact on management were evaluated. Surgery was done in 55% of patients-40% of group 1 and 86% of group 2. Completion of the circumcision was done in 63% of group 2. Hypospadias repair was performed in 56% of group 1 and in 34% of group 2. Penile curvature rate did not affect the rate or type of surgery performed. Urinary stream deviation did not affect the rate of repair, but was a significant factor leading to hypospadias repair. We concluded that providers performing neonatal circumcisions do not have to abort the procedure when a glanular hypospadias is noticed. Most patients will require circumcision completion only.