Comparison of open thoracoabdominal repair for chronic aortic dissections and aneurysms.

OBJECTIVE: Aortic dissection is common in patients undergoing open surgical repair of thoracoabdominal aortic aneurysms (TAAAs). Most often, dissection is chronic and is associated with progressive aortic dilatation. Because contemporary outcomes in chronic dissection are not clearly understood, we compared patient characteristics and outcomes after open TAAA repair between patients with chronic dissection and those with non-dissection aneurysm. METHODS: We retrospectively analyzed data from 3470 open TAAA repairs performed in a single practice. Operations were for non-dissection aneurysm in 2351 (67.8%) and chronic dissection in 1119 (32.2%). Outcomes included operative mortality and adverse events, a composite variable comprising operative death and persistent (present at discharge) stroke, paraplegia, paraparesis, and renal failure necessitating dialysis. Logistic regression identified predictors of operative mortality and adverse events. Time-to-event analyses examined survival, death, repair failure, subsequent progressive repair, and survival free of failure or subsequent repair. RESULTS: Compared with patients with non-dissection aneurysm, those with chronic dissection were younger, had fewer atherosclerotic risk factors, and were more likely to have heritable thoracic aortic disease and undergo extent II repair. The operative mortality rate was 8.5% (n = 296) overall and was higher in non-dissection aneurysm patients (n = 217; 9.2%) than in chronic dissection patients (n = 79; 7.1%; P = .03). Adverse events were less frequent (P = .01) in patients with chronic dissection (n = 145; 13.0%), 22 (2.0%) of whom had persistent paraplegia. Chronic dissection was not predictive of operative mortality (P = .5) or adverse events (P = .6). Operative mortality and adverse events, respectively, were independently predicted by emergency repair (odds ratio [OR], 3.46 and 2.87), chronic kidney disease (OR, 1.74 and 1.81), extent II TAAA repair (OR, 1.44 and 1.73), increasing age (OR, 1.04/year and 1.04/year), and increasing aortic cross-clamp time (OR, 1.02/minutes and 1.02/minutes). Patients with chronic dissection had lower 10-year unadjusted mortality (42% vs 69%) but more frequent repair failure (5% vs 3%) and subsequent repair for progressive aortic disease (11% vs 5%) than patients with non-dissection aneurysm (P < .001); these differences were no longer statistically significant after adjustment. CONCLUSIONS: Outcomes of open TAAA repair vary by aortic disease type. Emergency repairs and atherosclerotic diseases most commonly occur in patients with non-dissection aneurysm and independently predict operative mortality. Repair of chronic dissection is associated with low rates of adverse events, including operative mortality and persistent paraplegia, along with reasonable late survival and good durability. However, patients with chronic dissection tend to more commonly undergo subsequent repair to treat progressive aortic disease, which emphasizes the need for robust long-term imaging surveillance protocols.

Crosstalk between P2Y receptors and cyclooxygenase activity in inflammation and tissue repair.

The role of extracellular nucleotides as modulators of inflammation and cell stress is well established. One of the main actions of these molecules is mediated by the activation of purinergic receptors (P2) of the plasma membrane. P2 receptors can be classified according to two different structural families: P2X ionotropic ion channel receptors, and P2Y metabotropic G protein-coupled receptors. During inflammation, damaged cells release nucleotides and purinergic signaling occurs along the temporal pattern of the synthesis of pro-inflammatory and pro-resolving mediators by myeloid and lymphoid cells. In macrophages under pro-inflammatory conditions, the expression and activity of cyclooxygenase 2 significantly increases and enhances the circulating levels of prostaglandin E2 (PGE2), which exerts its effects both through specific plasma membrane receptors (EP1-EP4) and by activation of intracellular targets. Here we review the mechanisms involved in the crosstalk between PGE2 and P2Y receptors on macrophages, which is dependent on several isoforms of protein kinase C and protein kinase D1. Due to this crosstalk, a P2Y-dependent increase in calcium is blunted by PGE2 whereas, under these conditions, macrophages exhibit reduced migratory capacity along with enhanced phagocytosis, which contributes to the modulation of the inflammatory response and tissue repair.

From Surgical to Total Transcatheter Stage I Palliation: Exploring Evidence and Perspectives.

Neonates with single ventricle physiology and ductal-dependent systemic circulation, such as those with hypoplastic left heart syndrome, undergo palliation in the first days of life. Over the past decades, variations on the traditional Stage 1 palliation, also known as Norwood operation, have emerged. These include the hybrid palliation and the total transcatheter approach. Here, we review the current evidence and data on different Stage 1 approaches, with a focus on their advantages, challenges, and future perspectives. Overall, although controversy remains regarding the superiority or inferiority of one approach to another, outcomes after the Norwood and the hybrid palliation have improved over time. However, both procedures still represent high-risk approaches that entail exposure to sternotomy, surgery, and potential cardiopulmonary bypass. The total transcatheter Stage 1 palliation spares patients the surgical and cardiopulmonary bypass insults and has proven to be an effective strategy to bridge even high-risk infants to a later palliative surgery, complete repair, or transplant. As the most recently proposed approach, data are still limited but promising. Future studies will be needed to better define the advantages, challenges, outcomes, and overall potential of this novel approach.

Trabectedin and Lurbinectedin Modulate the Interplay between Cells in the Tumour Microenvironment-Progresses in Their Use in Combined Cancer Therapy.

Trabectedin (TRB) and Lurbinectedin (LUR) are alkaloid compounds originally isolated from Ecteinascidia turbinata with proven antitumoral activity. Both molecules are structural analogues that differ on the tetrahydroisoquinoline moiety of the C subunit in TRB, which is replaced by a tetrahydro-ß-carboline in LUR. TRB is indicated for patients with relapsed ovarian cancer in combination with pegylated liposomal doxorubicin, as well as for advanced soft tissue sarcoma in adults in monotherapy. LUR was approved by the FDA in 2020 to treat metastatic small cell lung cancer. Herein, we systematically summarise the origin and structure of TRB and LUR, as well as the molecular mechanisms that they trigger to induce cell death in tumoral cells and supporting stroma cells of the tumoral microenvironment, and how these compounds regulate immune cell function and fate. Finally, the novel therapeutic venues that are currently under exploration, in combination with a plethora of different immunotherapeutic strategies or specific molecular-targeted inhibitors, are reviewed, with particular emphasis on the usage of immune checkpoint inhibitors, or other bioactive molecules that have shown synergistic effects in terms of tumour regression and ablation. These approaches intend to tackle the complexity of managing cancer patients in the context of precision medicine and the application of tailor-made strategies aiming at the reduction of undesired side effects.

Defining the metabolic signatures associated with human macrophage polarisation.

Macrophages are essential components of the innate immune system that play both homeostatic roles in healthy organs, and host defence functions against pathogens after tissue injury. To accomplish their physiological role, macrophages display different profiles of gene expression, immune function, and metabolic phenotypes that allow these cells to participate in different steps of the inflammatory reaction, from the initiation to the resolution phase. In addition, significant differences exist in the phenotype of macrophages depending on the tissue in which they are present and on the mammalian species. From a metabolic point of view, macrophages are essentially glycolytic cells; however, their metabolic fluxes are dependent on the functional polarisation of these cells. This metabolic and cellular plasticity offers the possibility to interfere with the activity of macrophages to avoid harmful effects due to persistent activation or the release of molecules that delay tissue recovery after injury.

Readmissions After Surgical Aortic Valve Replacement: Influence of Prosthesis Type.

INTRODUCTION: Prosthesis choice during aortic valve replacement (AVR) weighs lifelong anticoagulation with mechanical valves (M-AVR) against structural valve degeneration in bioprosthetic valves (B-AVR). METHODS: The Nationwide Readmissions Database was queried to identify patients who underwent isolated surgical AVR between January 1, 2016 and December 31, 2018, stratifying by prothesis type. Propensity score matching was used to compare risk-adjusted outcomes. Readmission at 1 y was estimated with Kaplan-Meier (KM) analysis. RESULTS: Patients (n = 109,744) who underwent AVR (90,574 B-AVR and 19,170 M-AVR) were included. B-AVR patients were older (median 68 versus 57 y; P < 0.001) and had more comorbidities (mean Elixhauser score: 11.8 versus 10.7; P < 0.001) compared to M-AVR patients. After matching (n = 36,951), there was no difference in age (58 versus 57 y; P = 0.6) and Elixhauser score (11.0 versus 10.8; P = 0.3). B-AVR patients had similar in-hospital mortality (2.3% versus 2.3%; P = 0.9) and cost (mean: $50,958 versus $51,200; P = 0.4) compared with M-AVR patients. However, B-AVR patients had shorter length of stay (8.3 versus 8.7 d; P < 0.001) and fewer readmissions at 30 d (10.3% versus 12.6%; P < 0.001) and 90 d (14.8% versus 17.8%; P < 0.001), and 1 y (P < 0.001, KM analysis). Patients undergoing B-AVR were less likely to be readmitted for bleeding or coagulopathy (5.7% versus 9.9%; P < 0.001) and effusions (9.1% versus 11.9%; P < 0.001). CONCLUSIONS: B-AVR patients had similar early outcomes compared to M-AVR patients, but lower rates of readmission. Bleeding, coagulopathy, and effusions are drivers of excess readmissions in M-AVR patients. Readmission reduction strategies targeting bleeding and improved anticoagulation management are warranted in the first year following AVR.

Linear thinking does not reflect the newer 21st-century anesthesia concepts. A narrative review.

The brain constitutes a good example of a chaotic, nonlinear biological system where large neuronal networks operate chaotically with random connectivity. This critical state is significantly affected by the anesthetic loss of consciousness induced by drugs whose pharmacological behavior has been classically based on linear kinetics and dynamics. Recent developments in pharmacology and brain monitoring during anesthesia suggest a different view that we tried to explore in this article. The concepts of effect-site for hypnotic drugs modeling a maximum effect, electroencephalographic dynamics during induction, maintenance, and recovery from anesthesia are discussed, integrated into this alternative view, and how it may be applied in daily clinical practice.

Mid-Term Efficacy of Subxiphoid Versus Transpleural Pericardial Window for Pericardial Effusion.

BACKGROUND: The optimal surgical technique for drainage of pericardial effusions is frequently debated. Transpleural drainage via thoracotomy or thoracoscopy is hypothesized to provide more durable freedom from recurrent pericardial effusion than a subxiphoid pericardial window. We sought to compare operative outcomes and mid-term freedom from recurrent effusion between both approaches in patients with nontraumatic pericardial effusions. METHODS: All patients at our institution who underwent a pericardial window from 2001 to 2018 were identified. After excluding those who underwent recent cardiothoracic surgery or trauma, patients (n = 46) were stratified by surgical approach and presence of malignancy. Primary outcome was freedom from recurrent moderate or greater pericardial effusion. Secondary outcomes included operative mortality and morbidity and mid-term survival. Follow-up was determined by medical record review, with a follow-up of 67 patient-years. Fisher's exact test and Wilcoxon rank-sum test were used to compare groups. Mid-term survival and freedom from effusion recurrence were determined using Kaplan-Meier method. RESULTS: Subxiphoid windows (n = 31; 67%) were more frequently performed than transpleural windows (n = 15; 33%) and baseline characteristics were similar. Effusion etiologies included malignancy (n = 22; 48%), idiopathic (n = 12; 26%), uremia (n = 8; 17%), and collagen vascular disease (n = 4; 9%). Perioperative outcomes were comparable between the two surgical approaches, except for longer drain duration (7 versus 4 d, P = 0.029) in the subxiphoid group. Operative mortality was 19.6% overall and 36.4% in patients with malignancy. Mid-term survival and freedom from moderate or greater pericardial effusion recurrence was 37% (95% confidence interval [CI]: 19%-54%) and 69% (95% CI: 52%-86%) at 5 y, respectively. There was no difference in mid-term survival (P = 0.90) or freedom from pericardial effusion recurrence (P = 0.70) between surgical approaches. Although malignant etiology had worse late survival (P < 0.01), freedom from effusion recurrence was similar to nonmalignant etiology (P = 0.70). CONCLUSIONS: Pericardial window provides effective mid-term relief of pericardial effusion. Subxiphoid and transpleural windows are equivalent in mid-term efficacy and both surgical approaches can be considered. Patients with malignancy have acceptable operative mortality with low incidence of recurrent effusion, supporting palliative indications.

Techno-Economic Analysis of Producing Glacial Acetic Acid from Poplar Biomass via Bioconversion.

Most of the current commercial production of glacial acetic acid (GAA) is by petrochemical routes, primarily methanol carbonylation. GAA is an intermediate in the production of plastics, textiles, dyes, and paints. GAA production from biomass might be an economically viable and sustainable alternative to petroleum-derived routes. Separation of acetic acid from water is a major expense and requires considerable energy. This study evaluates and compares the technical and economic feasibility of GAA production via bioconversion using either ethyl acetate or alamine in diisobutylkerosene (DIBK) as organic solvents for purification. Models of a GAA biorefinery with a production of 120,650 tons/year were simulated in Aspen software. This biorefinery follows the path of pretreatment, enzymatic hydrolysis, acetogen fermentation, and acid purification. Estimated capital costs for different scenarios ranged from USD 186 to 245 million. Recovery of GGA using alamine/DIBK was a more economical process and consumed 64% less energy, due to lower steam demand in the recovery distillation columns. The estimated average minimum selling prices of GGA were USD 756 and 877/ton for alamine/DIBK and ethyl acetate scenarios, respectively. This work establishes a feasible and sustainable approach to produce GGA from poplar biomass via fermentation.

Extracellular vesicles and soluble factors secreted by Escherichia coli Nissle 1917 and ECOR63 protect against enteropathogenic E. coli-induced intestinal epithelial barrier dysfunction.

BACKGROUND: Enteric pathogens have developed mechanisms to disrupt tight junctions and increase gut permeability. Many studies have analysed the ability of live probiotics to protect intestinal epithelial cells against tight junction damage caused by bacterial pathogens. Escherichia coli Nissle 1917 (EcN) is among the probiotics that positively modulates the intestinal epithelial barrier by regulating expression and distribution of tight junction proteins. We previously reported that regulation of ZO-1, claudin-14 and claudin-2 is mediated by EcN secreted factors, either free-released or associated with outer membrane vesicles (OMVs). Factors secreted by commensal ECOR63 elicited comparable effects in intact epithelial T-84 and Caco-2 cell monolayers. RESULTS: Here we analyse the ability of OMVs and soluble secreted factors to protect epithelial barrier function in polarized T-84 and Caco-2 cells infected with enteropathogenic Escherichia coli (EPEC). Transepithelial electrical resistance, paracellular permeability, mRNA levels and subcellular distribution of tight junction proteins were monitored in the absence or presence of EcN and ECOR63 extracellular fractions. EPEC downregulated expression of ZO-1 ZO-2, occludin and claudin-14 and altered the subcellular localization of ZO-1, occludin and F-actin cytoskeleton. OMVs and soluble factors secreted by EcN and ECOR63 counteracted EPEC-altered transepithelial resistance and paracellular permeability, preserved occludin and claudin-14 mRNA levels, retained ZO-1 and occludin at tight junctions in the cell boundaries and ameliorated F-actin disorganization. Redistribution of ZO-1 was not accompanied by changes at mRNA level. CONCLUSION: This study provides new insights on the role of microbiota secreted factors on the modulation of intestinal tight junctions, expanding their barrier-protective effects against pathogen-induced disruption.

Endovascular management of inferior vena cava filter thrombotic occlusion.

Objective Inferior vena cava occlusion is a potentially life-threatening complication related to caval filters. We present our experience with filter-induced inferior vena cava occlusion in order to assess the feasibility, safety, and effectiveness of endovascular management. Methods A retrospective review of all patients undergoing inferior vena cava filter placement over a 60-month study period was performed. From this cohort, a total of 10 cases of inferior vena cava occlusion after filter placement were identified. Demographics, clinical data, procedures, and outcomes were extracted. Patients were followed to the last clinic visit or until they died. Results One-hundred eighty filters were placed by our group practice during the study period. Of those, a total of 10 patients were identified. Overall, there were 7 males; the mean age was 57.1 years (25-78 years). The median time between inferior vena cava filter placement and filter occlusion was 105 days (range 5-4745 days). All patients were clinically symptomatic at the time of their presentation. Nine out of 10 patients were successfully managed endovascularly. Trellis™-8 thrombectomy was the most common endovascular strategy performed ( n = 9). Four patients had balloon angioplasty, two of those with stent placement for chronically occluded inferior vena cava/iliac veins. No thromboembolic complications developed during a median follow-up period of 233 days (range 4-1083 days). Conclusions Endovascular management of inferior vena cava occlusion is feasible, safe, and effective in decreasing thrombus burden in the presence of an inferior vena cava filter. Further studies evaluating long-term inferior vena cava patency and optimal surveillance regimen after endovascular management of filter-related inferior vena cava occlusion are warranted.

Cervical left aortic arch with distal tortuosity causing coarctation and aneurysmal formation in a child.

We present a case of a 10-year-old female with a cervical aortic arch and distal transverse arch tortuosity causing coarctation and aneurysmal formation and describe the surgical repair of this rare congenital anomaly.

Acute humoral rejection in an infant without risk factors after heart transplantation.

Graft rejection is the most common factor that limits graft survival after transplantation. During infancy, the humoral immune system is partially suppressed and humoral rejection of a cardiac allograft has not been reported in the absence of risk factors such as prior transplantation, blood transfusions, ventricular assist devices, and elevation of panel reactive antibodies. We present a case of an infant with dilated cardiomyopathy who developed multiple episodes of acute humoral rejection after heart transplantation in the absence of risk factors.

Effects of turning aeration and the initial carbon/nitrogen ratio on the biodegradation of polylactic acid under controlled conditions.

Plastic pollution is primarily caused by the accumulation of petroleum-derived plastics, as they tend to degrade slowly. Sustainable alternatives to these materials are bio-based and biodegradable plastics, such as polylactic acid (PLA). In this study, we assessed how turning aeration and the initial carbon/nitrogen (C/N) ratio impact PLA biodegradation. The study was carried out under controlled composting conditions, over 180 days, with the aim of decreasing the biodegradation time of the PLA. Apple pomace, rice husk, grape pomace compost, and PLA were used as substrates in the composting process. The experiments were conducted using three types of turning aeration: without turning, one turn per week, and two turns per week. Three initial C/N ratios were used: 20, 30, and 40. A stepwise temperature ramp was designed and implemented to simulate industrial composting conditions, which influence microbial activity and thus the rate of decomposition of substrates, including PLA. The data showed behavior; hence, a nonlinear regression model based on the logistic growth equation was used to predict the PLA biodegradation at the end of the composting process. The results showed that two turns per week with an initial C/N ratio of 30 or 40 led to a 90 % biodegradation of the PLA in 130 days. This degradation was verified by Fourier-Transform Infrared Spectroscopy (FTIR) and Scanning Electron Microscopy (SEM).

Genomic and phylogenomic characterization of carbapenem-resistant Pseudomonas aeruginosa 'high-risk' clone O4/ExoS+/ST654 circulating in Chilean hospitals.

INTRODUCTION: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a serious threat to public health. Globally, carbapenemases-producing CRPA isolates mainly belong to 'high-risk' clones; however, the molecular epidemiology of CRPA isolates circulating in Chile are scarce, where this pathogen is the main aetiological agent of ventilator-associated pneumonia. OBJECTIVES: To characterize the phylogenomics and molecular features of ST654 CRPA isolates collected in Chile between 2016 - 2022. METHODS: 89 CRPA isolates collected in different Chilean hospitals from clinical specimens between 2005 and 2022 were analyzed. Antibiotic susceptibility tests and carbapenemases production were carried out on the CRPA ST654 isolates. Also, they were subjected to whole-genome sequencing (WGS) from which in silico analyses were performed. RESULTS: Thirty-four strains (38.2%) belonged to the ST654 'high risk' clone, being the most predominant lineage of the collection. Most of these isolates belonged to a sub-clade including KPC-producers that also clustered with strains from Argentina and the USA, whereas few VIM and NDM co-producers clustered in two different smaller sub-clades. The isolates exhibited a broad resistome encompassing genes mediating resistance to several other clinically relevant drugs. Additionally, all the 34 ST654 isolates were ExoS+ as a virulence factor and associated to the O4-serotype. CONCLUSIONS: Our report represents the most comprehensive phylogenomic study of CRPA 'high risk' clone ST654 to date. Our analyses suggest that this lineage is undergoing a divergent evolutionary path in Chile, since most of the isolates were KPC-producers and were O4-serotype, differing from previous descriptions, which underline the relevance of performing molecular surveillance on this pathogen.

A retrospective study suggests 55 days of persistence of SARS-CoV-2 during the first wave of the pandemic in Santiago de Chile.

Background: As the COVID-19 pandemic persists, infections continue to surge globally. Presently, the most effective strategies to curb the disease and prevent outbreaks involve fostering immunity, promptly identifying positive cases, and ensuring their timely isolation. Notably, there are instances where the SARS-CoV-2 virus remains infectious even after patients have completed their quarantine. Objective: Understanding viral persistence post-quarantine is crucial as it could account for localized infection outbreaks. Therefore, studying and documenting such instances is vital for shaping future public health policies. Design: This study delves into a unique case of SARS-CoV-2 persistence in a 60-year-old female healthcare worker with a medical history of hypertension and hypothyroidism. The research spans 55 days, marking the duration between her initial and subsequent diagnosis during Chile's first COVID-19 wave, with the analysis conducted using RT-qPCR. Results: Genomic sequencing-based phylogenetic analysis revealed that the SARS-CoV-2 detected in both Nasopharyngeal swab samples (NPSs) was consistent with the 20B clade of the Nextstrain classification, even after a 55-day interval. Conclusion: This research underscores the need for heightened vigilance concerning cases of viral persistence. Such instances, albeit rare, might be pivotal in understanding sporadic infection outbreaks that occur post-quarantine.

Outcomes After Extent I Thoracoabdominal Aortic Repair: Focus on Heritable Aortic Disease.

BACKGROUND: Crawford extent I thoracoabdominal aortic aneurysm (TAAA) repairs are increasingly performed by an endovascular approach, including in patients with heritable thoracic aortic disease (HTAD). We evaluated outcomes after open extent I TAAA repair in patients with and without HTAD. METHODS: This retrospective study included 992 patients (median age, 67 years; quartile 1-quartile 3, 57-73 years) who underwent extent I TAAA (1990-2022), stratified by the presence of HTAD (n = 177 [17.8%]). Patients with HTAD had genetic aortopathies or presented at age ≤50 years, and 35% (62 of 177) had Marfan syndrome. Logistic regression was used to identify predictors of operative death and adverse event, a composite of operative death and persistent (present at discharge) stroke, paraplegia, paraparesis, and renal failure necessitating dialysis. Long-term outcomes were analyzed with competing risks analysis. RESULTS: Patients with HTAD had lower rates of operative mortality (1.7% vs 7.0%, P = .01) and composite adverse event (2.8% vs 12.3%, P < .001) than non-HTAD patients. Most HTAD patients were discharged home (92.6% vs 76.9%, P < .001). Predictors of operative death were increasing age, aortic dissection, tobacco use, chronic symptoms, and rupture. Predictors for adverse event were increasing age, acute symptoms, chronic dissection, and rupture. Patients with HTAD had substantially better repair-failure-free survival (P < .001). CONCLUSIONS: Open extent I TAAA repair was effective in patients with HTAD, with low operative mortality and adverse event rates, better late survival, and excellent long-term durability, making a compelling argument for preferring open repair in these patients.

Platelets derived from the bone marrow of diabetic animals show dysregulated endoplasmic reticulum stress proteins that contribute to increased thrombosis.

OBJECTIVE: Patients with diabetes mellitus have an increased risk of suffering atherothrombotic syndromes and are prone to clustering cardiovascular risk factors. However, despite their dysregulated glucose metabolism, intensive glycemic control has proven insufficient to reduce thrombotic complications. Therefore, we aimed to elucidate the determinants of thrombosis in a model of type 2 diabetes mellitus with cardiovascular risk factors clustering. METHODS AND RESULTS: Intravital microscopy was used to analyze thrombosis in vivo in Zucker diabetic fatty rats (ZD) and lean normoglycemic controls. Bone marrow (BM) transplants were performed to test the contribution of each compartment (blood or vessel wall) to thrombogenicity. ZD showed significantly increased thrombosis compared with lean normoglycemic controls. BM transplants demonstrated the key contribution of the hematopoietic compartment to increased thrombogenicity. Indeed, lean normoglycemic controls transplanted with ZD-BM showed increased thrombosis with normal glucose levels, whereas ZD transplanted with lean normoglycemic controls-BM showed reduced thrombosis despite presenting hyperglycemia. Significant alterations in megakaryopoiesis and platelet-endoplasmic reticulum stress proteins, protein disulfide isomerase and 78-kDa glucose-regulated protein, were detected in ZD, and increased tissue factor procoagulant activity was detected in plasma and whole blood of ZD. CONCLUSIONS: Our results indicate that diabetes mellitus with cardiovascular risk factor clustering favors BM production of hyperreactive platelets with altered protein disulfide isomerase and 78-kDa glucose-regulated protein expression that can contribute to increase thrombotic risk independently of blood glucose levels.

Molecular Characterization of the Convergent Carbapenem-Resistant and Hypervirulent Klebsiella pneumoniae Strain K1-ST23, Collected in Chile during the COVID-19 Pandemic.

The aim of this study was to investigate the genomic features of a carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKp) isolate (K-2157) collected in Chile. Antibiotic susceptibility was determined using the disk diffusion and broth microdilution methods. Whole-genome sequencing (WGS) and hybrid assembly were performed, using data generated on the Illumina and Nanopore platforms. The mucoid phenotype was analyzed using both the string test and sedimentation profile. The genomic features of K-2157 (e.g., sequence type, K locus, and mobile genetic elements) were retrieved using different bioinformatic tools. Strain K-2157 exhibited resistance to carbapenems and was identified as a high-risk virulent clone belonging to capsular serotype K1 and sequence type 23 (ST23). Strikingly, K-2157 displayed a resistome composed of ß-lactam resistance genes (blaSHV-190, blaTEM-1, blaOXA-9, and blaKPC-2), the fosfomycin resistance gene fosA, and the fluoroquinolones resistance genes oqxA and oqxB. Moreover, several genes involved in siderophore biosynthesis (ybt, iro, and iuc), bacteriocins (clb), and capsule hyperproduction (plasmid-borne rmpA [prmpA] and prmpA2) were found, which is congruent with the positive string test displayed by K-2157. In addition, K-2157 harbored two plasmids: one of 113,644 bp (KPC+) and another of 230,602 bp, containing virulence genes, in addition to an integrative and conjugative element (ICE) embedded on its chromosome, revealing that the presence of these mobile genetic elements mediates the convergence between virulence and antibiotic resistance. Our report is the first genomic characterization of a hypervirulent and highly resistant K. pneumoniae isolate in Chile, which was collected during the coronavirus disease 2019 (COVID-19) pandemic. Due to their global dissemination and public health impact, genomic surveillance of the spread of convergent high-risk K1-ST23 K. pneumoniae clones should be highly prioritized. IMPORTANCE Klebsiella pneumoniae is a resistant pathogen involved primarily in hospital-acquired infections. This pathogen is characterized by its notorious resistance to last-line antibiotics, such as carbapenems. Moreover, hypervirulent K. pneumoniae (hvKp) isolates, first identified in Southeast Asia, have emerged globally and are able to cause infections in healthy people. Alarmingly, isolates displaying a convergence phenotype of carbapenem resistance and hypervirulence have been detected in several countries, representing a serious threat to public health. In this work, we analyzed the genomic characteristics of a carbapenem-resistant hvKp isolate recovered in 2022 from a patient with COVID-19 in Chile, representing the first analysis of this type in the country. Our results will provide a baseline for the study of these isolates in Chile, which will support the adoption of local measures aimed at controlling their dissemination.

Contemporary Midterm Outcomes After Primary Repair of Chronic Type A Aortic Dissection.

BACKGROUND: Without surgical repair, acute type A aortic dissection (TAAD) is usually fatal. However, some patients survive without an early operation and progress to the chronic phase. Contemporary outcomes of primary surgical repair of chronic TAAD are unclear, so we evaluated them at our single-practice service. METHODS: During 1990 to 2021, 205 patients underwent repair of TAAD in the chronic phase (>60 days after onset). The 2 relevant DeBakey classifications were nearly equally represented: type I, 52% (n = 107), and type II, 48% (n = 98). The median interval between dissection onset and repair was 7 months (interquartile range, 3-25 months). Kaplan-Meier and competing-risk analyses provided time-dependent outcomes. RESULTS: At the time of intervention, most patients (40%) had chronic symptoms. Type I patients were younger than type II patients; however, comorbidities were similar. Most patients (n = 183 [87%]) underwent hemiarch or total arch repair, although total arch replacement was more common in type I dissection (P < .001). There were 15 operative deaths (7%), and 7 strokes (3%) persisted to the time of death or discharge. No patient had persistent paraplegia. Median follow-up was 5 years (interquartile range, 2-11 years). The 5-year reoperation-free survival was 61% (95% CI, 54%-68%), and the incidence of reoperation was 3% (95% CI, 0.4%-5%). Patients with type I and type II dissection did not differ significantly in survival (P = .2). CONCLUSIONS: Durable repair can be achieved with reasonable operative risk. Treatment is individualized and is associated with low rates of persistent neurologic complications. Despite differing operative approaches by DeBakey type, early and late outcomes were similar.