A 5-Week Guided Active Play Program Modulates Skin Microvascular Reactivity in Healthy Children.

PURPOSE: Children's poor levels of physical activity (PA) participation and early-onset vascular aging are identified as global health challenges. Children's guided activity play (GAP)-based PA programs have emerged as effective strategies to improve cardiovascular risk factors and health-related fitness. This study proposes to investigate whether GAP improves children's cutaneous microvascular reactivity and health-related fitness. METHODS: Children's (n = 18; 9.8 [1.5] y) PA during a 5-week (4 d/wk; 1 h/d) GAP program was assessed (accelerometry) with preassessments and postassessments for anthropometric, musculoskeletal fitness, blood pressure, estimated aerobic power, and cutaneous microvascular reactivity. RESULTS: PA averaged 556 (132) kcal·week-1 at 34.7% (7.5%) time at moderate to vigorous intensity. Resting heart rate (-9.5%) and diastolic blood pressure (-7.8%) were reduced without changes in health-related fitness indices. Cutaneous microvascular reactivity to sodium nitroprusside iontophoresis increased the average perfusion (+36.8%), average cutaneous vascular conductance (+30%), the area under the curve (+28.8%), and a faster rise phase (+40%) of perfusion (quadratic modeling; P ≤ .05). Chi-square and crosstabulation analysis revealed significant association between children's PA levels and sodium nitroprusside average perfusion levels, where children with PA levels ≥205.1 kcal.55 minute-1 were overrepresented in the medium/high levels of sodium nitroprusside perfusion. CONCLUSION: A 5-week GAP modified the microvascular reactivity in children without changes in body mass, musculoskeletal fitness, or estimated aerobic power.

Impact of cardiac history and myocardial scar on increase of myocardial perfusion after revascularization.

PURPOSE: We sought to assess the impact of coronary revascularization on myocardial perfusion and fractional flow reserve (FFR) in patients without a cardiac history, with prior myocardial infarction (MI) or non-MI percutaneous coronary intervention (PCI). Furthermore, we studied the impact of scar tissue. METHODS: Symptomatic patients underwent [15O]H2O positron emission tomography (PET) and FFR before and after revascularization. Patients with prior CAD, defined as prior MI or PCI, underwent scar quantification by magnetic resonance imaging late gadolinium enhancement. RESULTS: Among 137 patients (87% male, age 62.2 ± 9.5 years) 84 (61%) had a prior MI or PCI. The increase in FFR and hyperemic myocardial blood flow (hMBF) was less in patients with prior MI or non-MI PCI compared to those without a cardiac history (FFR: 0.23 ± 0.14 vs. 0.20 ± 0.12 vs. 0.31 ± 0.18, p = 0.02; hMBF: 0.54 ± 0.75 vs. 0.62 ± 0.97 vs. 0.91 ± 0.96 ml/min/g, p = 0.04). Post-revascularization FFR and hMBF were similar across patients without a cardiac history or with prior MI or non-MI PCI. An increase in FFR was strongly associated to hMBF increase in patients without a cardiac history or with prior MI/non-MI PCI (r = 0.60 and r = 0.60, p < 0.01 for both). Similar results were found for coronary flow reserve. In patients with prior MI scar was negatively correlated to hMBF increase and independently predictive of an attenuated CFR increase. CONCLUSIONS: Post revascularization FFR and perfusion were similar among patients without a cardiac history, with prior MI or non-MI PCI. In patients with prior MI scar burden was associated to an attenuated perfusion increase.

Resolution of aortic regurgitation due to Venturi effect after device closure of ruptured sinus of Valsalva aneurysm.

We describe a case of a ruptured sinus of Valsalva with severe aortic regurgitation treated by transcatheter device closure. The regurgitation was purely due to leaflet entrapment because of the hemodynamic Venturi effect which was effectively treated.

A quality improvement initiative to increase adult ECMO decision-making abilities in a perfusion education program: The use of 3D ECMO simulation.

INTRODUCTION: Adult and pediatric ECMO procedures have been increasingly established as conventional life-saving modalities in critical care services across the world. Since 2017, a multidisciplinary team of program advisors for our perfusion education program have aimed to increase cardiovascular perfusion (CVP) student ECMO exposure and improve clinical decision-making. In this QI intervention, the use of 3D computer-based simulation was assessed in establishing a standardized process to improve the diagnosis and treatment of adult ECMO complications among first year CVP students. METHODS: The Califia 3D Patient Simulator was incorporated into the curriculum for first year CVP students (n = 26) along with traditional lecture for the adult ECMO complication laboratory session. Pre-class knowledge assessments using de-identified polling software were compared to post-class assessments following the first assigned learning activity. Assessments from students that received simulation before lecture (SIM, n = 15) were compared to students receiving lecture before simulation (LEC, n = 11). User experience questionnaires (UEQ) consisting of 26 questions for six scales of simulation instruction were administered to measure the comprehensive impression of the student experience. RESULTS: Overall median [IQR] pre- and -post knowledge assessment scores were 74% [11] and 84% [11], respectively (p = 0.01). There were no significant differences in pre-class assessment scores between the SIM and LEC groups (74.0% and 74.0%, respectively, p = 0.959). The LEC group achieved higher median post-assessment scores than the SIM group (84% vs 79%, p = 0.032). Among the 26 UEQ survey scales, 23 were positively evaluated (>0.8), and three were a neutral evaluation (-0.8 to 0.8). Cronbach Alpha-Coefficients of >0.78 were measured for attractiveness, perspicuity, efficacy, and stimulation. The coefficient for dependability was 0.37. 25 (96.2%) students indicated that 3D simulation was beneficial to improving ECMO clinical decision-making. CONCLUSIONS: In this QI intervention, the implementation of computer-based 3D simulation following lecture was perceived by learners to help improve the diagnosis and treatment of ECMO-related complications.

[Reconstruction of total portosystemic shunt into selective portosystemic shunt in a child]. / Rekonstruktsiya total'nogo portosistemnogo shunta v selektivnyi portosistemnyi shunt u rebenka.

To date, side-to-side splenorenal shunt (SRS) and its analogues (splenosuprarenal shunts (SSRS)) are mainly used for portal hypertension. These are total portosystemic shunts characterized by total blood shunt from portal vein into inferior vena cava. The latter is fraught with a significant risk of complications such as pulmonary hypertension, decreased portal liver perfusion, liver failure and hepatic encephalopathy. Prevention of these complications is still an urgent problem in modern surgery. However, we proposed a new method of treatment, i.e. reconstruction of SRS and SSRS into selective shunt. This procedure was performed in 37 patients after 2020. We present laparoscopic reconstruction in an 11-year-old girl with portal hypertension and signs of hepatic encephalopathy identified after previous SSRS.

Thrombectomy With and Without Computed Tomography Perfusion Imaging in the Early Time Window: A Pooled Analysis of Patient-Level Data.

BACKGROUND: The optimal imaging paradigm for endovascular thrombectomy (EVT) patient selection in early time window (0-6 hours) treated acute ischemic stroke patients remains uncertain. We aimed to compare post-EVT outcomes between patients who underwent prerandomization basic (noncontrast computed tomography [CT], CT angiography only) versus additional advanced imaging (computed tomography perfusion [CTP] imaging) and to determine the association of performance of prerandomization CTP imaging with clinical outcomes. METHODS: The HERMES collaboration (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials) pooled patient-level data from randomized controlled trials comparing EVT with usual care for acute ischemic stroke due to anterior circulation large vessel occlusion. Good functional outcome, defined as modified Rankin Scale score 0 to 2 at 90 days, was compared between randomized patients with and without CTP baseline imaging. Univariable and multivariable binary logistic regression analysis was performed to determine the association of baseline CTP imaging and good functional outcome. RESULTS: We analyzed 1348 patients 610 (45.3%) of whom underwent CTP prerandomization. The benefit of EVT compared with best medical management was maintained irrespective of the baseline imaging paradigm (90-day modified Rankin Scale score 0-2 in EVT versus control patients: with CTP: 46.0% (137/298) versus 28.9% (88/305), without CTP: 44.1% (162/367) versus 27.3% (100/366). Performance of CTP baseline imaging compared with baseline noncontrast CT and CT angiography only yielded similar rates of good outcome (odds ratio, 1.05 [95% CI, 0.82-1.33], adjusted odds ratio, 1.04, [95% CI, 0.80-1.35]). CONCLUSIONS: Rates of good functional outcome were similar among patients in whom CTP was or was not performed, and EVT treatment effect in the 0- to 6-hour time window was similar in patients with and without baseline CTP imaging.

Perfusion Imaging and Clinical Outcome in Acute Minor Stroke With Large Vessel Occlusion.

BACKGROUND: Whether bridging therapy (intravenous thrombolysis [IVT] followed by mechanical thrombectomy) is superior to IVT alone in minor stroke with large vessel occlusion is unknown. Perfusion imaging may identify subsets of large vessel occlusion-related minor stroke patients with distinct response to bridging therapy. METHODS: We conducted a multicenter international observational study of consecutive IVT-treated patients with minor stroke (National Institutes of Health Stroke Scale score ≤5) who had an anterior circulation large vessel occlusion and perfusion imaging performed before IVT, with a subset undergoing immediate thrombectomy. Propensity score with inverse probability of treatment weighting was used to account for baseline between-groups differences. The primary outcome was 3-month modified Rankin Scale score 0 to 1. We searched for an interaction between treatment group and mismatch volume (critical hypoperfusion-core volume). RESULTS: Overall, 569 patients were included (172 and 397 in the bridging therapy and IVT groups, respectively). After propensity-score weighting, the distribution of baseline variables was similar across the 2 groups. In the entire population, bridging was associated with lower odds of achieving modified Rankin Scale score 0 to 1: odds ratio, 0.73 [95% CI, 0.55-0.96]; P=0.03. However, mismatch volume modified the effect of bridging on clinical outcome (Pinteraction=0.04 for continuous mismatch volume); bridging was associated with worse outcome in patients with, but not in those without, mismatch volume <40 mL (odds ratio, [95% CI] for modified Rankin Scale score 0-1: 0.48 [0.33-0.71] versus 1.14 [0.76-1.71], respectively). Bridging was associated with higher incidence of symptomatic intracranial hemorrhage in the entire population, but this effect was present in the small mismatch subset only (Pinteraction=0.002). CONCLUSIONS: In our population of large vessel occlusion-related minor stroke patients, bridging therapy was associated with lower rates of good outcome as compared with IVT alone. However, mismatch volume was a strong modifier of the effect of bridging therapy over IVT alone, notably with worse outcome with bridging therapy in patients with mismatch volume ≤40 mL. Randomized trials should consider adding perfusion imaging for patient selection.

Role of Intravenous Thrombolytics Prior to Endovascular Thrombectomy.

Intravenous thrombolytics and endovascular thrombectomy for ischemic stroke have evolved in parallel. However, the best approach to combine these reperfusion therapies in patients eligible for both strategies remains uncertain. Initial randomized trials of endovascular thrombectomy included administration of intravenous thrombolytics to all eligible patients. However, whether that is of net benefit has been questioned and parallels drawn with treatment of ST-segment-elevation myocardial infarction, where intravenous thrombolytics are only given if first medical contact to percutaneous intervention is expected to be >90 minutes. Six randomized trials of a direct thrombectomy approach versus intravenous thrombolytics followed by endovascular thrombectomy have now reported their results. With exception of a minority of patients in one trial, the trials all used alteplase rather than potentially more effective tenecteplase. This review examines the current state of evidence and implications for clinical practice. Importantly, these trials only apply to patients who present to a hospital with immediate access to endovascular thrombectomy and are not relevant to patients who receive thrombolytic and are then transferred to an endovascular-capable hospital. Although 2 of the 6 randomized trials met their prespecified noninferiority margin, these margins were large compared with the absolute benefit of alteplase. Overall, functional outcome was similar, with slight trends favoring bridging thrombolytics and a significant increase in final reperfusion. Symptomatic hemorrhage was increased by ≈1.8% in the bridging group but death was nonsignificantly lower. The workflow in direct thrombectomy trials involved delaying thrombolytic administration until eligibility for thrombectomy and the trials was established and randomization completed. This reduced the time available for thrombolytics to occur prethrombectomy compared with standard practice. We conclude that, pending individual-patient data meta-analyses, intravenous thrombolytics retain an important role alongside endovascular thrombectomy. Further efforts to accelerate and enhance reperfusion with thrombolytics and perform individual patient-level pooled subgroup analyses are warranted.

Terlipressin and the Treatment of Hepatorenal Syndrome: How the CONFIRM Trial Moves the Story Forward.

Hepatorenal syndrome (HRS) is a form of acute kidney injury (AKI) occurring in patients with advanced cirrhosis and is associated with significant morbidity and mortality. The pathophysiology underlying HRS begins with increasing portal pressures leading to the release of vasodilatory substances that result in pooling blood in the splanchnic system and a corresponding reduction in effective circulating volume. Compensatory activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system and release of arginine vasopressin serve to defend mean arterial pressure but at the cost of severe constriction of the renal vasculature, leading to a progressive, often fulminant form of AKI. There are no approved treatments for HRS in the United States, but multiple countries, including much of Europe, use terlipressin, a synthetic vasopressin analogue, as a first-line therapy. CONFIRM (A Multi-Center, Randomized, Placebo Controlled, Double-Blind Study to Confirm Efficacy and Safety of Terlipressin in Subjects With Hepatorenal Syndrome Type 1), the third randomized trial based in North America evaluating terlipressin, met its primary end point of showing greater rates of HRS reversal in the terlipressin arm. However, due to concerns about the apparent increased rates of respiratory adverse events and a lack of evidence for mortality benefit, terlipressin was not approved by the Food and Drug Administration (FDA). We explore the history of regulatory approval for terlipressin in the United States, examine the results from CONFIRM and the concerns they raised, and consider the future role of terlipressin in this critical clinical area of continued unmet need.

Efficacy and safety of cardiac shock wave therapy for patients with severe coronary artery disease: A randomized, double-blind control study.

BACKGROUND: Previous studies proved the efficacy of cardiac shock wave therapy (CSWT) for coronary artery disease (CAD) patients who are not candidate for reperfusion therapy. Randomized control trials are limited. We try to explore the efficacy and safety of CSWT for patients with severe CAD. METHODS: Thirty patients with severe CAD who had obvious ischemia on myocardial perfusion imaging (MPI) were enrolled and randomly assigned to the CSWT group or the control group. They had received optimal medication treatment for at least three months. Nine sessions of shock wave therapy were conducted over 3 months. CSWT group received the real treatment, while the control group received the pseudo-treatment. Clinical symptom, imaging outcomes and safety parameters were compared between two groups. RESULTS: After treatment, regional stress score (P = .023), improvement rate (IR) of ischemic area (IA) stress (P < .001) and IR of IA difference (P < .001) were significantly favor CSWT group. The interaction of summed rest score (P < .001), summed stress score (P = .004), summed difference score (P = .036) were significantly improved in the CSWT group compared to the control group. Seattle angina questionnaire, quality of life (QOL) and the distance of six-minute walking test (6MWT) were improved in both groups without significant difference between them. Hemodynamic parameters were stable during procedure. Myocardial injury markers showed no changes in two groups. CONCLUSIONS: Our study demonstrated CSWT could effectively and safely improve myocardial perfusion in patients with severe CAD. Clinical symptom, QOL and 6MWT were all improved after treatment, but no significant difference between two groups.

Successive surgical repair of a progressive aortic dissection in a case of Loeys-Dietz Syndrome.

INTRODUCTION: The Frozen Elephant Trunk technique is a well-established treatment for aortic dissections (Stanford Type A) involving the aortic arch and descending aorta. The Thoraflex™ Hybrid prosthesis (Vascutek Ltd.), consisting of a proximal flexible conduit and a distal self-expanding covered stent, has consistently shown positive results in the treatment of this condition. CASE DESCRIPTION: The following is a description of such a staged reconstruction using the Thoraflex™ Hybrid Ante-Flo™ device, performed in a patient previously diagnosed with Loeys-Dietz Syndrome. After clamping the aorta proximally, an incision was taken at the distal end of the stent. Here, the distal end of the new prosthesis was inserted into the true lumen of the descending aorta and the stent was deployed. Following this, a bypass was established via the left atrium, and blood was returned to the lower body using the perfusion arm of the prosthesis with the proximal part of the descending aorta clamped. The collar of the prosthesis was sutured proximally to the aorta near the inlying previous stent. Air was removed via the perfusion arm of the prosthesis, which was then oversewn. DISCUSSION: To date, hybrid prostheses have only been used on the proximal aorta in patients with aortic aneurysms and aortic dissections (Stanford Type A). CONCLUSION: Using the described technique, it is possible to reconstruct the aortic anatomy using the available prostheses with accuracy and minimal complications.

Delayed Frozen Elephant Trunk without hypothermic circulatory arrest.

Aortic arch disease is one of the most complex and challenging field in cardiac surgery. The recent growing experience in endovascular procedures has allowed the surgeons to approach more complex cases with different strategies. We report herein a complicated Zone 0 Hybrid Arch Repair through a delayed Frozen Elephant Trunk with continuous perfusion of the brain and visceral organ and mild hypothermia avoiding circulatory arrest. This strategy, allowed using endovascular technologies, should be considered useful to reduce the operative risks.

[Analysis of heparin sodium prescribing practices with an electric syringe pump]. / Analyse des pratiques de prescription de l'héparine sodique au pousse-seringue électrique.

OBJECTIVES: Report on the practices of prescribing continuous infusion of heparin sodium by syringe pump in our hospital and shed qualitative light on the protocols used in other French hospitals. METHODS: We interviewed prescribers about the protocol they were using through the computerized provider order entry system. At the same time, we asked hospital pharmacists, particularly through a social network, whether in their hospital one or more protocols were used and which ones. RESULTS: In all, 81 prescribers responded to our request: 22 indicated prescribing the 25,000IU/50mL protocol, 7 the 20,000IU/48mL protocol, 2 the 25,000IU/48mL protocol and 14 indicated that they had no preference for one of them. Ten responded that they did not prescribe any protocols and 26 left the question unanswered. The responses of 42 pharmacists practicing in other establishments allowed us to identify 16 different protocols. Of these 42 establishments, 10 had at least two protocols. CONCLUSIONS: Several protocols for the administration by continuous infusion of heparin sodium with a syringe pump can coexist within a hospital. This diversity is confusing and puts patients and caregivers at risk of medication errors. Among all these protocols, it is not known whether some are riskier than others and research to clarify this unknown is warranted. Defining a national standard concentration of heparin and bringing to the market ready-to-administer solutions are measures to be promoted in order to reduce the risk of errors.

Early Infarct Growth Rate Correlation With Endovascular Thrombectomy Clinical Outcomes: Analysis From the SELECT Study.

BACKGROUND AND PURPOSE: Time elapsed from last-known well (LKW) and baseline imaging results are influential on endovascular thrombectomy (EVT) outcomes. METHODS: In a prospective multicenter cohort study of imaging selection for endovascular thrombectomy (SELECT [Optimizing Patient's Selection for Endovascular Treatment in Acute Ischemic Stroke], the early infarct growth rate (EIGR) was defined as ischemic core volume on perfusion imaging (relative cerebral blood flow<30%) divided by the time from LKW to imaging. The optimal EIGR cutoff was identified by maximizing the sum of the sensitivity and specificity to correlate best with favorable outcome and to improve its the predictability. Patients were stratified into slow progressors if EIGR2. The primary outcome was 90-day functional independence (modified Rankin Scale score =0-2). RESULTS: Of 445 consented, 361 (285 EVT, 76 medical management only) patients met the study inclusion criteria. The optimal EIGR was <10 mL/h; 200 EVT patients were slow and 85 fast progressors. Fast progressors had a higher median National Institutes of Health Stroke Scale (19 versus 15, P<0.001), shorter time from LKW to groin puncture (180 versus 266 minutes, P<0.001). Slow progressors had better collaterals on computed tomography perfusion: hypoperfusion intensity ratio (adjusted odds ratio [aOR]: 5.11 [2.43-10.76], P<0.001) and computed tomography angiography: collaterals-score (aOR: 4.43 [1.83-10.73], P=0.001). EIGR independently correlated with functional independence after EVT, adjusting for age, National Institutes of Health Stroke Scale, time LKW to groin puncture, reperfusion (modified Thrombolysis in Cerebral Infarction score of ≥2b), IV-tPA (intravenous tissue-type plasminogen activator), and transfer status (aOR: 0.78 [0.65-0.94], P=0.01). Slow progressors had higher functional independence rates (121 [61%] versus 30 [35%], P<0.001) and had 3.5 times the likelihood of achieving modified Rankin Scale score =0-2 with EVT (aOR=2.94 [95% CI, 1.53-5.61], P=0.001) as compared to fast progressors, who had substantially worse clinical outcomes both in early and late time window. The odds of good outcome decreased by 14% for each 5 mL/h increase in EIGR (aOR, 0.87 [0.80-0.94], P<0.001) and declined more rapidly in fast progressors. CONCLUSIONS: The EIGR strongly correlates with both collateral status and clinical outcomes after EVT. Fast progressors demonstrated worse outcomes when receiving EVT beyond 6 hours of stroke onset as compared to those who received EVT within 6 hours. Registration: URL: https://clinicaltrials.gov. Unique identifier: NCT02446587.

The effect of the head-up position on cardiopulmonary resuscitation: a systematic review and meta-analysis.

OBJECTIVE: Experimental studies of head-up positioning (HUP) during cardiopulmonary resuscitation (CPR) have had some degree of conflicting published results. The current study aim was to analyze and reconcile those discrepancies in order to better clarify the effects of HUP CPR compared to conventional supine (SUP) CPR. METHODS: Three databases (PubMed, EMBASE and Cochrane Library) were searched comprehensively (from each respective database's inception to May 2021) for articles addressing HUP CPR. The primary outcome to be observed was cerebral perfusion pressure (CerPP), and secondary outcomes were mean intracranial pressure (ICP), mean arterial pressure (MAP), coronary perfusion pressure (CoPP) and frequencies of return of spontaneous circulation (ROSC). RESULTS: Seven key studies involving 131 animals were included for analysis. Compared to SUP CPR, CerPP (MD 10.37; 95% CI 7.11-13.64; p < 0.01; I2 = 58%) and CoPP (MD 7.56; 95% CI 1.84-13.27, p = 0.01; I2 = 75%) increased significantly with HUP CPR, while ICP (MD - 13.66; 95% CI - 18.6 to -8.71; p < 0.01; I2 = 96%) decreased significantly. Combining all study methodologies, there were no significant differences detected in MAP (MD - 1.63; 95% CI - 10.77-7.52; p = 0.73; I2 = 93%) or frequency of ROSC (RR 0.9; 95% CI 0.31-2.60; p = 0.84; I2 = 65%). However, in contrast to worse outcomes in studies using immediate elevation of the head in a reverse Trendelenburg position, study outcomes were significantly improved when HUP (head and chest only) was introduced in a steady, graduated manner following a brief period of basic CPR augmented by active compression-decompression (ACD) and impedance threshold (ITD) devices. CONCLUSION: In experimental models, gradually elevating the head and chest following a brief interval of circulatory priming with ACD and ITD devices can enhance CoPP, lower ICP and improve CerPP significantly while maintaining MAP. This effect is immediate, remains sustained and is associated with improved outcomes.

Treatment strategies for malperfusion syndrome secondary to acute aortic dissection.

OBJECTIVE: Presenting our experience of treating patients with organ malperfusion secondary to acute aortic dissection. PATIENTS: Among 383 patients who underwent aortic repair for acute type A aortic dissection from 1999 to 2017, 107 patients were operated on because of vascular complications. Fourteen patients had coronary, 50 had brain, 3 had paraplegia, 13 had superior mesenteric artery, 21 had lower limb, and 16 had combined organ malperfusion. Age was 65.8 years. RESULTS: In coronary malperfusion, three had a preoperative percutaneous coronary intervention, and two had mechanical support. All underwent repair of the aorta. Hospital mortality was 28.5%. Fifty patients had brain malperfusion. Hemiplegia was found in 28 patients, transient ischemic attack in 10, and coma in 12. The level of consciousness was severe in 12, moderate in 18, and mild in 20. Twenty-eight percent died of a stroke. Nine had direct perfusion from the right common carotid artery, and the consciousness level was improved in 5 patients. Eight patients had mesenteric malperfusion. Four patients had a central aorta repair first, and four patients had peripheral intervention first. Three patients had a bypass grafting to the superior mesenteric artery, and one had a catheter intervention. Postoperative mortality was found in four patients due to bowel necrosis and six required resections of the bowel. CONCLUSION: Acute organ malperfusion caused by the aortic dissection requires accurate and prompt diagnosis to proceed with an appropriate intervention before repairing the central aorta for preventing irreversible organ damage.

Methods of Attenuating Ischemia-Reperfusion Injury in Liver Transplantation for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most frequent indications for liver transplantation. However, the transplantation is ultimately associated with the occurrence of ischemia-reperfusion injury (IRI). It affects not only the function of the graft but also significantly worsens the oncological results. Various methods have been used so far to manage IRI. These include the non-invasive approach (pharmacotherapy) and more advanced options encompassing various types of liver conditioning and machine perfusion. Strategies aimed at shortening ischemic times and better organ allocation pathways are still under development as well. This article presents the mechanisms responsible for IRI, its impact on treatment outcomes, and strategies to mitigate it. An extensive review of the relevant literature using MEDLINE (PubMed) and Scopus databases until September 2020 was conducted. Only full-text articles written in English were included. The following search terms were used: "ischemia reperfusion injury", "liver transplantation", "hepatocellular carcinoma", "preconditioning", "machine perfusion".

Administration of the vasopressin analog desmopressin for the management of bleeding in rectal cancer patients: results of a phase I/II trial.

Purpose The vasopressin analog desmopressin (dDAVP) is known to increase plasma levels of hemostatic factors, and preclinical studies in colorectal cancer models have demonstrated that it hampers tumor vascularization and metastatic progression. We evaluated safety and preliminary efficacy of dDAVP in rectal cancer patients with bleeding, before receiving specific oncologic treatment with surgery, chemotherapy and/or radiotherapy. Methods Patients with rectal cancer having moderate or severe rectal bleeding were enrolled in an open-label, dose-finding trial. Intravenous infusions of dDAVP were administered during two consecutive days in doses from 0.25 to 2.0 µg/kg, using single or twice daily regimen. Bleeding was graded using a score based on the Chutkan scale and tumor perfusion was evaluated by dynamic contrast-enhanced magnetic resonance imaging. Results The trial accrued a total of 32 patients. Dose-limiting toxicity occurred in patients receiving 1 µg/kg or higher. The most prominent treatment-related severe adverse event was hyponatremia. Most patients receiving the maximum tolerated dose of 0.5 µg/kg showed at least a partial hemostatic response and 58% developed a complete response with absence of bleeding at day 4 and/or at the last follow-up at day 14. Tumor perfusion was decreased in two-thirds of patients after dDAVP treatment. Conclusions dDAVP appeared as a promising hemostatic agent in rectal cancer patients with bleeding. Randomized clinical trials to confirm its effectiveness are warranted.Clinical trial registration www.clinicaltrials.gov NCT01623206.

Addressing a real-life problem: treatment with intravenous thrombolysis and mechanical thrombectomy in acute stroke patients with an extended time window beyond 4.5 h based on computed tomography perfusion imaging.

BACKGROUND AND PURPOSE: Acute ischemic stroke treatment with intravenous thrombolysis (IVT) is restricted to a time window of 4.5 h after known or presumed onset. Recently, magnetic resonance imaging-guided treatment decision-making in wake-up stroke (WUS) was shown to be effective. The aim of this study was to determine the safety and outcome of IVT in patients with a time window beyond 4.5 h selected by computed tomography perfusion (CTP) imaging. METHODS: We analyzed all consecutive patients last seen well beyond 4.5 h after stroke onset treated with IVT based on CTP between January 2015 and October 2018. CTP was visually assessed to estimate the mismatch between cerebral blood flow and cerebral blood volume maps. Early infarct signs were documented according to Alberta Stroke Program Early CT Score (ASPECTS). Safety data were obtained for mortality and symptomatic intracerebral hemorrhage (sICH). Follow-up was assessed with the modified Rankin Scale (mRS). RESULTS: A total of 70 patients fulfilled the inclusion criteria (mean age ± SD 77.6 ± 11.5 years, 50.0% female). Median National Institutes of Health Stroke Scale score on admission was 8.0 [interquartile range (IQR), 4-14]. The most frequent reasons for an extended time window were WUS (60.0%) and delayed hospital admission (27.1%). Median time from last seen well to IVT was 11.4 h. Median ASPECTS was 10 (IQR, 9-10) and CTP mismatch 90% (IQR, 80%-100%). A total of 24 patients (34.3%) underwent additional mechanical thrombectomy. sICH occurred in four patients (5.7%). At follow-up, 49.3% had an mRS score of 0-2 and 22.4% had an mRS score of 0-1. CONCLUSIONS: In patients presenting in an extended time window beyond 4.5 h, IVT treatment with decision-making based on CTP might be a safe procedure. Further evaluation in clinical trials is needed.

Intraoperative angiography with indocyanine green to assess anastomosis perfusion in patients undergoing laparoscopic colorectal resection: results of a multicenter randomized controlled trial.

BACKGROUND: Insufficient vascular supply is one of the main causes of anastomotic leak in colorectal surgery. Intraoperative indocyanine-green (ICG) angiography has been shown to provide information on tissue perfusion, identifying a well-perfused location for colonic and rectal transections, and thus possibly reducing the leak rate. Aim of this study was to evaluate the usefulness of intraoperative assessment of anastomotic perfusion using ICG angiography in patients undergoing left-sided colon or rectal resection with colorectal anastomosis. METHODS: This randomized trial involved 252 patients undergoing laparoscopic left-sided colon and rectal resection randomized 1:1 to intraoperative ICG or to subjective visual evaluation of the bowel perfusion without ICG. The primary aim was to assess whether ICG angiography could lead to a reduction in anastomotic leak rate. Secondary outcomes were possible changes in the surgical strategy and postoperative morbidity. RESULTS: After randomization, 12 patients were excluded. Accordingly, 240 patients were included in the analysis; 118 were in the study group, and 122 in the control group. ICG angiography showed insufficient perfusion of the colic stump, which led to extended bowel resection in 13 cases (11%). An anastomotic leak developed in 11 patients (9%) in the control group and in 6 patients (5%) in the study group (p = n.s.). CONCLUSIONS: Intraoperative ICG fluorescent angiography can effectively assess vascularization of the colic stump and anastomosis in patients undergoing colorectal resection. This method led to further proximal bowel resection in 13 cases, however, there was no statistically significant reduction of anastomotic leak rate in the ICG arm. CLINICAL TRIAL: ClinicalTrials.gov NCT02662946.