Association between repeat imaging and readmission in patients with acute ischaemic stroke: a 16-year nationwide population-based study.

OBJECTIVES: This study aims to evaluate such usage patterns and identify factors that may contribute to the need for repeat imaging in acute ischaemic stroke patients and determine the association between repeat imaging and readmission in Taiwan. METHODS: We searched and analysed data from the Taiwan National Health Insurance Research Database for patients admitted for acute ischaemic stroke between 2002 and 2017. Cases where repeat brain imaging during the initial hospital admission occurred and where patients were readmitted within 30 days following discharge were documented. RESULTS: Of a total of 195 016 patients with new onset ischaemic stroke, 51 798 (26.6%) underwent repeat imaging during their initial admission. Factors associated with repeat brain imaging included younger age, longer hospital stay, use of recombinant tissue plasminogen activator (rt-PA) therapy (odds ratio = 2.10 [95% CI, 1.98-2.22]), more recent year of diagnosis, higher National Institutes of Health Stroke Scale (NIHSS) score, and admission to a hospital offering a higher level of care. Repeat imaging was also associated with an increased risk of ischaemic stroke and all types of stroke readmission. CONCLUSIONS: Repeat brain imaging of patients with stroke has increased in recent years, and it is associated with certain factors including age, length of stay, use of rt-PA, hospital level of care, and NIHSS score. It is also associated with increased readmission. ADVANCES IN KNOWLEDGE: Knowledge of the associations of repeat imaging may help clinicians use repeat imaging more carefully and efficaciously.

Persistent urinary incontinence in female Golden Retrievers following laser ablation of intramural ectopic ureters may be associated with the presence of historical urinary tract infection.

OBJECTIVE: To identify predictive factors for postoperative continence in female Golden Retrievers following cystoscopic-guided laser ablation of intramural ectopic ureters (CLA-EU). ANIMALS: 41 client-owned female entire Golden Retrievers with uni- or bilateral intramural ectopic ureter(s) were retrospectively enrolled. METHODS: Patients were diagnosed with ectopic ureters with a combination of ultrasonography and cystoscopy. CLA-EU was performed for all dogs so that each ureteral opening was considered to be in an appropriate position by a single operator. All dogs had short-term follow-up 4 weeks and long-term follow up > 10 weeks after the procedure via telephone, which included urinary continence scoring. Clinical factors and ultrasonographic and cystoscopic findings from initial presentation were evaluated to identify predictive factors for postoperative continence. RESULTS: Short-term urinary continence was achieved in 46.3% of dogs with no additional medical therapies. Presence of historical urinary tract infections prior to CLA-EU (OR, 0.130; 95% CI, 0.020 to 0.621; P = .018) was negatively correlated and ureteral dilatation (OR, 34.260; 95% CI, 1.813 to 2,143; P = .043) was positively correlated with likelihood of urinary continence. Long-term urinary continence was achieved in 63.4% of dogs, and presence of historical urinary tract infections was negatively prognostic (OR, 0.173; 95% CI, 0.023 to 0.856; P = .048). CLINICAL RELEVANCE: Female Golden Retrievers undergoing CLA-EU have similar outcomes to those reported for other mixed-breed cohorts with > 30% of dogs failing to regain urinary continence. Historical urinary tract infections were significantly associated with both short- and long-term urinary continence in our population.

Clinical remission of feline sino-nasal aspergillosis despite evidence of persistent infection.

Case summary: Feline sino-nasal aspergillosis is a rare condition with only sparse heterogeneous reports in the literature regarding its treatment. This report describes the presentation, treatment and outcome of a cat with sino-nasal aspergillosis treated by meticulous debridement in combination with topical and systemic azole therapy. Diagnosis was based on MRI, in combination with rhinoscopic assessment and visualisation of fungal plaques, followed by histopathology, fungal culture and panfungal PCR. The cat was treated by debridement of fungal plaques via anterior rhinoscopy and frontal sinusotomy and local instillation of 1% clotrimazole solution, followed by a 4-week course of oral itraconazole. Histopathology confirmed fungal rhinitis and culture identified Aspergillus fumigatus and Aspergillus versicolor. Clinical remission was achieved after treatment; however, evidence of persistent infection was confirmed in the post-mortem examination 8 months after the cat was euthanased for unrelated reasons. Relevance and novel information: Despite clinical remission, the persistence of fungal infection post mortem highlights the challenges of monitoring the response to treatment and illustrates that the resolution of clinical signs does not necessarily equate with a disease cure.

Resistance Exercise Training Rescues Mitochondrial Dysfunction in Skeletal Muscle of Patients with Myotonic Dystrophy Type 1.

BACKGROUND: Myotonic dystrophy type 1 (DM1) is a dominant autosomal neuromuscular disorder caused by the inheritance of a CTG triplet repeat expansion in the Dystrophia Myotonica Protein Kinase (DMPK) gene. At present, no cure currently exists for DM1 disease. OBJECTIVE: This study investigates the effects of 12-week resistance exercise training on mitochondrial oxidative phosphorylation in skeletal muscle in a cohort of DM1 patients (n = 11, men) in comparison to control muscle with normal oxidative phosphorylation. METHODS: Immunofluorescence was used to assess protein levels of key respiratory chain subunits of complex I (CI) and complex IV (CIV), and markers of mitochondrial mass and cell membrane in individual myofibres sampled from muscle biopsies. Using control's skeletal muscle fibers population, we classified each patient's fibers as having normal, low or high levels of CI and CIV and compared the proportions of fibers before and after exercise training. The significance of changes observed between pre- and post-exercise within patients was estimated using a permutation test. RESULTS: At baseline, DM1 patients present with significantly decreased mitochondrial mass, and isolated or combined CI and CIV deficiency. After resistance exercise training, in most patients a significant increase in mitochondrial mass was observed, and all patients showed a significant increase in CI and/or CIV protein levels. Moreover, improvements in mitochondrial mass were correlated with the one-repetition maximum strength evaluation. CONCLUSIONS: Remarkably, 12-week resistance exercise training is sufficient to partially rescue mitochondrial dysfunction in DM1 patients, suggesting that the response to exercise is in part be due to changes in mitochondria.

Parkinson's disease neurons exhibit alterations in mitochondrial quality control proteins.

Mitochondrial dysfunction has been suggested to contribute to Parkinson's disease pathogenesis, though an understanding of the extent or exact mechanism of this contribution remains elusive. This has been complicated by challenging nature of pathway-based analysis and an inability simultaneously study multiple related proteins within human brain tissue. We used imaging mass cytometry (IMC) to overcome these challenges, measuring multiple protein targets, whilst retaining the spatial relationship between targets in post-mortem midbrain sections. We used IMC to simultaneously interrogate subunits of the mitochondrial oxidative phosphorylation complexes, and several key signalling pathways important for mitochondrial homoeostasis, in a large cohort of PD patient and control cases. We revealed a generalised and synergistic reduction in mitochondrial quality control proteins in dopaminergic neurons from Parkinson's patients. Further, protein-protein abundance relationships appeared significantly different between PD and disease control tissue. Our data showed a significant reduction in the abundance of PINK1, Parkin and phosphorylated ubiquitinSer65, integral to the mitophagy machinery; two mitochondrial chaperones, HSP60 and PHB1; and regulators of mitochondrial protein synthesis and the unfolded protein response, SIRT3 and TFAM. Further, SIRT3 and PINK1 did not show an adaptive response to an ATP synthase defect in the Parkinson's neurons. We also observed intraneuronal aggregates of phosphorylated ubiquitinSer65, alongside increased abundance of mitochondrial proteases, LONP1 and HTRA2, within the Parkinson's neurons with Lewy body pathology, compared to those without. Taken together, these findings suggest an inability to turnover mitochondria and maintain mitochondrial proteostasis in Parkinson's neurons. This may exacerbate the impact of oxidative phosphorylation defects and ageing related oxidative stress, leading to neuronal degeneration. Our data also suggest that that Lewy pathology may affect mitochondrial quality control regulation through the disturbance of mitophagy and intramitochondrial proteostasis.

T cell differentiation drives the negative selection of pathogenic mitochondrial DNA variants.

Pathogenic mitochondrial DNA (mtDNA) single-nucleotide variants are a common cause of adult mitochondrial disease. Levels of some variants decrease with age in blood. Given differing division rates, longevity, and energetic requirements within haematopoietic lineages, we hypothesised that cell-type-specific metabolic requirements drive this decline. We coupled cell-sorting with mtDNA sequencing to investigate mtDNA variant levels within progenitor, myeloid, and lymphoid lineages from 26 individuals harbouring one of two pathogenic mtDNA variants (m.3243A>G and m.8344A>G). For both variants, cells of the T cell lineage show an enhanced decline. High-throughput single-cell analysis revealed that decline is driven by increasing proportions of cells that have cleared the variant, following a hierarchy that follows the current orthodoxy of T cell differentiation and maturation. Furthermore, patients with pathogenic mtDNA variants have a lower proportion of T cells than controls, indicating a key role for mitochondrial function in T cell homeostasis. This work identifies the ability of T cell subtypes to selectively purify their mitochondrial genomes, and identifies pathogenic mtDNA variants as a new means to track blood cell differentiation status.

PINK1-Dependent Mitophagy Inhibits Elevated Ubiquitin Phosphorylation Caused by Mitochondrial Damage.

Ubiquitin phosphorylation by the mitochondrial protein kinase PTEN-induced kinase 1 (PINK1), upon mitochondrial depolarization, is an important intermediate step in the recycling of damaged mitochondria via mitophagy. As mutations in PINK1 can cause early-onset Parkinson's disease (PD), there has been a growing interest in small-molecule activators of PINK1-mediated mitophagy as potential PD treatments. Herein, we show that N6-substituted adenosines, such as N6-(2-furanylmethyl)adenosine (known as kinetin riboside) and N6-benzyladenosine, activate PINK1 in HeLa cells and induce PINK1-dependent mitophagy in primary mouse fibroblasts. Interestingly, pre-treatment of HeLa cells and astrocytes with these compounds inhibited elevated ubiquitin phosphorylation that is induced by established mitochondrial depolarizing agents, carbonyl cyanide m-chlorophenyl-hydrazine and niclosamide. Together, this highlights N6-substituted adenosines as progenitor PINK1 activators that could potentially be developed, in the future, as treatments for aged and sporadic PD patients who have elevated phosphorylated ubiquitin levels in the brain.

Utilization of CT and MRI scanning in Taiwan, 2000-2017.

OBJECTIVES: This population-based study aimed to collect, analyze, and summarize the long-term trends in medical imaging use in Taiwan. METHODS: A retrospective cohort population-based study of medical imaging usage for the individuals who received care under the National Health Insurance system from 2000 to 2017. CT and MRI utilization rates were determined overall as well as across certain variables including patient age, hospital type, health care type, hospital characteristics, and geographic area. RESULTS: Individuals registered in our health insurance system have received 21,766,745 CT scans and 7,520,088 MRI scans from 2000 to 2017. Annual growth rates for both imaging types were positive over that period, though growth rates have slowed in recent years. The growth rate for CT use was greatest (9-12%) between 2001 and 2004, dropped to 2% in 2005, then generally rose thereafter, reaching 3% in 2017. Similarly, MRI use growth peaked at 24% between 2001 and 2003, dropped to 4% in 2005, then increased in a fluctuating manner, reaching 2% in 2017. CONCLUSION: Over the past 2 decades, CT and MRI use in Taiwan has increased sharply, especially in the oldest age group (≥ 60 years old), but growth rates have slowed in recent years. Increases in imaging use have corresponded with improved clinical outcomes, including greater life expectancy and reduced mortality rates, though further assessment is required to demonstrate a direct link with imaging. Nevertheless, the better clinical outcomes are also predisposed by the comprehensive care covered by the NHI system.

Novel <i>DNM1L</i> variants impair mitochondrial dynamics through divergent mechanisms.

Imbalances in mitochondrial and peroxisomal dynamics are associated with a spectrum of human neurological disorders. Mitochondrial and peroxisomal fission both involve dynamin-related protein 1 (DRP1) oligomerisation and membrane constriction, although the precise biophysical mechanisms by which distinct DRP1 variants affect the assembly and activity of different DRP1 domains remains largely unexplored. We analysed four unreported de novo heterozygous variants in the dynamin-1-like gene <i>DNM1L</i>, affecting different highly conserved DRP1 domains, leading to developmental delay, seizures, hypotonia, and/or rare cardiac complications in infancy. Single-nucleotide DRP1 stalk domain variants were found to correlate with more severe clinical phenotypes, with in vitro recombinant human DRP1 mutants demonstrating greater impairments in protein oligomerisation, DRP1-peroxisomal recruitment, and both mitochondrial and peroxisomal hyperfusion compared to GTPase or GTPase-effector domain variants. Importantly, we identified a novel mechanism of pathogenesis, where a p.Arg710Gly variant uncouples DRP1 assembly from assembly-stimulated GTP hydrolysis, providing mechanistic insight into how assembly-state information is transmitted to the GTPase domain. Together, these data reveal that discrete, pathological <i>DNM1L</i> variants impair mitochondrial network maintenance by divergent mechanisms.

Pharmacological Prevention of Hypersensitivity Reactions Caused by Iodinated Contrast Media: A Systematic Review and Meta-Analysis.

Objectives: Hypersensitivity reactions (HSRs) are uncommon but serious adverse events following the administration of iodinated contrast media (ICM) prior to CT imaging. While premedication is almost universally given in high-risk patients, there is a lack of evidence regarding the efficacy of such premedication. This study aims to determine the efficacy of premedication with corticosteroids prior to ICM administration in the prevention of HSRs through meta-analysis. Materials and Methods: An extensive review of the literature yielded 404 potentially relevant studies. Of these, five studies met the inclusion criteria of this meta-analysis. Pooled HSR event rates were obtained from each of the studies for both patients who had and who had not received premedication with corticosteroids. Heterogeneity between studies was also determined. Results: A total of 736 patients across all five studies were included in the analysis. Patients who did not receive premedication had initial pooled HSR rates of 0.16 (95% CI, 0.07−0.35) across all studies. Following premedication, pooled HSR rates dropped to 0.02 (95% CI, 0.01−0.06). Patients who had prior HSRs were significantly less likely to experience HSRs (OR = 0.09; 95% CI, 0.03−0.25; p < 0.00001) after treatment with premedication. Conclusions: This meta-analysis offers evidence for the reduction in the recurrence of moderate and severe HSRs in patients who have a history of such reactions. Premedication with corticosteroids prior to ICM administration is thus highly recommended in high-risk patients.

Correlation between hand grip strength and regional muscle mass in older Asian adults: an observational study.

BACKGROUND: Previous research has demonstrated a correlation between hand grip strength (HGS) and muscle strength. This study aims to determine the relationship between HGS and muscle mass in older Asian adults. METHODS: We retrospectively reviewed the dual-energy X-ray absorptiometry (DXA) records of 907 older adults (239 (26.4%) men and 668 (73.6%) women) at one medical institution in Taipei, Taiwan, from January 2019, to December 2020. Average age was 74.80 ± 9.43 and 72.93 ± 9.09 for the males and females respectively. The inclusion criteria were: 1) aged 60 and older, 2) underwent a full-body DXA scan, and 3) performed hand grip measurements. Patients with duplicate results, incomplete records, stroke history, and other neurological diseases were excluded. Regional skeletal muscle mass was measured using DXA. HGS was measured using a Jamar handheld dynamometer. RESULTS: Total lean muscle mass (kg) averaged 43.63 ± 5.81 and 33.16 ± 4.32 for the males and females respectively. Average HGS (kg) was 28.81 ± 9.87 and 19.19 ± 6.17 for the males and females respectively. In both sexes, HGS and regional muscle mass consistently declined after 60 years of age. The rates of decline per decade in upper and lower extremity muscle mass and HGS were 7.06, 4.95, and 12.30%, respectively, for the males, and 3.36, 4.44, and 12.48%, respectively, for the females. In men, HGS significantly correlated with upper (r = 0.576, p < 0.001) and lower extremity muscle mass (r = 0.532, p < 0.001). In women, the correlations between HGS and upper extremity muscle mass (r = 0.262, p < 0.001) and lower extremity muscle mass (r = 0.364, p < 0.001) were less strong, though also statistically significant. CONCLUSION: Muscle mass and HGS decline with advancing age in both sexes, though the correlation is stronger in men. HGS measurements are an accurate proxy for muscle mass in older Asian adults, particularly in males.

Detecting respiratory chain defects in osteoblasts from osteoarthritic patients using imaging mass cytometry.

Osteoporosis is a skeletal disease which is characterised by reduced bone mass and microarchitecture, with a subsequent loss of strength that predisposes to fragility and risk of fractures. The pathogenesis of falling bone mineral density, ultimately leading to a diagnosis of osteoporosis is incompletely understood but the disease is currently thought to be multifactorial. Humans are known to accumulate mitochondrial mutations and respiratory chain deficiency with age and mounting evidence suggests that this may indeed be the overarching cause intrinsic to the changing phenotype in advancing age and age-related disease. Mitochondrial mutations are detectable from the age of about 30 years onwards. Mitochondria contain their own genome which encodes 13 essential mitochondrial proteins and accumulates somatic variants at up to 10 times the rate of the nuclear genome. Once the concentration of any pathogenic mitochondrial genome variant exceeds a threshold, respiratory chain deficiency and cellular dysfunction occur. The PolgD257A/D257A mouse model is a knock-in mutant that expresses a proof-reading-deficient version of PolgA, a nuclear encoded subunit of mtDNA polymerase. These mice are a useful model of age-related accumulation of mtDNA mutations in humans since their defective proof-reading mechanism leads to a mitochondrial DNA mutation rate 3-5 times higher than in wild-type mice. These mice showed enhanced levels of age-related osteoporosis along with respiratory chain deficiency in osteoblasts. To explore whether respiratory chain deficiency is also seen in human osteoblasts, we developed a protocol and analysis framework for imaging mass cytometry in bone tissue sections to analyse osteoblasts in situ. By comparing bone tissue sampled at one timepoint from femoral neck of 10 older healthy volunteers aged 40-85 with samples from young patients aged 1-19, we have identified complex I defect in osteoblasts from 6 out of 10 older volunteers, complex II defect in 2 out of 10 older volunteers, complex IV defect in 1 out of 10 older volunteers and complex V defect in 4 out of 10 older volunteers. These observations are consistent with findings from the PolgD257A/D257A mouse model and suggest that respiratory chain deficiency, as a consequence of the accumulation of age-related pathogenic mitochondrial DNA mutations, may play a significant role in the pathogenesis of human age-related osteoporosis.

Gut microbiota changes and its potential relations with thyroid carcinoma.

Introduction: Emerging evidence suggests that the essence of life is the ecological balance of the neural, endocrine, metabolic, microbial, and immune systems. Gut microbiota have been implicated as an important factor affecting thyroid homeostasis. Objectives: This study aims to explore the relationship between gut microbiota and the development of thyroid carcinoma. Methods: Stool samples were collected from 90 thyroid carcinoma patients (TCs) and 90 healthy controls (HCs). Microbiota were analyzed using 16S ribosomal RNA gene sequencing. A cross-sectional study of an exploratory cohort of 60 TCs and 60 HCs was conducted. The gut microbiota signature of TCs was established by LEfSe, stepwise logistic regression, lasso regression, and random forest model analysis. An independent cohort of 30 TCs and 30 HCs was used to validate the findings. Functional prediction was achieved using Tax4Fun and PICRUSt2. TC patients were subsequently divided into subgroups to analyze the relationship between microbiota and metastatic lymphadenopathy. Results: In the exploratory cohorts, TCs had reduced richness and diversity of gut microbiota compared to HCs. No significant difference was found between TCs and HCs on the phylum level, though 70% of TCs had increased levels of Proteobacteria-types based on dominant microbiota typing. A prediction model of 10 genera generated with LEfSe analysis and lasso regression distinguished TCs from HCs with areas under the curves of 0.809 and 0.746 in the exploration and validation cohorts respectively. Functional prediction suggested that the microbial changes observed in TCs resulted in a decline in aminoacyl-tRNA biosynthesis, homologous recombination, mismatch repair, DNA replication, and nucleotide excision repair. A four-genus microbial signature was able to distinguish TC patients with metastatic lymphadenopathy from those without metastatic lymphadenopathy. Conclusion: Our study shows that thyroid carcinoma patients demonstrate significant changes in gut microbiota, which will help delineate the relationship between gut microbiota and TC pathogenesis.

Acute Mesenteric Vein Thrombosis in a Pregnant Patient at 10 Weeks Gestation: A Case Report.

Acute abdominal pain during pregnancy is challenging, both from a diagnostic and management perspective. A non-localized, persistent pain out of proportion to physical examination is a sign that advanced imaging may be necessary. Mesenteric venous thrombosis in a pregnant patient is extremely rare, but if diagnosis is delayed, can be potentially fatal to both the mother and the fetus. We present here a pregnant patient in the tenth week of gestation with classic clinical manifestations of mesenteric vein thrombosis and the corresponding findings on magnetic resonance imaging (MRI) and computed tomography (CT).

Today's radiologists meet tomorrow's AI: the promises, pitfalls, and unbridled potential.

Advances in information technology have improved radiologists' abilities to perform an increasing variety of targeted diagnostic exams. However, due to a growing demand for imaging from an aging population, the number of exams could soon exceed the number of radiologists available to read them. However, artificial intelligence has recently resounding success in several case studies involving the interpretation of radiologic exams. As such, the integration of AI with standard diagnostic imaging practices to revolutionize medical care has been proposed, with the ultimate goal being the replacement of human radiologists with AI 'radiologists'. However, the complexity of medical tasks is often underestimated, and many proponents are oblivious to the limitations of AI algorithms. In this paper, we review the hype surrounding AI in medical imaging and the changing opinions over the years, ultimately describing AI's shortcomings. Nonetheless, we believe that AI has the potential to assist radiologists. Therefore, we discuss ways AI can increase a radiologist's efficiency by integrating it into the standard workflow.

APQS consensus regarding patient shielding during routine radiographic imaging.

Shielding, particularly of the gonads, has been a routine part of diagnostic radiographic imaging for many years. However, recent thinking suggests that such shielding may offer little benefit, and in some cases may actually cause harm, e.g. by obscuring anatomy or paradoxically increasing patient radiation dose secondary to the need for repeat imaging. This thinking has led many institutions in the West to abandon routine shielding. However, in Asia, shielding is still commonplace. It was felt that the Asia-Pacific Forum on Quality and Safety in Medical Imaging (APQS) was an ideal place to discuss the merits of shielding and deliver a pan-Asian consensus. The APQS is an annual meeting that convenes radiation safety and imaging quality experts from all of the major Asian regions. During the 2020 APQS meeting, radiation safety experts from each region discussed their opinions of shielding during a dedicated session. These experts' views were mostly in line with the views of Western radiologists. However, important country specific and cultural factors were noted by each of the experts. A pan-Asian consensus was issued by the forum. It is hoped that this consensus will guide the development of future shielding policies throughout Asia.

Impacts of the COVID-19 Pandemic on Preexisting Racial and Ethnic Disparities, and Results of an Integrated Safety Net Response in Arlington County, Virginia.

This paper presents research conducted by the Arlington County Department of Human Services to understand the use of safety net services during the pandemic, identify disparities, and reduce or eliminate them. Arlington County's levels of health and economic wellbeing are generally high; however, residents of color experience significant disparities compared with White residents, with lower median incomes, lower rates of college completion, lower life expectancies, and higher rates of chronic illness. During the COVID-19 pandemic, these disparities were amplified as Black and Latinx residents experienced disproportionately high rates of COVID-19 infection, hospitalization, and death, as well as disproportionately high rates of job loss. During the COVID-19 pandemic, Arlington County mounted an interdisciplinary response to stabilize community needs, including food security, eviction prevention, isolation housing, behavioral health stabilization, and digital equity. This integrated approach was especially important during the pandemic, as the direct and indirect effects of the pandemic disproportionately impacted health and economic wellbeing among Arlington's Black and Latinx residents, low-income residents, and vulnerable communities.

Management and infection control practices in a Taiwanese radiology department during the COVID-19 outbreak.

The radiology department was categorized as a "high risk area" during the severe acute respiratory syndrome (SARS) outbreak in 2003 and is similarly considered a "high risk area" during the current coronavirus (COVID-19) pandemic. The purpose of infection control is to isolate patients with suspected or confirmed COVID-19 from uninfected people by utilizing separate equipment, spaces, and healthcare workers. Infection control measures should be prioritized to prevent the nosocomial spread of infection. We established a COVID-19 infection control team in our radiology department. The team's responsibilities include triaging patients with confirmed or suspected COVID-19, performing imaging and reporting, using dedicated equipment, disinfecting the equipment and the immediate environment, and staff scheduling.