Longitudinal Free-Water Changes in Dementia with Lewy Bodies.

BACKGROUND: Diffusion-weighted magnetic resonance imaging (dMRI) examines tissue microstructure integrity in vivo. Prior dementia with Lewy bodies (DLB) diffusion tensor imaging studies yielded mixed results. OBJECTIVE: We employed free-water (FW) imaging to assess DLB progression and correlate with clinical decline in DLB. METHODS: Baseline and follow-up MRIs were obtained at 12 and/or 24 months for 27 individuals with DLB or mild cognitive impairment with Lewy bodies (MCI-LB). FW was analyzed using the Mayo Clinic Adult Lifespan Template. Primary outcomes were FW differences between baseline and 12 or 24 months. To compare FW change longitudinally, we included 20 cognitively unimpaired individuals from the Alzheimer's Disease Neuroimaging Initiative. RESULTS: We followed 23 participants to 12 months and 16 participants to 24 months. Both groups had worsening in Montreal Cognitive Assessment (MoCA) and Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) scores. We found significant FW increases at both time points compared to baseline in the insula, amygdala, posterior cingulum, parahippocampal, entorhinal, supramarginal, fusiform, retrosplenial, and Rolandic operculum regions. At 24 months, we found more widespread microstructural changes in regions implicated in visuospatial processing, motor, and cholinergic functions. Between-group analyses (DLB vs. controls) confirmed significant FW changes over 24 months in most of these regions. FW changes were associated with longitudinal worsening of MDS-UPDRS and MoCA scores. CONCLUSIONS: FW increased in gray and white matter regions in DLB, likely due to neurodegenerative pathology associated with disease progression. FW change was associated with clinical decline. The findings support dMRI as a promising tool to track disease progression in DLB. © 2024 International Parkinson and Movement Disorder Society.

Innate immunity in Aedes mosquitoes: from pathogen resistance to shaping the microbiota.

Discussions of host-microbe interactions in mosquito vectors are frequently dominated by a focus on the human pathogens they transmit (e.g. Plasmodium parasites and arboviruses). Underlying the interactions between a vector and its transmissible pathogens, however, is the physiology of an insect living and interacting with a world of bacteria and fungi including commensals, mutualists and primary and opportunistic pathogens. Here we review what is known about the bacteria and fungi associated with mosquitoes, with an emphasis on the members of the Aedes genus. We explore the reciprocal effects of microbe on mosquito, and mosquito on microbe. We analyse the roles of bacterial and fungal symbionts in mosquito development, their effects on vector competence, and their potential uses as biocontrol agents and vectors for paratransgenesis. We explore the compartments of the mosquito gut, uncovering the regionalization of immune effectors and modulators, which create the zones of resistance and immune tolerance with which the mosquito host controls and corrals its microbial symbionts. We examine the anatomical patterning of basally expressed antimicrobial peptides. Finally, we review the relationships between inducible antimicrobial peptides and canonical immune signalling pathways, comparing and contrasting current knowledge on each pathway in mosquitoes to the model insect Drosophila melanogaster. This article is part of the theme issue 'Sculpting the microbiome: how host factors determine and respond to microbial colonization'.

Galleria mellonella (Lepidoptera: Pyralidae) Hemocytes Release Extracellular Traps That Confer Protection Against Bacterial Infection in the Hemocoel.

Extracellular traps (ETs) released from vertebrate and invertebrate immune cells consist of chromatin and toxic granule contents that are capable of immobilizing and killing microbes. This recently described innate immune response is not well documented in insects. The present study found that ETs were released by hemocytes of Galleria mellonella (Linnaeus) (Lepidoptera: Pyralidae) in vivo and ex vivo after bacterial stimulation. ET release (ETosis), hemolymph coagulation, and melanization likely contributed to the immobilization and killing of the bacteria. The injection of G. mellonella hemocyte deoxyribonucleic acid (DNA) in the presence of bacteria increased bacterial clearance rate and prolonged insect survival. Taken together, these results indicate the presence of insect hemocyte extracellular traps (IHETs) that protect the insect against microbial infection in the hemocoel and represent the first documentation of ETs in insects in vivo.

The Galleria mellonella-Enteropathogenic Escherichia coli Model System: Characterization of Pathogen Virulence and Insect Immune Responses.

The use of Galleria mellonella (Linnaeus) (Lepidoptera: Pyralidae), an economical insect model, for the study of enteropathogenic Escherichia coli (Migula) (EPEC), a diarrheagenic human pathogen, has been demonstrated previously but remains poorly understood. The present study characterizes the Galleria-EPEC system extensively for future studies using this system. We found that EPEC causes disease in G. mellonella larvae when injected intrahemocoelically but not orally. Disease manifests as increased mortality, decreased survival time, delayed pupation, decreased pupal mass, increased pupal duration, and hemocytopenia. Disease symptoms are dose-dependent and can be used as metrics for measuring EPEC virulence in future studies. The type III secretion system was only partially responsible for EPEC virulence in G. mellonella while the majority of the virulence remains unknown in origin. EPEC elicits insect anti-bacterial immune responses including melanization, hemolymph coagulation, nodulation, and phagocytosis. The immune responses were unable to control EPEC replication in the early stage of infection (≤3 h post-injection). EPEC clearance from the hemocoel does not guarantee insect survival. Overall, this study provided insights into EPEC virulence and pathogenesis in G. mellonella and identified areas of future research using this system.

Migrated Avalon-Elite cannula in an infant transcatheter repositioning without interruption of ECMO flow.

Inadvertent migration of Avalon-Elite cannula in patients receiving veno-venous extracorporeal membrane oxygenation (VV-ECMO) support is often difficult to manage. Cannula repositioning conventionally requires temporary discontinuation of the ECMO support which is often poorly tolerated in small infants with poor pulmonary reserve. We reported a case of a small infant weighing 3.9 kg requiring VV-ECMO support with a 13Fr Avalon-Elite cannula for respiratory failure secondary to severe pneumonitis, complicated by 2 episodes of cannula migration which were both successfully managed by transcatheter repositioning in the cardiac catheterization laboratory without interruption of ECMO flow.

Preoperative Venovenous Extracorporal Membrane Oxygenation for Transposition of Great Arteries With Severe Pulmonary Hypertension in a Newborn.

Severe persistent pulmonary hypertension in a newborn combined with transposition of great arteries increases the risk of early death before the arterial switch operation. We report the case of a newborn with transposition of great arteries and ventricular septal defect associated with severe pulmonary hypertension. Profound hypoxemia, despite successful balloon atrial septostomy and conventional supportive measures with mechanical ventilation, inhaled nitric oxide, and inotropes, led to the use of venovenous extracorporeal membrane oxygenation to rapidly stabilize the child preoperatively. Different from most reported cases on this scenario, we intentionally opted for a venovenous mode of support despite the presence of circulatory compromise.

Achieving biventricular circulation in patients with moderate hypoplastic right ventricle in pulmonary atresia intact ventricular septum after transcatheter pulmonary valve perforation.

OBJECTIVE: Transcatheter valve perforation for pulmonary atresia intact ventricular septum is the standard of care for patients with mild right ventricular hypoplasia. However, its role in moderate right ventricular hypoplasia has been less well defined. We sought to report the long-term outcome of patients with moderate hypoplastic right ventricle who had undergone the procedure. DESIGN, SETTINGS, AND PATIENTS: We performed a retrospective analysis on patients who had undergone transcatheter pulmonary valve perforation from January 1996 to January 2015 at our institution. The procedures would be carried out irrespective of the right ventricular size, as long as there were no absolute contraindications. INTERVENTION AND OUTCOME MEASURES: Demographic and procedural data were correlated with outcome measures. Outcomes analyzed included procedural success, reintervention rates, final circulation type, and functional class. Multivariate analysis and receiver operator curve were used to identify for parameters in predicting biventricular circulation. RESULTS: The procedural success rate was 92% (33 out of 36) in this group with moderate right ventricular hypoplasia (tricuspid valve z score -4.2 ± 3.0, 69.4% of patients with z score <-2.5). Early reintervention rate was 39%, mostly being insertion of modified Blalock-Taussig shunt. Overall reintervention-free survival was 53%, 30%, and 19% at 1, 6, and 12 months postintervention. Despite no significant catch-up right ventricular growth, majority of survivors (84%) enjoyed a biventricular circulation with good functional status. A tricuspid to mitral valve ratio >0.79 was a good predictor of biventricular outcome. (specificity of 100%, positive predictive value 100%) CONCLUSION: Encouraging long-term results with biventricular circulation and functional status were demonstrated with transcatheter pulmonary valve perforation in patients even with moderate hypoplastic right ventricle, which is comparable to that with mild right ventricular hypertrophy. The baseline tricuspid to mitral valve ratio was identified as a potentially useful tool in predicting biventricular circulation.

Duct Stenting Versus Modified Blalock-Taussig Shunt in Neonates With Duct-Dependent Pulmonary Blood Flow: Associations With Clinical Outcomes in a Multicenter National Study.

BACKGROUND: Infants born with cardiac abnormalities causing dependence on the arterial duct for pulmonary blood flow are often palliated with a shunt usually between the subclavian artery and either pulmonary artery. A so-called modified Blalock-Taussig shunt allows progress through early life to an age and weight at which repair or further more stable palliation can be safely achieved. Modified Blalock-Taussig shunts continue to present concern for postprocedural instability and early mortality such that other alternatives continue to be explored. Duct stenting (DS) is emerging as one such alternative with potential for greater early stability and improved survival. METHODS: The purpose of this study was to compare postprocedural outcomes and survival to next-stage palliative or reparative surgery between patients undergoing a modified Blalock-Taussig shunt or a DS in infants with duct-dependent pulmonary blood flow. All patients undergoing cardiac surgery and congenital interventions in the United Kingdom are prospectively recruited to an externally validated national outcome audit. From this audit, participating UK centers identified infants <30 days of age undergoing either a Blalock-Taussig shunt or a DS for cardiac conditions with duct-dependent pulmonary blood flow between January 2012 and December 31, 2015. One hundred seventy-one patients underwent a modified Blalock-Taussig shunt, and in 83 patients, DS was attempted. Primary and secondary outcomes of survival and need for extracorporeal support were analyzed with multivariable logistic regression. Longer-term mortality before repair and reintervention were analyzed with Cox proportional hazards regression. All multivariable analyses accommodated a propensity score to balance patient characteristics between the groups. RESULTS: There was an early (to discharge) survival advantage for infants before next-stage surgery in the DS group (odds ratio, 4.24; 95% confidence interval, 1.37-13.14; P=0.012). There was also a difference in the need for postprocedural extracorporeal support in favor of the DS group (odds ratio, 0.22; 95% confidence interval, 0.05-1.05; P=0.058). Longer-term survival outcomes showed a reduced risk of death before repair in the DS group (hazard ratio, 0.25; 95% confidence interval, 0.07-0.85; P=0.026) but a slightly increased risk of reintervention (hazard ratio, 1.50; 95% confidence interval, 0.85-2.64; P=0.165). CONCLUSIONS: DS is emerging as a preferred alternative to a surgical shunt for neonatal palliation with evidence for greater postprocedural stability and improved patient survival to destination surgical treatment.

Left ventricular contractile reserve in young adults long-term after repair of coarctation of the aorta.

We assessed the left ventricular (LV) contractile reserve in young adults with repaired coarctation of the aorta and interrupted aortic arch by determination of LV force-frequency relation (FFR). Eighteen (7 men) patients aged 24.2 ± 5.4 years and 20 (9 men) healthy controls were studied. Blood pressures in the right arm were measured by oscillometry. Transmitral early (E) and late (A) diastolic velocities, tissue Doppler-derived mitral annular systolic (sm), early diastolic (em) and late diastolic (am) velocities, and myocardial isovolumic acceleration (IVA) were measured. The LV FFR and average slope were derived from the IVA measured at different heart rates during supine bicycle exercise. Blood pressures at rest were similar between patients and controls (all p >0.05). At baseline, patients compared with controls had significantly greater E velocity, E/A and E/em ratios, and lower sm and em velocities (all p <0.05) but similar IVA (p = 0.18). At submaximal exercise, diastolic (p = 0.001) and mean (p = 0.003) blood pressures became significantly higher in patients than controls, sm (p = 0.001) and em (p <0.001) velocities remained reduced, whereas the IVA became lower (p <0.001). The weighted average FFR was flattened (p <0.001), and average FFR slope was lower (p <0.001) in patients compared with controls. The average FFR slope correlated negatively with the magnitude of exercise-induced increase in systolic (r = -0.32, p = 0.050), mean (r = -0.41, p = 0.011), and diastolic (r = -0.40, p = 0.013) blood pressures. In conclusion, young adults after coarctation of the aorta and interrupted aortic arch repair exhibit reduced LV contractile reserve, which is related to the blood pressure response during exercise stress.

Population-based hospitalization burden of influenza a virus subtypes and antigenic drift variants in children in Hong Kong (2004-2011).

OBJECTIVES: We aim to document and analyze influenza hospitalization burden in light of antigenic changes in circulating influenza viruses in Hong Kong. METHODS: The pediatric age-specific rates of influenza A hospitalization in Hong Kong for 2004-2011 which encompassed the emergence of H1N1pdm09 were extrapolated from admissions to 2 hospitals that together catered for 72.5% of all pediatric admissions on Hong Kong Island. Influenza A was detected by immunofluorescence, culture and/or PCR on nasopharyngeal aspirates. RESULTS: Influenza A caused high rates of hospitalization in children with year to year fluctuations. The highest hospitalization burden was seen with H1N1pdm09 in 2009. Additional factors affecting hospitalization were the proportion of viral circulation among different subtypes, and antigenic drifts. Taking these into effect, an H3N2 dominated year was not always associated with more hospitalizations than a 'seasonal' H1N1 year. Hospitalization burden was higher in seasons when drifted viruses of H1N1 or H3N2 dominated. No hospitalization was documented in infants <6 months of age during years when an undrifted virus circulated (2006 for H1N1 and 2008 for H3N2) but significant hospitalization was observed with a drifted or shifted virus (2004, 2005, 2007 and 2010 for H3N2, and 2009 for H1N1pdm09). CONCLUSIONS: We documented a consistently high pediatric hospitalization burden of influenza A. Knowledge of antigenic changes and their proportion of circulation aids in the interpretation of impact of the subtypes. Year-to-year variation in hospitalization rates in young infants appeared to correlate with antigenic variation, lending support to the role of protection from maternal antibodies.

Pseudohyperkalaemia with acute leukaemia: association with pneumatic tube transport of blood specimens.

Falsely elevated serum or plasma potassium level can be the result of mechanical injury to blood cells. We describe pseudohyperkalaemia caused by pneumatic tube transport of blood specimens from a patient with leukaemia. Clinicians should be aware of this possibility when interpreting the clinical significance of hyperkalaemia. In leukaemic patients, pneumatic tube transport of blood specimens for potassium analysis should be avoided.

Arterial mechanics at rest and during exercise in adolescents and young adults after arterial switch operation for complete transposition of the great arteries.

We sought to determine the arterial mechanics at rest and during exercise in adolescents and young adults with complete transposition of the great arteries after arterial switch operation and their relations with neoaortic complications. Thirty patients (22 men) aged 16.2 ± 2.1 years and 22 controls (15 men) were studied. Central and peripheral arterial pulse wave velocities, carotid and radial augmentation indices, and central systolic blood pressure (cSBP) were determined by oscillometry and applanation tonometry, whereas arterial dimensions were measured by 2-dimensional echocardiography. Arterial strain, distensibility, and stiffness were determined at rest and during supine bicycle exercise testing. At rest, patients had significantly higher heart-carotid pulse wave velocity, carotid and radial augmentation indices, and cSBP than controls. At rest and during submaximal exercise, patients had significantly lower aortic strain and distensibility, greater aortic and carotid stiffness, and higher SBP than controls. Dilated aortic sinus found in 23 (76.7%) patients was associated with lower aortic distensibility, greater aortic stiffness, and higher cSBP at rest and lower aortic distensibility and strain at submaximal exercise. Significant aortic regurgitation found in 20% (6 of 30) of patients was associated with significantly higher neoaortic z scores. Multivariate analysis identified aortic stiffness at rest (ß = 0.46, p = 0.003) and age at operation (ß = 0.44, p = 0.004) as significant determinants of aortic sinus z scores. In conclusion, altered mechanics of the central arteries are present at rest and during exercise in adolescents and young adults after arterial switch operation. These findings may have important implications on progression of neoaortic root dilation, exercise recommendations, and medical therapy.

Left ventricular contractile reserve after arterial switch operation for complete transposition of the great arteries: an exercise echocardiographic study.

AIMS: This study tested the hypothesis that left ventricular (LV) contractile reserve is altered in patients after arterial switch operation (ASO) for complete transposition of the great arteries (TGA) by non-invasive determination of LV force-frequency relationship (FFR). METHODS AND RESULTS: Thirty-two patients aged 16.2 ± 2.1 years and 22 healthy controls were studied. M-mode parameters, transmitral early (E) and late (A) diastolic velocities, and tissue Doppler-derived systolic (sm), early (em), and late (am) diastolic mitral annular velocities were determined at baseline and during submaximal exercise testing. The LV myocardial isovolumic acceleration (IVA) was measured at different heart rates during exercise for derivation of LV FFR and the average slope of IVA increment with heart rate. At baseline, patients had significantly greater E velocity, E/A and E/em ratios, shorter E deceleration time, and reduced mitral annular sm, em, and am velocities (all P < 0.05), but similar IVA (P = 0.29) compared with controls. During exercise, sm and em remained significantly reduced (P < 0.001), and LV IVA became lower (P < 0.001) in patients. The average FFR slope was significantly lower in patients (0.039 ± 0.019 vs. 0.070 ± 0.024 m/s(2) bpm, P < 0.001). The weighted average FFR curve of patients was flattened compared with the reported positive FFR reference curve based on a healthy paediatric cohort (P < 0.0001). Patients with variant compared with those with usual coronary arterial anatomy had significant flattening of FFR (P < 0.001) and a reduced FFR slope (P = 0.007). CONCLUSION: In adolescents and young adults after ASO, exercise stress revealed reduced LV contractile reserve, which is worse in those having variant coronary arterial anatomy.

Transcatheter ablation of atrioventricular junctional re-entrant tachycardia in children and adolescents in Hong Kong: comparison of cryothermal with radiofrequency energy.

OBJECTIVE: To compare the outcome of cryothermal and radiofrequency energy transcatheter ablation of atrioventricular junctional re-entrant tachycardia in children and adolescents. DESIGN: Case series with internal comparison. SETTING: Two hospitals in Hong Kong. PATIENTS: Consecutive transcatheter ablation procedures for atrioventricular junctional re-entrant tachycardia in children and adolescents in our unit from August 2000 to September 2008 were retrospectively reviewed. Radiofrequency ablation was performed from August 2000 to June 2005, and cryoablation from July 2005 to September 2008. MAIN OUTCOME MEASURES: Demographic data, outcome and procedural details. RESULTS: Thirty-eight procedures were reviewed. The radiofrequency ablation group (n=20) and cryoablation group (n=18) had similar demographic characteristics, except that there were more patients with congenital heart disease in the latter group (P=0.03). Acute procedural success rate was 100% in both groups. One patient from the radiofrequency ablation group had recurrence of atrioventricular junctional re-entrant tachycardia. The frequency of post-ablation persistent heart block was higher in the radiofrequency ablation than cryoablation group (10% vs 0%, P=0.17), but this difference was not statistically significant. A shorter fluoroscopy time was noted in the cryoablation group (31 ± 13 vs 38 ± 18 minutes; P=0.03). CONCLUSIONS: Transcatheter cryoablation for atrioventricular junctional re-entrant tachycardia in children and adolescents is as effective as radiofrequency ablation over the medium term. It has an excellent safety profile in terms of avoiding heart block.

The population based socioeconomic burden of pediatric influenza-associated hospitalization in Hong Kong.

We described the monetary and non-monetary cost incurred by children hospitalized for virologically confirmed influenza virus infection in a population-based prospective 3-year study. The mean direct and indirect cost of each child hospitalized was $1217.82 (95% CI, 1111.54-1324.23) and $1328.33 (95% CI, $1136.79-1520.00) for influenza A and B, respectively. School age patients took a mean (SD) of 4.70 (3.05) days and 5.31 (3.62) days of sick leave for influenza A and B infection, respectively. Pediatric influenza A and B hospitalization was associated with 662-1046 days of school absenteeism and 214-336 days of parental work loss per 10,000 population <18 years of age per year. We showed that the cost incurred by hospitalization alone, was comparable to the cost of annual universal pediatric influenza vaccination especially in children 6 months to under 6 years of age and vaccination would result in much larger cost-savings when non-monetary costs are included.