Splanchnic Research Articles

Microbiota transplantation in portal hypertension: promises and pitfalls.

In this commentary, we discuss new findings indicating that microbiota transplantation has favorable impact on portal hypertension (PH) in the experimental model of cirrhosis induced by bile duct ligation (BDL) (Huang et al.; Clin Sci (Lond) (2021) 135(24): 2709-2728, doi: 10.1042/CS20210602). Sinusoidal PH is an ominous outcome of advanced chronic liver disease, characterized by increased intrahepatic vascular resistance (IHVR), splanchnic hyperemia, and the development of portosystemic collaterals. In the work of Huang et al., microbiota transplantation not only alleviated splanchnic hyperdynamic circulation by improving vascular responsiveness and decreasing mesenteric angiogenesis, but also reduced blood flow in portosystemic collaterals. Surprisingly, however, microbiota transplantation had no effect on intrahepatic vasoconstriction in this experimental model. We discuss these observations in the context of recent literature showing that manipulation of the gut microbiota (either by transplantation or through the use of probiotics) may improve IHVR, which is one of the earliest abnormalities in the pathogenesis of sinusoidal PH. Further research is needed to explore the specific molecular and cellular targets associated with the correction of dysbiosis in liver disease.

Fontan-associated liver disease.

Fontan-associated liver disease.

Targeting Preload in Heart Failure: Splanchnic Nerve Blockade and Beyond.

Preload augmentation represents a critical mechanism for the cardiovascular system to increase effective circulating blood volume to increase cardiac filling pressures and, subsequently, for the heart to increase cardiac output. The splanchnic vascular compartment is the primary source of vascular capacity and thus the primary target for preload recruitment in humans. Under normal conditions, sympathetic stimulation of these primary venous vessels promotes the shift of blood from the splanchnic to the thoracic compartment and elevates preload and cardiac output. However, in heart failure, since filling pressures may be elevated at rest due to decreased venous capacitance, incremental recruitment of preload to enhance cardiac output may exacerbate congestion and limit exercise capacity. Accordingly, recent attention has focused on therapies designed to regulate splanchnic vascular redistribution to improve cardiac filling pressures and patient-centered outcomes such as quality of life and exercise capacity in patients with heart failure. In this review, we discuss the relevance of splanchnic circulation as a venous reservoir, the contribution of stressed blood volume to heart failure pathogenesis, and the implications for pharmacological therapeutic interventions to prevent heart failure decompensation. Further, we review emerging device-based approaches for cardiac preload reduction such as partial/complete occlusion of the superior vena cava or the inferior vena cava.

Вплив основних положень Міжнародного керівництва з інтенсивної терапії тяжкого сепсису та септичного шоку — 2012 із додатковою ентеропротекцією на перебіг септичного процесу і вираженість енцефалопатії в структурі поліорганної недостатності

У статті проведено аналіз результатів впливу ключових положень Міжнародного керівництва з інтенсивної терапії тяжкого сепсису та септичного шоку — 2012, доповнених ентеропротекцією, на перебіг септичного процесу і вираженість енцефалопатії в структурі поліорганної недостатності. Заключення аналізу базувалося на підставі динаміки кількісних характеристик фізіологічного патерну CI-DO2-VO2; рН інтрамукозного, шкал GCS, APACHE II, SOFA; показників синдрому системної запальної відповіді; концентрації цитокінів (TNF-α, IL-1, IL-4, IFN-α); імуноглобулінів (IgA, IgM, IgG). Незважаючи на відновлення загальної оксигенації в умовах супранормальних значень DO2-VO2, на 3-тю — 5-ту добу відмічали чотири критерії SIRS, що розцінювалося як імовірність ризику уповільненої регресії синдрому запальної відповіді в подальшому. Сказане вище знайшло своє підтвердження в клінічному показнику лейкоцитів на 7-му добу — 15,18 • 109/л і незрілих форм — 11,88 %. Бали за шкалами APACHE II і SOFA, знизившись порівняно з такими на 5-ту добу, «застигли» на цьому рівні на 7-му добу. Неврологічна симптоматика на 7-му добу оцінювалася як сопор — 10,88 бала. Максимально високі концентрації прозапальних цитокінів на 5-ту — 7-му добу можна пояснити їх реперфузійним походженням після відновлення спланхнічного кровообігу. При цьому позитивним було перевищення IL-4 на 7-му добу свого рівня на 5-ту добу на 77,42 %. Використання сорбентів виявилося неефективним за наявності гострих ерозій і виразок шлунково-кишкового тракту для регенерації ентероцитів і запобігання шлунково-кишковим кровотечам навіть у поєднанні з інгібіторами протонної помпи. Початково передбачувана летальність за сумою балів шкали APACHE II становила 51 %, справжня летальність — 35,5 %, тобто застосування ентеросорбенту призвело до зниження летальності на 15,5 %.

High-altitude exposures and intestinal barrier dysfunction.

Gastrointestinal complaints are often reported during ascents to high altitude (>2,500 m), though their etiology is not known. One potential explanation is injury to the intestinal barrier which has been implicated in the pathophysiology of several diseases. High-altitude exposures can reduce splanchnic perfusion and blood oxygen levels causing hypoxic and oxidative stress. These stressors might injure the intestinal barrier leading to consequences such as bacterial translocation and local/systemic inflammatory responses. The purpose of this mini-review is to 1) discuss the impact of high-altitude exposures on intestinal barrier dysfunction and 2) present medications and dietary supplements which may have relevant impacts on the intestinal barrier during high-altitude exposures. There is a small but growing body of evidence which shows that acute exposures to high altitudes can damage the intestinal barrier. Initial data also suggest that prolonged hypoxic exposures can compromise the intestinal barrier through alterations in immunological function, microbiota, or mucosal layers. Exertion may worsen high-altitude-related intestinal injury via additional reductions in splanchnic circulation and greater hypoxemia. Collectively these responses can result in increased intestinal permeability and bacterial translocation causing local and systemic inflammation. More research is needed to determine the impact of various medications and dietary supplements on the intestinal barrier during high-altitude exposures.

Hemodynamics of superior mesenteric artery by doppler flow velocimetry in enterally fed moderately asphyxiated newborns

Introduction: Asphyxia is an important cause of neonatal mortality and morbidity. The disturbed hemodynamics caused by asphyxia can damage a number of organ systems including gastrointestinal system. Enteral feedings can therefore be risky in the asphyxiated newborns with jeopardized blood supply. Objective: The objective of this study was to estimate the abnormal Doppler flow indices of splanchnic circulation in moderately asphyxiated term newborns on the 1st day of life. Design: This was a prospective case–control study. Study setting: This study was conducted in the Neonatology Division, Department of Pediatrics and Department of Radiodiagnosis, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh. Materials and Methods: This study included thirty hemodynamically stable asphyxiated babies as cases. The controls were gestation- as well as weight-matched normal newborns. Blood flow in the superior mesenteric artery (SMA) was estimated by Doppler ultrasonography within the first 24 h of birth of the baby. The peak systolic velocity, end-diastolic velocity, time-averaged mean velocity, and the resistive index were recorded. The measurement was done before and 1 h after giving feed to the baby. The pre- and postfeed Doppler indices of the SMA were measured and compared with the controls. The tolerance of oral feeds by the babies was regularly monitored. Results: The baseline velocity in the study group prior to feeding was comparable to the control group. None of the cases developed feed intolerance and showed a similar postfeed hemodynamic response in the SMA as that of controls. Conclusion: Enteral feeds could be safely started and continued in all the moderately asphyxiated term neonates within the 1st day of life after demonstrating establishment of splanchnic flow in the Doppler study.

Popular Beverages Stimulate Oropharyngeal and Gut Receptors Eliciting Modulation of the Upper Digestive Processes

This paper reports clinical studies on the effect of agonists of taste and chemethesis receptors in the oropharyngeal cavity and the gut. The peripheral nerve system plays a vital role in our selection or rejection of what we eat and drink. Although the degree to which it is hard-wired has not been determined, it is known that our food and drink choices change with age. Scientific studies on the impact of food and drink on the body have been concerned predominantly with nutritional factors and, more recently, impacts on cholesterol and blood sugar levels. On the other hand, the sensations we experience during eating and drinking have long been regarded, perhaps even dismissed, as purely hedonistic. The idea that foods and drinks may actually influence digestion is a novel one and is based on the discovery 20 years ago of taste buds, innervated by the vagi, in stomach and intestinal tissues. Studies indicate some of our most popular drinks modulate both postprandial hyperaemia and gastric emptying. It is proposed that the bitter taste experienced with some foods and drinks promotes increased blood flow to the splanchnic circulation and slows the flow of chyme to the small intestine. In cases of toxicity, these actions promote emesis whereas at non-toxic levels, bitter substances promote digestion by increasing postprandial hyperaemia and slowing gastric emptying. Additionally, chemethesis agonists can act on the oropharyngeal receptors resulting in a slower gastric emptying. These effects may lead to a learned behaviour and subsequent enjoyment of bitter tastants, rather than their rejection, amongst those with reduced digestive capacity. It provides a rationale for the popularity of certain bitter tasting aperitifs and digestive alcoholic beverages originating in southern Europe.

Microbiota transplants from feces or gut content attenuated portal hypertension and portosystemic collaterals in cirrhotic rats.

Liver cirrhosis and portal hypertension is the end of chronic liver injury with hepatic, splanchnic and portosystemic collateral systems dysregulation. Liver injury is accompanied by gut dysbiosis whereas dysbiosis induces liver fibrosis, splanchnic angiogenesis and dysregulated vascular tones vice versa, making portal hypertension aggravated. It has been proved that intestinal microbiota transplantation alleviates dysbiosis. Nevertheless, the influences of microbiota transplantation on cirrhosis-related portal hypertension are not so clear. Liver cirrhosis with portal hypertension was induced by bile duct ligation (BDL) in rats. Sham rats were surgical controls. Rats randomly received vehicle, fecal or gut (terminal ileum) material transplantation. The results showed that microbiota transplantation from feces or gut material significantly reduced portal pressure in cirrhotic rats (P=0.010, 0.044). Hepatic resistance, vascular contractility, fibrosis and relevant protein expressions were not significantly different among cirrhotic rats. However, microbiota transplantation ameliorated splanchnic hyperdynamic flow and vasodilatation. Mesenteric angiogenesis, defined by whole mesenteric window vascular density, decreased in both transplantation groups and phosphorylated endothelial nitric-oxide synthase (eNOS) was down-regulated. Portosystemic shunts determined by splenorenal shunt (SRS) flow decreased in both transplantation groups (P=0.037, 0.032). Shunting severity assessed by microsphere distribution method showed consistent results. Compared with sham rats, cirrhotic rats lacked Lachnospiraceae. Both microbiota transplants increased Bifidobacterium. In conclusion, microbiota transplantation in cirrhotic rats reduced portal pressure, alleviated splanchnic hyperdynamic circulation and portosystemic shunts. The main beneficial effects may be focused on portosystemic collaterals-related events, such as hepatic encephalopathy and gastroesophageal variceal hemorrhage. Further clinical investigations are mandatory.

Is There a Role for Direct Oral Anticoagulants in the Primary and Secondary Prevention of Myeloproliferative Neoplasm Associated Thrombosis?

Philadelphia chromosome negative myeloproliferative neoplasms (MPN) are clonal haematopoietic stem cell disorders. Of the MPNs, polycythaemia vera (PV) and essential thrombocythaemia (ET) confer a high thrombotic risk which may be the presenting feature of the disease. Thrombotic complications consist of both arterial and venous events and the presence of the JAK2 V617F mutation is associated with higher risk. Patients presenting with an unprovoked thrombus, particularly at an unusual site, e.g., splanchnic circulation, should be screened for the presence of this mutation. Historically, warfarin has been the only option for oral anticoagulation; however, there is now increasing evidence and practise to use direct oral anticoagulants (DOACs) in cancer. The seminal randomised control trials have demonstrated non-inferiority compared to low molecular weight heparin (LMWH) with a preferable bleeding profile. DOACs are now the first line treatment for atrial fibrillation and venous thromboembolic disease, as recommended by NICE, and therefore there is increasing familiarity with these agents. Furthermore, there are now targeted antidotes available. This paper reviews evidence for efficacy and safety of DOACs in MPN. Whilst no randomised control trials have been performed, several retrospective studies and reviews of registry data have reproducibly demonstrated that, alongside cytoreduction, DOACs represent an effective modality of anticoagulation for treatment of venous thromboembolism in MPN. Furthermore, dosing regimens provide the option for longer term secondary prophylaxis. Use of DOACs in arterial thrombosis is an area for future development and there is already some evidence for utility in peripheral vascular disease.

Colonoscopy-related colonic ischemia.

Colonoscopy is a risk factor for colon ischemia. The colon is susceptible to ischemia due to its minor blood flow compared to other abdominal organs; the etiology of colon ischemia after colonoscopy is multifactorial. The causative mechanisms include splanchnic circulation impairment, bowel preparation, drugs used for sedation, bowel wall ischemia due to insufflation/barotrauma, and introduction of the endoscope. Gastroenterologists must be aware of this condition and its risk factors for risk minimization, early diagnosis, and proper treatment.

Clinical Features and Long-Term Outcomes in a Molecularly-Annotated Cohort of Adolescents and Young Adults with Myeloproliferative Neoplasms

▪Background:Myeloproliferative neoplasms (MPNs) are a heterogenous group of chronic hematologic malignancies that lead to morbidity and early mortality primarily due to thrombotic complications and progression to acute leukemia. Clinical and mutational risk factors have been demonstrated to predict outcomes in patients with MPNs, and are used commonly to guide therapeutic decisions (including allogenic stem cell transplant) in myelofibrosis. Adolescents and young adults (AYA, age ≤45 years) comprise less than 10% of all MPN patients, and have unique clinical and therapeutic considerations. The prevalence and clinical impact of somatic mutations implicated in myeloid disease has not been extensively reported in this population.Methods:We conducted a retrospective review of patients evaluated at the Princess Margaret Cancer Centre (PMCC) between 1/1/2000 and 30/6/2021 for an MPN diagnosed at ≤45 years of age. Diagnoses were defined per 2016 WHO criteria using available information on chart review. Targeted mutational profiling of clinically relevant myeloid genes (49- or 54-gene panel) was previously performed on peripheral blood or bone marrow samples. Pathologic variants in ASXL1, EZH2, IDH1/2, SRSF2, and U2AF1 Q157 were categorized as high-molecular risk (HMR). Categorical variables were compared using the χ2 test. Kaplan-Meier method was used for overall survival (OS) and time-to-event analysis; and were compared using the log-rank test.Results:A total of 237 patients with initial MPN diagnosis ≤45 years were included in the study, with median age of diagnosis 35 (range 12-45) years. MPN diagnosis included: essential thrombocythemia (ET, n=100), polycythemia vera (PV, n=75), prefibrotic primary myelofibrosis (Pre-PMF, N=29), overt PMF (n=24), and MPN-unclassifiable (MPN-u, n=9). Driver mutation data, available for 230 (97%) patients, were: JAK2 in 134 (56%), CALR in 70 (30%), MPL in 6 (2.5%), and triple-negative in 20 (8.4%) patients.Median follow-up was 10.2 (range 0.3-45.3) years, and median OS was the shortest for those with overt PMF (21.4 years, P=0.001) compared with PV (33.0 years), ET (31.4 years), and Pre-PMF (median OS not reached). No difference in OS based on driver mutation was observed. Progression to a secondary MF (SMF) was observed in 84 patients (47% of ET, 48% of PV) after median time of 19.7 years; with no difference in time to progression due to diagnosis or driver mutation. Progression to an accelerated/blast phase (AP/BP) was observed in 26 patients and was associated with diagnosis of overt PMF (P=0.04) and triple-negative for driver mutation (P=0.04).Thrombosis was observed in 61 (26%) patients: 34 (14%) patients with thrombosis prior to/concurrent with MPN diagnosis, and 34 (14%) patients with thrombosis after diagnosis. Splanchnic circulation thrombosis was found in 29 (12%) patients and 12 (5%) patients had Budd-Chiari syndrome. Portal hypertension was reported in 37 (16%) patients. CALR type-2 mutations were associated with the lowest frequency of total thrombosis (4%, P=0.02); while JAK2 had the greatest frequency of splanchnic circulation clot (17%, P=0.03).Targeted mutational profile was obtained for 202 (85%) of patients: 135 samples obtained during the initial disease phase, 51 samples during a secondary MF phase, and 16 during an AP/BP. For the patients with mutation analysis in the initial phase, 24 pathogenic mutations were observed in 16 (12%) patients including 3 patients with HMR mutations. The most frequent mutations observed were in TET2 (n=12, 9%), and ASXL1 (n=3, 2%). Presence of additional mutations did not predict OS, AP/BP progression, or thrombosis; though TET2 mutation was associated with shorter time to SMF progression in patients with PV/ET (P=0.002). Additional mutations were found in 34/51 (67%) patients in whom mutational analysis was first performed during a SMF disease phase.Conclusions:A long-term follow-up study of a large molecularly annotated cohort of AYA patients with MPN demonstrated excellent long-term survival for these patients. Overt PMF is associated with the lower OS and higher risk of AP/BP transformation. Thrombotic complications including splanchnic circulation thrombosis are frequent complications. Mutations aside from JAK2/MPL/CALR are uncommon and HMR mutations rare in the initial phase of MPN in the AYA population. [Display omitted] DisclosuresGupta: Roche: Consultancy; Pfizer: Consultancy; AbbVie: Consultancy, Honoraria; BMS-Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sierra Oncology: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Honoraria, Research Funding; Constellation Pharma: Consultancy, Honoraria. Maze: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene-BMS: Honoraria; Takeda: Research Funding; PharmaEssentia: Research Funding; Kronos Bio: Research Funding.

Safety and Efficacy of JAK Inhibitor Therapy in BCR-ABL Negative MPN Patients with Underlying Portal Hypertension

▪BackgroundThe BCR-ABL-negative Myeloproliferative neoplasms (MPNs) are clonal stem cell disorders characterized by constitutive activation of the JAK-STAT pathway that include Polycythemia Vera, Essential Thrombocytosis, Primary (PMF) and Secondary Myelofibrosis (SMF). Splenomegaly is a characteristic feature of MPNs that can be ameliorated by JAK inhibitors (JAKi). Up-to one-third of MPN patients also experience portal hypertension (PH). Thrombosis of the splanchnic circulation is the most widely recognized etiology of PH in MPNs, however PH also occurs in the absence of intra-abdominal thrombosis. The influence of PH on outcomes of JAKi therapy in MPN patients has not been characterized. To this end, we aimed to determine the safety and efficacy of JAKi therapy in MPN patients complicated by PH with and without underlying splanchnic circulation thrombosis (ST).MethodsAll patients with MPNs assessed at Princess Margaret Hospital between 01/1998 and 01/2021 were identified from the MPN program's database. Patients who had undergone esophagogastroduodenoscopy (EGD) and had endoscopic evidence of PH, namely esophageal or gastric varices or portal hypertensive gastropathy were included. The study population was further limited to patients who started JAKi therapy following diagnosis of PH. Outcomes were compared between patients with and without underlying ST. The primary endpoint was palpable spleen reduction at 24 weeks. Secondary endpoints included best palpable spleen reduction within one year of starting JAKi, improvement in PH severity as determined by serial EGD assessments during JAKi therapy, overall survival, and ≥grade 3treatment emergent adverse events. Statistical differences in the frequencies of baseline characteristics were assessed using the Wilcoxon rank sum and Chi-Square tests. Overall-survival (OS) estimates were calculated by the Kaplan-Meier method using STATA/IC 16.1 software.ResultsAll MPN patients with evidence of PH on endoscopy who started JAKi therapy after diagnosis of PH were included (n=33). Thirteen patients experienced ST prior to the start of JAKi. The proportion of younger patients and those with PH-related complications (i.e., variceal bleeding and/or ascites) was higher in patients with underlying ST (5/20 [25%] vs 9/13 [69%], p=0.01). The median palpable spleen change at approximately 24 weeks of therapy and the best palpable spleen reduction within the first year of therapy was -40.5% ([-100%[ -[+100%]) and-50% ([-100%]-0%) in the entire cohort, respectively. Better spleen responses with JAKi therapy were observed in PH patients without prior ST compared to those with underlying ST (median palpable spleen change at approximately 24 weeks was -58% (-24%-(-100%)] (n=13) vs -26.5% ([-100%]-[+100%]) (n=9), p=0.062; median best palpable spleen change at any time within 1 year of JAKi therapy start was -71% ([-14%]) -[-100%]) (n=17) vs -35% ([0%-[-100%]) (n=9), p=0.045). Of 21 patients with serial EGDs during JAKi treatment, improvement in PH severity as observed in 8 (38%). There were no differences in survival between patients with and without prior ST. Grade 3 treatment-emergent adverse events included anemia (5/33 [15%]), thrombocytopenia (5/33 [15%]), neutropenia (1/33 [3%]), and suspected Wernicke encephalopathy associated with Momelotinib (1/33 [3%]).Conclusion:In this observational study, JAK inhibitor therapy appears to be safe and effective in MPN patients complicated by PH, with a trend towards improved spleen responses among portal hypertensive patients without splanchnic circulation thrombosis. DisclosuresMaze: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene-BMS: Honoraria; Takeda: Research Funding; PharmaEssentia: Research Funding; Kronos Bio: Research Funding. Gupta: AbbVie: Consultancy, Honoraria; Incyte: Honoraria, Research Funding; Sierra Oncology: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Constellation Pharma: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Consultancy; Pfizer: Consultancy; BMS-Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.

46 Impact of early versus late medical treatment of a hemodynamically significant patent ductus arteriosus on time to reach full feeds in preterm neonates

Abstract Primary Subject area Neonatal-Perinatal Medicine Background Prolonged exposure to a hemodynamically significant patent ductus arteriosus (hsPDA) in preterm infants has been associated with an increase in neonatal morbidities. Objectives To examine the effect of timing of medical treatment (within first 7 days of life versus after 7 days of life) for a hsPDA on the duration to achieve full feeds in infants born at <30 weeks of gestation. Design/Methods This was a retrospective cohort study in a quaternary neonatal intensive care unit (NICU) with a targeted neonatal echocardiography service. Infants admitted between July 2015 – June 2019 who received medical treatment for an hsPDA were included and grouped based on those who received first medical therapy within 7 days of life (early treatment) and after 7 days of life (late treatment). An hsPDA was defined using both clinical (worsening ventilation, pulmonary hemorrhage/edema, or hypotension requiring inotrope or hydrocortisone) and echocardiographic findings (LA/Ao ratio >1.4; LVO >350 mL/kg/min, PDA >1.4 mm, IVRT < 35 ms). Duration to reach full feeds was calculated based on number of days to reach a total enteral feed ≥ 120 mL/kg/day with no parenteral source of nutrition. Results Forty-six infants met the inclusion criteria. Of the 46 infants, 24 were identified as receiving early treatment and 22 received late treatment. Infants in the early treatment group had lower median birth weight than the late treatment group (802 g vs. 1016 g, p=0.022). All other clinical characteristics were not significantly different. No significant difference was found in the use of indomethacin, ibuprofen, or acetaminophen as the initial medical treatment (Table 1). The late treatment group had elevated left ventricular output (median: 286 vs. 369 mL/kg/min, p=0.013) and tricuspid annular plane systolic excursion (median: 6 vs. 8 mm, p=0.002) (Table 2). Infants in the early treatment group reached full feeds earlier than those in the late treatment group (19 vs. 30 days, p=0.042) (Table 1). Conclusion Early medical treatment of hsPDA was associated with shorter duration to reach full feeds in our cohort of preterm infants. Further larger scale study is needed to understand the association between the timing of medical therapy and prolonged exposure of splanchnic circulation to hemodynamically significant ductus.

В помощь практикующему врачу: энтеральный путь коррекции синдрома кишечной недостаточности у больных после хирургических вмешательств

В статье в помощь практикующему врачу рассмотрена такая важная проблема современной хирургии, как развившаяся кишечная недостаточность, и возможные пути ее разрешения. Целью работы было изучение особенностей, необходимости и возможности раннего энтерального питания в комплексном лечении хирургических больных с синдромом кишечной недостаточности с целью уменьшения осложнений, оптимизации лечения. Энтеральное питание начинали после выведения больных из состояния шока, проведения неотложных оперативных вмешательств и стабилизации гемодинамических показателей. Для анализа возможности и сравнительной эффективности различных способов и сроков нутритивной поддержки все больные в зависимости от сроков начала питания были разбиты на три группы: в I группу вошли больные с пероральным питанием, которым начинали энтеральное питание в течение 1–2-х суток (15 больных); II группа объединила пациентов, которым назначали питание в течение 4–5-х суток (15 больных); и в IІІ группу включили больных, кормление которых начали после 5-х суток, с одновременным проведением комплексной интенсивной терапии, направленной на стабилизацию витальных функций (15 больных). Изучены особенности, необходимость и возможность раннего энтерального питания в комплексном лечении хирургических больных с синдромом кишечной недостаточности с целью уменьшения осложнений, оптимизации лечения. Показана важность подготовки кишечника на фоне комплексной интенсивной терапии, направленной на улучшение спланхнического кровообращения, к энтеральному питанию путем капельного введения теплых сбалансированных кристаллоидных растворов, введения сорбентов, пре- и пробиотиков. Отмечена важность капельного применения теплых полуэлементных смесей, приближенных к осмолярности химуса. Показано влияние раннего энтерального питания на уменьшение инфекционных осложнений и длительности лечения в стационаре. Включение в терапию раннего энтерального питания позволило сократить время достижения целевых значений внутрибрюшного и абдоминального перфузионного давления, т.е. оптимизировать восстановление кровообращения на системном, регионарном и тканевом уровнях. Разработанный в нашей клинике метод раннего (через 6–12 часов) введения сбалансированного раствора стерофундин в кишку с дальнейшим определением всасывающей функции кишечника и началом раннего введения теплого энтерального питания имеет преимущества по снижению осложнений у больных.

Effect of ingesting a meal and orthostasis on the regulation of splanchnic and systemic hemodynamics and the responsiveness of cardiovascular α1-adrenoceptors.

Postprandial orthostasis activates mechanisms of cardiovascular homeostasis to maintain normal blood pressure (BP) and adequate blood flow to vital organs. The underlying mechanisms of cardiovascular homeostasis in postprandial orthostasis still require elucidation. Fourteen healthy volunteers were recruited to investigate the effect of an orthostatic challenge (60°-head-up-tilt for 20 min) on splanchnic and systemic hemodynamics before and after ingesting an 800-kcal composite meal. The splanchnic circulation was assessed by ultrasonography of the superior mesenteric and hepatic arteries and portal vein. Systemic hemodynamics were assessed noninvasively by continuous monitoring of BP, heart rate (HR), cardiac output (CO), and the pressor response to an intravenous infusion on increasing doses of phenylephrine, an α1-adrenoceptor agonist. Neurohumoral regulation was assessed by spectral analysis of HR and BP, plasma catecholamine and aldosterone levels and plasma renin activity. Postprandial mesenteric hyperemia was associated with an increase in CO, a decrease in SVR and cardiac vagal tone, and reduction in baroreflex sensitivity with no change in sympathetic tone. Arterial α1-adrenoceptor responsiveness was preserved and reduced in hepatic sinusoids. Postprandial orthostasis was associated with a shift of 500 mL of blood from mesenteric to systemic circulation with preserved sympathetic-mediated vasoconstriction. Meal ingestion provokes cardiovascular hyperdynamism, cardiac vagolysis, and resetting of the baroreflex without activation of the sympathetic nervous system. Meal ingestion also alters α1-adrenoceptor responsiveness in the hepatic sinusoids and participates in the redistribution of blood volume from the mesenteric to the systemic circulation to maintain a normal BP during orthostasis.NEW & NOTEWORTHY A unique integrated investigation on the effect of meal on neurohumoral mechanisms and blood flow redistribution of the mesenteric circulation during orthostasis was investigated. Food ingestion results in cardiovascular hyperdynamism, reduction in cardiac vagal tone, and baroreflex sensitivity and causes a decrease in α1-adrenoceptor responsiveness only in the venous intrahepatic sinusoids. About 500-mL blood shifts from the mesenteric to the systemic circulation during orthostasis. Accordingly, the orthostatic homeostatic mechanisms are better understood.

Obituary for Roberto J. Groszmann—The Father of Portal Hypertension

After a year of fellowship in liver disease with Dr. Zimmerman at the Boston VA Hospital (1968-1969) he returned to Washington as a Research Fellow and Instructor in Medicine, Georgetown University, to work with Dr. Cohn (1969-1971). Dr. Cohn was a cardiologist, who was interested in systemic hemodynamics. It is here that Dr. Groszmann recognized that hemodynamic alterations were fundmental to the pathogenesis of cirrhosis. These seminal observations that the splanchnic circulation was hyperdynamic, rather than congestive, gave rise to his paradigm changing publications and set the ground work for subsequenet use of beta-blockers and splanchnic vasoconstrictor therapy leading to his becoming the father of the syndrome of Portal Hypertension (PH).

MPN-388: Assessment of Prevalence and Risk Factors for Subclinical Splanchnic Thrombosis in Patients with Myelofibrosis

Context Splanchnic thrombosis (ST) is a characteristic feature of MPN-associated prothrombotic state. Objective To determine the prevalence of subclinical ST in patients with myelofibrosis and assess disease-related and hereditary factors as potential risk predictors. Design Single-center, cross-sectional. Setting Clinic of Medical Oncology, University Hospital “Sveti Georgi” EAD, Plovdiv, Bulgaria. Patients or Other Participants Patients were considered eligible if diagnosed with myelofibrosis according to WHO 2016 criteria (incl. post-PV and post-ET), >18 years, no symptoms of overt ST, and no previous history of thrombosis. 21 subjects were recruited. Interventions Patients underwent CT scan angiography to detect the presence of vascular occlusion in the splanchnic circulation. Digital droplet PCR was performed to quantitate JAK2 mutant and wild-type allele burden in copies per nanogram DNA. Hereditary thrombophilia was analyzed for a panel of four genes: f.V(R506Q), f.II(20210G>A), PAI(4G/5G), and MTHFR(677C>T) by RT-PCR. Statistical analysis was performed in R v.4.0.4. All patients provided written informed consent. Main Outcome Measures Primary outcome was presence of thrombosis (arterial and/or venous) in the splanchnic circulation. Potential predictors were Jak2mut/ng DNA, WBC, HGB, PLT, spleen size, ruxolitinib therapy, and presence of hereditary thrombophilia. Results Baseline characteristics: mean age 67 ±10.51 years, 53% (11) females, 48% (10) with IPSS int-2/high, 57% (12) on ruxolitinib. FV(R506Q) and f.II(20210G>A) were detected in two patients each (9%), PAI(4G/4G) was detected in 10 patients, only one patient was wild-type homozygous, 3 patients were MTHFR(677TT), and 9 were heterozygous. ST was detected in 7 patients (33%). Jak2mut/ng DNA, WBC, HGB, PLT, spleen size, and ruxolitinib were not found to be significant predictors by logistic regression. 6 out of 7 patients with thrombosis were homozygous mutant [either PAI(4G/4G): 5 patients or MTHFR(677TT): 1 patient] and heterozygous for at least one of the other three genes. The presence of mutant homozygosity and heterozygous carrier state were significantly predictive of ST (Bhereditary = 3.497, 95%CI: 1.22–6.76, p=0.008). Conclusions Subclinical ST has a relatively high incidence in myelofibrosis. However, hereditary rather than disease-related factors emerge as risk factors. Further investigation of PAI(4G/5G) and MTHFR(677C>T) screening utility is warranted. This study was funded by Medical University-Plovdiv [grant SDPD-18/2019].

Effect of intraabdominal hypertension on splanchnic blood flow in children with appendicular peritonitis.

Background and Aims:Intraabdominal hypertension (IAH) is poorly diagnosed condition that cause splanchnic hypoperfusion and abdominal organs ischemia and can lead to multiple organ failure. There are no scientific data regarding effect of intraabdominal pressure (IAP) on splanchnic circulation in children.Material and Methods:Ninety-four children after surgery for appendicular peritonitis were enrolled in the study. After IAP measurement children were included in one of two groups according IAP levels: “without IAH” (n = 51) and “with IAH” (n = 43). Superior mesenteric artery (SMA) and portal vein (PV) blood flows (BFSMA, BFPV, mL/min) were measured, and SMA and PV blood flow indexes (BFISMA, BFIPV, ml/min*m2) and abdominal perfusion pressure (APP) were calculated in both groups.Results:Median BFISMA and BFIPV in group “with IAH” were lower by 54.38% (P < 0.01) and 63.11% (P < 0.01) respectively compared to group “without IAH”. There were strong significant negative correlation between IAP and BFISMA (rs = –0.66; P < 0.0001), weak significant negative correlation between IAP and BFIPV (rs = –0.36; P = 0.0001) in group “with IAH” and weak significant negative correlation between IAP and BFISMA (rs = –0.30; P = 0.0047) in group “without IAH”. There were no statistically significant correlations between IAP and BFIPV in group “without IAH”, between BFISMA and APP in both groups and between BFIPV and APP in both groups.Conclusion:Elevated IAP significantly reduces splanchnic blood flow in children with appendicular peritonitis. BFISMA and BFIPV negatively correlate with IAP in these patients. There is no correlation between BFISMA/BFIPV and APP in children with IAH due to appendicular peritonitis.

Not all fluid overloads are the same: some practical considerations for better decongestion

Not all fluid overloads are the same: some practical considerations for better decongestion

Hemodynamic and Intestinal Microcirculatory Changes in a Phenylephrine Corrected Porcine Model of Hemorrhage.

Intraoperative hypotension is a common event, and a recent study suggests that maintenance of blood pressure may reduce complications. The splanchnic circulation provides a reservoir of blood that can be mobilized during hemorrhage; hence, intestinal microcirculation is sensitive to volume changes. The aim of this study was to assess the impact of hemorrhage on intestinal microcirculation and hemodynamics, and the effects of phenylephrine on these parameters. Eight anesthetized, mechanically ventilated Yorkshire/Landrace crossbreed pigs were studied. Graded hemorrhage was performed with the removal of 20% of blood volume in 5% increments. Hemodynamic and intestinal microcirculatory measurements were performed at each stage with side-stream dark field microscopy, following which mean arterial pressure (MAP) was corrected with phenylephrine to baseline values and measurements repeated. A repeated measurement 1-way analysis of variance (ANOVA) was used to compared changes from baseline measurements. The mean baseline microcirculation score was 42 (standard deviation [SD] = 5). A 5% hemorrhage decreased the microcirculation score by a mean difference of 19 (95% confidence interval [CI], 12-27; P < .0001), and an additional 5% hemorrhage further reduced the microcirculation score by a mean difference of 12 (95% CI, 4-19; P = .0001). Subsequent hemorrhage or administration of phenylephrine did not significantly change the microcirculation scores except when phenylephrine was administered at the 15% hemorrhage stage, which increased the microcirculation score by a mean difference of 7 (95% CI, 1-13; P = .003). All hemodynamic variables were returned to baseline values following hemorrhage by the phenylephrine infusion. Intestinal microcirculatory flow is reduced early in hemorrhage and is uncorrected by phenylephrine infusion. Hemodynamic changes associated with hemorrhage are corrected by phenylephrine and do not reflect microcirculatory flow status.