The COVANOS trial - insight into post-COVID olfactory dysfunction and the role of smell training.

BACKGROUND: Olfactory dysfunction is a cardinal symptom of COVID-19 infection, however, studies assessing long-term olfactory dysfunction are limited and no randomised-controlled trials (RCTs) of early olfactory training have been conducted. METHODOLOGY: We conducted a prospective, multi-centre study consisting of baseline psychophysical measurements of smell and taste function. Eligible participants were further recruited into a 12-week RCT of olfactory training versus control (safety information). Patient-reported outcomes were measured using an electronic survey and BSIT at baseline and 12 weeks. An additional 1-year follow-up was open to all participants. RESULTS: 218 individuals with a sudden loss of sense of smell of at least 4-weeks were recruited. Psychophysical smell loss was observed in only 32.1%; 63 participants were recruited into the RCT. The absolute difference in BSIT improvement after 12 weeks was 0.45 higher in the intervention arm. 76 participants completed 1-year follow-up; 10/19 (52.6%) of participants with an abnormal baseline BSIT test scored below the normal threshold at 1-year, and 24/29 (82.8%) had persistent parosmia. CONCLUSIONS: Early olfactory training may be helpful, although our findings are inconclusive. Notably, a number of individuals who completed the 1-year assessment had persistent smell loss and parosmia at 1-year. As such, both should be considered important entities of long-Covid and further studies to improve management are highly warranted.

The Role of High-Density Lipoprotein in Lowering Risk of Dementia in the Elderly: A Review.

Dementia is one of the major causes of disability and hospitalization in the elderly. As far as non-invasive markers of dementia are concerned, we only have age and Apolipoprotein-E (Apo-E) gene, which can be considered as clinically relevant. Modifiable risk factors have been found to be the cause in one-third of the patients who develop dementia. The compatible data supporting the same, in particular for dyslipidemia, is limited, which in turn makes it difficult to devise prevention and interventional methods for both dementia and mild cognitive impairment. Hence, the objective of the review is to summarize the findings on the relation established between the high-density lipoprotein type C( HDL-C) levels and lower the chance of dementia in the elderly, and the possible role of HDL-C as a potential predictive biomarker for cases of dementia in elderly people. Dyslipidemia, a known risk factor for the occurrence of cardiovascular diseases, seems to be linked to Alzheimer's disease. Elevated levels of serum cholesterol in mid-adult life increases the risk of dementia in older age. But elevated high-density lipoprotein (HDL) level and its principal apolipoprotein A-I (ApoA-I ) equates with a low risk of dementia in the elderly population HDL cholesterol has been found to promote endothelial nitric oxide synthase activity which in turn reduces the neural and vascular inflammation and suppresses vascular adhesion thereby exhibiting its vasoprotective function. It has been believed that all these factors have a role to play in the pathogenesis of dementia. The relation between the higher levels of HDL cholesterol or its key protein component ApoA-I and the lower dementia prevalence in the elderly had been documented in numerous observational studies. Some studies have reported conflicting results. Yet, observational studies measuring the baseline HDL level in middle age found a significant association between HDL level and dementia risk in the elderly, whereas those studies measuring HDL cholesterol level only in old age found no association. Likewise, a significant association between HDL cholesterol and dementia risk has been reported with studies that carry through to 10 years or longer. However, the studies with follow-up of fewer than 10 years had failed to document any such association between HDL cholesterol and dementia.  HDL assays may also be used as a predictive biomarker for dementia patients to target the interventions. Although statins do not target HDL directly but can be an area of interest for dementia.

Optimising trial outcomes and patient retention for the MACRO trial for chronic rhinosinusitis.

BACKGROUND: This study aimed to evaluate current subjective and objective outcome assessments for the MACRO (defining best Management for Adults with Chronic RhinOsinusitis) Trial which compares antibiotics, placebo and sinus surgery. This was to identify any redundant assessments and to include patient perspectives to determine acceptability for confirmation in the trial. METHODS: Adults CRS patients meeting the provisional eligibility criteria for the MACRO trial were recruited to this mixed-method study at 2 sites. Correlations between the objective outcome measures and SNOT-22 scores were evaluated. Selected participants took part in a semi-structured telephone interview to explore their experiences and views of undergoing outcome measures. RESULTS: Seventy patients (37% male) were recruited, 36 had CRS without nasal polyps, 34 had CRS with nasal polyps. There was a weak inverse correlation between the SNOT-22 â€Blockage†ratings and Peak Nasal Inspiratory Flow readings, a moderate inverse correlation between the SNOT-22 â€Smell†ratings and Sniffin’ Sticks scores, but no significant correlation between the SNOT-22 and Saccharin test results. The participants’ experience of the trial visit was positive with an acceptable duration of trial visit. Most proposed outcome measures were valued by participants with the exception of the Saccharin test. DISCUSSION: The Sniffin’ Sticks test and PNIF correlate with their respective component SNOT-22 scores but are considered important by patients; PNIF is simple, cheap test to perform. The Saccharin test will be removed as participants did not value it and was not highly rated in parallel work on a core outcome set for CRS.

Unilateral visual loss resulting from orbital encroachment of an ethmoidal juvenile trabecular ossifying fibroma.

Ossifying fibromas are mainly found in the mandible and maxilla. Reports of them arising in the ethmoid sinuses and orbits are rare. We present a case of an otherwise healthy 20-year-old man with gradual onset of right visual disturbance signified by right relative afferent pupillary defect due to a large unilateral ossifying fibroma arising from the ethmoid sinus compressing the medial half of the right orbit. We emphasise the multidisciplinary combined endoscopic endonasal and external approach to ensure a successful debulking of the fibroma.

Wooden spatula sinusitis following maxillary expansion surgery.

Sinusitis is a recognised rare complication of palatine expansion procedures and is usually caused by the presence of an oroantral fistula. We report the first case of unilateral sinusitis as a result of a retained foreign body (a wooden spatula) following a surgically assisted rapid palatine expansion procedure.

Will we ever cure nasal polyps?

BACKGROUND: Nasal polyposis is a benign hyperplastic growth of nasal mucosa. There is a paucity of evidence on the prevalence and incidence of nasal polyposis. Although nasal polyps can be asymptomatic, they can cause a spectrum of nasal problems including nasal obstruction, rhinorrhoea, nasal congestion, anosmia resulting in ageusia. Nasal polyps are mostly associated with chronic rhinosinusitis, The current management of chronic rhinosinusitis with nasal polyps is controversial and is not curative. METHODS: A Medline search was conducted, using the keywords 'rhinosinusitis', 'sinusitis', 'classification' and ''aetiology. FINDINGS: The current treatment of nasal polyposis in chronic rhinosinusitis with nasal polyps is still challenging. Emerging research through endotypes profiling aims to better understand the complexities of this heterogeneous disease to personalise treatment and provide a cure. Randomised controlled trials aim to provide robust evidence for current management options.

ENT in the context of global health.

Global health is a fashionable term frequently used in the twenty-first century's news that is rarely understood by ear, nose and throat (ENT) professionals. Communicable diseases such as HIV, tuberculosis and malaria have been in the headlines of global health for decades. Despite the recent public health concerns about noncommunicable diseases, including ENT disorders, these disorders still receive little attention on the global health stage. Despite the 'benign' nature and a large number of patients affected at a given time, noncommunicable diseases were found to account for 60% of international mortality in 2008. More specifically to ENT, disabling hearing impairment has been found to be the most common disability globally. Therefore, it is now critical for otolaryngologists worldwide to get involved in the overlooked ENT global issues. This article discusses the main challenges faced by the ENT community in the developing world and proposes what can be done to help.

Isolation and expansion of cytomegalovirus-specific cytotoxic T lymphocytes to clinical scale from a single blood draw using dendritic cells and HLA-tetramers.

Cytomegalovirus (CMV) reactivation in immunocompromised recipients of allogeneic stem cell transplantation is a cause of morbidity and mortality from viral pneumonitis. Antiviral drugs given to reactivating patients have reduced the mortality from CMV but have toxic side effects and do not always prevent late CMV disease. Cellular immunotherapy to prevent CMV disease is less toxic and could provide prolonged protection. However, a practical approach to generating sufficient quantities of CMV-specific cytotoxic T cells (CTLs) is required. This study describes a system for generating sufficient CMV-specific CTLs for adoptive immunotherapy of HLA-A*0201 bone marrow transplant recipients from 200 mL donor blood. Donor monocytes are used to generate dendritic cells (DCs) in medium with autologous plasma, interleukin 4, granulocyte-macrophage colony-stimulating factor, and CD40 ligand. The DCs are pulsed with the immunodominant HLA-A*0201-restricted CMV peptide pp65(495-503), and incubated with donor T cells. These cultures are restimulated twice with peptide-pulsed lymphoblastoid cell lines (LCLs) or CD40-ligated B cells and purified with phycoerythrin (PE)-labeled pp65(495-503)/HLA-A*0201 tetramers by flow sorting, or with anti-PE paramagnetic beads. The pure tetramer-positive population is then rapidly expanded to obtain sufficient cells for clinical immunotherapy. The expanded CTLs are more than 80% pure, of memory phenotype, with a Tc1 cytokine profile. They efficiently kill CMV-infected fibroblasts and express the integrin VLA-4, suggesting that the CTLs could cross endothelial barriers. This technique is reproducible and could be used for generating CMV-specific CTLs to prevent CMV disease after allogeneic blood and marrow transplantation. (Blood. 2001;98:505-512)

Novel phosphoserine phosphatase inhibitors.

Phosphoserine phosphatase (EC 3.1.1.3) catalyzes the final step in the major pathway of L-serine biosynthesis in brain. This enzyme may also regulate the levels of glycine and D-serine, the known and putative co-agonists for the glycine site of the N-methyl-D-aspartate receptor in caudal and rostral brain regions, respectively. Using L-phosphoserine as substrate, the rank order potency for inhibition of phosphoserine phosphatase was p-chloromercuriphenylsulfonic acid (CMPSA) > glycerophosphorylcholine >> hexadecylphosphocholine > or = phosphorylcholine > N-ethylmaleimide > or = L-serine > fluoride > D-2-amino-3-phosphonopropionic acid (D-AP3). Glycerylphosphorylcholine (IC50 18 microM) was found to be an uncompetitive inhibitor of phosphoserine phosphatase. Glycerylphosphorylcholine probably binds a novel site on the enzyme since the known allosteric inhibitor L-serine is highly selective for its feedback regulatory site, indicated by the inactivity of 25 L-serine analogs. Fluoride ion (IC50 770 microM) may bind the active site as has been shown for other Mg2+-dependent enzymes. The sulfhydryl reagent CMPSA is a potent, noncompetitive inhibitor of the enzyme using L-phosphoserine as substrate (IC50 9 microM) but is > 300-fold less potent using D-phosphoserine as substrate. Substrate-dependent differences are also observed with the sulfhydryl alkylator N-ethylmaleimide, which inhibits L-phosphoserine, but stimulates D-phosphoserine hydrolysis. These sulfhydryl reagents may dissociate multimeric forms of the enzyme to form monomers; the multimeric forms and monomers may preferentially cleave L- and D-phosphoserine, respectively. Phosphorylcholine esters and sulfhydryl reagents may prove useful in determining the contribution of phosphoserine phosphatase to the biosynthesis of glycine and D-serine in neuronal tissue in vitro.