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Everything I never told you
\"Lydia is the favorite child of [Chinese Americans] Marilyn and James Lee: their middle daughter, a girl who inherited her mother's bright blue eyes and her father's jet-black hair. Her parents are determined that Lydia will fulfill the dreams they were unable to pursue--in Marilyn's case that her daughter become a doctor rather than a homemaker, in James's case that Lydia be popular at school, a girl with a busy social life and the center of every party. When Lydia's body is found in the local lake, the delicate balancing act that has been keeping the Lee family together is destroyed, [forcing them to confront the long-kept secrets that have been slowly pulling them apart]\"--Dust jacket flap.
Book
Effects of thyroiditis on the diagnostic performance of fine-needle aspiration cytology– clinico-radiologico-cytological analysis of risk factors for discordance
Introduction
Thyroiditis is known to induce atypical cytomorphological changes in the thyroid accompanied by increased cancer risk. The current study aims to determine the effect of thyroiditis on the risk of neoplasm (RON), risk of malignancy (ROM), diagnostic concordance and clinico-radiological features associated with discordance in thyroid aspirates.
Methods
A cohort of histology (thyroidectomy) matched thyroid aspirates were reviewed for medical history of thyroiditis, cytological and histological diagnosis, and clinico-radiological information. Cytology-histology concordance was determined in accordance with the Bethesda system 2023.
Results
There were 770 thyroid aspirates with lymphocytic thyroiditis (
n
= 106), Graves’ disease (
n
= 19), granulomatous thyroiditis (
n
= 3), IgG4-associated thyroiditis (
n
= 2), and non-specified autoimmune thyroiditis (
n
= 2). In the thyroiditis group, the RON/ROM in the Bethesda I to VI categories were 25.0%/21.4% (non-diagnostic/unsatisfactory), 31.3%/25.0% (benign), 45.2%/24.1% (atypia of undetermined significance (AUS)/follicular lesion of undetermined significance (FLUS)), 33.3%/0% (follicular neoplasm/suspicious for follicular neoplasm), 100%/100% (suspicious for malignancy), and 100%/100% (malignant), respectively. In the non-thyroiditis group, the RON/ROM were respectively 51.5%/34.9%, 23.3%/8.9%, 44.8%/23.0%, 68.4%/21.1%, 94.8%/87.9%, and 100%/97.7%. The RON for non-diagnostic/unsatisfactory was higher in the non-thyroiditis group (
p
= 0.009). There were more AUS/FLUS aspirates in the thyroiditis group (47.0% vs. 37.5%,
p
= 0.042). With AUS/FLUS aspirates considered positive over negative, the concordance rate decreased (59.6% to 51.9%) in the thyroiditis group with a trended towards lower concordance than the non-thyroiditis group (51.9% vs. 61.4%,
p
= 0.074). Cases with lymphocytic thyroiditis showed a lower concordance rate (
p
= 0.010), and reciprocally Graves’ disease higher (
p
= 0.031). Other clinico-radiological parameters demonstrated no significant correlations.
Conclusion
Decisions arising from AUS/FLUS aspirates in patients with thyroiditis may better err on the conservative side with assumptive negative diagnosis. In managing patients with lymphocytic thyroiditis, the lowered diagnostic accuracy of aspiration cytology should be taken into consideration.
Clinical trial number
Not applicable.
Journal Article
Pharmacology and Pharmacokinetics of Vitamin E: Nanoformulations to Enhance Bioavailability
Vitamin E belongs to the family of lipid-soluble vitamins and can be divided into two groups, tocopherols and tocotrienols, with four isomers (alpha, beta, gamma and delta). Although vitamin E is widely known as a potent antioxidant, studies have also revealed that vitamin E possesses anti-inflammatory properties. These crucial properties of vitamin E are beneficial in various aspects of health, especially in neuroprotection and cardiovascular, skin and bone health. However, the poor bioavailability of vitamin E, especially tocotrienols, remains a great limitation for clinical applications. Recently, nanoformulations that include nanovesicles, solid-lipid nanoparticles, nanostructured lipid carriers, nanoemulsions, and polymeric nanoparticles have shown promising outcomes in improving the efficacy and bioavailability of vitamin E. This review focuses on the pharmacological properties and pharmacokinetics of vitamin E and current advances in vitamin E nanoformulations for future clinical applications. The limitations and future recommendations are also discussed in this review.
Journal Article
A real-world comparison of outcomes between fractional flow reserve-guided versus angiography-guided percutaneous coronary intervention
Fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) has been shown to be superior to angiography-guided PCI in randomized controlled studies. However, real-world data on the use and outcomes of FFR-guided PCI remain limited. Thus, we investigated the outcomes of patients undergoing FFR-guided PCI compared to angiography-guided PCI in a large, state-wide unselected cohort.
All patients undergoing PCI between June 2017 and June 2018 in New South Wales, Australia, were included. The cohort was stratified into the FFR-guided group when concomitant FFR was performed, and the angiography-guided group when no FFR was performed. The primary outcome was a combined endpoint of death or myocardial infarction (MI). Secondary outcomes included all-cause death, cardiovascular (CVS) death, and MI. The cohort comprised 10,304 patients, of which 542 (5%) underwent FFR-guided PCI. During a mean follow-up of 12±4 months, the FFR-guided PCI group had reduced occurrence of the primary outcome (hazard ratio [HR] 0.34, 95% confidence intervals [CI] 0.20-0.56, P<0.001), all-cause death (HR 0.18, 95% CI 0.07-0.47, P = 0.001), CVS death (HR 0.21, 95% CI 0.07-0.66, P = 0.01), and MI (HR 0.46, 95% CI 0.25-0.84, P = 0.01) compared to the angiography-guided PCI group. Multivariable Cox regression analysis showed FFR-guidance to be an independent predictor of the primary outcome (HR 0.45, 95% CI 0.27-0.75, P = 0.002), all-cause death (HR 0.22, 95% CI 0.08-0.59, P = 0.003), and CVS death (HR 0.27, 95% CI 0.09-0.83, P = 0.02).
In this real-world study of patients undergoing PCI, FFR-guidance was associated with lower rates of the primary outcome of death or MI, as well as the secondary outcomes of all-cause death and CVS death.
Journal Article
Under the Pendulum Sun : a novel of the Fae
Catherine Helstone's brother, Laon, has disappeared in Arcadia, legendary land of the magical fae. Desperate for news of him, she makes the perilous journey, but once there, she finds herself alone and isolated in the sinister house of Gethsemane. At last there comes news: her beloved brother is riding to be reunited with her soon - but the Queen of the Fae and her insane court are hard on his heels.
Book
Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID-19
ObjectiveAlthough COVID-19 is primarily a respiratory illness, there is mounting evidence suggesting that the GI tract is involved in this disease. We investigated whether the gut microbiome is linked to disease severity in patients with COVID-19, and whether perturbations in microbiome composition, if any, resolve with clearance of the SARS-CoV-2 virus.MethodsIn this two-hospital cohort study, we obtained blood, stool and patient records from 100 patients with laboratory-confirmed SARS-CoV-2 infection. Serial stool samples were collected from 27 of the 100 patients up to 30 days after clearance of SARS-CoV-2. Gut microbiome compositions were characterised by shotgun sequencing total DNA extracted from stools. Concentrations of inflammatory cytokines and blood markers were measured from plasma.ResultsGut microbiome composition was significantly altered in patients with COVID-19 compared with non-COVID-19 individuals irrespective of whether patients had received medication (p<0.01). Several gut commensals with known immunomodulatory potential such as Faecalibacterium prausnitzii, Eubacterium rectale and bifidobacteria were underrepresented in patients and remained low in samples collected up to 30 days after disease resolution. Moreover, this perturbed composition exhibited stratification with disease severity concordant with elevated concentrations of inflammatory cytokines and blood markers such as C reactive protein, lactate dehydrogenase, aspartate aminotransferase and gamma-glutamyl transferase.ConclusionAssociations between gut microbiota composition, levels of cytokines and inflammatory markers in patients with COVID-19 suggest that the gut microbiome is involved in the magnitude of COVID-19 severity possibly via modulating host immune responses. Furthermore, the gut microbiota dysbiosis after disease resolution could contribute to persistent symptoms, highlighting a need to understand how gut microorganisms are involved in inflammation and COVID-19.
Journal Article
Increasing returns and economic efficiency
Recognizing increasing returns disrupts much of the established wisdom in economic analysis, making money non-neutral, equity conflict with freedom, & encouraging goods with increasing returns efficient. This book discusses these problems & ways they can be handled, helping to explain phenomena in the real world.
Book
Phase 1 Trial of a Therapeutic Anti–Yellow Fever Virus Human Antibody
A phase 1a–1b trial of TY014, an IgG1 anti–yellow fever virus monoclonal antibody, did not identify worrisome safety signals. Ten participants were randomly assigned to receive TY014 or placebo 24 hours after live yellow fever vaccination (YF17D-204). YF17D-204 viremia was detectable in no participants in the TY014 group and in four in the placebo group, providing preliminary evidence of potential efficacy.
Journal Article