Structural Stability of Force-Regulated FLNa-Ig21/αⅡbβ3-CT Complexes by Molecular Dynamics Simulation / 医用生物力学

Objective To investigate the effects of force on mechanical stability of FLNa-Ig21/αⅡbβ3-CT complex and the regulation mechanism.Methods The FLNa-Ig21/αⅡbβ3-CT crystal structures were taken from the PDB database.The stability of the complexes in a physiological environment as well as the unfolding path and mechanical stability induced by mechanical forces were analyzed using equilibrium and steered molecular dynamics simulations.Results During the equilibration,the survival rate of most salt bridge and hydrogen bonds was below 0.5,and the interactions between FLNa-Ig21 and αⅡbβ3-CT was relatively weak.During stretching at a constant velocity,the complex could withstand a tensile force of 70-380 pN,and its mechanical strength depended on the force-induced dissociation path.Under a constant force of 0-60 pN,the complexes exhibited a slipping-bond trend,and the force increase facilitated the breakage of the R995-D723 salt bridge and the activation of αⅡbβ3 integrin.Conclusions The force-induced allostery of αⅡbβ3-MP enhanced the complex mechanical strength and delayed FLNa-Ig21 dissociation from αⅡbβ3-CT.After breaking through the 20 pN threshold,force positively regulated the activation of αⅡbβ3 integrin.These results provide insights into the molecular mechanism of αⅡbβ3 activation and the development of related targeted drugs.

Development of a mobile personnel radiation protection equipment / 中国辐射卫生

Objective To design a mobile personnel radiation protection equipment for operation in environments with high radiation such as spent fuel reprocessing plants, to achieve simultaneous protection against γ radiation, neutron radiation, and radioactive aerosol, to reduce the internal and external exposure dose of radioactive workers, and to meet the requirement of operation for two hours. Methods The core parts of the mobile personnel radiation protection equipment included a shielding chamber and a respiratory maintenance system. An automated chassis was used for the movement and lifting of the shielding chamber. MCNP software was used to simulate and calculate the protective effects of shielding chamber made of different materials and material thicknesses. Experimental verification of the shielding chamber design was conducted. Mathematical models were established to describe the variations in the content of various gases in the chamber with personnel operation time. A respiratory maintenance system, a harmful gas absorption device, and an automated mobile chassis were designed. Results The shielding chamber made of polyethylene with a thickness of 80 mm achieved an 80% neutron shielding rate. The respiratory maintenance system could support workers for 2 hours of operation inside the equipment. The mobile chassis allowed operation of the equipment with one person. Conclusion This mobile personnel radiation protection equipment can solve the problem in simultaneous protection against γ radiation, neutron radiation, and radioactive aerosol. The equipment can provide radiation protection for radioactive workers, reduce exposure dose, and reduce personnel burden. This system provides technical means for the operation and maintenance of equipment in high-radiation sites such as spent fuel reprocessing plants.

Prospective Clinical Study of Combined Treatment of Periodontal Orthodontics for Chronic Periodontitis / 昆明医科大学学报

Objective To investigate the effect of dynamic monitoring of occlusal force on the final therapeutic effect and the change of periodontal supporting tissue during combined periodontal orthodontic treatment.Methods The periodontal clinical index of 20 patients with traditional periodontal orthodontic treatment and 20 patients with combined periodontal orthodontic treatment assisted by T-Scan Ⅲ and Anycheck digital occlusion analysis system were compared before,during and after treatment,as well as the changes of bite force,bite time and tooth mobility in the experimental group.Results The depth of periodontal pocket(PD),loss of attachment(AL),bleeding index(BI)and tooth looseness were significantly reduced after combined periodontal orthodontic treatment in both groups.In the control group,the percentage of anterior and posterior biting force changed obviously,and the occlusion force balance was improved.Conclusion The combined treatment of periodontitis and orthodontics can improve the periodontal tissue of patients with periodontitis,and T-Scan system can observe and guide the adjustment of occlusal and better achieve occlusion force balance.

Influence of storage temperature and storage time on the optically stimulated luminescence characteristics of chip resistors in dose reconstruction for nuclear accident / 中国辐射卫生

Objective To assess the feasibility of employing chip resistors for retrospective dose reconstruction following nuclear accidents, to examine the effects of storage temperature and storage time on the optically stimulated luminescence (OSL) characteristics of the chip resistors, and to explore measures to mitigate these effects. Methods Chip resistors were analyzed using automated instruments for measuring thermoluminescence and OSL manufactured by Risø in Denmark with various parameters to understand the impact of storage temperature and storage time on OSL signals. Results The OSL signals of chip resistors exhibited exponential attenuation within 10 min after irradiation, and then stabilized (count change < 10%) within 2-7 days of storage. The chip resistors exhibited linear dose responses within 1-3 days of storage after 0.1-2 Gy irradiation. OSL signals diminished as the storage temperature increased. However, preheating at 130 ℃ for 1 min effectively eliminated the differences caused by temperatures between 25 ℃ and 45 ℃. Conclusion The OSL signals of chip resistors are influenced by storage temperature and storage time. When preheated at 130 ℃ for 1 min, chip resistors stored for 1-7 days and at 25-45 ℃ exhibited OSL signal errors of 10% or less. This result emphasizes the importance of preheating for measurements in practical applications, thus providing a scientific approach and a solid foundation for the use of chip resistors in retrospective dose reconstruction.

Development of a simplified phantom for calibration of whole-body counter / 中国辐射卫生

Objective To develop a simplified phantom for the calibration of whole-body counters. Methods A simplified phantom design method for the calibration of whole-body counters was established based on the process and method of calibrating whole-body counters. By using the established method and Monte Carlo method, a simplified phantom including the total body, thyroid, lungs, and gastrointestinal tract was designed to calibrate the ORTEC-Stand FAST II whole-body counter. The simplified phantom was compared with the BOMAB phantom through experimental measurements. Results Within the range of 50 keV to 2 MeV, for rays of the same energy in the same organ of the simplified phantom and BOMAB phantom, the simulated data of detection efficiency by whole-body counting showed an error within 5%, and the experimental measurements showed an error within 10%. Conclusion We developed a simplified phantom for the calibration of the whole-body counter, demonstrating the feasibility of using the simplified phantom instead of a physical body phantom for whole-body counter calibration, which can greatly facilitate whole-body counter calibration for internal radiation monitoring.

CD44-HA Mediate Adhesion of MDA-MB-231 Cells and HL60 Cells under Fluid Shear Flow / 医用生物力学

Objective To explore how hyaluronic acid ( HA) in extracellular matrix regulates the adhesion ofCD44+tumor cells. Methods MDA-MB-231 cells or HL60 cells were perfused in a parallel plate chamber. Themovement of cells over immobilized HA was observed and analyzed to obtain the characteristics of cell adhesionand rolling. Results The adhesion number of MDA-MB-231 cells on HA substrate was positively regulated by HAconcentration, but not by HA molecular weight. Compared with physically adsorbed HA, immobilized HA byavidin-biotin could significantly improve the cell adhesion ratio. With the increase of shear stress in the range of30-50 mPa, the rolling velocity of cells increased and the adhesion ratio decreased, but the tether lifetime of cellswas not affected. In the same flow field, compared with MDA-MB-231 cells, HL60 cells with low expression ofCD44 rolled more quickly on immobilized HA, with shorter tether lifetime and much lower adhesion ratio(<1. 5% ). Conclusions Fluid shear stress might mediate the rolling velocity of MDA-MB-231 cells by regulatingthe CD44-HA association rate rather than their dissociation rate. The interaction between CD44 and HA is involved in the initial adhesion of HL60 cells, but it does not play a major role. This study will provide references for the design of anti-tumor drugs.

The role of a simple Nomogram model in evaluating the severity of mycoplasma pneumonia pneumonia in adults / 中国基层医药

Objective:To investigate the role of a simple Nomogram model in evaluating the severity of mycoplasma pneumoniae pneumonia (MPP) in adults.Methods:The clinical data of 162 patients with MPP who received treatment in Wenzhou Central Hospital from March 2015 to October 2022 were retrospectively analyzed. These patients were divided into a severe group ( n = 67) and a common group ( n = 95) according to whether they were diagnosed with severe MPP. The clinical data of patients were recorded. Fourteen clinical variables were screened, including age, sex, onset season, fever, heat peak, fever duration, cough duration, white blood cell count, percentage of neutrophils, percentage of lymphocytes, hemoglobin, platelet count, C-reactive protein, and procalcitonin. Multivariate logistic regression analysis of statistically significant variables in univariate analysis was performed. The Nomogram model was constructed with the R language software package (version 3.6.2). The model was verified with a calibration curve and receiver operating characteristic curve. Results:Univariate analysis results showed that in the severe group, the fever peak ( Z = 5.03, P < 0.001) was higher, fever duration ( χ2 = 27.55, P < 0.001), and cough duration ( χ2 = 28.72, P < 0.001) were longer, white cell count ( t = 2.93, P = 0.004), percentage of neutrophils ( t = 9.08, P < 0.001), C-reactive protein ( t = 35.05, P < 0.001), and procalcitonin level ( t = 15.09, P < 0.001) were greater compared with the common group. The percentage of lymphocytes ( t = 1.16, P < 0.001), hemoglobin level ( t = 1.22, P < 0.001), and platelet count ( t = 2.82, P < 0.001) in the severe group were significantly lower than those in the common group. Multivariate logistic regression analysis results showed that heat peak, cough duration, and C-reactive protein were positively correlated with the severity of MPP (all P < 0.05). The percentage of lymphocytes, hemoglobin concentration, and platelet count were negatively correlated with the severity of MPP (all P < 0.05). The establishment and validation results of the Nomogram model showed that the accuracy of the model was good, with a sensitivity of 88.73%, a specificity of 77.61%, and a C-index of 0.904. Conclusion:Heat peak, cough duration, percentage of lymphocytes, platelet count, and C-reactive protein are closely related to the severity of early MPP. A simple Nomogram model can be one of the tools for early assessment of the severity of MPP.

Molecular dynamics simulation of force-regulated interaction between talin and Rap1b / 生物医学工程学杂志

The binding of talin-F0 domain to ras-related protein 1b (Rap1b) plays an important role in the formation of thrombosis. However, since talin is a force-sensitive protein, it remains unclear whether and how force regulates the talin-F0/Rap1b interaction. To explore the effect of force on the binding affinity and the dynamics mechanisms of talin-F0/Rap1b, molecular dynamics simulation was used to observe and compare the changes in functional and conformational information of the complex under different forces. Our results showed that when the complex was subjected to tensile forces, there were at least two dissociation pathways with significantly different mechanical strengths. The key event determining the mechanical strength difference between the two pathways was whether the β4 sheet of the F0 domain was pulled away from the original β1-β4 parallel structure. As the force increased, the talin-F0/Rap1b interaction first strengthened and then weakened, exhibiting the signature of a transition from catch bonds to slip bonds. The mechanical load of 20 pN increased the interaction index of two residue pairs, ASP 54-ARG 41 and GLN 18-THR 65, which resulted in a significant increase in the affinity of the complex. This study predicts the regulatory mechanism of the talin-F0/Rap1b interaction by forces in the intracellular environment and provides novel ideas for the treatment of related diseases and drug development.

Molecular dynamics simulation of force-regulated interaction between glycoprotein Ib α and filamin / 生物医学工程学杂志

In resting platelets, the 17 th domain of filamin a (FLNa17) constitutively binds to the platelet membrane glycoprotein Ibα (GPIbα) at its cytoplasmic tail (GPIbα-CT) and inhibits the downstream signal activation, while the binding of ligand and blood shear force can activate platelets. To imitate the pull force transmitted from the extracellular ligand of GPIbα and the lateral tension from platelet cytoskeleton deformation, two pulling modes were applied on the GPIbα-CT/FLNa17 complex, and the molecular dynamics simulation method was used to explore the mechanical regulation on the affinity and mechanical stability of the complex. In this study, at first, nine pairs of key hydrogen bonds on the interface between GPIbα-CT and FLNa17 were identified, which was the basis for maintaining the complex structural stability. Secondly, it was found that these hydrogen bonding networks would be broken down and lead to the dissociation of FLNa17 from GPIbα-CT only under the axial pull force; but, under the lateral tension, the secondary structures at both terminals of FLNa17 would unfold to protect the interface of the GPIbα-CT/FLNa17 complex from mechanical damage. In the range of 0~40 pN, the increase of pull force promoted outward-rotation of the nitrogen atom of the 563 rd phenylalanine (PHE 563-N) at GPIbα-CT and the dissociation of the complex. This study for the first time revealed that the extracellular ligand-transmitted axial force could more effectively relieve the inhibition of FLNa17 on the downstream signal of GPIbα than pure mechanical tension at the atomic level, and would be useful for further understanding the platelet intracellular force-regulated signal pathway.

Breast bracket combined with polyurethane foam improves the accuracy of immobilization in breast cancer radiotherapy / 中华放射肿瘤学杂志

Objective:To compare the difference between breast bracket combined with polyurethane foam and single polyurethane foam in the accuracy of immobilization, providing a better immobilization for breast cancer radiotherapy.Methods:Fifty breast cancer patients who received radiotherapy in Sun Yat-sen University Cancer Center from March 2021 to July 2021 were selected. Among them, 25 patients were immobilized with polyurethane foam (foam group), and the other 25 patients were immobilized with polyurethane foam combined with breast bracket (combination group). All patients were scanned by CBCT once a week to obtain setup errors in the SI, LR and AP directions for t-test. The formula M PTV=2.5 Σ+0.7 σ was used to calculate the margin of the planning target volume(M PTV). Results:The setup errors in the foam group were SI (2.0±3.26) mm, LR (0.88±2.76) mm, AP (1.22±3.55) mm, Rtn -0.24°±0.85°, Pitch 0.16°±1.11°, Roll -0.32°±1.05°, and the M PTV were 6.75 mm, 8.46 mm and 8.73 mm, respectively. The setup errors in the combination group were SI (1.0±3.01) mm, LR (0.62±2.74) mm, AP (1.82±3.21) mm, Rtn 0.64°±0.59°, Pitch 0.71°±1.22°, Roll 0.29°±0.73°, and the M PTV were 6.35 mm, 7.47 mm, and 7.61 mm, respectively. After comparing the setup errors in the three-dimensional directions between two groups, the t value of LR, SI, AP and Rtn, Pitch, Roll was -4.304, -2.681, 1.384, and -9.457, -3.683, -5.323, respectively. And the differences in the LR, SI, Rtn, Pitch and Roll directions were statistically significant (all P<0.05). Conclusions:The immobilization effect of polyurethane foam combined with breast bracket is better and the M PTV is also smaller than those of polyurethane foam alone. Therefore, it is recommended to use polyurethane foam combined with breast bracket for immobilization in breast cancer radiotherapy.

Circular RNA detection methods: A minireview.

Circular RNA (circRNA), a novel type of covalently closed RNA, is implicated in several developmental and metabolic disease processes. CircRNAs exhibit tissue-specific expression, and are stable, abundant, and highly conserved, making them ideal biomarkers for diagnosis and prognosis. Accurate profiling of circRNA, however, is a prerequisite for their clinical application. Traditional methods such as northern blotting, RT-qPCR, and microarray analysis provide useful but limited information. To address these issues, a number of novel assays have recently emerged, such as droplet digital PCR (ddPCR), isothermal exponential amplification, and rolling cycle amplification, which increase the sensitivity and specificity of circRNA detection. Herein, we summarize the advantages and limitations of the new detection methods and discuss the challenges as well as future directions.

Practice of improving scientific research capability of primary hospitals by means of a " three-full and two-tight" management mechanism / 中华医院管理杂志

Primary hospitals are engaged in such responsibilities as diagnosis and treatment of endemic diseases and common illnesses of the locality, as well as relevant research work which bears more prominent importance than ever before. Given the importance of research, the hospitals are mostly plagued by such setbacks as obsolete research management concepts, poor experiences, poor perception of research, poor professional competency and lack of academic exchange among the medical workers. A primary hospital had set up a novel management mechanism, featuring " full-staff involvement, full-process supervision and full-dimensional guidance" , and " tight formal examination and tight content examination" . This mechanism has been in place since 2016 in research project management practice, achieving such progresses as significant rise in the number of research project applications, that of approved projects, and project implementation capabilities.Future improvements in this regard should be made in higher pertinence, optimized management flow and better research service system.

Study on the bladder filling consistency of pelvic tumors prior to the radiotherapy / 中华放射肿瘤学杂志

Objective:Before the radiotherapy was performed, patients with pelvic tumors were analyzed for the consistency of bladder filling in the three steps of " Immobilization" , " CT Simulation" and " X-ray Simulation" .Methods:In 2014, 105 patients (68 cases of cervical cancer, 32 cases of rectal cancer, 3 cases of vaginal cancer and 2 cases of prostate cancer) with pelvic tumor radiotherapy were randomly assigned to monitor bladder urine volume to a target urine volume of 400 ml. First, patient were exhorted to empty the bladder, and the bladder volume meter BVI 9400 was used to measure the urine volume of the patient after emptying of the bladder. The patient immediately drank about 540 ml of water and suppressed urine, measurements were taken every 0.5 h. At the same time, when the patient complained of " urgency of urine" , bladder urine volume would be measured again and the time would also be recorded. Every other half an hour (emptying, 0.5 h after emptying, 1.0 h after emptying), when complaining of " urgency of urine" , when actually performing urine volume and time were described as: U 0 and t 0, U 0.5 and t 0.5, U 1.0 and t 1.0, U t and t, U T and T. Results:There was a statistically significant difference in gender and age, and women had stronger ability to urinate than men U 1.0( P=0.003), young people had stronger ability to urinate than middle-aged U 1.0( P=0.002). In the three-step comparison, there was no statistically difference between 1 hour after emptying urine volume U 1.0( P=0.177) and the actually performing urine volume U T ( P=0.052). And the final urine volume was concentrated at 298-526 ml. After the patient emptied the urine volume and complained of " urgency of urine" , the time slot was t=(75.2±49.9) min, with the urine volume of U t=(331.2±140.3) ml. And there was no statistically difference between U t and U T ( P=0.198) at X-ray Simulation. Conclusions:The patient emptied the bladder and immediately drank 540 ml of water. After 1 hour of suppressing urine, he complained of " urgency of urine" and achieved the target urine volume (400 ml). At this time, the bladder urine volume U 1.0 was consistency in the immobilization, CT Simulation, and X-ray Simulation.

Exploration and practice of using counterpart support resources to improve scientific research level of recipient hospitals / 中华医学科研管理杂志

Objective:Exploring the " bottle neck" factors in the scientific research management of recipient hospitals, making good use of counterpart support resources to help identifying appropriate, tailored strategies of scientific research management that might improve the research capacity of recipient hospitals.Methods:Data were collected according to questionnaire survey and on-site interview, ABC classification method were used to perform statistical analysis, and " bottleneck" factors that constraint the scientific research work of the recipient hospital were summarized.Results:" Insufficient scientific research skills and lacking of talents" and " lacking of scientific research environment and recognition" are the two most prominent factors that negatively affect the scientific research capacity building of the recipient hospitals, followed closely by " the out-dated scientific research policies and lacking support from the hospital leadership" , insufficient of research platform or resources including research funding, as well as other factors. Based on such findings, this article took the First People's Hospital of Kashgar (Guangdong counterpart support) as an example, and tried to discuss some corresponding measures on how to make good use of counterpart support resources.Conclusions:The ABC classification method were used to identify the main " bottleneck" factors, and a series of effective measures that help to making good use of counterpart support resources were explored. As a result, the efficiency of the scientific research management of the recipient hospitals, which in terms of management methods, management concepts and management models, were improved.

LPS stimulating neutrophils firmly adhered to ICAM-1 to form extracellular traps depends on integrin Mac-1 and cytoskeletal proteins / 生物医学工程学杂志

Neutrophil extracellular traps (NETs) play an important role in the formation of immunothrombosis. However, how vascular endothelial cells mediate the formation of NETs has not been fully understood. We stimulated neutrophils firmly attached on the endothelial cell surface intercellular adhesion molecule-1 (ICAM-1) with lipopolysaccharide (LPS) or phorbol-12-myristate-13-acetate (PMA) for 4 h, then labeled NETs-DNA with Sytox green dye and the formation of NETs was observed by fluorescent microscopy. The area and fluorescence intensity of NETs-DNA were analyzed to quantify the formation of NETs. The results showed that both PMA and LPS were able to induce firmly adhered neutrophils on ICAM-1 to produce NETs. NETs induced by PMA were independent of neither β2 integrin lymphocyte function-associated antigen-1 (LFA-1) nor macrophage antigen complex-1 (Mac-1). In contrast, LPS-stimulated NETs were mediated by Mac-1 integrin, but not by LFA-1. After inhibition of actin filaments or Talin-1, the formation of NETs irrespective of the stimulus was significantly reduced. This study reveals the mechanism of the direct interaction between neutrophils and endothelial cells to produce NETs under inflammatory conditions, providing a new theoretical basis for the treatment of related diseases and the development of new drugs.

Effects of material interfaces on orientation and function of fibrinogen / 生物医学工程学杂志

Fibrinogen (Fg) in human plasma plays an important role in hemostasis, vascular repair and tissue integrity. The surface chemistry of extracellular matrix or biological materials affects the orientation and distribution of Fg, and changes the exposure of integrin binding sites, thereby affecting its adhesion function to platelets. Here, the quantity, morphology and side chain exposure of Fg adsorbed on hydrophilic, hydrophobic and avidin surfaces were measured by atomic force microscopy (AFM) and flow cytometry (FCM), then the rolling behavior of platelets on Fg was observed through a parallel plate flow chamber system. Our results show that the hydrophobic surface leads to a large amount of cross-linking and aggregation of Fg, while the hydrophilic surface reduces the adsorption and accumulation of Fg while causing the exposure and spreading of the α chain on Fg and further mediating the adhesion of platelets. Fg immobilized by avidin / biotin on hydrophilic surface can maintain the monomer state, avoid over exposure and stretching of α chain, and bind to the platelets activated by the A1 domain of von Willebrand factor instead of inactivated platelets. This study would be helpful for improving the blood compatibility of implant biomaterials and reasonable experimental design of coagulation

Clinical Characteristics and Outcomes of COVID-19 Positive Acute Coronary Syndrome Patients; a multisource Electronic Healthcare Records Study from England

BackgroundPatients with underlying cardiovascular disease and Coronavirus disease 2019 (COVID-19) infection are at increased risk of morbidity and mortality. However, there is limited information on management and outcomes of patients presenting with acute coronary syndrome (ACS) and concomitant COVID19 infection. ObjectivesThis multisource national analysis of live data from England was designed to characterise the presenting profile and outcomes of patients hospitalized with ACS and COVID-19 infection. MethodsMultisource data from all acute NHS hospital in England was linked to study the characteristics and outcomes of patients hospitalized with COVID-19 ACS compared to non COVID-19 ACS patients. Hierarchical multilevel models were constructed to study the association between COVID19 ACS and in-hospital and 30-day mortality. ResultsBetween 1st March 2020 and 31st May 2020, 517 (4.0%) were admitted with COVID-19 ACS from a total of 12,958 ACS patients. COVID-19 ACS patients were generally older, BAME ethnicity, more comorbid and had unfavourable presenting characteristics compared to non-COVID-19 ACS patients. They were less likely to receive invasive coronary strategy in the form of coronary angiography (67.7% vs 81.0%), PCI (30.2% vs 53.9%), dual antiplatelet medication 76.3% vs 88.0%), and other important secondary medication. Patients with COVID-19 ACS had higher in-hospital (aOR 3.27 95%CI 2.41-4.42) and 30-day mortality (aOR 6.53 95%CI 5.1-8.36) compared to non COVID-19 ACS group. ConclusionCOVID-19 infection is prevalent but less frequent in the patients hospitalized with ACS in England. Presence of COVID-19 infection in patients with ACS is associated with significant mortality hazard.

Place and underlying cause of death during the COVID19 pandemic: retrospective cohort study of 3.5 million deaths in England and Wales, 2014 to 2020

BackgroundThe COVID-19 pandemic has resulted in a high death toll. We aimed to describe the place and cause of death during the COVID-19 pandemic. MethodsThis national death registry included all adult (aged [≥]18 years) deaths in England and Wales between 1st January 2014 and 30th June 2020. Analyses were based upon ICD-10 codes corresponding to the underlying cause of death as stated on the Medical Certificate of Cause of Death. Daily deaths during COVID-19 pandemic were compared against the expected daily deaths estimated using Farrington surveillance algorithm for daily historical data between 2014 and 2020, by place and cause of death. FindingsBetween 2nd March and 30th June 2020, there was an excess mortality of 57,860 (a proportional increase of 35%) compared with the expected deaths, of which 50,603 (86.2%) were COVID-19 related. Almost half the excess deaths occurred in care homes (25,611 deaths) where deaths were 55% higher than expected. One fifth of the excess deaths occurred in hospital (15,938 deaths; a proportional increase of 21%) with the remainder occurring at home (16,190 deaths; a proportional increase of 39%). At home, only 14% of 16,190 excess deaths were related to COVID-19, with 5,963 deaths due to cancer and 2,485 deaths due to cardiac disease, very few of which involved COVID-19. In care homes or hospices, 61% of the 25,611 excess deaths were related to COVID-19, 5,539 of which were due to respiratory disease and most of these (4,315 deaths) involved COVID-19. In hospital, there were 16,174 fewer deaths than expected which did not involve COVID-19, and there were 4,088 fewer deaths due to cancer and 1,398 fewer deaths due to cardiac disease than expected. InterpretationThe COVID-19 pandemic has resulted in a substantial increase in the absolute numbers of deaths occurring at home and care homes. There was a huge burden of excess deaths occurring in care homes, which were poorly characterised, and were likely to be, at least in part, the result of undiagnosed COVID-19. There was a smaller but important and ongoing excess in deaths at home, particularly from cancer and cardiac disease, which suggests avoidance of hospital care for non-COVID-19 conditions. FundingThe study is unfunded.

Indirect Impact of the COVID-19 Pandemic on Activity and Outcomes of Transcatheter and Surgical Treatment of Severe Aortic Stenosis in England

BackgroundAortic stenosis requires timely treatment with either surgical aortic valve replacement (SAVR) or transcatheter aortic valve replacement (TAVR). This study aimed to investigate the indirect impact of COVID-19 on national SAVR and TAVR activity and outcomes. MethodsThe UK TAVR Registry and the National Adult Cardiac Surgery Audit were used to identify all TAVR and SAVR procedures in England, between January 2017 and June 2020. The number of isolated AVR, AVR+coronary artery bypass graft (CABG) surgery, AVR+other surgery and TAVR procedures per month was calculated. Separate negative binomial regression models were fit to monthly procedural counts, with functions of time as covariates, to estimate the expected change in activity during COVID-19. ResultsWe included 13376 TAVR cases, 12328 isolated AVR cases, 7829 AVR+CABG cases, and 6014 AVR+Other cases. Prior to March 2020 (UK lockdown), monthly TAVR activity was rising, with a slight decrease in SAVR activity during 2019. We observed a rapid and significant drop in TAVR and SAVR activity during the COVID-19 pandemic, especially for elective cases. Cumulatively, over the period March to June 2020, we estimated an expected 2294 (95% CI 1872, 2716) cases of severe aortic stenosis who have not received treatment. ConclusionThis study has demonstrated a significant decrease in TAVR and SAVR activity in England following the COVID-19 outbreak. This situation should be monitored closely, to ensure that monthly activity rapidly returns to expected levels. There is potential for significant backlog in the near-to-medium term, and potential for increased mortality in this population.

Trends of in-hospital and 30-day mortality after percutaneous coronary intervention in England before and after the COVID-19 era

ObjectivesTo examine short-term primary causes of death after percutaneous coronary intervention (PCI) in a national cohort before and during COVID-19. BackgroundPublic reporting of PCI outcomes is a performance metric and a requirement in many healthcare systems. There are inconsistent data on the causes of death after PCI, and what proportion of these are attributable to cardiac causes. MethodsAll patients undergoing PCI in England between 1st January 2017 and 10th May 2020 were retrospectively analysed (n=273,141), according to their outcome from the date of PCI; no death and in-hospital, post-discharge, and 30-day death. ResultsThe overall rates of in-hospital and 30-day death were 1.9% and 2.8%, respectively. The rate of 30-day death declined between 2017 (2.9%) and February 2020 (2.5%), mainly due to lower in-hospital death (2.1% vs. 1.5%), before rising again from 1st March 2020 (3.2%) due to higher rates of post-discharge mortality. Only 59.6% of 30-day deaths were due to cardiac causes, the most common being acute coronary syndrome, cardiogenic shock and heart failure, and this persisted throughout the study period. 10.4% of 30-day deaths after 1st March 2020 were due to confirmed COVID-19. ConclusionsIn this nationwide study, we show that 40% of 30-day deaths are due to non-cardiac causes. Non-cardiac deaths have increased even more from the start of the COVID-19 pandemic, with one in ten deaths from March 2020 being COVID-19 related. These findings raise a question of whether public reporting of PCI outcomes should be cause-specific.