Valve-sparing aortic root replacement versus composite valve graft with bioprosthesis in patients under age 50.

BACKGROUND: Although the unique risks of implanting a prosthetic valve after aortic valve (AV) surgery in young patients are well established, studies of aortic root replacement (ARR) are lacking. We investigated long-term outcomes after valve-sparing root replacement (VSRR) versus the use of a composite valve graft with bioprosthesis (b-CVG) in patients age <50 years. METHODS: A total of 543 patients age <50 years underwent VSRR (n = 335) or b-CVG (n = 208) between 2004 and 2021 from 2 aortic centers, excluding those with dissection or endocarditis. Endpoints included mortality over time, reoperative aortic valve replacement (AVR), and development of greater than moderate aortic insufficiency (AI) or aortic stenosis (AS). Fine and Gray competing risk regression was used to compare the risk of reintervention. Propensity score matching (PSM) balanced patient comorbidities, and landmark analysis isolated outcomes beginning 4 years postoperatively. RESULTS: Compared with VSRR, b-CVG was associated with lower 12-year survival (88.6% vs 92.9%; P = .036) and a higher rate of AV reintervention (37.6% vs 12.0%; P = .018). After PSM, survival was similar in the 2 arms (93.4% for b-CVG vs 93.0% for VSRR; P = .72). However, both Fine and Gray multivariable risk regression and PSM showed that b-CVG was independently associated with AV reintervention at >4 years postoperatively (Fine and Gray: subdistribution hazard ratio, 4.3 [95% confidence interval, 1.8-10.2; P = .001]; PSM: 35.7% for b-CVG versus 14.3% for VSRR; P = .024]). PSM rates of greater than moderate AI/AS at 10 years were more than 2-fold greater in the b-CVG arm compared with the VSRR arm (37.1% vs 15.9%; P = .571). CONCLUSIONS: b-CVG in young patients is associated with early valvular degeneration, with increasing rates of reoperative AVR occurring even within 10 years. In contrast, VSRR is durable with excellent survival. In eligible young patients, every effort should be made to retain the native AV.

A literature review of severity scores for adults with influenza or community-acquired pneumonia - implications for influenza vaccines and therapeutics.

Influenza vaccination and antiviral therapeutics may attenuate disease, decreasing severity of illness in vaccinated and treated persons. Standardized assessment tools, definitions of disease severity, and clinical endpoints would support characterizing the attenuating effects of influenza vaccines and antivirals. We review potential clinical parameters and endpoints that may be useful for ordinal scales evaluating attenuating effects of influenza vaccines and antivirals in hospital-based studies. In studies of influenza and community-acquired pneumonia, common physiologic parameters that predicted outcomes such as mortality, ICU admission, complications, and duration of stay included vital signs (hypotension, tachypnea, fever, hypoxia), laboratory results (blood urea nitrogen, platelets, serum sodium), and radiographic findings of infiltrates or effusions. Ordinal scales based on these parameters may be useful endpoints for evaluating attenuating effects of influenza vaccines and therapeutics. Factors such as clinical and policy relevance, reproducibility, and specificity of measurements should be considered when creating a standardized ordinal scale for assessment.

Differentiating severe and non-severe lower respiratory tract illness in patients hospitalized with influenza: Development of the Influenza Disease Evaluation and Assessment of Severity (IDEAS) scale.

BACKGROUND: Experimental studies have shown that vaccination can reduce viral replication to attenuate progression of influenza-associated lower respiratory tract illness (LRTI). However, clinical studies are conflicting, possibly due to use of non-specific outcomes reflecting a mix of large and small airway LRTI lacking specificity for acute lung or organ injury. METHODS: We developed a global ordinal scale to differentiate large and small airway LRTI in hospitalized adults with influenza using physiologic features and interventions (PFIs): vital signs, laboratory and radiographic findings, and clinical interventions. We reviewed the literature to identify common PFIs across 9 existing scales of pneumonia and sepsis severity. To characterize patients using this scale, we applied the scale to an antiviral clinical trial dataset where these PFIs were measured through routine clinical care in adults hospitalized with influenza-associated LRTI during the 2010-2013 seasons. RESULTS: We evaluated 12 clinical parameters among 1020 adults; 210 (21%) had laboratory-confirmed influenza, with a median severity score of 4.5 (interquartile range, 2-8). Among influenza cases, median age was 63 years, 20% were hospitalized in the prior 90 days, 50% had chronic obstructive pulmonary disease, and 22% had congestive heart failure. Primary influencers of higher score included pulmonary infiltrates on imaging (48.1%), heart rate ≥110 beats/minute (41.4%), oxygen saturation <93% (47.6%) and respiratory rate >24 breaths/minute (21.0%). Key PFIs distinguishing patients with severity < or ≥8 (upper quartile) included infiltrates (27.1% vs 90.0%), temperature ≥ 39.1°C or <36.0°C (7.1% vs 27.1%), respiratory rate >24 breaths/minute (7.9% vs 47.1%), heart rate ≥110 beats/minute (29.3% vs 65.7%), oxygen saturation <90% (14.3% vs 31.4%), white blood cell count >15,000 (5.0% vs 27.2%), and need for invasive or non-invasive mechanical ventilation (2.1% vs 15.7%). CONCLUSION: We developed a scale in adults hospitalized with influenza-associated LRTI demonstrating a broad distribution of physiologic severity which may be useful for future studies evaluating the disease attenuating effects of influenza vaccination or other therapeutics.

Biologically Inspired Total Synthesis of Ulbactin F, an Iron-Binding Natural Product.

Natural products from environmental microbiomes provide exquisite templates for elucidating biological activity in the search for new drugs. A recently discovered marine Brevibacillus sp. metabolite, ulbactin F, was found to inhibit tumor cell migration and invasion at IC50 < 3 µM. Herein, we disclose the first total synthesis of ulbactin F and epi-ulbactin F, which was modeled after the biosynthetic pathway. The scaffold bears structural similarity to siderophores of human pathogens but contains a novel tricyclic ring system derived from cysteine. We have found that ulbactin F forms low-affinity metal complexes, with a preference for Fe3+ and Cu2+, which may hint both at its environmental role and its antimetastatic mechanism of action.