Progression of Aortic Regurgitation After Different Repair Techniques for Congenital Aortic Valve Stenosis

We sought to characterize the incidence of AR progression and determine risk factors for AR progression in a consecutive series of infants and children after surgical correction of congenital aortic valvular and supravalvular stenosis. N = 30 patients underwent repair of the aortic valve for isolated congenital aortic valve stenosis (n = 14, 47 %) or combined with aortic regurgitation (AR, n = 16, 53 %). N = 27 (90 %) had a valvular and n = 3 patients (10 %) presented with supravalvular pathology of their aortic valve. In n = 16 patients (53 %) a bicuspid and in n = 2 (6 %) patients, a unicuspid valve was present. Comparative survival was analyzed using the Cox model and log-rank calculations. Log-rank calculations were performed for variables reaching statistical significance in order to identify differences in survival between groups. Commissurotomy was performed in n = 20 patients, patch implantation in n = 4, cusp shaving in n = 8, cusp prolapse correction in n = 3, and cusp augmentation in n = 4 patients. In patients with combined dysfunction and preoperative AR, AR was successfully reduced by the initial procedure, and postoperatively the overall median AR grade was 1+ (range 0–2.5+, p = 0.001, for AR reduction among patients with any grade of preoperative AR). By the time of follow-up echocardiography, the median AR grade had significantly progressed toward 1.5+ (p = 0.004). At the time of mid-term follow-up at 3.2 years, none of the patients had moderate or severe AR grades >2.5+. Patients with a monocuspid aortic valve and patients who had some kind of patch implantation into their cusps or commissures or shaving of thickened cusps were more likely to present with progression of aortic regurgitation. Monocuspid aortic valve and patch implantation, as well as cusp shaving, are probably linked to AR progression. The standard procedure of commissurotomy results in an absolute rate of AR progression of 40 % over a medium-term follow-up period.     

Expanding the donor pool: regional variation in pediatric organ donation rates

There are limited published data on pediatric organ donation rates. The aim of this study was to describe the trends in pediatric organ donation over time and to assess the regional variation in pediatric deceased organ donation. OPTN data were utilized to assess the trends in pediatric organ donation over time. The number of deceased pediatric organ donors was indexed using regional mortality data obtained from the National Center for Health Statistics and compared across UNOS regions and two different eras. The number of pediatric deceased organ donors has declined in the recent era, largely driven by fewer adolescent donors. For all age groups, there is significant regional variation in organ donation rates, with identifiable high‐ and low‐performing regions. Expansion of the donor pool may be possible by optimizing organ donation in regions demonstrating lower recruitment of pediatric donors. Using the region with the highest donation rate for each age group as the gold standard, we estimate a potential 24% increase in the number of donors if all regions performed comparably, equating to 215 new pediatric donors annually.     

An outbreak of Q fever associated with parturient cat exposure at an animal refuge and veterinary clinic in southeast Queensland

Objective: To determine the source of a Q fever outbreak in humans at an animal refuge and veterinary clinic in southeast Queensland from October to December 2016. Methods: Case interviews and a retrospective cohort study of animal refuge and veterinary clinic staff using a self‐administered questionnaire related to clinical history of Q fever, Q fever vaccination status and workplace activities during the exposure period. Results: Seven cases (six confirmed, one probable) were identified. Forty‐three questionnaires were completed (92% response rate). Workplace activities associated with the greatest risk of illness were the disposal of deceased cats or dogs (RR, 14.0; 95%CI, 1.9–104.1) and participating in euthanasia of cats or dogs (RR, 4.6; 95%CI, 1.3–16.9). Five feline birthing events occurred at the animal refuge from 25 September to 19 October 2016, each with subsequent euthanasia of the queen cat and litter. All cases had likely exposure to a specific queen cat and her litter that were euthanised the same day as the birthing event. Conclusions: A parturient cat was the most likely source of the outbreak. Implications for public health: Occupational groups and others with regular exposure to feline or canine parturient products should receive Q fever vaccine.     

Effect of voxelotor on cardiopulmonary testing in youths with sickle cell anemia in a pilot study

Background

Individuals with sickle cell anemia (SCA) exhibit decreased exercise capacity. Anemia limits oxygen-carrying capacity and affects cardiopulmonary fitness. The drug voxelotor raises hemoglobin in SCA. We hypothesized that voxelotor improves exercise capacity in youths with SCA.

Methods

In a single-center, open-label, single-arm, longitudinal interventional pilot study (NCT04581356), SCA patients aged 12 and older, stably maintained on hydroxyurea, were treated with 1500 mg voxelotor daily, and performed cardiopulmonary exercise testing before (CPET#1) and after voxelotor (CPET#2). A modified Bruce Protocol was performed on a motorized treadmill, and breath-by-breath gas exchange data were collected. Peak oxygen consumption (peak VO₂), anaerobic threshold, O₂ pulse, VE/VCO₂ slope, and time exercised were compared for each participant. The primary endpoint was change in peak VO₂. Hematologic parameters were measured before each CPET. Patient Global Impression of Change (PGIC) and Clinician Global Impression of Change (CGIC) surveys were collected.

Results

Ten hemoglobin SS patients aged 12–24 completed the study. All demonstrated expected hemoglobin rise, with average +1.6 g/dL (p = .003) and P₅₀ left shift of average −11 mmHg (p < .0001) with decreased oxygen off-loading at low pO₂. The change in % predicted peak VO₂ from CPET#1 to CPET#2 ranged from −12.8% to +11.3%, with significant improvement of more than 5% in one subject, more than 5% decrease in five subjects, and insignificant change of less than 5% in four subjects. All 10 CGIC and seven of 10 PGIC responses were positive.

Conclusion

In a plot study of 10 youths with SCA, voxelotor treatment did not improve peak VO₂ in 9 out of 10 patients.     

Outcome of Patients with Esophageal Perforations: A Multicenter Study

Background

Recent studies have suggested that stent-grafting may improve the treatment outcome of patients with esophageal perforation, but evidence on this is still lacking.

Methods

Data on 194 patients who underwent conservative (43 patients), endoclip (4 patients) stent-grafting (63 patients) or surgical treatment (84 patients) for esophageal perforation were retrieved from nine medical centers.

Results

In-hospital/30-day mortality was 17.5 %. Three-year survival was 67.1 %. Age, coronary artery disease, and esophageal malignancy were independent predictors of early mortality. Chi squared automatic interaction detection analysis showed that patients without coronary artery disease, without esophageal malignancy and younger than 70 years had the lowest early mortality (4.1 %). Surgery was associated with slightly lower early mortality (conservative 23.3, endoclips 25.0 %, stent-grafting 19.0 %, surgery 13.1 %; p = 0.499). One center reported a series of more than 20 patients treated with stent-grafting which achieved an early mortality of 7.7 % (2/26 patients). Stent-grafting was associated with better survival with salvaged esophagus (conservative 76.7 %, endoclips 75.0 %, stent-grafting 77.8 %, surgery 56.0 %; p = 0.019). Propensity score adjusted analysis showed that stent-grafting achieved similar early mortality (p = 0.946), but significantly higher survival with salvaged esophagus than with surgical treatment (p = 0.001, OR 0.253, 95 % CI 0.110–0.585). Primary surgical repair was associated with somewhat lower early mortality (14.6 vs. 19.0 %; p = 0.561) and better survival with salvaged esophagus (85.4 vs. 77.8 %; p = 0.337) than stent-grafting.

Conclusions

Esophageal perforation was associated with a rather high mortality rate in this all-comers population. Stent-grafting failed to decrease operative mortality, but it improved survival with salvaged esophagus. The results of one of the centers indicate that increasing experience with this less invasive procedure may possibly improve the outcome of these patients.     

A systematic review of surfactant delivery via laryngeal mask airway,pharyngeal instillation,and aerosolization: Methods,limitations, and outcomes

Less invasive surfactant administration methods without laryngoscopy and endotracheal catheterization include delivery via laryngeal mask airway, pharyngeal instillation, and aerosolization. These less invasive techniques are promising and have several advantages over INSURE (Intubation-Surfactant-Extubation) and thin catheter techniques. The objective of this review is to discuss the requisites, techniques, short-term outcomes, and adverse events associated with these methods.     

Targeted deletion of histidine decarboxylase gene in mice increases bone formation and protects against ovariectomy-induced bone loss

Targeted disruption of the histidine decarboxylase gene (HDC(-/-)), the only histamine-synthesizing enzyme, led to a histamine-deficient mice characterized by undetectable tissue histamine levels, impaired gastric acid secretion, impaired passive cutaneous anaphylaxis, and decreased mast cell degranulation. We used this model to study the role of histamine in bone physiology. Compared with WT mice, HDC(-/-) mice receiving a histamine-free diet had increased bone mineral density, increased cortical bone thickness, higher rate of bone formation, and a marked decrease in osteoclasts. After ovariectomy, cortical and trabecular bone loss was reduced by 50% in HDC(-/-) mice compared with WT. Histamine deficiency protected the skeleton from osteoporosis directly, by inhibiting osteoclastogenesis, and indirectly, by increasing calcitriol synthesis. Quantitative RT-PCR showed elevated 25-hydroxyvitamin D-1alpha-hydroxylase and markedly decreased 25-hydroxyvitamin D-24-hydroxylase mRNA levels. Serum parameters confirming this indirect effect included elevated calcitriol, phosphorus, alkaline phosphatase, and receptor activator of NF-kappaB ligand concentrations, and suppressed parathyroid hormone concentrations in HDC(-/-) mice compared with WT mice. After ovariectomy, histamine-deficient mice were protected from bone loss by the combination of increased bone formation and reduced bone resorption.