Journal of Cardiac SurgeryEditorial

Neuromuscular respiratory medicine has traditionally focused on mechanically assisted lung ventilation and mucus clearance. These therapies have prolonged survival for patients with Duchenne muscular dystrophy (DMD). However, the field is rapidly evolving in a new direction: it is being revolutionized by molecular and genetic therapies. A good correlation between a patient’s dystrophin mutation and his cardiopulmonary phenotype would allow accurate prediction of patient prognosis and would facilitate the design of studies that assess new DMD therapies. Instead, patient prognosis and the design of valid therapeutic studies are complicated by cardiopulmonary phenotypic discordance and variability, by which a notable proportion of DMD patients have unexpectedly good or poor cardiopulmonary function. The likely cause of phenotypic variability and discordance is genetic modifiers. Once the modifiers that affect cardiopulmonary function are better understood, it should be possible to create a personalized genetic profile that accurately predicts the prognosis of each individual DMD patient. This would allow investigators to assess the effect of new therapies in the context of each patient’s particular cardiopulmonary natural history. Amplification of beneficial cardiopulmonary genetic modifiers and blocking of detrimental modifiers is a promising strategy for creating new DMD therapies. When patients with chronic respiratory failure are treated with assisted ventilation, cardiac function determines their survival. Therefore, prioritizing new cardiac therapies is most likely to prolong patient survival. By focusing on these topics we aim to move neuromuscular respiratory medicine beyond assisted ventilation and coughing and into the age of translational medicine.

Introduction Oral sotalol initiation requires a multiple-day, inpatient admission to monitor for QT prolongation during loading. A one-day intravenous (IV) sotalol loading protocol was approved by the FDA in March 2020, but limited data on clinical use and administration currently exists. This study describes implementation of an IV sotalol protocol within an integrated health system, provides initial efficacy and safety outcomes, and examines length of stay compared to oral sotalol initiation. Methods IV sotalol was administered according to a pre-specified initiation protocol to adult patients with refractory atrial or ventricular arrhythmias. Baseline characteristics, safety and feasibility outcomes, and length of stay (LOS) were compared to patients receiving oral sotalol over a similar time period. Results From January 2021 to June 2022, a total of 29 patients (average age 66.0 ± 8.6 years, 27.6% women) underwent IV sotalol load and 20 patients (average age 60.4 ± 13.9 years, 65.0% women) underwent PO sotalol load. The load was successfully completed in 22/29 (75.9%) patients receiving IV sotalol and 20/20 (100%) of patients receiving oral sotalol, although 7/20 of the oral sotalol patients (35.0%) required dose reduction. Adverse events interrupting IV sotalol infusion included bradycardia (7 patients, 24.1%) and QT prolongation (3 patients, 10.3%). No patients receiving IV or oral sotalol developed sustained ventricular arrhythmias prior to discharge. LOS for patients completing IV load was 2.6 days shorter (mean 1.0 vs 3.6, p < 0.001) compared to LOS with oral load. Conclusion Intravenous sotalol loading has a safety profile that is similar to oral sotalol. It significantly shortens hospital LOS, potentially leading to large cost savings.

Submerged macrophytes play a key role in maintaining a clear-water phase and promoting biodiversity in shallow aquatic ecosystems. Since their abundance has declined globally due to anthropogenic activities, it is important to include them in aquatic ecosystem restoration programs. That macrophytes establish in early spring is crucial for maintaining the macrophyte communities for the remainder of the year. However, factors affecting this early establishment of submerged macrophytes have not been fully explored yet. Here, we conducted an outdoor experiment from winter to early spring using the submerged macrophytes Potamogeton crispus and Vallisneria spinulosa to study the effects of shading, nutrient loading, snail herbivory (Radix swinhoei) and their interactions on the early growth and stoichiometric characteristics of macrophytes. The results show that the effects strongly depend on macrophyte species. Biomass and number of shoots of P. crispus decreased, and internode length increased during low light conditions, but were not affected by nutrient loading. P. crispus shoot biomass and number showed hump-shaped responses to increased snail biomass under full light. In contrast, the biomass of the plant linearly decreased with snail biomass under low light. This indicates an interaction of light with snail herbivory. Since snails prefer grazing on periphyton over macrophytes, a low density of snails promoted growth of P. crispus by removing periphyton competition, while herbivory on the macrophyte increased during a high density of snails. The growth of V. spinulosa was not affected by any of the factors, probably because of growth limitation by low temperature. Our study demonstrates that the interaction of light with snail herbivory may affect establishment and growth of submerged macrophytes in early spring. Macrophyte restoration projects may thus benefit from lowering water levels to increase light availability and making smart use of cold-adapted herbivores to reduce light competition with periphyton.

We examined whether the presence or absence of different environmental stressors influenced the reproductive potential of a saltmarsh species - Plantago maritima. We focused on total seed output, seed quality and biomass of progeny. So far, there are no studies trying to answer the question of how different saltmarsh management affects the quality of seed in saltmarsh species. For the purposes of the study, plots subjected to light mowing, light or heavy grazing, trampling or rooting were designated in three nature reserves in Poland. On each plot, the abundance of infructescences per sq. metre was calculated. Mature infructascences were collected and their length and no of fruit capsules were measured. The seeds obtained from fruit capsules were weighted and sown in controlled conditions. The germination rate and the final germination percentage were calculated. A representative number of sprouts were grown. After a period of two months, the specimens were harvested and their total dry mass was measured. It was found that heavy grazing had the greatest effect on all of the studied characteristics. The presence of this factor resulted in shorter infructescences with a smaller number of fruit capsules. However, this phenomenon was compensated by the higher abundance of infructescences per sq. metre. At the same time seeds produced by grazed specimens were significantly lighter. Intensive trampling by people affected specimens in a similar way to heavy grazing, while mowing and rooting had less impact on the considered characteristics. Although a positive correlation between seed mass and germination success was found, the altogether lower seed mass had a negligible effect on germination parameters. Also, the differences in seed parameters did not affect dry mass of obtained progeny grown in lab conditions.

Background: Influenza-associated pulmonary aspergillosis (IAPA) is an important complication of severe influenza with high morbidity and mortality. Methods: We conducted a retrospective multicenter study in tertiary hospitals in Switzerland during 2017/18 and 2019/20 influenza seasons. All adults with PCR-confirmed influenza infection and treatment on intensive-care unit (ICU) for >24h were included. IAPA was diagnosed according to previously published clinical, radiological and microbiological criteria. We assessed risk factors for IAPA and predictors for poor outcome which was a composite of in-hospital mortality, ICU length of stay ≥7d, mechanical ventilation ≥7d or extracorporeal membrane oxygenation. Results: 158 patients (median age 64 years, 45% females) with influenza were included, of which 17 (10.8%) had IAPA. Asthma was more common in IAPA patients (17% vs. 4% in non-IAPA, p=0.05). Asthma (OR 12.0 (95% CI 2.1-67.2)) and days of mechanical ventilation (OR 1.1 (1.1 – 1.2)) were associated with IAPA. IAPA patients frequently required organ supportive therapies including mechanical ventilation (88% in IAPA vs. 53% in non-IAPA, p=0.001) and vasoactive support (75% vs. 45%, p=0.03) and had more complications including ARDS (53% vs. 26%, p=0.04), respiratory bacterial infections (65% vs. 37%, p=0.04) and higher ICU-mortality (35% vs. 16.4%, p=0.05). IAPA (OR 28.8 (3.3–253.4)), influenza A (OR 3.3 (1.4-7.8)) and higher SAPS II score (OR 1.07 (1.05—1.10)) were independent predictors of poor outcome. Interpretation: High clinical suspicion, early diagnostics and therapy are indicated in IAPA because of high morbidity and mortality. Asthma is likely an underappreciated risk factor for IAPA.

Background: Bicuspid aortic valve is the most common congenital heart defect and predisposes patients to developing aortic stenosis more frequently and at a younger age than the general population. However, the influence of bicuspid aortic valve on the rate of progression of aortic stenosis remains unclear. Methods: In 236 patients (177 tricuspid aortic valve, 59 bicuspid aortic valve) matched by initial severity of mild or moderate aortic stenosis, we retrospectively analyzed baseline echocardiogram at diagnosis with latest available follow-up echocardiogram. Baseline comorbidities, annualized progression rate of hemodynamic parameters, and hazard of aortic valve replacement were compared between valve phenotypes. Results: Median echocardiographic follow-up was 2.6 (IQR 1.6-4.2) years. Patients with tricuspid aortic stenosis were significantly older with more frequent comorbid hypertension and congestive heart failure. Median annualized progression rate of mean gradient was 2.3 (IQR 0.6-5.0) mmHg/year vs. 1.5 (IQR 0.5-4.1) mmHg/year (p=0.5), and that of peak velocity was 0.14 (IQR 0-0.31) m/s/year vs. 0.10 (IQR 0.04-0.26) m/s/year (p=0.7) for tricuspid vs. bicuspid aortic valve, respectively. On multivariate analyses, bicuspid aortic valve was not significantly associated with more rapid progression of aortic stenosis. In a stepwise Cox proportional hazards model adjusted for baseline mean gradient, bicuspid aortic valve was associated with increased hazard of aortic valve replacement (HR: 1.7, 95% CI [1.0, 3.0], p=0.049). Conclusion: Bicuspid aortic valve may not significantly predispose patients to more rapid progression of mild or moderate aortic stenosis. Guidelines for echocardiographic surveillance of aortic stenosis need not be influenced by valve phenotype.

In this study, hesperetin was shown to inhibit the replication of multiple poxviruses, including buffalopox virus (BPXV), vaccinia virus, and lumpy skin disease virus (LSDV). Hesperetin mainly suppressed viral protein synthesis without affecting other steps of the viral life cycle such as attachment, entry, and budding. In a chromatin immunoprecipitation (CHIP) assay, we further demonstrated that hesperetin-induced reduction in BPXV protein synthesis is due to disruption of the binding of the 5’ cap of viral mRNA with the cellular translation initiation factor eIF4E. The molecular docking and MD simulation studies, also confirmed binding of the hesperetin with the cap-binding pocket of eIF4E, in a similar conformation as m7GTP binds. In a BPXV egg infection model, hesperetin was shown to suppress the development of pock lesions on the chorioallantoic membrane, as well as the associated mortality of the chicken embryos. Most importantly, long-term culture of BPXV in the presence of hesperetin did not induce the generation of drug-resistant viral mutants. In conclusion, we for the first time demonstrated the antiviral activity of hesperetin against poxviruses, besides providing novel mechanistic insights into the antiviral action of hesperetin.

Background: The introduction of primary HPV cervical cancer screening requires the implementation of an appropriate triage strategy that will be effective in detecting high-grade cervical disease without losing diagnostic specificity. Methods: From the 30.066 screening tests results, a total of 1086 with available high-risk human papillomavirus (HRHPV) with limited genotyping, cytology and p16/Ki67 dual-stain were selected. Two triage strategies for primary HPV screening were analyzed retrospectively based on the study group. Performance characteristics for p16/Ki67 and cytology triage in detection of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and grade 3 or worse (CIN3+) were calculated, detected in colposcopic biopsy. Results: In HPV16/18-positive cases, primary HPV with p16/Ki67 triage was significantly more specific than cytology (53.1%/16.8% for CIN2+; p<0.0001; 45.9%/17.0% for CIN3+; p<0.0001), with yielded sensitivity (95.7%/84.8% for CIN2+; p=0.0955; 100.0%/87.5% for CIN3+; p=0.0832). In other HRHPV-positive cases (N16/N18), p16/Ki67 triage was also significantly higher specific (51.3%/15.3% for CIN2+; p<0.0001; 44.5%/16.5% for CIN3+; p<0.0001), with sensitivity (92.3%/74.4% for CIN2+; p=0.0522; 90.9%/81.8% for CIN3+; p=0.5637). Diagnostic predictive values were significantly higher for p16/Ki67 triage with the highest PPV in HPV16/18-positive cases for CIN2+ (45.4%; 95% CI: 35.2-55.8; p<0.0001) and very high NPV in all HPV-positive cases regardless of detected genotype (96.3%-100.0%). The risk (1-NPV) for CIN3+ in HRHPV16/18-positive/p16/Ki67-negative women was 0.0%. Conclusions: Superior diagnostic performance compared to cytology for detecting cervical cancer precursors indicates that p16/Ki67 dual-immunostain may be a highly effective tool of triage in primary HPV screening with limited HPV 16/18 genotyping in the secondary cervical cancer prevention.

To account for the effect of liquid viscosity, the bubble breakup model considering turbulent eddy collision based on the inertial subrange turbulent spectrum was extended to the entire turbulent spectrum that included the energy-containing, inertial, and energy-dissipation subranges. The computational fluid dynamics-population balance model (CFD-PBM) coupled model was modified to include this extended bubble breakup model for simulations of a bubble column. The effect of turbulent energy spectrum on the bubble breakup and hydrodynamic behaviors was studied in a bubble column under different liquid viscosities. The results showed that when the liquid viscosity was < 80 mPas, the bubble breakup and hydrodynamics were almost independent on the turbulent spectrum. At liquid viscosity > 80 mPas, the bubble breakup rate and gas holdup were significantly under-predicted when the inertial turbulent spectrum was used, and when using the entire turbulent spectrum the predictions were more consistent with experimental data.

BJOG mini commentary on study BJOG-21-1829TITLE: Putting patients at the centre of pain managementAlexandra Wojtaszewskaa, Arvind Vashishtb, Martin Hirschc,daWatford General Hospital, Watford, United KingdombInstitute for Women’s Health, University College London, London, United Kingdom.cThe John Radcliffe Hospital, Oxford University Hospitals, Oxford, United Kingdom.dOxford Endometriosis CaRe Centre, Nuffield Department of Women’s & Reproductive Health, University of Oxford, Oxford, United Kingdom.Conflict of interest : noneFinancial support received : none

Bicuspid aortic valve is the most common congenital cause for the development of aortic valve calcification and stenosis. Calcification cause valvular stenosis or valvular insufficiency due to coaptation failure. We report a unique case of calcification of bicuspid valve was extending to left ventricular outflow tract and attached to interventricular septum which caused subvalvular stenosis.

Papillary fibroelastomes are rare benign neoformations usually originating from the valvular endocardium, presenting with cerebral ischemia and/or myocardial infarction due to embolization from the mass. We report an exceedingly rare case of aortic wall papillary fibroelastoma simulating unstable angina, diagnosed with trans-thoracic/trans-esophageal echocardiography and CT scan and surgically successfully removed

Monoclonal gammopathy of undetermined significance (MGUS) may be associated with pathologies with severe neuromuscular manifestations such as sporadic late-onset nemaline myopathy (SLONM). We describe a difficult to diagnose case of SLNOM with marked clinical improvement after achieving gammopathy complete hematologic response.

This article is concerned with an initial-boundary value problem (IBVP) for a new phase-field model describing the evolution of structural phase transition in elastically deformable solid materials. The model consists of an elliptic-parabolic system in which the displacement field and the order parameter both satisfy periodic boundary conditions. We prove the existence of global solutions to this IBVP by applying the method of continuation of local solutions and perform numerical simulations to investigate the microstructure evolution of MnNi alloys by using this new phase-field model.

ETI treatment reduces inflammatory markers and positive bacterial cultures on BAL in PwCF. These findings suggest that ETI has a greater impact on chronic infection and inflammation than ivacaftor alone. However, airway inflammation persists in a fraction of treated individuals, indicating an ongoing need to optimize other treatments in a subset of patients.

Objective: Re-exploration after cardiac surgery still remained a troublesome complication. There is still scarcity of data about the effect of re-exploration after off-pump coronary arterial bypass grafting (OPCABG). We here represent our experience of re-exploration following OPCABG. Method: Total 5990 OPCABG were performed at our center, out-off these 132 (2.2%) patients were re-explored in the OR and were included in this study. The medical records of these patients were retrospectively reviewed. Results: The most common cause of re-exploration was bleeding (83.3%) and most common site of bleeding was from graft/anastomosis (53.8%). Mean time to re-exploration was 9.75±8.65 hours. 30-day mortality was 1.41%.On univariate and multiple regression analysis, emergency surgery, preoperative low platelet count, and number of grafts were found to be an independent risk factor for re-exploration. On multiple regression, emergency surgery, euroscoreII, low platelet count, low ejection fraction, re-exploration, time to re-exploration, blood products used, high post-op serum creatinine and bilirubin, were found to be an independent factor (p<0.001) for mortality. On receiver-operating characteristic analysis, optimum cut off for time to re-exploration was 14 hours with sensitivity 81.3%, specificity of 80% and area under curve of 0.798. Patients who re-explored late (>14 hour) had significantly high mortality (30.55%vs7.3%) and morbidity. Conclusion: Delaying the re-exploration is associated with three-fold increase in mortality and morbidity. So strategy of minimizing the incidence of re-exploration like use of minimally invasive surgery and early re-exploration with judicial use of products should be use to improve outcome after re-exploration following off-pump CABG.

This paper is devoted to the study of a nonlinear pseudoparabolic equation in an annular with Robin-Dirichlet conditions. At first, by applying the standard Faedo-Galerkin method, we prove existence and uniqueness results. Next, using concavity method, we prove blow-up results for solutions when the initial energy is nonnegative or negative, then we also establish the lifespan for the equation via finding the upper bound and the lower bound for the blow-up times. Finally, we give a sufficient condition for the global existence and decay of weak solutions.