Transient hyperthyroidism following L-asparaginase therapy for acute lymphoblastic leukemia

The effect of L-asparaginase on the thyroid gland has not been well documented. We report the first two cases of hyperthyroidism associated with thyroid nodule following L-asparaginase therapy for acute lymphoblastic leukemia (ALL). The thyroid function abnormalities were not severe, short-lived and did not require specific therapy.     

Immunogenicity and Reactogenicity of Ad26.COV2.S in Korean Adults: A Prospective Cohort Study

BackgroundAs the coronavirus disease 2019 (COVID-19) pandemic continues, there are concerns regarding waning immunity and the emergence of viral variants. The immunogenicity of Ad26.COV2.S against wild-type (WT) and variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) needs to be evaluated.MethodThis prospective cohort study was conducted between June 2021 and January 2022 at two university hospitals in South Korea. Healthy adults who were scheduled to be vaccinated with Ad26.COV2.S were enrolled in this study. The main outcomes included anti-spike (S) IgG antibody and neutralizing antibody responses, S-specific T-cell responses (interferon-γ enzyme-linked immunospot assay), solicited adverse events (AEs), and serious AEs.ResultsFifty participants aged ≥ 19 years were included in the study. Geometric mean titers (GMTs) of anti-S IgG were 0.4 U/mL at baseline, 5.2 ± 3.0 U/mL at 3–4 weeks, 55.7 ± 2.4 U/mL at 5–8 weeks, and 81.3 ± 2.5 U/mL at 10–12 weeks after vaccination. GMTs of 50% neutralizing dilution (ND50) against WT SARS-CoV-2 were 164.6 ± 4.6 at 3-4 weeks, 313.9 ± 3.6 at 5–8 weeks, and 124.4 ± 2.6 at 10–12 weeks after vaccination. As for the S-specific T-cell responses, the median number of spot-forming units/10⁶ peripheral blood mononuclear cell was 25.0 (5.0–29.2) at baseline, 60.0 (23.3–178.3) at 5-8 weeks, and 35.0 (13.3–71.7) at 10–12 weeks after vaccination. Compared to WT SARS-CoV-2, ND50 against Delta and Omicron variants was attenuated by 3.6-fold and 8.2-fold, respectively. The most frequent AE was injection site pain (82%), followed by myalgia (80%), fatigue (70%), and fever (50%). Most AEs were grade 1–2, and resolved within two days.ConclusionSingle-dose Ad26.COV2.S was safe and immunogenic. NAb titer and S-specific T-cell immunity peak at 5–8 weeks and rather decrease at 10–12 weeks after vaccination. Cross-reactive neutralizing activity against the Omicron variant was negligible.     

Omega-9 Modifies Viscoelasticity and Augments Bone Strength and Architecture in a High-Fat Diet-Fed Murine Model

The influence of diet on the development of osteoporosis is significant and not fully understood. This study investigated the effect of diets of varying lipid profiles and ω-3, ω-6 and ω-9 composition on the structural and mechanical properties of bone. The hypothesis studied was that a diet high in saturated fat would induce osteoporosis and produce an overall increased detrimental bony response when compared with a diet high in unsaturated ω-6, or ω-9. Male C57BL/6J mice were fed either a control diet, 50:50 mix (saturated:unsaturated) high in ω-9 (HFD^50:50), a diet high in saturated fat (HSF) or a polyunsaturated fat diet high in ω-6 (PUFA) over an 8-week duration. Tibiae were retrieved and evaluated using DMA, 3-point-bending, histomorphometry, and microCT. Mice fed a HSF diet displayed key features characteristic of osteoporosis. The loss tangent was significantly increased in the HFD^50:50 diet group compared with control (p = 0.016) and PUFA-fed animals (p = 0.049). HFD^50:50-fed mice presented with an increased viscous component, longer tibiae, increased loss modulus (p = 0.009), and ultimate stress, smaller microcracks (p < 0.001), and increased trabecular width (p = 0.002) compared with control animals. A diet high in ω-9 resulted in an overall superior bone response and further analysis of its role in bone health is warranted.     

Nanoscale mapping of temperature-dependent conduction in an epitaxial VO2 film grown on an Al2O3 substrate

Vanadium dioxide (VO₂) is one of the extensively studied strongly correlated oxides due to its intriguing insulator–metal transition near room temperature. In this work, we investigated temperature-dependent nanoscale conduction in an epitaxial VO₂ film grown on an Al₂O₃ substrate using conductive-atomic force microscopy (C-AFM). We observed that only the regions near the grain boundaries are conductive, producing intriguing donut patterns in C-AFM images. Such donut patterns were observed in the entire measured temperature range (300–355 K). The current values near the grain boundaries increased by approximately two orders of magnitude with an increase in the temperature, which is consistent with the macroscopic transport data. The spatially-varied conduction behavior is ascribed to the coexistence of different monoclinic phases, i.e., M1 and M2 phases, based on the results of temperature-dependent Raman spectroscopy. Furthermore, we investigated the conduction mechanism in the relatively conductive M1 phase regions at room temperature using current–voltage (I–V) spectroscopy and deep data analysis. Bayesian linear unmixing and k-means clustering showed three distinct types of conduction behavior, which classical C-AFM cannot resolve. We found that the conduction in the M1 phase regions can be explained by the Poole–Frenkel mechanism. This work provides deep insight into IMT behavior in the epitaxial VO₂ thin film at the nanoscale, especially the coexistence and evolution of the M1 and M2 phases. This work also highlights that I–V spectroscopy combined with deep data analysis is very powerful in investigating local transport in complex oxides and various material systems.

We investigated temperature-dependent nanoscale conduction in an epitaxial VO₂ film grown on an Al₂O₃ substrate using conductive-atomic force microscopy and deep data analysis.     

Clinical Characteristics and Risk Factors for Mortality in Critical Coronavirus Disease 2019 Patients 50 Years of Age or Younger During the Delta Wave: Comparison With Patients > 50 Years in Korea

BackgroundNumerous patients around the globe are dying from coronavirus disease 2019 (COVID-19). While age is a known risk factor, risk analysis in the young generation is lacking. The present study aimed to evaluate the clinical features and mortality risk factors in younger patients (≤ 50 years) with a critical case of COVID-19 in comparison with those among older patients (> 50 years) in Korea.MethodsWe analyzed the data of adult patients only in critical condition (requiring high flow nasal cannula oxygen therapy or higher respiratory support) hospitalized with PCR-confirmed COVID-19 at 11 hospitals in Korea from July 1, 2021 to November 30, 2021 when the delta variant was a dominant strain. Patients’ electronic medical records were reviewed to identify clinical characteristics.ResultsDuring the study period, 448 patients were enrolled. One hundred and forty-two were aged 50 years or younger (the younger group), while 306 were above 50 years of age (the older group). The most common pre-existing conditions in the younger group were diabetes mellitus and hypertension, and 69.7% of the patients had a body mass index (BMI) > 25 kg/m². Of 142 younger patients, 31 of 142 patients (21.8%, 19 women) did not have these pre-existing conditions. The overall case fatality rate among severity cases was 21.0%, and it differed according to age: 5.6% (n = 8/142) in the younger group, 28.1% in the older group, and 38% in the ≥ 65 years group. Age (odds ratio [OR], 7.902; 95% confidence interval [CI], 2.754–18.181), mechanical ventilation therapy (OR, 17.233; 95% CI, 8.439–35.192), highest creatinine > 1.5 mg/dL (OR, 17.631; 95% CI, 8.321–37.357), and combined blood stream infection (OR, 7.092; 95% CI, 1.061–18.181) were identified as independent predictors of mortality in total patients. Similar patterns were observed in age-specific analyses, but most results were statistically insignificant in multivariate analysis due to the low number of deaths in the younger group. The full vaccination rate was very low among study population (13.6%), and only three patients were fully vaccinated, with none of the patients who died having been fully vaccinated in the younger group. Seven of eight patients who died had a pre-existing condition or were obese (BMI > 25 kg/m²), and the one remaining patient died from a secondary infection.ConclusionAbout 22% of the patients in the young critical group did not have an underlying disease or obesity, but the rate of obesity (BMI > 25 kg/m²) was high, with a fatality rate of 5.6%. The full vaccination rate was extremely low compared to the general population of the same age group, showing that non-vaccination has a grave impact on the progression of COVID-19 to a critical condition. The findings of this study highlight the need for measures to prevent critical progression of COVID-19, such as vaccinations and targeting young adults especially having risk factors.     

Safety,tolerability, and pharmacokinetics of single and multiple topical ophthalmic administration of imatinib mesylate in healthy subjects

For the long‐term efficacy of dry eye disease treatment, relieving underlying inflammation is necessary. Imatinib mesylate is a novel ophthalmic formulation of imatinib mesylate, which is expected to alleviate inflammation by inhibiting the discoidin domain receptor 1 activity. This study aims to evaluate the safety and pharmacokinetics of imatinib mesylate in healthy subjects. A randomized, double‐blind, placebo‐controlled study was conducted. In a single ascending dose, 16 subjects received a single eye drop of imatinib mesylate 0.1%, 0.3%, or matching placebo. In the multiple ascending dose (MAD), subjects received multiple eye drops of imatinib mesylate 0.1%, 0.3%, or matching placebo once daily for 7 days. Safety and tolerability were assessed by ophthalmic examination, including the visual analog scale (VAS) to monitor the burning sensation in the eyes. A total of four treatment‐emergent adverse events (TEAEs) occurred during the study. All TEAEs were mildly severe with no serious cases. VAS results in the 0.1% MAD group exhibited highest score of two points, whereas it was less than one point in others. Insignificant difference between the imatinib mesylate and placebo groups in the VAS results was seen. After a single dose administration of imatinib mesylate 0.1%, all plasma concentrations were below the lower limit of quantification. The peak plasma concentrations of imatinib were less than 0.54 µg/L in all groups. In conclusion, a single and multiple topical ophthalmic administration of imatinib mesylate was well‐tolerated in healthy subjects. Because there was minimal systemic exposure to imatinib, the adverse effect in the body seems to be insignificant.     

Alfentanil co-induction for laryngeal mask insertion

We assessed the effect of two different doses of alfentanil (5 and 10 micrograms.kg-1) on the conditions for laryngeal mask airway insertion in ASA 1 and 2 patients who received propofol for induction of anaesthesia. One hundred and fifty unpremedicated patients were randomly allocated to receive either propofol 2.5 mg.kg-1 only (Group P), alfentanil 5 micrograms.kg-1 and propofol 2.5 mg.kg-1 (Group A5), or alfentanil 10 micrograms.kg-1 and propofol 2.5 mg.kg-1 (Group A10). The addition of alfentanil to propofol resulted in a greater ease of insertion and a better quality of airway patency. Pretreatment with alfentanil also resulted in a significantly higher success rate during the first attempt at inserting the laryngeal mask airway compared with Group P (Group P 58%, Group A5 96%, Group A10 94%). Patients in Group P were apnoeic for a mean (+/- SD) time of 3.3(+/- 1.9) min, 4.71 (+/- 2.2) min in Group A5, and 7.32(+/- 4.3) min in Group A10. The use of alfentanil 10 micrograms.kg-1 with propofol, however, led to a significant decrease in mean arterial pressure and heart rate. We concluded that pretreatment with intravenous alfentanil 5 micrograms.kg-1 prior to propofol provides excellent conditions for insertion of laryngeal mask with minimal adverse haemodynamic changes.     

Quantitative Shear Wave Elastography as a Prognostic Implication of Papillary Thyroid Carcinoma (PTC): Elasticity Index Can Predict Extrathyroidal Extension (ETE)

Objective

To investigate whether the quantitative elasticity index of shear wave elastography (SWE) can predict extrathyroidal extension (ETE) of papillary thyroid carcinoma (PTC) preoperatively.

Methods

A total of 208 patients with pathology confirmed PTC whom underwent SWE during preoperative staging US between April 2011 to June 2012 were included.SWE indices of E _mean, E _max, E _min of the index malignancy, the ratios between E _mean of the lesion and parenchyma (E _ratio-P), and muscle (E _ratio-M), and grayscale US findings, including ETE, multifocality, bilaterality, and central and lateral lymph node (LN) metastasis were evaluated. The correlations of SWE indices and grayscale US findings with pathologic prognostic factors of PTC were analyzed by Chi square or Fisher’s exact test, and multivariate regression analysis.

Results

ETE was associated with E _mean, E _max, E _min, and E _ratio-M (P = 0.005, 0.009, 0.016 and <0.001, respectively), multifocality was associated with E _mean, E _max, and E _min (P = 0.028, 0.007, and 0.004, respectively), and central LN metastasis was associated with E _ratio-M (P = 0.03). On multivariate analysis, E _mean and E _min were independent factors for predicting ETE (P = 0.032, 0.049, respectively).

Conclusions

Quantitative elasticity index of SWE could predict pathologic ETE, and SWE could be a complimentary method to grayscale US for preoperative prediction of prognostic factors of PTC.