Infective endocarditis: do we have an effective risk score model? A systematic review

Background Infective endocarditis (IE) is a rare, highly morbid condition with 17% in-hospital mortality. 25-30% require surgery and there is ongoing debate with regard to markers predicting patient outcomes and guiding intervention. This systematic review aims to evaluate all IE risk scores currently available. Methods Standard methodology (PRISMA guideline) was used. Papers with risk score analysis for IE patients were included, with attention to studies reporting area under the receiver-operating characteristic curve(AUC/ROC). Qualitative analysis was carried out, including assessment of validation processes and comparison of these results to original derivation cohorts where available. Risk-of-bias analysis illustrated according to PROBAST guidelines. Results Of 75 articles initially identified, 32 papers were analysed for a total of 20 proposed scores, (range 66-13,000 patients), 14 of which were specific for IE. The number of variables per score ranged from 3 to 14 with only 50% including microbiological variables and 15% including biomarkers. The following scores had good performance (AUC>0.8) in studies proposing the score (often the derivation cohort); however fared poorly when applied to a new cohort: PALSUSE, DeFeo, ANCLA, RISK-E, EndoSCORE, MELD-XI, COSTA, SHARPEN. DeFeo score demonstrated the largest discrepancy with initial AUC of 0.88, compared to 0.58 when applied to different cohorts. The inflammatory response in IE has been well documented and CRP has been found to be an independent predictor for worse outcomes. There is ongoing investigation on alternate inflammatory biomarkers which may assist in IE management. Of the scores identified in this review, only 3 have included a biomarker as a predictor. Conclusion Despite the variety of available scores, their development has been limited by small sample size, retrospective collection of data and short-term outcomes, with lack of external validation, limiting their transportability. Future population studies and large comprehensive registries are required to address this unmet clinical need

Иммунопатогенез формирования атопических заболеваний

The aim of this investigation is the comparative study of changes in the surface phenotype of lymphocyte in patients with different forms of atopic diseases and latent sensitization.Materials and methods. The study was conducted on peripheral blood lymphocytes from 22 latent sensitization patients, 30 pollinosis patients, 44 atopic bronchial asthma patients and 36 atopic dermatitis patients. The control group consisted of 26 healthy people.The results of our studies demonstrate that atopic diseases are different not only in clinical manifestations, but also in mechanisms of disturbances in the functions of the immune system. Comparative study of surface markers of lymphocytes in patients with different forms of atopic diseases revealed a significant increase of surface changes of lymphocyte phenotype according to the severity of the clinical manifestations of the disease. All patients with studied forms of atopy had an increase in content of B-lymphocytes expressing CD72 marker in the peripheral blood and of lymphocytes expressing early activation antigens CD23, CD25, CD71 and adhesion receptor CD54. The developments of pollinosis, atopic bronchial asthma and atopic dermatitis are accompanied by an additional increase levels of lymphocytes expressing the late activation marker HLADR, the CD38+ precursors of plasma cells, and of lymphocytes carrying surface immunoglobulins in peripheral blood. In the blood of patients with atopic disease during exacerbation with evident clinical symptoms revealed a significant increase in all the studied populations and subpopulations of B-lymphocytes. Patients with latent sensitization had increasing blood lymphocytes expressing the CD95 receptor of Fas inducing apoptosis and low content of cells expressing its ligand CD178. Content of CD95+ lymphocytes in peripheral blood at atopic bronchial asthma and atopic dermatitis patients is reduced, and CD178+ lymphocytes increased, reflecting infringement of Fas-dependent apoptosis in severe atopic diseases.Цель работы – сравнительное изучение изменений поверхностного фенотипа лимфоцитов крови у больных с различными формами атопических заболеваний и латентной сенсибилизацией.Материал и методы. Исследование проведено на лимфоцитах периферической крови 22 больных с латентной сенсибилизацией, 30 больных поллинозом, 44 больных атопической бронхиальной астмой и 36 пациентов с атопическим дерматитом. Контрольную группу составили 26 здоровых людей.Результаты проведенных исследований убедительно свидетельствуют, что атопические болезни различаются не только клиническими проявлениями, но и механизмами нарушений функций иммунной системы. Сравнительное изучение поверхностного фенотипа лимфоцитов у больных с различными формами атопии позволило выявить существенное нарастание изменений их субпопуляционного состава по мере усиления тяжести клинических проявлений заболеваний. У больных всеми исследованными формами атопии отмечалось повышение содержания в периферической крови В-лимфоцитов, экспрессирующих маркер CD72, и лимфоцитов, несущих ранние активационные антигены CD23, CD25, CD71 и рецепторы адгезии CD54. Развитие поллиноза, атопической бронхиальной астмы и атопического дерматита сопровождалось дополнительным повышением содержания в периферической крови лимфоцитов, экспресси- рующих поздний маркер активации HLA-DR,предшественников плазматических клеток и лимфоцитов CD38+, несущих поверхностные иммуноглобулины. В крови у больных атопией с выраженными клиническими проявлениями выявлено достоверное повышение содержания всех изученных субпопуляций В-лимфоцитов. У больных с латентной сенсибилизацией зарегистрировано повышенное содержание в крови лимфоцитов, экспрессирующих CD95-рецептор запуска Fas-индуцированного апоптоза, и снижение количества клеток, экспрессирующих его лиганд – рецептор CD178. У больных с атопической бронхиальной астмой и атопическим дерматитом содержание в крови CD95+ лимфоцитов, напротив, снижено, а CD178+-лимфоцитов – повышено, что отражает нарушение Fas-зависимого апоптоза при тяжелых атопических заболеваниях.

Prerequisites for the creation of an atlas of postcovid inflammation as a way of personalized pharmacotherapy, as well as predicting and preventing organ and systemic dysfunctions

SARS-CoV-2 is a novel coronavirus that has been identified as the cause of the 2019 coronavirus infection (COVID-19), which originated at Wuhan city of PRC in late 2019 and widespread worldwide. As the number of patients recovering from COVID-19 continue to grow, it’s very important to understand what health issues they may keep experiencing. COVID-19 is now recognized as an infectious disease that can cause multiple organ diseases of various localization. It is against this background that a new term was introduced: post-acute post-COVID-19 syndrome characterized by several persistent symptoms inherent in the acute phase of the disease, as well as the occurrence of delayed and (or) long-term complications beyond 4 weeks from the onset of the disease. The work reflected in this article revealed a portrait of a patient with post-COVID-19 syndrome, the most common complications of this period, as well as the mechanisms of their development and the resulting metabolic, cellular, tissue disorders leading to the tissue and organ dysfunctions. A comprehensive biochemical and immunological screening was carried out using the example of three clinical cases to identify the most significant disorders in these patients and to correlate with their clinical status over time. In point of fact, such patients were diagnosed with vascular dysfunction factors (development of endothelial dysfunction), metabolic dysfunction factors (metabolic acidosis, mitochondrial dysfunction, carbohydrate metabolism disorder, insulin resistance, altered branched-chain and aromatic amino acid metabolism), neurological disorder factors (neurotoxicity of the resulting metabolites), immunological disorder factors (decreased efficiency of detoxification systems, secondary immunodeficiency, risk of secondary bacterial infection)

Постковидный синдром ассоциирован с повышением внеклеточных пуриновых оснований и нейтрофильных экстраклеточных ловушек в плазме крови

Post-COVID syndrome is characterized by fatigue, reduced exercise tolerance, muscle and joint pain, and psychoemotional disorders. In the development of a generalized body response in a viral infection, abnormal defense responses are of great importance. We studied neutrophils, neutrophil extracellular traps (NETs), DNA degradation products (purine nitrogenous bases, PNBs), and traditional biochemical parameters.Aim. To determine biochemical parameters and the number of NETs and PNBs in the peripheral blood of patients with post-COVID syndrome.Materials and methods. The study included outpatients (n = 21) aged 18–59 years (36 [27 ÷ 50]). The control group consisted of 20 individuals aged 18–59 years (38.5 [29 ÷ 51.5]) without a past medical history of the coronavirus infection. All patients underwent a physical examination, their medical history was assessed, and the level of NETs and PNBs in the venous blood was determined.Results. 11 patients had a mild form of the disease in their past medical history, 7 – moderate, and 3 – severe. The most common symptoms in the patients were fatigue, headache, epigastric pain, dizziness, and joint pain. Hair loss and dyspnea were less common. The concentration of NETs and PNBs was higher in the patients with post-COVID syndrome than in the control group (p < 0.05). We detected NETs in the patients with post-COVID syndrome only in the form of filamentous structures. The concentration of extracellular purine bases in the blood of the patients with post-COVID syndrome was the highest in patients with moderate and severe acute periods. In patients with a mild acute period, the concentration of PNBs was 7.38 [0.0 ÷ 60.7] mg / ml, and in patients with moderate and severe acute periods – 19.15 [0.0 ÷ 33.5] and 34.19 [3.35 ÷ 70.0] mg / ml, respectively.Conclusion. Extracellular purine bases in concentrations capable of causing secondary alteration of cells are found in the peripheral blood of patients with post-COVID syndrome. Post-COVID syndrome is accompanied by the formation of filamentous NETs in the blood of patients. Постковидный синдром характеризуется высокой утомляемостью, снижением толерантности к физической нагрузке, болями в мышцах и суставах, наличием психоэмоциональных проблем. В развитии генерализованной реакции организма при вирусном инфицировании большое значение имеют аномальные реакции защитных систем. Мы исследовали нейтрофилы и формируемые ими экстраклеточные ловушки (НЭЛ) совместно с продуктами деградации волокон ДНК (пуриновые азотистые основания, ПАО), а также традиционные клинико-лабораторные показатели.Цель. Определение ряда лабораторных показателей, а также количества НЭЛ и уровня ПАО в периферической крови больных с постковидным синдромом.Материалы и методы. В исследование включены амбулаторные пациенты (n = 21) в возрасте 18–59 лет (36 [27÷50]). Группу сравнения составили 20 лиц в возрасте 18–59 лет (38,5 [29÷51,5]) без перенесенной коронавирусной инфекции. Всем пациентам проводились сбор жалоб, оценка анамнеза, физикальный осмотр, определение НЭЛ и ПАО в венозной крови.Результаты. Легкое течение заболевания в анамнезе имелось у 11, среднетяжелое – у 7, тяжелое – у 3 пациентов. Наиболее частыми симптомами в нашей группе обследованных пациентов были слабость, головная боль, боль в эпигастрии, головокружение, боль в суставах. Более редкими симптомами являлись выпадение волос и одышка. Концентрация НЭЛ и ПАО была выше в основной группе, чем в группе сравнения (p < 0,05). Мы выявляли НЭЛ у больных с постковидным синдромом только в нитевидной форме. Концентрация внеклеточных пуриновых азотистых оснований в плазме крови больных с постковидным синдромом была наиболее высокой у больных со среднетяжелым и тяжелым течением острого периода. У больных, перенесших острый период заболевания в легкой форме, концентрация ПАО составляет 7,38 [0,0÷60,7] мг/мл, а у больных со среднетяжелой и тяжелой формой острого периода – 19,15 [0,0÷33,5] и 34,19 [3,35÷70,0] мг/мл соответственно.Заключение. В периферической крови больных с посткоронавирусным синдромом обнаруживаются внеклеточные ПАО в концентрации, способной вызвать вторичную альтерацию клеток. Постковидный синдром сопровождался формированием в периферической крови больных НЭЛ в нитевидной форме

A randomised trial of non-invasive cardiac output monitoring to guide haemodynamic optimisation in high risk patients undergoing urgent surgical repair of proximal femoral fractures (ClearNOF trial NCT02382185)

Background: Hip fracture is a procedure with high mortality and complication rates, and there exists a group especially at risk of these outcomes identified by their Nottingham Hip Fracture Score (NHFS). Meta-analysis suggests a possible benefit to this patient group from intravascular volume optimisation. We investigated whether intraoperative fluid and blood pressure optimisation improved complications in this group. Methods: Patients with a NHFS ≥ 5 were enrolled into this multicentre observer-blinded randomised control trial. Patients were allocated to either standard care or a combination of fluid optimisation and blood pressure control using a non-invasive system. The primary outcome was the number of patients with one or more complications in each group. Secondary outcomes included hospital length of stay (LOS), incidence of hypotension and fluid and vasopressor usage. Results: Forty-six percent of patients in the intervention group suffered one or more complications compared to the 51% in the control group (OR 0.82 (95% CI 0.49-1.36)). Per-protocol analysis improved the OR to 0.73 (95% CI 0.43-1.24). Median LOS was the same between both groups; however, the mean LOS on a per-protocol analysis was longer in the control group compared to the intervention group (23.2 (18.0) days vs. 18.5 (16.5), p = 0.047). Conclusions: Haemodynamic optimisation including blood pressure management in high-risk patients undergoing repair of a hip fracture did not result in a statistically significant reduction in complications; however, a potential reduction in length of stay was seen. Trial registration: A randomised trial of non-invasive cardiac output monitoring to guide haemodynamic optimisation in high risk patients undergoing urgent surgical repair of proximal femoral fractures (ClearNOF trial NCT02382185)

Analysis of the impact of length of stay on the quality of service experience, satisfaction and loyalty

Although length of stay is a relevant variable in destination management, little research has been produced connecting it with tourists' post-consumption behaviour. This research compares the post-consumption behaviour of same-day visitors with overnight tourists in a sample of 398 domestic vacationers at two Mediterranean heritage-and-beach destinations. Although economic research on length of stay posits that there are destination benefits in longer stays, same-day visitors score higher in most of the post-consumption variables under study. Significant differences arise in hedonic aspects of the tourist experience and destination loyalty. Thus, we propose that length of stay can be used as a segmentation variable. Furthermore, destination management organisations need to consider length of stay when designing tourism policies. The tourist product and communication strategies might be adapted to different vacation durations

Postoperative acute kidney injury in adult non-cardiac surgery:joint consensus report of the Acute Disease Quality Initiative and PeriOperative Quality Initiative

Postoperative acute kidney injury (PO-AKI) is a common complication of major surgery that is strongly associated with short-term surgical complications and long-term adverse outcomes, including increased risk of chronic kidney disease, cardiovascular events and death. Risk factors for PO-AKI include older age and comorbid diseases such as chronic kidney disease and diabetes mellitus. PO-AKI is best defined as AKI occurring within 7 days of an operative intervention using the Kidney Disease Improving Global Outcomes (KDIGO) definition of AKI; however, additional prognostic information may be gained from detailed clinical assessment and other diagnostic investigations in the form of a focused kidney health assessment (KHA). Prevention of PO-AKI is largely based on identification of high baseline risk, monitoring and reduction of nephrotoxic insults, whereas treatment involves the application of a bundle of interventions to avoid secondary kidney injury and mitigate the severity of AKI. As PO-AKI is strongly associated with long-term adverse outcomes, some form of follow-up KHA is essential; however, the form and location of this will be dictated by the nature and severity of the AKI. In this Consensus Statement, we provide graded recommendations for AKI after non-cardiac surgery and highlight priorities for future research

Tobacco control policies and perinatal health:A national quasi-experimental study

We investigated whether changes in perinatal outcomes occurred following introduction of key tobacco control policies in the Netherlands: smoke-free legislation in workplaces plus a tobacco tax increase and mass media campaign (January-February 2004); and extension of the smoke-free law to the hospitality industry, accompanied by another tax increase and mass media campaign (July 2008). This was a national quasi-experimental study using Netherlands Perinatal Registry data (2000-2011; registration: ClinicalTrials.gov NCT02189265). Primary outcome measures were: perinatal mortality, preterm birth, and being small-for-gestational age (SGA). The association with timing of the tobacco control policies was investigated using interrupted time series logistic regression analyses with adjustment for confounders. Among 2,069,695 singleton births, there were 13,027 (0.6%) perinatal deaths, 116,043 (5.6%) preterm live-births and 187,966 (9.1%) SGA live-births. The 2004 policies were not associated with significant changes in the odds of developing any of the primary outcomes. After the 2008 policy change, a -4.4% (95% CI -2.4; -6.4, p < 0.001) decrease in odds of being SGA was observed. A reduction in SGA births, but not preterm birth or perinatal mortality, was observed in the Netherlands after extension of the smoke-free workplace law to bars and restaurants in conjunction with a tax increase and mass media campaign