Low-dose corticosteroid therapy for cardiogenic shock in adults (COCCA): study protocol for a randomized controlled trial

Background Cardiogenic shock (CS) is a life-threatening condition characterized by circulatory insufficiency caused by an acute dysfunction of the heart pump. The pathophysiological approach to CS has recently been enriched by the tissue consequences of low flow, including inflammation, endothelial dysfunction, and alteration of the hypothalamic-pituitary-adrenal axis. The aim of the present trial is to evaluate the impact of early low-dose corticosteroid therapy on shock reversal in adults with CS. Method/design This is a multicentered randomized, double-blind, placebo-controlled trial with two parallel arms in adult patients with CS recruited from medical, cardiac, and polyvalent intensive care units (ICU) in France. Patients will be randomly allocated into the treatment or control group (1:1 ratio), and we will recruit 380 patients (190 per group). For the treatment group, hydrocortisone (50 mg intravenous bolus every 6 h) and fludrocortisone (50 μg once a day enterally) will be administered for 7 days or until discharge from the ICU. The primary endpoint is catecholamine-free days at day 7. Secondary endpoints include morbidity and all-cause mortality at 28 and 90 days post-randomization. Pre-defined subgroups analyses are planned, including: postcardiotomy, myocardial infarction, etomidate use, vasopressor use, and adrenal profiles according the short corticotropin stimulation test. Each patient will be followed for 90 days. All analyses will be conducted on an intention-to-treat basis. Discussion This trial will provide valuable evidence about the effectiveness of low dose of corticosteroid therapy for CS. If effective, this therapy might improve outcome and become a therapeutic adjunct for patients with CS. Trial registration ClinicalTrials.gov, NCT03773822. Registered on 12 December 2018

A Review on the Mechanism and Application of Keishibukuryogan

The concept of “blood stasis” – called yū xiě in Chinese, Oketsu in Japanese – is one of the unique pathophysiology of traditional medicine that originated in China and inherited in Korea and Japan. This concept is related to the multiple aspects of hemodynamic disorders brought on by quantitative and qualitative changes. It theorizes that the quantitative changes of “blood stasis” are related to peripheral circulatory insufficiency. When chronic qualitative changes of “blood stasis” produce stagnant blood that turns into a pathological product, it could cause inflammation and lead to organic changes. Trauma induced hematomas, that are considered to be a quantitative change of blood, are also a form of blood stasis. The basic medicine research on Keishibukuryogan (KBG)–a Japanese name in Traditional Japanese Medicine (Kampo) for one of the most common anti- “blood stasis” prescriptions, also known as gui-zhi-fu-ling-wan (GFW) in Chinese in Traditional Chinese Medicine (TCM)–indicated that the initiation of quantitative changes was closely related to loss of redox balances on endothelial function induced by oxidative stress. The following qualitative changes were related to coagulopathy, hyper viscosity; anti-platelet aggregation, lipid metabolism; a regulation of systemic leptin level and/or lipid metabolism, inflammatory factor; cyclooxygenase-1,2 (COX-1, 2), interleukin-6, 8 tumor necrosis factor-α, macrophage infiltration, hyperplasia, tissue fibrosis and sclerosis caused by transforming growth factor-β1 and fibronectin, the dysfunction of regulated cell deaths, such as, apoptosis, autophagy, ferroptosis and ovarian hormone imbalance. Clinically, KBG was often used for diseases related to Obstetrics and Gynecology, Endocrine Metabolism, Rheumatology and Dermatology. In this review, we give an overview of the mechanism and its current clinical application of KBG through a summary of the basic and clinical research and discuss future perspective.

Hemodynamics changes in late manifestation of natal trauma of spinal cord’s cervical department

Hemodynamics of children with natal trauma of spinal cords cervical department was studied. It was determined, that among numerous manifestations of late complications of natal cervical traumas amyotrophy syndrome of shoulder girdle is widely spread, in which in 65% of cases hemodynamics insufficiency is determined in the carotid region, and in 37% - in vertebro-basilar region. Functional tests allowed to determine occult blood flow insufficiency in vertebro-basilar region in 80% of cases, thus confirming presence of chronic circulatory insufficiency in the system of vertebral arteries in patients with amyotrophy syndrome of shoulder girdle.

Clinical impact of visually assessed right ventricular dysfunction in patients with septic shock

We retrospectively analyzed data from the Medical Information Mart for Intensive Care-III critical care database to determine whether visually-assessed right ventricular (RV) dysfunction was associated with clinical outcomes in septic shock patients. Associations between visually-assessed RV dysfunction by echocardiography and in-hospital mortality, lethal arrhythmia, and hemodynamic indicators to determine the prognostic value of RV dysfunction in patients with septic shock were analyzed. Propensity score analysis showed RV dysfunction was associated with increased risk of in-hospital death in patients with septic shock (adjusted odds ratio [OR] 2.15; 95% confidence interval [CI] 1.99–2.32; P < 0.001). In multivariate logistic regression analysis, RV dysfunction was associated with in-hospital death (OR 2.19; 95% CI 1.91–2.53; P < 0.001), lethal arrhythmia (OR 2.19; 95% CI 1.34–3.57; P < 0.001), and tendency for increased blood lactate levels (OR 1.31; 95% CI 1.14–1.50; P < 0.001) independent of left ventricular (LV) dysfunction. RV dysfunction was associated with lower cardiac output, pulmonary artery pressure index, and RV stroke work index. In patients with septic shock, visually-assessed RV dysfunction was associated with in-hospital mortality, lethal arrhythmia, and circulatory insufficiency independent of LV dysfunction. Visual assessment of RV dysfunction using echocardiography might help to identify the short-term prognosis of patients with septic shock by reflecting hemodynamic status.

A mitralis billentyű sebészete atrioventricularis septumdefektusban

Összefoglaló. A veleszületett szívbetegségek egyik gyakori formáját jelentő atrioventricularis septumdefektus korrekciós műtétjének kritikus pontja a közös atrioventricularis szájadék elválasztásával a mitralis billentyű kialakítása. A korrekció sikere számos anatómiai variáns függvénye, ezért nem lehet minden esetben a tökéletes anatómiai viszonyokat kialakítani. A fennmaradó billentyűstenosisok, regurgitatiók a későbbi életkorban progressziót mutatva olyan hemodinamikai kórképeket, keringési elégtelenséget okozhatnak, melyek további beavatkozásokat igényelhetnek. A mitralis billentyűnek az atrioventricularis septumdefektushoz társuló betegsége koraszülöttkortól aggkorig minden életkorban előfordul, más-más műtéti megoldást igényelve. A szerzők részletezik a különböző életkorokra vonatkozóan a napjainkban lehetséges és szükséges műtéti megoldásokat, sebészi kihívásokat. A mitralis billentyű műbillentyűre történő cseréjében a klasszikus sebészi megoldások mellett napjainkban új beavatkozásokként jelentős számban jelentkeznek a katéteres intervenciós és hibrid megoldások. A felnőttkort egyre nagyobb számban megélő betegek fokozott odafigyelést, speciális ellátást igényelnek a kardiológusoktól, szívsebészektől. Orv Hetil. 2021; 162(35): 1397–1401. Summary. The critical point of the atrioventricular septal defect correction is to separate the common atrioventricular orifice, which results in the reconstruction of the mitral valve. The success of the correction depends on many anatomical aspects, therefore a perfect anatomical outcome is not always possible. The remaining valvular stenoses and regurgitations, showing progression at a later age, may result in hemodynamic disorders and circulatory insufficiency that may require further interventions. Mitral valve disease associated with atrioventricular septal defect occurs at all ages from preterm to adulthood, requiring different surgical solutions. The authors detail the possible and necessary surgical solutions and surgical challenges at different ages. In addition to the classic surgical solutions, a significant number of catheter interventional and hybrid solutions are emerging as new interventions in the replacement of the mitral valve with an artificial valve. An increasing number of patients living in adulthood require increased attention and special care from cardiologists and cardiac surgeons. Orv Hetil. 2021; 162(35): 1397–1401.

Our Experience in the Treatment of Vertebrobasilar Insufficiency Due to Cervical Spine Disorders

This article defines vertebra-related causes of vertebrobasilar insufficiency in patients with the signs of tortuosity of segment VI of the VA. The aim of this study is to present the results of diagnostics of discirculatory phenomena in the vertebrobasilar system and to show their importance for differentiated surgical treatment of stenotic lesions of segment V1 of VA in pathological disorders of cerebral circulation in the VBS caused by osteochondrosis of the cervical spine. The following traditional methods are used in diagnostics: Doppler ultrasonography, multispiral computed tomography with contrast enhancement. Also using developed by the author method for determining VA reactivity and circulatory insufficiency in the vertebrobasilar system (VBS). Based on our methodology and criteria, patients were selected for different types of surgical treatment with clinical outcome prediction following interventions on the arteries of the VBS. To determine the pathologies of the intracranial segments of the vertebral and basilar arteries, taking into account the pathways of collateral compensation in the VBS, cerebral angiography is recommended before surgery on the arteries of the VBS. Reconstructive techniques used on segment VI of the VA will predictably show the best long-term clinical results. The excision of a tortuous segment VI of the VA may be effective in obtaining reliable results of successful interventions in the early postoperative period. The conservative treatment of the patients with multiple VBD lesions is possible. early outcomes of their use are satisfactory.

Urgent liver retransplantation in patient with sepsis, multiple organ failure and unstable hemodynamics

In the presented case, the patient after orthotopic liver transplantation from an optimal cadaveric donor against the background of a smooth postoperative period and satisfactory graft function was followed by a series of biliary complications in the form of ongoing necrosis of the bile ducts of the graft, which required repeated surgical interventions, which led to the formation of a separate bicholangiostomy. The patient was put on the waiting list for a repeated liver transplantation. The developed complications led to sepsis, multiple organ failure and unstable hemodynamics, that required using of substitution therapy and high doses of inotropic, vasopressor drugs. A decision was made to assign the patient a «high-urgency» status with priority graft obtaining, and the coordination centers of St. Petersburg, Moscow, Leningrad and Moscow Regions and FMBA were notified. From the assignment of the «high urgency» status to receiving an organ has passed 10 hours. Hepatectomy with the formation of a temporary portocaval shunt began in advance of the donor liver’s admission to the clinic, which made it possible to stabilize the hemodynamic parameters and the recipient’s condition. However, against the background of massive blood loss, at the stage of graft revascularization, two episodes of cardiac arrest occurred, requiring indirect heart massage with chest and diaphragm compressions. Due to severe peripheral circulatory insufficiency, dry gangrene of the nail phalanx of the right forefinger was developed. Nevertheless, from the first postoperative day and thereafter, the graft demonstrated satisfactory function. Two months after the repeated transplantation, the patient was discharged in satisfactory condition. Subsequently, the index finger was amputated. Six months after the second operation, the patient returned to the work of a teacher.

Nutritional Intervention Strategies Using Dietary Antioxidants and Organic Trace Minerals to Reduce the Incidence of Wooden Breast and Other Carcass Quality Defects in Broiler Birds

Wooden breast (WB) is a degenerative myopathy seen in modern broiler birds resulting in quality downgrade of breast fillets. Affected filets show increased toughness both before as well as after cooking and have decreased water holding capacity and marinade pick up compared to normal fillets. Although the exact etiology is unknown, the circulatory insufficiency and increased oxidative stress in the breast muscles of modern broiler birds could be resulting in damage and degeneration of muscle fibers leading to myopathies. Three independent experiments were conducted to evaluate the effect of various dietary interventions on the incidence of WB when birds are exposed to oxidative stress associated with feeding oxidized fat and mild heat stress. Feed additives such as dietary antioxidant [Ethoxyquin (ETX)], mineral methionine hydroxy analog chelate (MMHAC) of Zn, Cu, and Mn, and organic selenium (Org Se) were tested at recommended levels. In experiment 1, ETX reduced (P &lt; 0.05) the incidence of severe WB induced by oxidized fat diet. The magnitude of improvement in percentage of normal (no WB) filets and reduction in muscle lipid peroxidation was greater (P &lt; 0.05) when ETX and MMHAC were fed together as shown by experiment 2. In birds exposed to mild heat stress (Experiment 3), feeding MMHAC by itself reduced (P &lt; 0.05) tissue damage by reducing incidence of tibial head lesions, skin scratches, breast blisters, in addition to increasing the incidence of normal (no WB) fillets. When MMHAC was combined with ETX and Org Se, further improvement (P &lt; 0.05) in normal (no WB) filets was observed. In summary, under different oxidative stress conditions, dietary intervention programs that contain ETX, MMHA-Zn, -Cu, and -Mn and Org Se can improve performance and increase carcass integrity, reducing problems, such as WB, either independently or with additive effect. This effect is most likely attained by simultaneously improving the exogenous and endogenous antioxidant status, reducing oxidative stress, and improving tissue healing process of the bird.

Clinical Impact of Visually Assessed Right Ventricular Dysfunction in Patients With Septic Shock

This study retrospectively analyzed data from the Medical Information Mart for Intensive Care-III critical care database to determine whether visually-assessed right ventricular (RV) dysfunction was associated with clinical outcomes in septic shock patients. Associations between visually-assessed RV dysfunction by echocardiography and in-hospital mortality, lethal arrhythmia, and hemodynamic indicators to determine the prognostic value of RV dysfunction in patients with septic shock were analyzed. Propensity score analysis showed RV dysfunction increased risk of in-hospital death in patients with septic shock (adjusted odds ratio [OR], 2.15; 95% confidence interval [CI], 1.99–2.32; P<0.0010. In multivariate logistic regression analysis, RV dysfunction was associated with in-hospital death (OR, 2.19; 95%CI, 1.91–2.53; P<0.001), lethal arrhythmia (OR, 2.19; 95%CI, 1.34–3.57; P<0.001), and tendency for increased blood lactate levels (OR, 1.31; 95%CI, 1.14–1.50; P<0.001) independent of left ventricular (LV) dysfunction. RV dysfunction patients had lower cardiac output, pulmonary artery pressure index, and RV stroke work index than those without RV dysfunction. In patients with septic shock, visually-assessed RV dysfunction was associated with in-hospital mortality, lethal arrhythmia, and circulatory insufficiency independent of LV dysfunction. Visual assessment of RV dysfunction using echocardiography might predict the short-term prognosis of patients with septic shock by reflecting hemodynamic status.

Analysis of Herbal Mechanisms and Prescriptions for Chronic Cerebral Circulatory Insufficiency Based on Data Mining and Network Pharmacology

Background: Traditional Chinese medicine has accumulated rich resources and experience through clinical research to explore the prevention and treatment of chronic cerebral circulatory insufficiency, but current medicine lacks in-depth research and confirmation on the established protocols and mechanism of prescribed TCMs at the macro and micro levels. Objective: To explore the prescription of Chinese medicines for the treatment of chronic cerebral circulation insufficiency (CCCI) and to explore the mechanism of core drugs. Methods: 229 Chinese prescriptions for CCCI were collected from CNKI, CBM, VIP and WANFANG databases. Analyze the frequency and association rules of drugs and to extract the core drugs by TCMISSV2.5 software. The active ingredients and targets were obtained by TCMSP, and genes of CCCI were collected from the DisGeNET, OMIM, DrugBank disease databases. The intersection targets of herbal medicine and disease was imported into the STRING database for PPI network. The key targets were screened by network topology algorithm. The Systems Dock website was used to verify the molecular docking. The GOEAST and DAVID tools were used to perform GO and KEGG pathway analysis with the key target genes. Results: 117 drugs involved in 229 prescriptions were identified, 2 core drugs were identified. We identified 8 active ingredients, which were mandenol, myricanone, perlolyrine, senkyunone, wallichilide, sitosterol, beta-sitosterol and stigmasterol. 371 herbal targets predicted and 335 disease targets. The enrichment analysis showed that the core herbal medicines could prevent CCCI by 15 key signaling pathways. Conclusion: There are direct or indirect connections in key signaling pathways, which not only participate in energy metabolism, hormone regulation, signal transduction, but also play a role in the comprehensive intervention of nervous system, immune system, circulatory system and other systems, which is consistent with the comprehensive pathogenesis of CCCI induced by multiple factors.