Hyperosmia after COVID-19: hedonic perception or hypersensitivity?

OBJECTIVE: COVID-19 has been associated with a wide range of quantitative and qualitative disorders of smell, including hyposmia/anosmia, parosmia, and phantosmia; however, no reports to date have reported hyperosmia as a sequela of SARS-CoV-2 infection. PATIENTS AND METHODS: We present two cases of subjective hyperosmia in a South Tyrolean Alps family, occurring within days after recovery from SARS-CoV-2 infection with transient anosmia. RESULTS: The subjects, a mother and son, exhibited subjective hyperosmia despite normal objective olfactory testing. During independent assessments, the severity of hyperosmia and specific odors affected were highly correlated, consistent with shared genetic and environmental factors. In contrast, two other family members with COVID-19 had no perceptual distortion and normal recovery of smell. CONCLUSIONS: Subjective hyperosmia after COVID-19 infection exhibited striking similarity in two affected family members, suggesting interaction of environment, genetics, and perception.

Practice of tracheostomy in patients with acute respiratory failure related to COVID-19 - Insights from the PRoVENT-COVID study.

OBJECTIVE: Invasively ventilated patients with acute respiratory failure related to coronavirus disease 2019 (COVID-19) potentially benefit from tracheostomy. The aim of this study was to determine the practice of tracheostomy during the first wave of the pandemic in 2020 in the Netherlands, to ascertain whether timing of tracheostomy had an association with outcome, and to identify factors that had an association with timing. METHODS: Secondary analysis of the 'PRactice of VENTilation in COVID-19' (PRoVENT-COVID) study, a multicenter observational study, conducted from March 1, 2020 through June 1, 2020 in 22 Dutch intensive care units (ICU) in the Netherlands. The primary endpoint was the proportion of patients receiving tracheostomy; secondary endpoints were timing of tracheostomy, duration of ventilation, length of stay in ICU and hospital, mortality, and factors associated with timing. RESULTS: Of 1023 patients, 189 patients (18.5%) received a tracheostomy at median 21 [17 to 28] days from start of ventilation. Timing was similar before and after online publication of an amendment to the Dutch national guidelines on tracheostomy focusing on COVID-19 patients (21 [17-28] vs. 21 [17-26] days). Tracheostomy performed ≤ 21 days was independently associated with shorter duration of ventilation (median 26 [21 to 32] vs. 40 [34 to 47] days) and higher mortality in ICU (22.1% vs. 10.2%), hospital (26.1% vs. 11.9%) and at day 90 (27.6% vs. 14.6%). There were no patient demographics or ventilation characteristics that had an association with timing of tracheostomy. CONCLUSIONS: Tracheostomy was performed late in COVID-19 patients during the first wave of the pandemic in the Netherlands and timing of tracheostomy possibly had an association with outcome. However, prospective studies are needed to further explore these associations. It remains unknown which factors influenced timing of tracheostomy in COVID-19 patients.

Randomized clinical trial "olfactory dysfunction after COVID-19: olfactory rehabilitation therapy vs. intervention treatment with Palmitoylethanolamide and Luteolin": preliminary results.

OBJECTIVE: Approximately 30% of patients with confirmed COVID-19 report persistent smell or taste disorders as long-term sequalae of infection. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection is associated with inflammatory changes to the olfactory bulb, and treatments with anti-inflammatory properties are hypothesized to attenuate viral injury and promote recovery of olfaction after infection. Our study investigated the efficacy of a supplement with Palmitoylethanolamide (PEA) and Luteolin to support recovery of olfaction in COVID-19 patients. PATIENTS AND METHODS: We conducted a randomized-controlled pilot study in outpatients with history of confirmed COVID-19 with post-infection olfactory impairment that persisted ≥ 90 days after SARS-CoV-2 negative testing. Patients were randomized to two times a day olfactory rehabilitation alone or weekly olfactory rehabilitation plus daily oral supplement with PEA and Luteolin. Subjects with preexisting olfactory disorders were excluded. Sniffin' Sticks assessments were performed at baseline and 30 days after treatment.  Data on gender, age, and time since infection were collected. Kruskal-Wallis (KW) test was used to compare variances of Sniff scores between groups over time, and Spearman's correlation coefficients were calculated to assess for correlations between Sniff Score and gender or duration of infection. RESULTS: Among 12 patients enrolled (n=7, supplement; n=5, controls), patients receiving supplement had greater improvement in olfactory threshold, discrimination, and identification score versus controls (p=0.01). Time since infection was negatively correlated with Sniff Score, and there was no correlation between gender. CONCLUSIONS: Treatment combining olfactory rehabilitation with oral supplementation with PEA and Luteolin was associated with improved recovery of olfactory function, most marked in those patients with longstanding olfactory dysfunction. Further studies are necessary to replicate these findings and to determine whether early intervention including olfactory rehabilitation and PEA+Luteolin oral supplement might prevent SARS-CoV-2 associated olfactory impairment.

Modern external beam radiation therapy for refractory dissecting cellulitis of the scalp.

BACKGROUND: Dissecting cellulitis of the scalp can be an extremely painful and disfiguring dermatological condition. The associated pain can be severe enough in some cases to require opioid analgesics, and this pain in conjunction with the disfigurement can induce significant emotional distress. Conservative treatments often fail to provide relief. Radiation therapy has been successfully used in the past but with outdated equipment and techniques. OBJECTIVES: To evaluate the efficacy and toxicity of modern external beam radiation therapy techniques for the treatment of dissecting cellulitis of the scalp. METHODS: Four patients with intractable dissecting cellulitis of the scalp were treated with electrons or a combination of electrons and photons to the entire scalp. Daily fraction sizes were 2.5 or 3 Gy and initially prescribed to 15-21 Gy. Patients were re-evaluated 3-4 weeks after completion of therapy. Any residual hair growth was treated with additional radiation treatments to ensure full epilation, up to a maximum dose of 35 Gy. RESULTS: Rapid resolution of pain was seen in all patients with pain. Regression of nodules and decreased discharge was seen in all patients following treatment and cosmesis was subjectively improved. No long-term toxicity has been observed. CONCLUSIONS: Using modern techniques and equipment, radiation therapy appears to be a reasonable option for patients with severe/refractory dissecting cellulitis of the scalp. Acute effects are mild and well tolerated. Aside from alopecia, which was present to some extent in all patients before treatment, no long-term complications have been observed.

The effect of growth hormone on the bursting strength of ileal anastomotic segments in radiation-injured rat bowel.

The potential for postoperative complications in irradiated intestinal anastomoses is well known. There has been limited evaluation of factors that may improve wound healing in radiation-injured bowel. Growth hormone (GH) has been shown to improve wound healing. In animal models GH has been demonstrated to increase strength of large bowel anastomoses in nonirradiated bowel. The purpose of this study was to evaluate, in a rat model, the effect of GH on the bursting pressure of radiation-injured terminal ileal anastomoses in a rat model. Fifty-four rats were treated with 1700 cGy of pelvic irradiation in a single dose. Seventeen weeks later resection of a segment of terminal ileum and an ileo-ileostomy was performed. Half the rats received GH (2.0 mg/kg/day) and the rest received normal saline subcutaneously for 7 days starting on the day of surgery. On the seventh postoperative day the anastomosis site was identified at reoperation and bursting pressure was measured in vivo. A significantly greater bursting pressure was observed in the GH-treated rats compared to the control group (208.9 +/- 27 cm H2O vs 177 +/- 53 cm H2O, P < 0.025). GH treatment resulted in an 18% greater strength of radiation-injured terminal ileal anastomotic segments, as measured by bursting pressure. These findings suggest a possible role for GH in decreasing the morbidity in patients who undergo intestinal surgery after radiation treatment.

Replacement of finger and growth factor domains of tissue plasminogen activator with plasminogen kringle 1. Biochemical and pharmacological characterization of a novel chimera containing a high affinity fibrin-binding domain linked to a heterologous protein.

A novel triple-kringle plasminogen activator protein, PK1 delta FE1X, has been produced which is a genetic chimera between the fibrin binding kringle 1 domain of plasminogen and the two kringles and serine protease domains of naturally occurring wild-type tissue plasminogen activator (wt t-PA). This chimera also contains a modification to prevent high mannose type N-linked glycosylation on kringle 1 of t-PA. PK1 delta FE1X is biochemically and fibrinolytically similar to wt t-PA in vitro but retains the decreased plasma clearance rate characteristic of other t-PA variants which lack fibronectin finger-like and epidermal growth factor domains. The serine protease domain of PK1 delta FE1X exhibits the amidolytic activity characteristic of wt t-PA. In an indirect coupled plasminogen activator assay, the specific activity of PK1 delta FE1X is approximately 1.4 times greater than that of wt t-PA. In a fibrin film-binding assay, greater binding to untreated fibrin is observed with wt t-PA than with PK1 delta FE1X. However, following limited plasmin digestion of the fibrin film, PK1 delta FE1X binding increases to the level observed with wt t-PA. The incremental binding to plasmin-digested fibrin observed with PK1 delta FE1X is eliminated if plasmin digestion of the fibrin film is followed by carboxypeptidase B treatment. This result suggests that plasminogen kringle 1 binds plasmin-digested fibrin even after recombination with a heterologous protein. The fibrinolytic activity of PK1 delta FE1X in human plasma clot lysis assays was similar to that of wt t-PA at activator concentrations of approximately 1 microgram/ml. At substantially lower concentrations, approximately 0.1 microgram/ml, PK1 delta FE1X was only slightly less active than wt t-PA. Pharmacokinetic analysis showed that wt t-PA activity is cleared approximately 15 times as rapidly as PK1 delta FE1X following intravenous bolus injection. In a rabbit jugular vein clot lysis model, intravenous bolus injection of 0.06 mg/kg of PK1 delta FE1X showed greater thrombolytic potency than a similar administration of 0.5 mg/kg of wt t-PA. Thus it appears that in vitro exon shuffling techniques can be used to generate novel fibrinolytic agents which biochemically and pharmacologically represent the combination of individual domains of naturally occurring proteins.

Cell-free synthesis and processing of multiple precursors to glucagon.

Glucagon, a polypeptide hormone of 29 amino acids, is synthesized in the islets of Langerhans and immunoreactive forms of the molecule have been found in several tissues. Like many other polypeptide hormones, glucagon is synthesized via a larger precursor molecular, proglucagon; however, estimates of its size vary considerably and the biosynthetic relationship between some of the putative precursors and authentic secreted glucagon is unclear. Consequently it was of interest to investigate the primary translation product of glucagon mRNA to relate its size to that of previously described glucagon precursors. Here we provide evidence for three distinct immunoreactive preproglucagon molecules, two of which have an apparent molecular weight (MW) of approximately 16,000 (16K). Furthermore, when microsomal membranes were present during translation, the nascent 14K preproglucagon polypeptides were processed to proglucagon with a higher apparent MW of 15,000. In contrast, the nascent 16K preproglucagon was co-translationally processed to a slightly smaller polypeptide. The data indicate that the 14K and 16K preproglucagons undergo different types of post-translational modification.