PREVENTION AND TREATMENT OF ISCHEMIA-REPERFUSION INJURY IN LIVER TRANSPLANTATION-POSSIBLE WAY TO EXPAND THE DONOR POOL

The shortage of donor organs results in the search for alternative ways to increase the donor pool. One of these is the expansion of marginal donor criteria. The use of liver grafts from donors in this group is associated with a high risk of primary non-functioning graft which lies at the basis of ischemia-reperfusion injury of the liver. In this regard, in this review, we examined the main stages of the pathogenesis of liver disturbances as well as modern methods of prevention and treatment

ПРОФИЛАКТИКА И ЛЕЧЕНИЕ ИШЕМИЧЕСКИ-РЕПЕРФУЗИОННЫХ ПОВРЕЖДЕНИЙ ПРИ ТРАНСПЛАНТАЦИИ ПЕЧЕНИ – ВОЗМОЖНЫЙ ПУТЬ К РАСШИРЕНИЮ ДОНОРСКОГО ПУЛА

The shortage of donor organs results in the search for alternative ways to increase the donor pool. One of these is the expansion of marginal donor criteria. The use of liver grafts from donors in this group is associated with a high risk of primary non-functioning graft which lies at the basis of ischemia-reperfusion injury of the liver. In this regard, in this review, we examined the main stages of the pathogenesis of liver disturbances as well as modern methods of prevention and treatment. Дефицит донорских органов индуцирует поиск альтернативных путей увеличения донорского пула. Од- ним из таковых является расширение критериев маргинального донора. Применение трансплантатов печени от доноров данной группы сопряжено с высоким риском развития ранней дисфункции транс- плантата, в основе которого лежит ишемически-реперфузионное повреждение (ИРП) печени. В связи с этим в обзоре рассмотрены основные этапы патогенеза ИРП печени, а также современные методы его профилактики и лечения.

Role of portocaval shunts in development of complications after liver transplantation

Rationale. Portal blood flow is a key component in the viability of the liver transplant. Portocaval shunts formed on the background of the liver cirrhosis before transplantation can cause portal vein steal syndrome, with subsequent development of ischemic necrosis of the graft. To date, the tactics of treating patients with portal vein steal syndrome during liver transplantation has not been sufficiently developed. This paper presents a literature review and our own experience on this important, but little-studied issue. Purpose. The purpose of this research is to study the role of portocaval shunts in the development of complications after liver transplantation, based on a retrospective analysis of clinical cases. Conclusions. In liver transplantation, portocaval shunts can cause the development of portal vein steal syndrome with subsequent development of liver failure. For the diagnosis of portal vein steal syndrome, it is important to use the data obtained at all stages of liver transplantation. Surgical correction of portal vein steal syndrome can be performed during liver transplantation and in the early postoperative period. © 2022 by the authors

ИССЛЕДОВАНИЕ АССОРТИМЕНТА ГАЗОАНАЛИЗАТОРОВ, ПРЕДСТАВЛЕННЫХ НА РОССИЙСКОМ РЫНКЕ И ПРЕДНАЗНАЧЕННЫХ ДЛЯ МОНИТОРИНГА CO2, SO2, NO2, NH3

Our research of russian market of gas-analyzers for monitoring gases which are polluting the environment by chemical and oil-chemical manufacturing companies, such as:  CO<sub>2</sub>, SO<sub>2</sub>, NO<sub>2</sub> and NH<sub>3</sub>.Проведено исследование российского рынка газоанализаторов, предназначенных для мониторинга газообразных веществ, выбрасываемых в максимальных количествах предприятиями химической и нефтехимической промышленности в окружающую среду: CO<sub>2</sub>, SO<sub>2</sub>, NO<sub>2</sub> и  NH<sub>3</sub&gt

Гендерные аспекты развития уролитиаза у пациентов с метаболическим синдромом

The review summarizes and analyzes the results of domestic and major foreign studies of recent years concerning gender characteristics of the epidemiology and development mechanisms of metabolic syndrome and urolithiasis as an associated disease. A deep understanding of gender aspects in the pathogenesis of these pathologies can form the basis for development of high-quality diagnostic algorithms and pathogenetically grounded approaches to treatment. В обзоре обобщены и проанализированы результаты отечественных и крупных зарубежных исследований последних лет, касающиеся гендерных особенностей эпидемиологии и механизмов развития метаболического синдрома и мочекаменной болезни как ассоциированного с ним заболевания. Глубокое понимание гендерных аспектов в патогенезе данных патологических процессов может лечь в основу разработки качественных диагностических алгоритмов и патогенетически обоснованных подходов к лечению.

Longitudinal clinical, cognitive and biomarker profiles in dominantly inherited versus sporadic early-onset Alzheimer's disease

Approximately 5% of Alzheimer's disease cases have an early age at onset (<65 years), with 5-10% of these cases attributed to dominantly inherited mutations and the remainder considered as sporadic. The extent to which dominantly inherited and sporadic early-onset Alzheimer's disease overlap is unknown. In this study, we explored the clinical, cognitive and biomarker profiles of early-onset Alzheimer's disease, focusing on commonalities and distinctions between dominantly inherited and sporadic cases. Our analysis included 117 participants with dominantly inherited Alzheimer's disease enrolled in the Dominantly Inherited Alzheimer Network and 118 individuals with sporadic early-onset Alzheimer's disease enrolled at the University of California San Francisco Alzheimer's Disease Research Center. Baseline differences in clinical and biomarker profiles between both groups were compared using t-tests. Differences in the rates of decline were compared using linear mixed-effects models. Individuals with dominantly inherited Alzheimer's disease exhibited an earlier age-at-symptom onset compared with the sporadic group [43.4 (SD +/- 8.5) years versus 54.8 (SD +/- 5.0) years, respectively, P < 0.001]. Sporadic cases showed a higher frequency of atypical clinical presentations relative to dominantly inherited (56.8% versus 8.5%, respectively) and a higher frequency of APOE-epsilon 4 (50.0% versus 28.2%, P = 0.001). Compared with sporadic early onset, motor manifestations were higher in the dominantly inherited cohort [32.5% versus 16.9% at baseline (P = 0.006) and 46.1% versus 25.4% at last visit (P = 0.001)]. At baseline, the sporadic early-onset group performed worse on category fluency (P < 0.001), Trail Making Test Part B (P < 0.001) and digit span (P < 0.001). Longitudinally, both groups demonstrated similar rates of cognitive and functional decline in the early stages. After 10 years from symptom onset, dominantly inherited participants experienced a greater decline as measured by Clinical Dementia Rating Sum of Boxes [3.63 versus 1.82 points (P = 0.035)]. CSF amyloid beta-42 levels were comparable [244 (SD +/- 39.3) pg/ml dominantly inherited versus 296 (SD +/- 24.8) pg/ml sporadic early onset, P = 0.06]. CSF phosphorylated tau at threonine 181 levels were higher in the dominantly inherited Alzheimer's disease cohort (87.3 versus 59.7 pg/ml, P = 0.005), but no significant differences were found for t-tau levels (P = 0.35). In summary, sporadic and inherited Alzheimer's disease differed in baseline profiles;sporadic early onset is best distinguished from dominantly inherited by later age at onset, high frequency of atypical clinical presentations and worse executive performance at baseline. Despite these differences, shared pathways in longitudinal clinical decline and CSF biomarkers suggest potential common therapeutic targets for both populations, offering valuable insights for future research and clinical trial design

The Mechanism for RNA Recognition by ANTAR Regulators of Gene Expression

ANTAR proteins are widespread bacterial regulatory proteins that have RNA–binding output domains and utilize antitermination to control gene expression at the post-initiation level. An ANTAR protein, EutV, regulates the ethanolamine-utilization genes (eut) in Enterococcus faecalis. Using this system, we present genetic and biochemical evidence of a general mechanism of antitermination used by ANTARs, including details of the antiterminator structure. The novel antiterminator structure consists of two small hairpins with highly conserved terminal loop residues, both features being essential for successful antitermination. The ANTAR protein dimerizes and associates with its substrate RNA in response to signal-induced phosphorylation. Furthermore, bioinformatic searches using this conserved antiterminator motif identified many new ANTAR target RNAs in phylogenetically diverse bacterial species, some comprising complex regulons. Despite the unrelatedness of the species in which they are found, the majority of the ANTAR–associated genes are thematically related to nitrogen management. These data suggest that the central tenets for gene regulation by ANTAR antitermination occur widely in nature to specifically control nitrogen metabolism

Comparison of Pheochromocytoma-Specific Morbidity and Mortality among Adults with Bilateral Pheochromocytomas Undergoing Total Adrenalectomy vs Cortical-Sparing Adrenalectomy

Importance: Large studies investigating long-term outcomes of patients with bilateral pheochromocytomas treated with either total or cortical-sparing adrenalectomies are needed to inform clinical management. Objective: To determine the association of total vs cortical-sparing adrenalectomy with pheochromocytoma-specific mortality, the burden of primary adrenal insufficiency after bilateral adrenalectomy, and the risk of pheochromocytoma recurrence. Design, Setting, and Participants: This cohort study used data from a multicenter consortium-based registry for 625 patients treated for bilateral pheochromocytomas between 1950 and 2018. Data were analyzed from September 1, 2018, to June 1, 2019. Exposures: Total or cortical-sparing adrenalectomy. Main Outcomes and Measures: Primary adrenal insufficiency, recurrent pheochromocytoma, and mortality. Results: Of 625 patients (300 [48%] female) with a median (interquartile range [IQR]) age of 30 (22-40) years at diagnosis, 401 (64%) were diagnosed with synchronous bilateral pheochromocytomas and 224 (36%) were diagnosed with metachronous pheochromocytomas (median [IQR] interval to second adrenalectomy, 6 [1-13] years). In 505 of 526 tested patients (96%), germline mutations were detected in the genes RET (282 patients [54%]), VHL (184 patients [35%]), and other genes (39 patients [7%]). Of 849 adrenalectomies performed in 625 patients, 324 (52%) were planned as cortical sparing and were successful in 248 of 324 patients (76.5%). Primary adrenal insufficiency occurred in all patients treated with total adrenalectomy but only in 23.5% of patients treated with attempted cortical-sparing adrenalectomy. A third of patients with adrenal insufficiency developed complications, such as adrenal crisis or iatrogenic Cushing syndrome. Of 377 patients who became steroid dependent, 67 (18%) developed at least 1 adrenal crisis and 50 (13%) developed iatrogenic Cushing syndrome during median (IQR) follow-up of 8 (3-25) years. Two patients developed recurrent pheochromocytoma in the adrenal bed despite total adrenalectomy. In contrast, 33 patients (13%) treated with successful cortical-sparing adrenalectomy developed another pheochromocytoma within the remnant adrenal after a median (IQR) of 8 (4-13) years, all of which were successfully treated with another surgery. Cortical-sparing surgery was not associated with survival. Overall survival was associated with comorbidities unrelated to pheochromocytoma: of 63 patients who died, only 3 (5%) died of metastatic pheochromocytoma. Conclusions and Relevance: Patients undergoing cortical-sparing adrenalectomy did not demonstrate decreased survival, despite development of recurrent pheochromocytoma in 13%. Cortical-sparing adrenalectomy should be considered in all patients with hereditary pheochromocytoma

ОТДАЛЕННЫЕ РЕЗУЛЬТАТЫ ТРАНСПЛАНТАЦИИ ТРУПНОЙ ПЕЧЕНИ

Aim of the study was to evaluate patient and graft survival after liver transplantation (LT) and to determine if primary disease diagnosis, early graft dysfunction or other factors affect it. Furthermore, we analyzed the reasonsof short-term and long-term deaths or retransplantations.Materials and methods. 192 LTs from donors with brain death were performed from December 2004 until June 2014. Recipient age varied from 5 to 71 years. Most frequent diagnosis was liver cirrhosis (mainly due to hepatitis C), then hepatocellular carcinoma (HCC), liver graft dysfunction, etc.Results and discussion. 1-year patient survival is 89.5%, graft survival is 87.7%, 3-year –87% and 84.6%, respectively, and 5-year – 83.5% and 83.0%, respectively. Early mortality (in fi rst 30 days after transplantation) was 8%, long-term mortality – 5.9%. Primary non-function graft (PNF) was the reason of 66.7% early deaths. In the long term, infections and oncology were the reasons of death with the same frequency – 36.4%. Early graft dysfunction including primary non-function signifi cantly decreases short term survival (p = 0.0002). Nevertheless, in the majority of cases graft function improves and doesn’t affect survival. Donor factors play role in outcomes: early dysfunction is higher (40.6%) in extended criteria donor group than in standard donor group (р = 0.0431). PNF has the same trend – 8.5% and 0.0%, respectively, but without signifi cance (р =0.0835). 5-year survival is remarkably lower in HCC group 40.8% (p = 0.003) than in other groups.Conclusion: survival after liver transplantation in our Center is comparable with the results of the world’s centers.Цель данного исследования – изучить выживаемость больных и трансплантатов в зависимости от диагно-за первичного заболевания, наличия ранней дисфункции трансплантата, причины летальности на разныхсроках, проанализировать результаты ретрансплантаций.Материалы и методы. С декабря 2004 года по июнь 2014 года в ФНЦТИО было выполнено 192 трансплантации печени от доноров с диагнозом «смерть мозга» 186 реципиентам в возрасте от 5 лет до 71 года. В структуре показаний к трансплантации на первом месте по частоте находился цирроз печени, чаще всего в исходе гепатита С, затем гепатоцеллюлярная карцинома, дисфункция трансплантата печени и другие заболевания.Результаты и обсуждение. Однолетняя выживаемость реципиентов составляет 89,5%, трансплантатов – 87,7%, трехлетняя – 87 и 84,6%, пятилетняя – 83,5 и 83,0% соответственно. Периоперационная летальность составила 8%, отдаленная – 5,9%. Основной причиной смерти в раннем послеоперационном периоде являлись первично не функционирующие трансплантаты (ПНФТ) – 66,7% потерь, в отдаленном – одинаково часто (36,4% потерь) злокачественные новообразования и инфекции. Ранняя дисфункция трансплантата (РДТ), включая ПНФТ, статистически значимо снижает выживаемость в раннем послеоперационном периоде (p = 0,0002). Однако у большинства больных РДТ обратима и в этом случае в дальнейшем не влияет на выживаемость. При использовании трансплантата от стандартного донора частота РДТ была статистически значимо меньше – 21,2%, чем при расширении критериев – 40,6% (р = 0,0431), а частота ПНФТ составила 0,0 и 8,5%, соответственно (р = 0,0835). Пятилетняя выживаемость при трансплантации по поводу ГЦК значимо ниже, чем при наличии других показаний – 40,8% (p = 0,003).Заключение: выживаемость реципиентов после трансплантации печени в нашем центре на сроке до 10 лет сопоставима с результатами мировых регистров