Plasmids pick a bacterial partner before committing to conjugation.

Bacterial conjugation was first described by Lederberg and Tatum in the 1940s following the discovery of the F plasmid. During conjugation a plasmid is transferred unidirectionally from one bacterium (the donor) to another (the recipient), in a contact-dependent manner. Conjugation has been regarded as a promiscuous mechanism of DNA transfer, with host range determined by the recipient downstream of plasmid transfer. However, recent data have shown that F-like plasmids, akin to tailed Caudovirales bacteriophages, can pick their host bacteria prior to transfer by expressing one of at least four structurally distinct isoforms of the outer membrane protein TraN, which has evolved to function as a highly sensitive sensor on the donor cell surface. The TraN sensor appears to pick bacterial hosts by binding compatible outer membrane proteins in the recipient. The TraN variants can be divided into specialist and generalist sensors, conferring narrow and broad plasmid host range, respectively. In this review we discuss recent advances in our understanding of the function of the TraN sensor at the donor-recipient interface, used by F-like plasmids to select bacterial hosts within polymicrobial communities prior to DNA transfer.

Recurrent emergence of Klebsiella pneumoniae carbapenem resistance mediated by an inhibitory ompK36 mRNA secondary structure.

Outer membrane porins in Gram-negative bacteria facilitate antibiotic influx. In Klebsiella pneumoniae, modifications in the porin OmpK36 are implicated in increasing resistance to carbapenems. An analysis of large K. pneumoniae genome collections, encompassing major healthcare-associated clones, revealed the recurrent emergence of a synonymous cytosine-to-thymine transition at position 25 (25c > t) in ompK36. We show that the 25c > t transition increases carbapenem resistance through depletion of OmpK36 from the outer membrane. The mutation attenuates K. pneumoniae in a murine pneumonia model, which accounts for its limited clonal expansion observed by phylogenetic analysis. However, in the context of carbapenem treatment, the 25c > t transition tips the balance toward treatment failure, thus accounting for its recurrent emergence. Mechanistically, the 25c > t transition mediates an intramolecular messenger RNA (mRNA) interaction between a uracil encoded by 25t and the first adenine within the Shine-Dalgarno sequence. This specific interaction leads to the formation of an RNA stem structure, which obscures the ribosomal binding site thus disrupting translation. While mutations reducing OmpK36 expression via transcriptional silencing are known, we uniquely demonstrate the repeated selection of a synonymous ompK36 mutation mediating translational suppression in response to antibiotic pressure.

Intramolecular London Dispersion Interactions in Single-Molecule Junctions.

This work shows the first example of using intramolecular London dispersion interactions to control molecular geometry and quantum transport in single-molecule junctions. Flexible σ-bonded molecular junctions typically occupy straight-chain geometries due to steric effects. Here, we synthesize a series of thiomethyl-terminated oligo(dimethylsilmethylene)s that bear [CH2-Si(CH3)2]n repeat units, where all backbone dihedral states are sterically equivalent. Scanning tunneling microscopy break-junction (STM-BJ) measurements and theoretical calculations indicate that in the absence of a strong steric bias concerted intramolecular London dispersion interactions staple the carbosilane backbone into coiled conformations that remain intact even as the junction is stretched to its breakpoint. As these kinked conformations are highly resistive to electronic transport, we observe record-high conductance decay values on an experimental junction length basis (ß = 1.86 ± 0.12 Å-1). These studies reveal the potential of using intramolecular London dispersion interactions to design single-molecule electronics.

Widespread emergence of OmpK36 loop 3 insertions among multidrug-resistant clones of Klebsiella pneumoniae.

Mutations in outer membrane porins act in synergy with carbapenemase enzymes to increase carbapenem resistance in the important nosocomial pathogen, Klebsiella pneumoniae (KP). A key example is a di-amino acid insertion, Glycine-Aspartate (GD), in the extracellular loop 3 (L3) region of OmpK36 which constricts the pore and restricts entry of carbapenems into the bacterial cell. Here we combined genomic and experimental approaches to characterise the diversity, spread and impact of different L3 insertion types in OmpK36. We identified L3 insertions in 3588 (24.1%) of 14,888 KP genomes with an intact ompK36 gene from a global collection. GD insertions were most common, with a high concentration in the ST258/512 clone that has spread widely in Europe and the Americas. Aspartate (D) and Threonine-Aspartate (TD) insertions were prevalent in genomes from Asia, due in part to acquisitions by KP sequence types ST16 and ST231 and subsequent clonal expansions. By solving the crystal structures of novel OmpK36 variants, we found that the TD insertion causes a pore constriction of 41%, significantly greater than that achieved by GD (10%) or D (8%), resulting in the highest levels of resistance to selected antibiotics. We show that in the absence of antibiotics KP mutants harbouring these L3 insertions exhibit both an in vitro and in vivo competitive disadvantage relative to the isogenic parental strain expressing wild type OmpK36. We propose that this explains the reversion of GD and TD insertions observed at low frequency among KP genomes. Finally, we demonstrate that strains expressing L3 insertions remain susceptible to drugs targeting carbapenemase-producing KP, including novel beta lactam-beta lactamase inhibitor combinations. This study provides a contemporary global view of OmpK36-mediated resistance mechanisms in KP, integrating surveillance and experimental data to guide treatment and drug development strategies.

Structured Tube Weaning Using the Hunger Provocation Method in Infants with Single Ventricle Heart Defects: A Multicenter Study.

Despite improvement in hemodynamics, children with single ventricle heart disease remain on feeding tubes long after stage 2 palliation (S2P). Use of a hunger provocation method in a multidisciplinary team setting has been successful at weaning these children from feeding tubes. The objective of this study is to describe patient characteristics and outcomes in the single ventricle population who underwent a formal tube weaning process using a standardized hunger provocation method. Single ventricle patients after S2P from six centers were included. Patient data collected included baseline demographics, swallow evaluation results, and feeding characteristics such as percent oral intake at the start of tube wean. Tube wean data included tube weaning process and duration, interruptions to the tube wean, adverse events, and weights before, during, and after the tube wean. 94% (60 of 64) of patients achieved oral independence. The median time to tube wean was 12.5 days. 62% of patients had transient weight loss during the tube wean. 61% of the cohort was taking less than 10% goal volumes by mouth with 90% of those patients successfully tube weaned. All patients with history of aspiration were successfully tube weaned. 75% of successfully weaned patients were above baseline weight at 1-month post-tube wean. The most common cause of tube wean interruption was contraction of a viral illness. Use of a standardized tube weaning process via hunger provocation method is both feasible and safe in the single ventricle population, resulting in successful feeding tube removal in a timely manner with minimal adverse effects.

Impacts of Deep Brain Stimulation of the Globus Pallidus Internus on Swallowing: A Retrospective, Cross-Sectional Study.

Deep brain stimulation (DBS) is a common treatment for motor symptoms of Parkinson disease (PD), a condition associated with increased risk of dysphagia. The effect of DBS on swallowing function has not been comprehensively evaluated using gold-standard imaging techniques, particularly for globus pallidus internus (GPi) DBS. The objective of this retrospective, cross-sectional study was to identify differences in swallowing safety and timing kinematics among PD subjects with and without GPi DBS. We investigated the effects of unilateral and bilateral GPi DBS as well as the relationship between swallowing safety and DBS stimulation parameters, using retrospective analysis of videofluoroscopy recordings (71 recordings from 36 subjects) from electronic medical records. Outcomes were analyzed by surgical status (pre-surgical, unilateral DBS, bilateral DBS). The primary outcome was percent of thin-liquid bolus trials rated as unsafe, with Penetration-Aspiration Scale scores of 3 or higher. Secondary analyses included swallowing timing measures, relationships between swallowing safety and DBS stimulation parameters, and Dynamic Imaging Grade of Swallowing Toxicity ratings. Most subjects swallowed all boluses safely (19/29 in the pre-surgical, 16/26 in the unilateral DBS, and 10/16 in the bilateral DBS conditions). Swallowing safety impairment did not differ among stimulation groups. There was no main effect of stimulation condition on timing metrics, though main effects were found for sex and bolus type. Stimulation parameters were not correlated with swallowing safety. Swallowing efficiency and overall impairment did not differ among conditions. These results provide evidence that GPi DBS does not affect pharyngeal swallowing function. Further, prospective, investigations are needed.

End-stage heart failure in congenitally corrected transposition of the great arteries: a multicentre study.

BACKGROUND AND AIMS: For patients with congenitally corrected transposition of the great arteries (ccTGA), factors associated with progression to end-stage congestive heart failure (CHF) remain largely unclear. METHODS: This multicentre, retrospective cohort study included adults with ccTGA seen at a congenital heart disease centre. Clinical data from initial and most recent visits were obtained. The composite primary outcome was mechanical circulatory support, heart transplantation, or death. RESULTS: From 558 patients (48% female, age at first visit 36 ± 14.2 years, median follow-up 8.7 years), the event rate of the primary outcome was 15.4 per 1000 person-years (11 mechanical circulatory support implantations, 12 transplantations, and 52 deaths). Patients experiencing the primary outcome were older and more likely to have a history of atrial arrhythmia. The primary outcome was highest in those with both moderate/severe right ventricular (RV) dysfunction and tricuspid regurgitation (n = 110, 31 events) and uncommon in those with mild/less RV dysfunction and tricuspid regurgitation (n = 181, 13 events, P < .001). Outcomes were not different based on anatomic complexity and history of tricuspid valve surgery or of subpulmonic obstruction. New CHF admission or ventricular arrhythmia was associated with the primary outcome. Individuals who underwent childhood surgery had more adverse outcomes than age- and sex-matched controls. Multivariable Cox regression analysis identified older age, prior CHF admission, and severe RV dysfunction as independent predictors for the primary outcome. CONCLUSIONS: Patients with ccTGA have variable deterioration to end-stage heart failure or death over time, commonly between their fifth and sixth decades. Predictors include arrhythmic and CHF events and severe RV dysfunction but not anatomy or need for tricuspid valve surgery.

Factors that mediate change in creatinine and acute kidney injury after the Norwood operation: insights from high-fidelity haemodynamic monitoring data.

BACKGROUND: Acute kidney injury is a common postoperative complication of paediatric cardiac surgery associated with increased morbidity and mortality. The purpose of this study is to characterise associations between haemodynamic parameters, clinical parameters, and medical interventions, on acute kidney injury. METHODS: Nine patients with univentricular physiology undergoing the Norwood procedure from a single-centre tertiary care paediatric cardiac ICU were included (September 2022 to March 2023). Patients were monitored with the T3 software. Data were analysed using a Fisher exact test, Mann-Whitney-U test, LASSO-based machine learning techniques, and receiver operator curve analyses. RESULTS: Over 27,000 datapoints were included. Acute kidney injury occurred in 2 patients (22%) during this period. Net fluid balance and renal oxygen extraction were independently associated with acute kidney injury, while commonly used metrics of pressure (systolic, diastolic, or mean arterial blood pressure) were not. The resulting acute kidney injury risk score was (4.1 × fluid balance) + (1.9 × renal oxygen extraction). The risk score was significantly higher in acute kidney injury with a score of 32.9 compared to 7.9 (p < 0.01). Optimal cut-offs for fluid balance (7 mL/hr) and renal oxygen extraction (29%) were identified. Higher serum creatinine:baseline creatinine ratio was associated with a higher mean airway pressure, higher renal oxygen extraction, higher mean arterial blood pressure, higher vasoactive inotropic score, and fluid balance. CONCLUSION: Among patients with univentricular physiology undergoing the Norwood procedure, renal oxygen extraction and a higher net fluid balance are independently associated with increased risk of acute kidney injury. Renal perfusion pressure is not significantly associated with acute kidney injury.

Factors associated with renal oxygen extraction in mechanically ventilated children after the Norwood operation: insights from high fidelity haemodynamic data.

BACKGROUND: Maintaining the adequacy of systemic oxygen delivery is of utmost importance, particularly in critically ill children. Renal oxygen extraction can be utilised as metric of the balance between systemic oxygen delivery and oxygen consumption. The primary aim of this study was to determine what clinical factors are associated with renal oxygen extraction in children after Norwood procedure. METHODS: Mechanically ventilated children who underwent Norwood procedure from 1 September, 2022 to 1 March, 2023 were identified as these patients had data collected and stored with high fidelity by the T3 software. Data regarding haemodynamic values, fluid balance, and airway pressure were collected and analysed using Bayesian regression to determine the association of the individual metrics with renal oxygen extraction. RESULTS: A total of 27,270 datapoints were included in the final analyses. The resulting top two models explained had nearly 80% probability of being true and explained over 90% of the variance in renal oxygen extraction. The coefficients for each variable retained in the best were -1.70 for milrinone, -19.05 for epinephrine, 0.129 for mean airway pressure, -0.063 for mean arterial pressure, 0.111 for central venous pressure, 0.093 for arterial saturation, 0.006 for heart rate, -0.025 for respiratory rate, 0.366 for systemic vascular resistance, and -0.032 for systemic blood flow. CONCLUSION: Increased milrinone, epinephrine, mean arterial pressure, and systemic blood flow were associated with decreased (improved) renal oxygen extraction, while increased mean airway pressure, central venous pressure, arterial saturation, and systemic vascular resistance were associated with increased (worsened) renal oxygen extraction.

Travel-Associated Dengue Cases - United States, 2010-2021.

Dengue, the leading cause of arboviral disease worldwide, can be fatal without appropriate treatment. Among 7,528 confirmed or probable travel-associated U.S. dengue cases reported during 2010-2021, one in five (1,474, 20%) was reported in 2019. This is 168% higher than the annual average number of cases reported during 2010-2018 and 2020-2021 (approximately 550 per year) and 61% higher than the 913 cases reported in 2016, the second highest year on record. The number of cases as a fraction of air traffic volume to international destinations outside North America or Europe was also highest in 2019, with 41.9 cases per million trips, compared with 21.0 per million in other years during 2010-2021. This report compares the number and characteristics of travel-associated dengue cases reported to national surveillance in the United States in 2019 with cases reported during 2010-2018 and 2020-2021. Areas with conditions suitable for dengue transmission as well as the population at risk for dengue are expected to increase, placing U.S. travelers at higher risk for infection. Health care providers should be aware that dengue is a common cause of fever in the returning traveler and be familiar with its signs and symptoms, testing, and management. Dengue vaccines are not currently recommended for U.S. travelers; therefore, persons should review areas of dengue risk and follow guidance for preventing mosquito bites.

Characterization of Secondary Interventions After Fenestrated-branched Endovascular Repair of Complex Aortic Aneurysms and Its Effect on Quality of Life and Patient Survival.

OBJECTIVE: To assess the impact of secondary intervention (SI) on health-related quality of life (HR-QOL) after fenestrated-branched endovascular aortic repair (FB-EVAR) for complex abdominal aortic aneurysms and thoracoabdominal aortic aneurysms. BACKGROUND: The effect of SI after FB-EVAR on physical and mental HR-QOL has not been described. METHODS: A cohort of 430 consecutive patients enrolled in a prospective, nonrandomized study to evaluate FB-EVAR (2013-2020) was assessed with 1325 short-form 36 HR-QOL questionnaires preoperatively and during follow-up visits. SIs were classified as major or minor procedures. Endpoints included patient survival, freedom from aortic-related mortality (ARM), freedom from SIs, and changes in HR-QOL physical component score (PCS) and mental component score. RESULTS: There were 302 male with mean age 74±8 years treated by FB-EVAR for 133 complex abdominal aortic aneurysms and 297 thoracoabdominal aortic aneurysms. After a mean follow up of 26±20 months, 97 patients (23%) required 137 SIs. At 5 years, freedom from any SI was 64%±4%, including freedom from minor SIs of 77%±4% and major SIs of 87%±3%. There was no difference in patient survival and freedom from ARM at same interval. On adjusted analysis, minor SIs correlated with improved survival. SIs had a negative correlation with PCS ( r =-0.8). There were no significant changes in mental component score with SIs. Predictors for SIs were fluoroscopy time, graft design, and aneurysm sac change. CONCLUSION: SIs were needed in nearly 1 out of 4 patients treated by FB-EVAR with no effect on patient survival or ARM. SI resulted in decline in PCS.

Autoantibodies against angiotensin-converting enzyme 2 (ACE2) after COVID-19 infection or vaccination.

Autoantibodies against angiotensin-converting enzyme 2 (ACE2) are frequently reported in patients during coronavirus disease 2019 (COVID-19) with evidence for a pathogenic role in severe infection. However, little is known of the prevalence or clinical significance of ACE2 autoantibodies in late convalescence or following COVID-19 vaccination. In this study, we measured ACE2 autoantibodies in a cohort of 182 COVID-19 convalescent patients, 186 COVID-19 vaccine recipients, and 43 adolescents with post-mRNA vaccine myopericarditis using two ACE2 enzymatic immunoassays (EIAs). ACE2 IgM autoantibody EIA median optical densities (ODs) were lower in convalescent patients than pre-COVID-19 control samples with only 2/182 (1.1%) convalescents testing positive. Similarly, only 3/182 (1.6%) convalescent patients tested positive for ACE2 IgG, but patients with history of moderate-severe COVID-19 tended to have significantly higher median ODs than controls and mild COVID-19 patients. In contrast, ACE2 IgG antibodies were detected in 10/186 (5.4%) COVID-19 vaccine recipients after two doses of vaccination. Median ACE2 IgG EIA ODs of vaccine recipients were higher than controls irrespective of the vaccine platform used (inactivated or mRNA). ACE2 IgG ODs were not correlated with surrogate neutralizing antibody levels in vaccine recipients. ACE2 IgG levels peaked at day 56 post-first dose and declined within 12 months to baseline levels in vaccine recipients. Presence of ACE2 antibodies was not associated with adverse events following immunization including myopericarditis. One convalescent patient with ACE2 IgG developed Guillain-Barre syndrome, but causality was not established. ACE2 autoantibodies are observed in COVID-19 vaccine recipients and convalescent patients, but are likely innocuous.

Outcomes of fenestrated-branched endovascular aortic repair in patients with or without prior history of abdominal endovascular or open surgical repair.

OBJECTIVE: The aim of this study was to compare outcomes of fenestrated-branched endovascular aortic repair (FB-EVAR) of complex abdominal (CAAAs) and thoracoabdominal aortic aneurysms (TAAAs) in patients with or without prior history of abdominal open surgical (OSR) or endovascular aortic repair (EVAR). METHODS: The clinical data of consecutive patients enrolled in a prospective, non-randomized study to evaluate FB-EVAR for treatment of CAAAs and TAAAs was reviewed. Clinical outcomes were analyzed in patients with no previous aortic repair (Controls), prior EVAR (Group 1), and prior abdominal OSR (Group 2), including 30-day mortality and major adverse events (MAEs), patient survival and freedom from aortic-related mortality (ARM), secondary interventions, any type II endoleak, sac enlargement (≥5 mm), and new-onset permanent dialysis. RESULTS: There were 506 patients (69% male; mean age, 72 ± 9 years) treated by FB-EVAR, including 380 controls, 54 patients in Group 1 (EVAR), and 72 patients in Group 2 (abdominal OSR). FB-EVAR was performed on average 7 ± 4 and 12 ± 6 years after the index EVAR and abdominal OSR, respectively (P < .001). All three groups had similar clinical characteristics, except for less coronary artery disease in controls and more TAAAs and branch stent graft designs in Group 2 (P < .05). Aneurysm extent was CAAA in 144 patients (28%) and TAAA in 362 patients (72%). Overall technical success, mortality, and MAE rate were 96%, 1%, and 14%, respectively, with no difference between groups. Mean follow up was 30 ± 21 months. Patient survival was significantly lower in Group 2 (P = .03), but there was no difference in freedom from ARM and secondary interventions at 5 years between groups. Group 1 patients had lower freedom from any type II endoleak (P = .02) and sac enlargement (P < .001), whereas Group 2 patients had lower freedom from new-onset permanent dialysis (P = .03). CONCLUSIONS: FB-EVAR was performed with high technical success, low mortality, and similar risk of MAEs, regardless of prior history of abdominal aortic repair. Patient survival was significantly lower in patients who had previous abdominal OSR, but freedom from ARM and secondary interventions were similar among groups. Patients with prior EVAR had lower freedom from type II endoleak and sac enlargement. Patients with prior OSR had lower freedom from new-onset dialysis.

Taste adaptations associated with host specialization in the specialist Drosophila sechellia.

Chemosensory-driven host plant specialization is a major force mediating insect ecological adaptation and speciation. Drosophila sechellia, a species endemic to the Seychelles islands, feeds and oviposits on Morinda citrifolia almost exclusively. This fruit is harmless to D. sechellia but toxic to other Drosophilidae, including the closely related generalists D. simulans and D. melanogaster, because of its high content of fatty acids. While several olfactory adaptations mediating D. sechellia's preference for its host have been uncovered, the role of taste has been much less examined. We found that D. sechellia has reduced taste and feeding aversion to bitter compounds and host fatty acids that are aversive to D. melanogaster and D. simulans. The loss of aversion to canavanine, coumarin and fatty acids arose in the D. sechellia lineage, as its sister species D. simulans showed responses akin to those of D. melanogaster. Drosophila sechellia has increased taste and feeding responses towards M. citrifolia. These results are in line with D. sechellia's loss of genes that encode bitter gustatory receptors (GRs) in D. melanogaster. We found that two GR genes which are lost in D. sechellia, GR39a.a and GR28b.a, influence the reduction of aversive responses to some bitter compounds. Also, D. sechellia has increased appetite for a prominent host fatty acid compound that is toxic to its relatives. Our results support the hypothesis that changes in the taste system, specifically a reduction of sensitivity to bitter compounds that deter generalist ancestors, contribute to the specialization of D. sechellia for its host.

Travel-Associated Dengue Cases - United States, 2010-2021.

Dengue, the leading cause of arboviral disease worldwide, can be fatal without appropriate treatment. Among 7,528 confirmed or probable travel-associated U.S. dengue cases reported during 2010-2021, one in five (1,474, 20%) was reported in 2019. This is 168% higher than the annual average number of cases reported during 2010-2018 and 2020-2021 (approximately 550 per year) and 61% higher than the 913 cases reported in 2016, the second highest year on record. The number of cases as a fraction of air traffic volume to international destinations outside North America or Europe was also highest in 2019, with 41.9 cases per million trips, compared with 21.0 per million in other years during 2010-2021. This report compares the number and characteristics of travel-associated dengue cases reported to national surveillance in the United States in 2019 with cases reported during 2010-2018 and 2020-2021. Areas with conditions suitable for dengue transmission as well as the population at risk for dengue are expected to increase, placing U.S. travelers at higher risk for infection. Health care providers should be aware that dengue is a common cause of fever in the returning traveler and be familiar with its signs and symptoms, testing, and management. Dengue vaccines are not currently recommended for U.S. travelers; therefore, persons should review areas of dengue risk and follow guidance for preventing mosquito bites.

Differential patterns of fish sensitization in Asian populations: Implication for precision diagnosis.

BACKGROUND: The current diagnostics of fish allergy lack sufficient accuracy such that more reliable tests such as component-resolved diagnosis (CRD) are urgently needed. This study aimed at identifying fish allergens of salmon and grass carp and evaluating the sensitization pattern in fish allergic subjects from two distinct populations in Asia. METHODS: One hundred and three fish allergic subjects were recruited from Hong Kong (67 subjects) and Japan (46 subjects). Western blot and mass spectrometry were used to identify allergens from salmon and grass carp. Fish allergens were purified and tested against 96 sera on ELISA to analyze patients' sensitization pattern. The protein profiles of salmon meat prepared under different cooking methods until core temperature reached 80 °C were evaluated by SDS-PAGE and mass spectrometry. RESULTS: Three common allergens between salmon and grass carp, namely enolase, glycerldehyde-3-phosphate dehydrogenase (GAPDH) and parvalbumin, and two salmon-specific allergens collagen and aldolase were identified. Parvalbumin was the major allergen for both fishes showing an overall sensitization rate of 74.7%, followed by collagen (38.9%), aldolase (38.5%) and enolase (17.8%). Japanese subjects showed more diverse allergen sensitization pattern and more frequent IgE-binding to heat-labile salmon allergens. Compared with steaming and boiling, cooking by baking and frying retained more fish proteins inclusive of heat-labile allergens. CONCLUSIONS: Fish allergic patients from different Asian populations show varying fish allergen sensitization profiles. The relevant extracts and components for diagnosis are population-dependent but parvalbumin and collagen are important biomarkers. Cooking methods modify allergen composition of salmon and appear to influence patients' allergic manifestations.

Epidemiology of Acute Myocarditis/Pericarditis in Hong Kong Adolescents Following Comirnaty Vaccination.

BACKGROUND: Age-specific incidence of acute myocarditis/pericarditis in adolescents following Comirnaty vaccination in Asia is lacking. This study aimed to study the clinical characteristics and incidence of acute myocarditis/pericarditis among Hong Kong adolescents following Comirnaty vaccination. METHODS: This is a population cohort study in Hong Kong that monitored adverse events following immunization through a pharmacovigilance system for coronavirus disease 2019 (COVID-19) vaccines. All adolescents aged between 12 and 17 years following Comirnaty vaccination were monitored under the COVID-19 vaccine adverse event response and evaluation program. The clinical characteristics and overall incidence of acute myocarditis/pericarditis in adolescents following Comirnaty vaccination were analyzed. RESULTS: Between 14 June 2021 and 4 September 2021, 33 Chinese adolescents who developed acute myocarditis/pericarditis following Comirnaty vaccination were identified. In total, 29 (87.88%) were male and 4 (12.12%) were female, with a median age of 15.25 years. And 27 (81.82%) and 6 (18.18%) cases developed acute myocarditis/pericarditis after receiving the second and first dose, respectively. All cases are mild and required only conservative management. The overall incidence of acute myocarditis/pericarditis was 18.52 (95% confidence interval [CI], 11.67-29.01) per 100 000 persons vaccinated. The incidence after the first and second doses were 3.37 (95% CI, 1.12-9.51) and 21.22 (95% CI, 13.78-32.28 per 100 000 persons vaccinated, respectively. Among male adolescents, the incidence after the first and second doses were 5.57 (95% CI, 2.38-12.53) and 37.32 (95% CI, 26.98-51.25) per 100 000 persons vaccinated. CONCLUSIONS: There is a significant increase in the risk of acute myocarditis/pericarditis following Comirnaty vaccination among Chinese male adolescents, especially after the second dose.

Dengue Vaccine: Recommendations of the Advisory Committee on Immunization Practices, United States, 2021.

Dengue is a vectorborne infectious disease caused by dengue viruses (DENVs), which are predominantly transmitted by Aedes aegypti and Aedes albopictus mosquitos. Dengue is caused by four closely related viruses (DENV-1-4), and a person can be infected with each serotype for a total of four infections during their lifetime. Areas where dengue is endemic in the United States and its territories and freely associated states include Puerto Rico, American Samoa, the U.S. Virgin Islands, the Federated States of Micronesia, the Republic of Marshall Islands, and the Republic of Palau. This report summarizes the recommendations of the Advisory Committee on Immunization Practices (ACIP) for use of the Dengvaxia vaccine in the United States. The vaccine is a live-attenuated, chimeric tetravalent dengue vaccine built on a yellow fever 17D backbone. Dengvaxia is safe and effective in reducing dengue-related hospitalizations and severe dengue among persons who have had dengue infection in the past. Previous natural infection is important because Dengvaxia is associated with an increased risk for severe dengue in those who experience their first natural infection (i.e., primary infection) after vaccination. Dengvaxia was licensed by the Food and Drug Administration for use among children and adolescents aged 9-16 years (referred to in this report as children). ACIP recommends vaccination with Dengvaxia for children aged 9-16 having evidence of a previous dengue infection and living in areas where dengue is endemic. Evidence of previous dengue infection, such as detection of anti-DENV immunoglobulin G with a highly specific serodiagnostic test, will be required for eligible children before vaccination.

Impact of gap distance between fenestration and aortic wall on target artery instability following fenestrated-branched endovascular aortic repair.

OBJECTIVE: Target artery (TA) instability has been the most frequent indication for secondary intervention after fenestrated and branched endovascular aortic repair (FB-EVAR) of pararenal and thoracoabdominal aortic aneurysms (TAAAs). The aim of the present study was to evaluate the effect of the gap distance between the endograft reinforced fenestration and TA origin at the aortic wall (fenestration gap [FG]) on target-related outcomes after FB-EVAR. METHODS: The clinical data and imaging studies of 430 patients enrolled in a prospective, nonrandomized study to evaluate FB-EVAR using manufactured stent grafts were reviewed. Of the 430 patients, 340 (79%) had had more than one vessel incorporated by fenestration. The FG was retrospectively measured on postoperative imaging studies and classified into three groups: no gap (FG, 0 mm), FG 1 to 4 mm, and FG ≥5 mm. The primary outcome was freedom from TA instability. The secondary end points included TA-related endoleak, TA secondary intervention, and TA patency. RESULTS: A total of 1558 renal-mesenteric TAs were incorporated by 1104 reinforced fenestrations and 454 directional branches (DBs), with a mean of 3.9 ± 0.5 vessels per patient. The mean FG was 2.8 ± 4.5 mm, with an FG of 0 mm for 646 TAs, 1 to 4 mm for 209 TAs, and ≥5 mm for 249 TAs. An FG of ≥5 mm was associated with significantly lower (P < .001) freedom from TA instability, type Ic or IIIc endoleak, and secondary interventions at 5 years. Compared with DBs, fenestrations with an FG of ≥5 mm had similar primary patency and freedom from TA instability but significantly lower freedom from type Ic or IIIc endoleak (91% ± 2% vs 95% ± 1%; log rank, P = .02) and secondary interventions (87% ± 3% vs 93% ± 2%; log-rank, P = .02) at 5 years. The independent predictors of TA instability included postdissection TAAAs (hazard ratio, 2.5; 95% confidence interval, 1.2-5.4) and FG ≥5 mm (hazard ratio, 1.6; 95% confidence interval, 1.2-1.8). TAs incorporated by reinforced fenestrations had higher primary (99% ± 0.8% vs 97% ± 1.0%; P = .039) and secondary (100% vs 98% ± 1.0%; P = .012) patency rates at 5 years compared with DBs, with the lowest primary patency observed for renal DBs (80% ± 6% vs 92% ± 2%; P = .008). CONCLUSIONS: An FG of ≥5 mm was independently associated with an increased risk of TA instability, type Ic or IIIc endoleaks, and secondary interventions for patients treated by FB-EVAR using fenestrated designs. TAs incorporated by DBs had lower 5-year primary and secondary patency compared with those with reinforced fenestrations, with the lowest 5-year patency of 80% for renal branches. Compared with DBs, fenestrations with an FG of ≥5 mm carried a greater risk of type Ic or IIIc endoleak and secondary interventions. Independent predictors of TA instability included postdissection TAAAs and a greater FG. In contrast, dual antiplatelet therapy and larger TA diameters were protective.

Comprehending the allergen repertoire of shrimp for precision molecular diagnosis of shrimp allergy.

BACKGROUND: Clinical management of shrimp allergy is hampered by the lack of accurate tests. Molecular diagnosis has been shown to more accurately reflect the clinical reactivity but the full spectrum of shrimp allergens and their clinical relevance are yet to be established. We therefore sought to comprehend the allergen repertoire of shrimp, investigate and compare the sensitization pattern and diagnostic value of the allergens in allergic subjects of two distinct populations. METHODS: Sera were collected from 85 subjects with challenge-proven or doctor-diagnosed shrimp allergy in Hong Kong and Thailand. The IgE-binding proteins of Penaeus monodon were probed by Western blotting and identified by mass spectrometry. Recombinant shrimp allergens were synthesized and analyzed for IgE sensitization by ELISA. RESULTS: Ten IgE-binding proteins were identified, and a comprehensive panel of 11 recombinant shrimp allergens was generated. The major shrimp allergens among Hong Kong subjects were troponin C (Pen m 6) and glycogen phosphorylase (Pen m 14, 47.1%), tropomyosin (Pen m 1, 41.2%) and sarcoplasmic-calcium binding protein (Pen m 4, 35.3%), while those among Thai subjects were Pen m 1 (68.8%), Pen m 6 (50.0%) and fatty acid-binding protein (Pen m 13, 37.5%). Component-based tests yielded significantly higher area under curve values (0.77-0.96) than shrimp extract-IgE test (0.70-0.75). Yet the best component test differed between populations; Pen m 1-IgE test added diagnostic value only in the Thai cohort, whereas sensitizations to other components were better predictors of shrimp allergy in Hong Kong patients. CONCLUSION: Pen m 14 was identified as a novel shrimp allergen predictive of challenge outcome. Molecular diagnosis better predicts shrimp allergy than conventional tests, but the relevant component is population dependent.