The paper discusses various partial solutions used for estimating fatigue life under variable amplitude multiaxial loading in the high-cycle fatigue domain. The concurring effects are treated, and their proposed solutions are commented upon. The major focus is on the categories of the phase shift effect and of cycle counting, and on the scope and quality of data, which support discussed theories. Results of own new experimental data set on specimens from S355 steel are provided. Fatigue life estimates for McDiarmid and Findley multiaxial methods and for two different methods of load path decomposition to cycles are shown to highlight some of the points open for discussion. It is concluded that the available experimental data are not sufficient to substantiate a clear decision to follow a definite algorithm.
Electrogram-guided Endomyocardial Biopsy Yield in Patients with Suspected Cardiac SarcoidosisAbbas Hoteit MD, Marwan M. Refaat, MDDivision of Cardiology, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, LebanonRunning Title: Electrogram-guided Biopsy in Cardiac SarcoidosisWords: 819 (excluding the title page and references)Keywords: Cardiac Sarcoidosis, Heart Diseases, Cardiovascular Diseases, Cardiac ArrhythmiasFunding: NoneDisclosures: NoneCorresponding Author:Marwan M. Refaat, MD, FACC, FAHA, FHRS, FASE, FESC, FACP, FAAMAAssociate Professor of MedicineDirector, Cardiovascular Fellowship ProgramDepartment of Internal Medicine, Cardiovascular Medicine/Cardiac ElectrophysiologyDepartment of Biochemistry and Molecular GeneticsAmerican University of Beirut Faculty of Medicine and Medical CenterPO Box 11-0236, Riad El-Solh 1107 2020- Beirut, LebanonUS Address: 3 Dag Hammarskjold Plaza, 8th Floor, New York, NY 10017, USAOffice: +961-1-350000/+961-1-374374 Extension 5353 or Extension 5366 (Direct)Sarcoidosis is a multisystem disease that is characterized by T-cell mediated formation of noncaseating granulomas in affected organs. The disease commonly might involve hilar lymphadenopathy, lungs, liver, spleen, heart, and other organs. The natural course and prognosis of the disease generally depends on the extent of the disease and the organs affected where spontaneous remission occurs in around two-thirds of patient.1 Involvement of the heart is recognized in around 30% of patients and is associated with poor prognosis.2 The presentation of patients with cardiac sarcoidosis varies significantly; it can range from mild to severe disease such as heart failure and fatal arrhythmias. Patients with cardiomyopathies might require implantable cardiac defibrillators or cardiac resynchronization therapy for sudden death prevention.3,4 Cardiac sarcoidosis can either present alongside extracardiac manifestations or isolated.5Diagnosis of cardiac sarcoidosis presents a particular challenge since there is no gold standard diagnostic tool and the presentation is variable.6 There are no disease-specific biomarkers that can reliably be used for diagnosis. Clinicians typically rely on current published guidelines for diagnostic criteria of cardiac sarcoidosis such as those of Heart Rhythm Society (HRS) and the Japanese Ministry of Health and Welfare (JMHW). The revised JMHW criteria provide a diagnosis either through histological evidence on biopsy or through the fulfillment of major and minor criteria that do not include cardiac PET whereas the HRS criteria provide either a definite pathway for diagnosis through histology or a clinical pathway for diagnosis of probable cardiac sarcoidosis that includes both cardiac PET and CMR as criteria.7,8 A definitive diagnosis of cardiac sarcoidosis can be obtained if endomyocardial biopsy can show noncaseating granulomas in the context of suspected cardiac sarcoidosis and other granulomatous diseases are excluded. However, endomyocardial biopsy has a low sensitivity of 20-30% since it is limited by several factors such as technique, sampling, patchy distribution of granulomas, location of lesions, and stage of the disease at the time of biopsy.5 Areas of inflammation and scarring typically show abnormal electrogram morphology, hence, it is thought that electrogram guidance may help in increasing the yield of endomyocardial biopsies. Electrogram guidance would potentially help avoiding normal myocardium during biopsy leading to increased yield and sensitivity.9In their study, Ezzedine et al. assessed the diagnostic yield of electrogram-guided endomyocardial biopsy and investigated association between positive endomyocardial biopsy and prognosis in patients with suspected cardiac sarcoidosis.10 This retrospective observational study included seventy-nine patients between 2011 and 2019 who had suspected cardiac sarcoidosis based on clinical presentation and findings on late gadolinium-enhancement cardiac magnetic resonance and/or cardiac positron emission tomography-computed tomography with N-13 NH3 perfusion imaging and F-18 fluorodeoxyglucose. Biopsy was done in patients suspicious of cardiac sarcoidosis in patients without extracardiac sarcoidosis or those with extracardiac disease but atypical/equivocal findings of cardiac sarcoidosis on imaging and meeting criteria in HRS guidelines as per the routine practice in Mayo Clinic. Mapping of the heart was performed prior to biopsy with partial guidance based on pre-procedural cardiac imaging. In patients with no identifiable abnormalities on electrogram, biopsies were taken from areas corresponding to those with abnormalities on pre-procedural imaging. Collected specimens were processed according to protocol and assessed by a blinded specialist. These specimens were considered positive if there was a combination of non-necrotizing granulomas, interstitial fibrosis, and scatted eosinophils. The study showed that electrogram-guided endomyocardial biopsy was associated with an adequate negative predictive value but low positive predictive value. A diagnosis of probable cardiac sarcoidosis can be made in patients with extracardiac manifestations according to established guidelines whereas in patients with suspected isolated cardiac sarcoidosis this is more difficult and as such biopsies play a more major role here. This study showed that, when guided by electrograms, endomyocardial biopsies had a higher diagnostic yield (41%) than that established in literature around 20-25%. Utilizing both abnormalities seen on both electrograms and on CMR or PET showed the highest diagnostic yield in endomyocardial biopsies. This acts as an important point of consideration for further research because accurate and timely diagnosis is paramount due to the diagnostics challenges and poor prognosis seen in cardiac sarcoidosis.10Previous evidence had shown that a positive endomyocardial biopsy for sarcoidosis was associated with poor prognosis.11However, LVAD and transplantation-free survival was found to be similar regardless of status of endomyocardial biopsy in this study.10 The authors explained that this could be explained by earlier detection of disease, differences in treatment, or more subtle detection of areas of involvement through electrograms. This study was well conducted but has been limited by its nature of being a retrospective observational study. Also, mapping was mostly limited to the right ventricle which may have underestimated the diagnostic yield of biopsies. This study represents the management done in a single tertiary care center which may not represent the same practice in other institutions with different facilities. Further multicenter and prospective studies are warranted to corroborate the data here and assess diagnostic and therapeutic modalities and long-term outcomes in patients.ReferencesStatement on sarcoidosis. Joint Statement of the American Thoracic Society (ATS), the European Respiratory Society (ERS) and the World Association of Sarcoidosis and Other Granulomatous Disorders (WASOG) adopted by the ATS Board of Directors and by the ERS Executive Committee, February 1999. Am J Respir Crit Care Med Aug 1999 ;160(2):736-55.Sekhri V, Sanal S, Delorenzo LJ, Aronow WS, Maguire GP. Cardiac sarcoidosis: a comprehensive review. Arch Med Sci Aug 2011; 7(4):546-54.AlJaroudi WA, Refaat MM, Habib RH, Al-Shaar L, Singh M, Gutmann R, Bloom HL, Dudley SC, Ellinor PT, Saba SF, Shalaby AA, Weiss R, McNamara DM, Halder I, London B; for the Genetic Risk Assessment of Defibrillator Events (GRADE) Investigators. Effect of Angiotensin Converting Enzyme Inhibitors and Receptor Blockers on Appropriate Implantable Cardiac Defibrillator Shock: Insights from the GRADE Multicenter Registry. Am J Cardiol Apr 2015; 115 (7): 115(7):924-31.Refaat M, Mansour M, Singh JP, Ruskin JN, Heist EK: Electrocardiographic Characteristics in Right Ventricular Versus Biventricular Pacing in Patients With Paced Right Bundle Branch Block QRS Pattern. J Electrocardiol Mar-Apr 2011; 44 (2): 289-95.Isobe M, Tezuka D. Isolated cardiac sarcoidosis: Clinical characteristics, diagnosis and treatment. Int J Cardiol Mar 2015; 182:132-40.Ahmed AI, Abebe AT, Han Y, Alnabelsi T, Agrawal T, Kassi M, Aljizeeri A, Taylor A, Tleyjeh IM, Al-Mallah MH. The prognostic role of cardiac positron emission tomography imaging in patients with sarcoidosis: A systematic review. J Nucl Cardiol Jul 2021; doi: 10.1007/s12350-021-02681-z. Online ahead of print.Sharma A, Okada DR, Yacoub H, Chrispin J, Bokhari S. Diagnosis of cardiac sarcoidosis: an era of paradigm shift. Ann Nucl Med Feb 2020;34(2):87-93.Ha FJ, Agarwal S, Tweed K, Palmer SC, Adams HS, Thillai M, Williams L. Imaging in Suspected Cardiac Sarcoidosis: A Diagnostic Challenge. Curr Cardiol Rev 2020;16(2):90-97.Liang JJ, Hebl VB, DeSimone CV, Madhavan M, Nanda S, Kapa S, Maleszewski JJ, Edwards WD, Reeder G, Cooper LT , Asirvatham SJ. Electrogram guidance: a method to increase the precision and diagnostic yield of endomyocardial biopsy for suspected cardiac sarcoidosis and myocarditis. JACC Heart Fail Oct 2014;2(5):466-73.Ezzedine FM, Kapa S, Rosenbaum A, Blauwet L, Deshmukh AJ, AbouEzzeddine OF, Maleszewski JJ, Asirvatham SJ, Bois JP, Schirger JA, Chareonthaitawee P, Siontis KC. Electrogram-guided Endomyocardial Biopsy Yield in Patients with Suspected Cardiac Sarcoidosis and Relation to Outcome. J Cardiovasc Electrophysiol Jul 2021; In Press.Ardehali H , Howard DL, Hariri A, Qasim A, Hare JM, Baughman KL, Kasper EK. A positive endomyocardial biopsy result for sarcoid is associated with poor prognosis in patients with initially unexplained cardiomyopathy. Am Heart J Sep 2005 ;150(3):459-63.
The case report by Sicim et al. is the placement of extra-anatomical bypasses in bilateral common carotid arteries. The similar previous reports of the extra-anatomical bypass usually indicate unilateral bypass. Whether or not the Willis' circle is incomplete is difficult to judge during emergency surgery, and the authors' judgment seems to have been correct in the sense that it could maintain cerebral perfusion reliably and quickly. The direct perfusion and extraanatomical bypass of carotid artery is a reasonable strategy in patients with cerebral malperfusion.
Background: The administration of L-glutamine (Gln) suppresses allergic airway inflammation via the rapid upregulation of MAPK phosphatase (MKP)-1, which functions as a negative regulator of inflammation by deactivating p38 and JNK mitogen-activated protein kinases (MAPKs). However, the role of endogenous Gln remains to be elucidated. Therefore, we investigated the mechanism by which endogenous Gln regulates MKP-1 induction and allergic airway inflammation in an ovalbumin-based murine asthma model. Methods: We depleted endogenous Gln levels using l-γ-glutamyl- p-nitroanilide (GPNA), an inhibitor of the Gln transporter ASCT2, and glutamine synthetase small interfering (si)RNA. Lentivirus expressing MKP-1 was injected to achieve overexpression of MKP-1. Asthmatic phenotypes were assessed using our previously developed ovalbumin-based murine model, which is suitable for examining sequential asthmatic events, including neutrophil infiltration. Gln levels were analyzed using a Gln assay kit. Results: GPNA or glutamine synthetase siRNA successfully depleted endogenous Gln levels. Importantly, homeostatic MKP-1 induction did not occur at all, which resulted in prolonged p38 MAPK and cytosolic phospholipase A 2 (cPLA 2) phosphorylation in Gln-deficient mice. Gln deficiency augmented all examined asthmatic reactions, but it exhibited a strong bias toward increasing the neutrophil count, which was not observed in MKP-1-overexpressing lungs. This neutrophilia was inhibited by a cPLA 2 inhibitor and a leukotriene B4 inhibitor, but not by dexamethasone. Conclusion: Gln deficiency leads to the impairment of MKP-1 induction and activation of p38 MAPK and cPLA 2, resulting in the augmentation of neutrophilic, more so than eosinophilic, airway inflammation.
In this paper a collaborative writing group explores how we, two rivers, express ourselves over time, place and space, our energies long interpreted as veins and arteries carrying the Country’s life affirming blood. Voiced as River: I, River, this position reflects a worldview in which interrelationship with living river is normal, and River Spirit is ever-present. It is a position underpinned by Indigenous narratives as riverine expressions of place-based love. At times the paper is also voiced as writing group or individuals, with voices being interchanged where required for smooth reading. We see this as part of the decolonising process, which feels liberating and healing amongst the writers. Each writer is equally valued as co-creator, contributor, narrator and story teller. The two Rivers, being Martuwarra Fitzroy River (Kimberley, Western Australia), and Unamen Shipu Romaine River (North Shore, Québec, Canada) illustrate a common condition of being, through heritage, life, change and possibility. Through stories and voices, the socio-scientific implications of colonisation and lost connections become clear, considering the interaction, the dialogue and the cultural synthesis of living water systems that have always incorporated all life forms into rivers of life. As a way of navigating towards wholeness, Aboriginal knowledge systems and narratives for healing are used to bring together findings of this intercultural river learning journey.
Background: After the detection of the first case of coronavirus disease 2019 (COVID-19) in South Korea on January 20, 2019, it has triggered three major outbreaks. To decrease the disease burden of COVID-19, social distancing and active mask wearing were encouraged, reducing the number of patients with influenza-like illness and altering the detection rate of influenza and respiratory viruses in the Korea Influenza and Respiratory Viruses Surveillance System (KINRESS). We examined the changes in respiratory viruses due to COVID-19 in South Korea and virological causes of the high detection rate of human rhinovirus (hRV) in 2020. Methods: We collected 52,684 oropharyngeal or nasopharyngeal swab samples from patients with influenza-like illness in cooperation with KINRESS from 2016 to 2020. Influenza virus and other respiratory viruses were confirmed using real-time RT-PCR. The weekly detection rate was used to compare virus detection patterns. Results: Non-enveloped virus (hRV, human bocavirus, and human adenovirus) detection rates during the COVID-19 pandemic were maintained. The detection rate of hRV significantly increased in 2020 compared with that in 2019 and was negatively correlated with number of COVID-19-confirmed cases in 2020. The distribution of strains and genetic characteristics in hRV did not differ between 2019 and 2020. Conclusions: The extremely low detection rate of enveloped viruses resulted from efforts to prevent the spread of COVID-19 in South Korea. The high detection rate of hRV may be related to resistance against environmental conditions as a non-enveloped virus and the long period of viral shedding from patients.
Sir,We welcome Gurol‐Urganci I and Bidwell et al’s evaluation of the impact of the care bundle to reduce obstetric anal sphincter injury (OASI) published in your August edition last year. The article reports much needed evidence on the efficacy of an intervention that has already taken hold in many maternity services across the country.Despite the article’s timely nature, we would like to voice our disappointment in the quality of the evidence of support for the care bundle Meulen and Thakar et al provide, and the recommendations made. The article fails to consider important evidence in this area of maternity care prompting this response. In particular, the authors miss the opportunity to contextualise the relatively low-level evidence they take from five articles – reporting three Scandinavian cohort studies and one educational intervention study on manual assistance during the final part of the second stage of labour (including gripping the baby’s chin through the perineum) - with the compelling findings from the Cochrane review on Perineal techniques during the second stage of labour for reducing perineal trauma.  This omission is important because the Cochrane review indicates that warm compresses have a bigger positive effect on OASI than the OASI care bundle reported by Meulen and Thakar et al’s. Furthermore, the Cochrane review provides evidence suggesting that hands off the perineum may protect women from episiotomy; an outcome which Meulen and Thakar et al acknowledge remained unchanged despite the third component in the care bundle aiming to ‘use of episiotomy when clinically indicated’. The selective nature of the evidence quoted, undermines the credibility of inferences that can be made from the findings. We suggest therefore, that caution should be taken when reading the authors conclusions.Our second concern rests upon the authors failure to account for the surprisingly small positive effect of the care bundle compared with the Scandinavian studies they quote. Meulen and Thakar et al report a 0.3% decrease in OASI compared with a 3.6% reduction;3% reduction; a 2.6% reduction for low risk women; and a 2.1% reduction in the various observational studies  Such a small effect in an open trial could easily be caused by ascertainment bias. Again, the quality of the previous Scandinavian studies make interpretation difficult but the marked difference in results between Scandinavia and England suggests caution should be taken when reading the authors conclusions.Our final concern pertains to women’s experience of the care bundle. Not only is the acceptability of the intervention not considered in this evaluation – a significant oversight given the conspicuous lack of evidence on this – there are ethical issues within the evaluation that deserve attention. The intervention description in figure 1 claims that women were informed about what could be done to reduce OASI. This does not appear to be entirely true given the lack of consideration of warm compresses and hands off to protect against episiotomy. Even more unsettling is the statement ‘MPP should be used unless the woman objects’, implying little consideration for autonomy and informed consent.For the above reasons, we are not only disappointed with the BJOG article but with the professional stakeholder investment in the intervention which seems to have been widely and uncritically supported, with some support even being somewhat evangelical, despite the limited evidence for support.Signatures,
The morphology variations of the so-called scimitar vein are many and varied. We present a synthesis of 92 published investigations of the overall scimitar syndrome. We reviewed the clinical presentations, diagnostic modalities, surgical approaches, and outcomes. Diagnostic information was provided by clinical presentations, radiographic findings, transthoracic and transesophageal echocardiography, computed-tomographic angiography, magnetic resonance imaging, angiocardiography, and ventilation/perfusion scans. These investigations served to elucidate the origin, course, and termination of the scimitar vein, the intracardiac anatomy, the presence of associated defects, and the patterns of any accompanying pulmonary lesions. In short, they defined the disease prior to surgical intervention. Of the patients described, up to four-fifths presented during infancy, with cardiac failure, increased pulmonary flow, and pulmonary hypertension. Associated cardiac and extracardiac defects, particularly hypoplasia of the right lung, are present in up to three-quarters of cases. Overall operative mortality has been cited between 4.8% and 5.9%. Mortality was highest in patients with preoperative pulmonary hypertension, and those undergoing surgery in infancy. Despite timely surgical intervention, post-repair obstruction of the scimitar vein, intra-atrial baffle obstruction, or stenosis of the inferior caval vein were reported in up to two-thirds of cases. The venous obstruction could not be related to any particular surgical technique. On long term follow-up, one sixth of patients reported persistent dyspnoea and recurrent respiratory infections. Any infants presenting with heart failure, right-sided heart, and hypoplastic right lung should be evaluated to exclude the syndrome. An increased appreciation of variables will contribute to improved surgical management.
WeChat and access to wireless communication may offer a continuum of care following medical and surgical intervention. This cardiac surgery research study evaluates the process of parental education and social support following pediatric cardiac surgery utilizing standard of care compared to telehealth.
The morphological variations when one, or both, of the atrial chambers is subdivided, are many and varied. We present a synthesis of 198 published investigations of this “family” of uncommon lesions. Almost three-quarters of patients with divided atrial chambers present during infancy with severe pulmonary hypertension and cardiac failure. Associated cardiac and extra-cardiac defects are present in between half and nine-tenths of cases. Acquired division of the left atrium has been reported after the Fontan operation, orthotopic cardiac transplantation, and complicated aortic valvar infective endocarditis. Surgery under cardiopulmonary bypass remains the definitive treatment. Balloon dilation may be considered in anatomically compatible variants in the setting of cardiac failure and pregnancy as a bridge to definitive treatment. Overall, mortality has been cited between nil to 29%. Presentation during infancy, associated congenital anomalies, pulmonary hypertension, and surgery in the previous era, have been the reported causes of death. The operative survivors have long-term favourable outcomes, with near normal cardiac dimensions and low risk of recurrence. While asymptomatic patients with division of the right atrium do not need treatment, surgical resection of the dividing partition under cardiopulmonary bypass is recommended in symptomatic patients with complex anatomy, the spinnaker malformation, or associated cardiac anomalies. Balloon dilation may be considered in uncomplicated patients with less obstructive lesions. Hybrid intervention and endoscopic robotic correction also have been performed. We submit that an increased appreciation of the anatomic background to division of the atrial chambers will contribute to improved surgical management.