Инвазивный аспергиллез легких после трансплантации сердца

Objective: to assess the incidence, determine the peculiarities of the course of invasive pulmonary aspergillosis (IPA) and identify risk factors for IPA in heart transplant recipients.Materials and methods. From January 2010 to December 2019, 137 heart transplantations (HT) were performed: mean age 46 ± 14 years; male 102 (74%) and female 35 (26%). All patients received a three-component immunosuppressive therapy: calcineurin inhibitors, mycophenolate mofetil (MMF) and Glucocorticoid (GCs). Induction therapy consisted of Basiliximab (81%, n = 111) and antithymocyte immunoglobulin (15%, n = 20). A retrospective analysis of patients with identified post-HT invasive IPA was performed; risk factors for IPA were assessed. In patients with early IPA, the length of stay in the intensive care unit (ICU), the duration of mechanical ventilation, and the initial severity of the condition were studied. All patients with suspected pneumonia underwent bronchoscopy with examination of bronchoalveolar lavage (BAL) and chest computed tomography (chest CT scan).Results. During the follow-up, there were 58 episodes of pneumonia, of which 16 (28%) were IPA (age 33 to 64 years). All patients had a target level of immunosuppressive drugs concentration in blood; basiliximab was used as induction therapy in 15 of 16 patients. Half of the recipients developed IPA in the early post-HT period (less than 3 months after HT), in the rest (n = 8) – at a later date (3 months to 1 year after HT). The diagnosis was verified: 14 out of 16 patients showed an increase in the Aspergillus antigen positivity in the BAL to 7.2 (2.8 ± 1.6); chest CT scan revealed specific changes. In two patients, there were no diagnostic criteria for IPA, but the diagnosis was made based on the results of histological examination after resection of the left lower lobe of the lung. All patients received voriconazole therapy for 2 to 6 months, their immunosuppressive therapy was adjusted (tacrolimus and MMF dose adjustment) and their white blood cell count was monitored. Complete cure of the disease was achieved in 13 (81%) patients. Two patients died within 30 days after HT in the intensive care unit, one died from urogenital diseases caused by bacterial flora and leading to urosepsis, 4 months after IPA treatment was initiated. All patients had risk factors for IPA: taking immunosuppression, including GCs (n = 16), prolonged ICU stay (n = 14), inotropic support exceeding 2 days in the early post-transplant period (n = 10), cachexia during HT (n = 6), leukopenia (n = 9) and neutropenia (n = 14).Conclusion. In heart transplantat recipients, the incidence of IPA among respiratory tract infections is 28%. The risk of developing IPA was highest during the first year following HT. In the majority of recipients, the disease was detected at the early stages; diagnosis required surgical intervention in 12% of cases. A decrease in the risk of developing IPA was associated with correction of the following risk factors for this disease in all patients: volume of immunosuppressive therapy during the first year after transplantation and prevention of the development of neutropenia as a marker of infectious complications or immunosuppression overdose. Early diagnosis of IPA allowed for initiation of timely specific therapy in most recipients and achievement of a positive effect in 80% of them.Цель. Оценить частоту развития, определить особенности течения инвазивного аспергиллеза легких (АСП) и выявить факторы риска развития заболевания у реципиентов после трансплантации сердца (ТС).Материалы и методы. C января 2010-го по декабрь 2019 г. было выполнено 137 ТС: средний возраст 46 ± 14 лет; мужчин – 102 (74%), женщин – 35 (26%). Все пациенты получали трехкомпонентную иммуносупрессивную терапию: ингибиторы кальциневрина, микофенолата мофетил (ММФ) и глюкокортикостероиды (ГКС). Индукционная терапия была представлена базиликсимабом (81%, n = 111) и антитимоцитарным иммуноглобулином (15%, n = 20). Проведен ретроспективный анализ пациентов с выявленным инвазивным АСП, перенесенным после ТС, оценены факторы риска развития АСП. У пациентов с ранним АСП изучены длительность нахождения в отделении реанимации (ОР) и продолжительность ИВЛ, исходная тяжесть состояния. Всем пациентам с подозрением на пневмонию проводились бронхоскопия с исследованием бронхоальвеолярного лаважа (БАЛ) и компьютерная томография грудной клетки (КТ ОГК).Результаты. За время наблюдения было зарегистрировано 58 эпизодов пневмоний, из них 16 (28%) – АСП (возраст от 33 до 64 лет). У всех пациентов был целевой уровень концентрации иммуносупрессивных препаратов в крови, у 15 из 16 пациентов в качестве индукционной терапии был применен базиликсимаб. У половины реципиентов АСП развился в ранние сроки после ТС (менее 3 месяцев после ТС), у остальных (n = 8) – в поздние сроки (3 месяца – 1 год после ТС). Диагноз был верифицирован: у 14 из 16 пациентов наблюдалось повышение коэффициента позитивности антиген Aspergillus в БАЛ до 7,2 (2,8 ± 1,6), имели место специфические изменения по КТ ОГК. У двух пациентов диагностические критерии АСП отсутствовали, но диагноз был поставлен по результатам гистологического исследования после резекции нижней доли левого легкого. Всем пациентам проводилась терапия вориконазолом продолжительностью от 2 до 6 месяцев, коррекция иммуносупрессивной терапии (коррекция дозы такролимуса и ММФ) и контроль уровня лейкоцитов в динамике. Полное излечение заболевания было достигнуто у 13 (81%) пациентов. Двое больных умерли в течение 30 дней после ТС в отделении реанимации, один – от заболеваний мочеполовой системы, вызванных бактериальной флорой и приведших к развитию уросепсиса, через 4 месяца после начала лечения АСП. У всех пациентов имели место факторы риска развития АСП: прием иммуносупрессии, в том числе ГКС (n = 16), длительное пребывание в ОР (n = 14), инотропная поддержка более 2 суток в раннем посттрансплантационном периоде (n = 10), кахексия на момент ТС (n = 6), лейкопения (n = 9) и нейтропения (n = 14).Заключение. У пациентов после ТС встречаемость АСП среди инфекций дыхательных путей составляет 28%. Наиболее высоким риск развития АСП был в течение первого года после ТС. У большинства реципиентов заболевание было выявлено на начальных стадиях, в 12% случаев для диагностики потребовалось проведение оперативного вмешательства. Снижение риска развития АСП было ассоциировано с коррекцией следующих факторов риска этого заболевания у всех пациентов: объем иммуносупрессивной терапии в течение первого года после трансплантации и предотвращение развития нейтропении как маркера инфекционных осложнений или переизбытка иммуносупрессии. Ранняя диагностика АСП позволила у большинства реципиентов начать своевременную специфическую терапию и добиться положительного эффекта у 80% из них

Chronoastrobiology : proposal, nine conferences, heliogeomagnetics, transyears, near-weeks, near-decades, phylogenetic and ontogenetic memories

"Chronoastrobiology: are we at the threshold of a new science? Is there a critical mass for scientific research?" A simple photograph of the planet earth from outer space was one of the greatest contributions of space exploration. It drove home in a glance that human survival depends upon the wobbly dynamics in a thin and fragile skin of water and gas that covers a small globe in a mostly cold and vast universe. This image raised the stakes in understanding our place in that universe, in finding out where we came from and in choosing a path for survival. Since that landmark photograph was taken, new astronomical and biomedical information and growing computer power have been revealing that organic life, including human life, is and has been connected to invisible (non-photic) forces, in that vast universe in some surprising ways. Every cell in our body is bathed in an external and internal environment of fluctuating magnetism. It is becoming clear that the fluctuations are primarily caused by an intimate and systematic interplay between forces within the bowels of the earth--which the great physician and father of magnetism William Gilbert called a 'small magnet'--and the thermonuclear turbulence within the sun, an enormously larger magnet than the earth, acting upon organisms, which are minuscule magnets. It follows and is also increasingly apparent that these external fluctuations in magnetic fields can affect virtually every circuit in the biological machinery to a lesser or greater degree, depending both on the particular biological system and on the particular properties of the magnetic fluctuations. The development of high technology instruments and computer power, already used to visualize the human heart and brain, is furthermore making it obvious that there is a statistically predictable time structure to the fluctuations in the sun's thermonuclear turbulence and thus to its magnetic interactions with the earth's own magnetic field and hence a time structure to the magnetic fields in organisms. Likewise in humans, and in at least those other species that have been studied, computer power has enabled us to discover statistically defined endogenous physiological rhythms and further direct effects that are associated with these invisible geo- and heliomagnetic cycles. Thus, what once might have been dismissed as noise in both magnetic and physiological data does in fact have structure. And we may be at the threshold of understanding the biological and medical meaning and consequences of these patterns and biological-astronomical linkages as well. Structures in time are called chronomes; their mapping in us and around us is called chronomics. The scientific study of chronomes is chronobiology. And the scientific study of all aspects of biology related to the cosmos has been called astrobiology. Hence we may dub the new study of time structures in biology with regard to influences from cosmo- helio- and geomagnetic rhythms chronoastrobiology. It has, of course, been understood for centuries that the movements of the earth in relation to the sun produce seasonal and daily cycles in light energy and that these have had profound effects on the evolution of life. It is now emerging that rhythmic events generated from within the sun itself, as a large turbulent magnet in its own right, can have direct effects upon life on earth. Moreover, comparative studies of diverse species indicate that there have also been ancient evolutionary effects shaping the endogenous chronomic physiological characteristics of life. Thus the rhythms of the sun can affect us not only directly, but also indirectly through the chronomic patterns that solar magnetic rhythms have created within our physiology in the remote past. For example, we can document the direct exogenous effects of given specific solar wind events upon human blood pressure and heart rate. We also have evidence of endogenous internal rhythms in blood pressure and heart rate that are close to but not identical to the period length of rhythms in the solar wind. These were installed genetically by natural selection at some time in the distant geological past. This interpretive model of the data makes the prediction that the internal and external influences on heart rate and blood pressure can reinforce or cancel each other out at different times. A study of extensive clinical and physiological data shows that the interpretive model is robust and that internal and external effects are indeed augmentative at a statistically significant level. Chronoastrobiological studies are contributing to basic science--that is, our understanding is being expanded as we recognize heretofore unelaborated linkages of life to the complex dynamics of the sun, and even to heretofore unelaborated evolutionary phenomena. Once, one might have thought of solar storms as mere transient 'perturbations' to biology, with no lasting importance. Now we are on the brink of understanding that solar turbulences have played a role in shaping endogenous physiological chronomes. There is even documentation for correlations between solar magnetic cycles and psychological swings, eras of belligerence and of certain expressions of sacred or religious feelings. Chronoastrobiology can surely contribute to practical applications as well as to basic science. It can help develop refinements in our ability to live safely in outer space, where for example at the distance of the moon the magnetic influences of the sun will have an effect upon humans unshielded by the earth's native magnetic field. We should be better able to understand these influences as physiological and mechanical challenges, and to improve our estimations of the effects of exposure. Chronoastrobiology moreover holds great promise in broadening our perspectives and powers in medicine and public health right here upon the surface of the earth. Even the potential relevance of chronoastrobiology for practical environmental and agricultural challenges cannot be ruled out at this early stage in our understanding of the apparently ubiquitous effects of magnetism and hence perhaps of solar magnetism on life. The evidence already mentioned that fluctuations in solar magnetism can influence gross clinical phenomena such as rates of strokes and heart attacks, and related cardiovascular variables such as blood pressure and heart rate, should illustrate the point that the door is open to broad studies of clinical implications. The medical value of better understanding magnetic fluctuations as sources of variability in human physiology falls into several categories: 1) The design of improved analytical and experimental controls in medical research. Epidemiological analyses require that the multiple sources causing variability in physiological functions and clinical phenomena be identified and understood as thoroughly as possible, in order to estimate systematic alterations of any one variable. 2) Preventive medicine and the individual patients'care. There are no flat 'baselines', only reference chronomes. Magnetic fluctuations can be shown statistically to exacerbate health problems in some cases. The next step should be to determine whether vulnerable individuals can be identified by individual monitoring. Such vulnerable patients may then discover that they have the option to avoid circumstances associated with anxiety during solar storms, and/or pay special attention to their medication or other treatments. Prehabilitation by self-help can hopefully complement and eventually replace much costly rehabilitation. 3) Basic understanding of human physiological mechanisms. The chronomic organization of physiology implies a much more subtle dynamic integration of functions than is generally appreciated. All three categories of medical value in turn pertain to the challenges for space science of exploring and colonizing the solar system. The earth's native magnetic field acts like an enormous umbrella that offers considerable protection on the surface from harsh solar winds of charged particles and magnetic fluxes. The umbrella becomes weaker with distance from the earth and will offer little protection for humans, other animals, and plants in colonies on the surface of the moon or beyond. Thus it is important before more distant colonization is planned or implemented to better understand those magnetism-related biological- solar interactions that now can be studied conveniently on earth. Thorough lifelong maps of chronomes should be generated and made available to the scientific world. Individual workers should not have to rediscover cycles and rhythms, which can be a confusing source of variation when ignored. By contrast, once mapped, the endpoints of a spectral element in chronomes can serve everybody, for instance for the detection of an elevation of vascular disease risk. Chronomic cartography from birth to death is a task for governments to implement, thereby serving the interests of transdisciplinary science and the general public alike. Governments have supported the systematic gathering of physical data for nearly two centuries on earth in order to serve exploration, trade, and battle on land and on the seas, and indeed agriculture. These government functions have been augmented enormously with satellite technology in more recent decades. The biological comparison with regard to government support and chronomic needs would be the mapping of the human genome. The complete sequences of DNA might have eventually become available due simply to countless individual laboratories publishing piecemeal results in scattered journals. But there would have been enormous redundancy and confusion in assembling and piecing the information together. The waste of time and money involved in the redundancy and confusion would have been considerable. 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