Randomized Trial of Interleukin-6 Receptor Inhibition in Patients With Acute ST-Segment Elevation Myocardial Infarction

BackgroundPrompt myocardial revascularization with percutaneous coronary intervention (PCI) reduces infarct size and improves outcomes in patients with ST-segment elevation myocardial infarction (STEMI). However, as much as 50% of the loss of viable myocardium may be attributed to the reperfusion injury and the associated inflammatory response.ObjectivesThis study sought to evaluate the effect of the interleukin-6 receptor inhibitor tocilizumab on myocardial salvage in acute STEMI.MethodsThe ASSAIL-MI trial was a randomized, double-blind, placebo-controlled trial conducted at 3 high-volume PCI centers in Norway. Patients admitted with STEMI within 6 h of symptom onset were eligible. Consenting patients were randomized in a 1:1 fashion to promptly receive a single infusion of 280 mg tocilizumab or placebo. The primary endpoint was the myocardial salvage index as measured by magnetic resonance imaging after 3 to 7 days.ResultsWe randomized 101 patients to tocilizumab and 98 patients to placebo. The myocardial salvage index was larger in the tocilizumab group than in the placebo group (adjusted between-group difference 5.6 [95% confidence interval: 0.2 to 11.3] percentage points, p = 0.04). Microvascular obstruction was less extensive in the tocilizumab arm, but there was no significant difference in the final infarct size between the tocilizumab arm and the placebo arm (7.2% vs. 9.1% of myocardial volume, p = 0.08). Adverse events were evenly distributed across the treatment groups.ConclusionsTocilizumab increased myocardial salvage in patients with acute STEMI. (ASSessing the effect of Anti-IL-6 treatment in Myocardial Infarction [ASSAIL-MI]; NCT03004703)     

Carbonic anhydrase XIV is enriched in specific membrane domains of retinal pigment epithelium, Muller cells, and astrocytes

Carbonic anhydrases (CAs) are ubiquitous enzymes important to many cell types throughout the body. They help determine levels of H(+) and HCO(-)(3) and thereby regulate intracellular and extracellular pH and volume. CA XIV, an extracellular membrane-bound CA, was recently shown to be present in brain and retina. Here, we analyze the subcellular distribution of CA XIV in retina by high-resolution immunogold cytochemistry and show that the distribution in retina (on glial cells but not neurons) is different from that reported for brain (on neurons but not glia). In addition, CA XIV is strongly expressed on retinal pigment epithelium (RPE). The specific membrane domains that express CA XIV were endfoot and nonendfoot membranes on Muller cells and astrocytes and apical and basolateral membranes of RPE. Gold particle density was highest on microvilli plasma membranes of RPE, where it was twice that of glial endfoot and Muller microvilli membranes and four times that of other glial membrane domains. Neither neurons nor capillary endothelial cells showed detectable labeling for CA XIV. This enrichment of CA XIV on specific membrane domains of glial cells and RPE suggests specialization for buffering pH and volume in retinal neurons and their surrounding extracellular spaces. We suggest that CA XIV is the target of CA inhibitors that enhance subretinal fluid absorption in macular edema. In addition, CA XIV may facilitate CO(2) removal from neural retina and modulate photoreceptor function.     

Is the brain water channel aquaporin‐4 a pathogenetic factor in idiopathic intracranial hypertension? Results from a combined clinical and genetic study in a Norwegian cohort

Purpose: Idiopathic intracranial hypertension (IIH) is a condition of increased intracranial pressure of unknown aetiology. Patients with IIH usually suffer from headache and visual disturbances. High intracranial pressure despite normal ventricle size and negative MRI indicate perturbed water flux across cellular membranes, which is provided by the brain water channel aquaporin‐4 (AQP4). IIH could be associated with malfunctioning intracerebral water homeostasis and cerebrospinal fluid (CSF) reabsorption based on functional or regulatory alterations of AQP4. Methods: Clinical data, blood and CSF samples were collected from 28 patients with IIH. Clinical characteristics were assessed, and a genetic association study was performed by sequencing the AQP4 gene on chromosome 18. Genetic data were compared with 52 healthy controls and matched by age, sex and ethnicity. Chi‐square test and linear discriminant analysis (LDA) were used in the search of a genotype–phenotype association. Results: While the majority of patients responded to medical treatment, four required shunt application. All, except one, had a good visual outcome. The 24 AQP4 gene SNPs showed no association with IIH. Full cross‐validation of the LDA modelling resulted in only 55.1% correct classification of the cases and controls, with a corresponding estimated p‐value 0.37. Conclusions: Our genetic case–control study did not indicate an association between AQP4 gene variants and IIH. However, the theory of an etiopathogenic link between IIH and AQP4 is tempting, and discussed in this article. Association studies with large sample size are difficult to perform owing is the rarity of the condition.     

Antiviral Immunoglobulins of Chicken Egg Yolk for Potential Prevention of SARS-CoV-2 Infection

Background: Some viruses cause outbreaks, which require immediate attention. Neutralizing antibodies could be developed for viral outbreak management. However, the development of monoclonal antibodies is often long, laborious, and unprofitable. Here, we report the development of chicken polyclonal neutralizing antibodies against SARS-CoV-2 infection. Methods: Layers were immunized twice with 14-day intervals using the purified receptor-binding domain (RBD) of the S protein of SARS-CoV-2/Wuhan or SARS-CoV-2/Omicron. Eggs were harvested 14 days after the second immunization. Polyclonal IgY antibodies were extracted. Binding of anti-RBD IgYs was analyzed by immunoblot and indirect ELISA. Furthermore, the neutralization capacity of anti-RBD IgYs was measured in Vero-E6 cells infected with SARS-CoV-2-mCherry/Wuhan and SARS-CoV-2/Omicron using fluorescence and/or cell viability assays. In addition, the effect of IgYs on the expression of SARS-CoV-2 and host cytokine genes in the lungs of Syrian Golden hamsters was examined using qRT-PCR. Results: Anti-RBD IgYs efficiently bound viral RBDs in situ, neutralized the virus variants in vitro, and lowered viral RNA amplification, with minimal alteration of virus-mediated immune gene expression in vivo. Conclusions: Altogether, our results indicate that chicken polyclonal IgYs can be attractive targets for further pre-clinical and clinical development for the rapid management of outbreaks of emerging and re-emerging viruses.     

Quality of Psychosocial Care of Suicide Attempters at General Hospitals in Norway—A Longitudinal Nationwide Study

The objective of this study was to identify predictors of a high level of quality of care for suicide attempters at general hospital emergency departments in Norway. Structured interviews with key informants covering the quality of care of patients admitted following attempted suicide were conducted in 1999 and 2006 at 87% of all general hospitals. Hospitals having implemented a chain of care program for suicide attempters in 1999 maintained significantly higher levels on quality of care indicators 7 years later. Predictors of a high quality of care level were training of staff in management and care of suicide attempters and to have written guidelines for the care.     

Outcome of local failures after oral cancer – recurrence vs. second primary

J Oral Pathol Med (2010) 39 : 657–661 Background/objective: A high risk of new mucosal malignancies of the upper aerodigestive tract (UADT) is seen in patients successfully treated for oral cancer. The prognosis is unclear for these patients. A typical failure may be located at the site of the first tumor i.e. a local recurrence; or separately as a second primary tumor (SPT). It is unknown whether these two types of local failures have different prognosis. Study design: Longitudinal observational cohort study employing prospectively collected data over 25 years. Methods: The rate of local recurrences and UADT SPTs was analyzed in 151 patients previously treated for T1N0M0 oral squamous cell carcinoma. Survival after failure was compared between patients with local recurrence and local SPT. Results: All patients had a 5‐year cancer specific survival of 86.3%. Of the 151 patients, 20 had a local recurrence, and 16 had an UADT SPT. After a local failure, survival was median 17.2 months for local recurrence and 18.9 for UADT SPT (cancer specific). Time from primary tumor treatment to local recurrence was median 42 and months vs. 125 months for UADT SPTs. A similar linear pattern of presentation over time was seen for both tumor types. Conclusion: Outcome was poor after the date of the local failure. No difference in survival was seen whether the failure was a local recurrence or a second primary tumor. The similarity in survival and pattern of presentation suggests that these two entities may be biologically analogous.