Provocative mesenteric angiography for localizing ambiguous gastrointestinal hemorrhage

Objectives: Five percent of patients with recurrent gastrointestinal (GI) hemorrhage have indeterminate origin by radiological and endoscopic examinations. To improve diagnostic accuracy and therapeutic embolization, the technique of provocative mesenteric angiography (PMA) has been developed. It involves the addition of pharmacologic agents to standard angiographic protocols to induce bleeding. Material and Methods: This is an institutional review board-approved, retrospective study of 20 patients who underwent PMA between 2014 and 2019. All patients had clinical evidence of GI hemorrhage without a definite source. PMA consisted of anticoagulation with 5000 units of heparin and selective transcatheter injection of up to 600 μg of nitroglycerine, followed by slow infusion of up to 24 mg of tissue plasminogen activator into the arterial distribution of the highest suspicion mesenteric artery. Results: Among the 20 patients who underwent PMA, 11/20 (55%) resulted in angiographically visible extravasation. Of these 11 patients, nine patients underwent successful embolization with coil or glue and were discharged upon achieving hemodynamic stability. Two patients spontaneously stopped bleeding. In our series, PMA resulted in the successful treatment of 9/20 (45%) patients with recurrent hemorrhage. No procedure-associated complications were reported with these 20 patients during the procedure and their course of hospitalization. Conclusion: In our experience, PMA is an effective and safe approach in localizing and treating the source of GI bleeding in about half of patients with an otherwise unidentifiable source.

RESULT OF SLOW INFUSION OF STREPTOKINASE THERAPY IN LEFT SIDED PROSTHETIC VALVE THROMBOTIC OCCLUSION- A CASE SERIES FROM A TERTIARY CARE HOSPITAL IN EASTERN INDIA

Prosthetic valve thrombosis (PVT) is a life threatening complication seen after heart valve replacement and is associated with high mortality and morbidity. Surgical approach or brinolysis and heparin therapy are considered as treatments of choice according to the clinical status of the patient. Thrombolytic therapy has been tried in cases with acute prosthetic valve thrombosis as an alternative to emergency operation with variable results. But fear of peripheral embolism has limited its use in left-sided valve occlusions. The incidence of complications decreases with low dose and slow infusion of brinolytic therapy. In this study we are presenting our experience of thrombolytic therapy with streptokinase in 40 patients who had presented with acute or subacute left-sided prosthetic valve thrombosis. In this study the mean age was 40.9 years (SD-11.2, range-19 to 64 year) with majority (77.5%) were below 50 year of age. Duration of valve replacement was 2.95 ± 1.74 years (1 to 7 years). Average time of presentation since onset of symptoms was 4.75 ± 2.77 days (1 to 12 days). Majority was presented with NYHA class IV symptoms (22/40) and 50% patients presented with cardiogenic shock. 85% patients had atrial brillation and the anticoagulation status was inadequate in 62.5% cases. Overall aortic valve involvement was 37.5% (15 patients) and mitral valve involvement was 62.5% (25 patients). Average mean gradient for aortic valve was 64.5 ±4.2 mm of Hg and that in case of mitral valve was 23.4±3.7 mm of Hg. Duration of thrombolytic therapy was individualized. Average total dose of streptokinase per patient was 25,25000 ± 8,69350 U (ranging from 20,00000 to 50,00000 U) with majority (28/40) had received a total 20,00000U of streptokinase. Patients were re-evaluated after thrombolysis with clinical, echocardiographic, and cine-uoroscopic evaluation. Total complications (both major and minor bleeding) occurred in 8 patients. Most of them were minor like injection site hematoma, gum bleeding transient GI bleed (hematemesis), hemoptysis and those were resolved spontaneously with conservative management/observational care. Thrombolysis was unsuccessful in 2 patients and death due to massive hemorrhagic CVA occurred in 2 patients. Overall success rate was 90% (36/40). In conclusion, the present study demonstrates the feasibility of thrombolytic therapy for left-sided prosthetic valve occlusion.

Effects of Fluid Rehydration Strategy on Correction of Acidosis and Electrolyte Abnormalities in Children With Diabetic Ketoacidosis

<b>IMPORTANCE: </b>Fluid replacement to correct dehydration, acidosis and electrolyte abnormalities is the cornerstone of treatment for diabetic ketoacidosis (DKA) but little is known about optimal fluid infusion rates and electrolyte content. <p><b>OBJECTIVE</b><b>: </b><a>To</a> evaluate whether different fluid protocols affect the rate of normalization of biochemical derangements during DKA treatment. </p> <p><b>DESIGN, SETTING, PaRTICIPANTS:</b><b> </b> The current analysis involved moderate or severe DKA episodes (n=714) in children <18 years enrolled in the Fluid Therapies Under Investigation in DKA (FLUID) Trial.</p> <p><b>INTERVENTION:</b> Children were assigned to one of four treatment groups using a 2-by-2 factorial design (0.90% or 0.45% saline and fast or slow rate of administration). </p> <p><b>Results: </b>The rate of change of pH did not differ by treatment arm, but PCO₂increased more rapidly in the fast vs slow fluid infusion arms during the initial 4 hours of treatment. The anion gap also decreased more rapidly in the fast vs slow infusion arms during the initial 4 and 8 hours. Glucose-corrected sodium levels remained stable in patients assigned to 0.90% saline but decreased in those assigned to 0.45% saline at 4 and 8 hours. Potassium levels decreased, while chloride levels increased more rapidly with 0.90% vs 0.45% saline. Hyperchloremic acidosis occurred more frequently in patients in the fast arms (46.1%) vs slow arms (35.2%). </p> <h4>CONCLUSIONS AND RELEVANCE: In children treated for DKA, faster fluid administration rates led to a more rapid normalization of anion gap and PCO₂ than slower fluid infusion rates but were associated with an increased frequency of hyperchloremic acidosis. </h4>

Effects of Fluid Rehydration Strategy on Correction of Acidosis and Electrolyte Abnormalities in Children With Diabetic Ketoacidosis

<b>IMPORTANCE: </b>Fluid replacement to correct dehydration, acidosis and electrolyte abnormalities is the cornerstone of treatment for diabetic ketoacidosis (DKA) but little is known about optimal fluid infusion rates and electrolyte content. <p><b>OBJECTIVE</b><b>: </b><a>To</a> evaluate whether different fluid protocols affect the rate of normalization of biochemical derangements during DKA treatment. </p> <p><b>DESIGN, SETTING, PaRTICIPANTS:</b><b> </b> The current analysis involved moderate or severe DKA episodes (n=714) in children <18 years enrolled in the Fluid Therapies Under Investigation in DKA (FLUID) Trial.</p> <p><b>INTERVENTION:</b> Children were assigned to one of four treatment groups using a 2-by-2 factorial design (0.90% or 0.45% saline and fast or slow rate of administration). </p> <p><b>Results: </b>The rate of change of pH did not differ by treatment arm, but PCO₂increased more rapidly in the fast vs slow fluid infusion arms during the initial 4 hours of treatment. The anion gap also decreased more rapidly in the fast vs slow infusion arms during the initial 4 and 8 hours. Glucose-corrected sodium levels remained stable in patients assigned to 0.90% saline but decreased in those assigned to 0.45% saline at 4 and 8 hours. Potassium levels decreased, while chloride levels increased more rapidly with 0.90% vs 0.45% saline. Hyperchloremic acidosis occurred more frequently in patients in the fast arms (46.1%) vs slow arms (35.2%). </p> <h4>CONCLUSIONS AND RELEVANCE: In children treated for DKA, faster fluid administration rates led to a more rapid normalization of anion gap and PCO₂ than slower fluid infusion rates but were associated with an increased frequency of hyperchloremic acidosis. </h4>

Prosthetic valve trhombosis

Funding Acknowledgements Type of funding sources: None. Background Prosthetic valve thrombosis (DVT) is a very serious complication, with high morbidity and mortality, a high risk of stroke during hospital admission, and which occurs especially in patients with poorly anticoagulated mechanical prostheses. Therapeutic options available for DVT are surgery, with or without prosthetic replacement, and intravenous thrombolysis. However, there is no randomized study comparing these two interventions. Therefore optional treatment is controversial. This is also reflected in the current clinical practice guidelines of international scientific societies of the year 2017, where the American College of Cardiology / American Heart Association considers surgery and thrombolysis as comparable treatments (Class I), and On the other hand, the European Society of Cardiology (ESC) opts for surgery, leaving thrombolysis only for when surgery is not available, has a very high risk or for cases of right valve thrombosis. Purpose In our center we have used a thrombolysis regimen with low doses of t-PA and in slow infusion with adequates results, proposed by Özkan et al. with 25 mg of t-PA administered over 25 hours, repeating this dose up to DVT resolution or a maximum of 8 times. Methods We reviewed eleven patients, all with mechanical valve prostheses, six treated with surgery and five with systemic thrombolysis. Of the latter, two cases were treated with a high-dose and accelerated t-PA regimen (10 mg bolus and 90 mg in 2 hours) and the other three cases with low and ultra-slow doses (25 mg in 25 hours). We consider the normalization of the mean transvalvular gradients and the resolution of regurgitation in cases of prosthetic insufficiency a successful result. The mean age was 62.6 years and the mean time from surgery to DVT of 84.9 months. Most of the patients belonged to class III and IV of the NYHA. Anticoagulation was subtherapeutic in 80% of cases. The thrombolysis success rate was 100%. Of the three cases of ultra-slow pattern, only one of them required a second dose. No side effects or complications were observed. In the surgery group, two patients died during hospital admission as a result of shock and a state of low postoperative cardiac output. In the thrombolysis group, there was only one deceased at 8 months, although not related to DVT related to metastatic melanoma. Results We observed a full success rate in the resolution of DVT, with no complications in cases of thrombolysis compared to surgery. Bolus ultra-slow infusion of t-PA is equally effective in resolving DVT, although logically with less bleeding risk due to the dose used and the time of administration, without embolic events having been observed due to slower lysis of the thrombus or new thrombosis during a year of follow-up. Conclusion According to our results treatment with low-dose and ultra-slow t-PA regimen will be the initial therapeutic option in clinical practice guidelines given the safety, low cost, and efficacy. Abstract Figure. valvular thrombosis. Evolution.

Intrabone transplantation of CD34+ cells with optimized delivery does not enhance engraftment in a rhesus macaque model

Intrabone (IB) injection of umbilical cord blood has been proposed as a potential mechanism to improve transplant engraftment and prevent graft failure. However, conventional IB techniques produce low retention of transplanted cells in the marrow. To overcome this barrier, we developed an optimized IB (OIB) injection method using low-volume, computer-controlled slow infusion that promotes cellular retention in the marrow. Here, we compare engraftment of CD34+ cells transplanted in a myeloablative rhesus macaque (RM) model using the OIB method compared with IV delivery. RM CD34+ cells obtained by apheresis were split equally for transduction with lentiviral vectors encoding either green fluorescent protein or yellow fluorescent protein reporters. Following conditioning, one marked autologous population of CD34+ cells was injected directly IB using the OIB method and the other was injected via slow IV push into the same animal (n = 3). Daily flow cytometry of blood quantified the proportion of engrafting cells deriving from each source. Marrow retention was examined using positron emission tomography/computed tomography imaging of 89Zirconium (89Zr)-oxine–labeled CD34+ cells. CD34+ cells injected via the OIB method were retained in the marrow and engrafted in all 3 animals. However, OIB-transplanted progenitor cells did not engraft any faster than those delivered IV and contributed significantly less to hematopoiesis than IV-delivered cells at all time points. Rigorous testing of our OIB delivery system in a competitive RM myeloablative transplant model showed no engraftment advantage over conventional IV infusion. Given the increased complexity and potential risks of IB vs IV approaches, our data do not support IB transplantation as a strategy to improve hematopoietic engraftment.

Safety of low-dose prolonged infusion of tissue plasminogen activator therapy in patients with thromboembolic events in the intensive care unit

Objective Thromboembolic events such as acute coronary syndrome related prosthetic heart valve thrombosis, pulmonary artery embolism and renal artery embolism are a rare condition but a major cause of morbidity and mortality. In this study we discussed low-dose thrombolytic therapy, in patients with thromboembolic events in the intensive care unit.Methods The study was performed on 12 consecutive patients [8 female; 50.3±16.0 (35–95) years] with acute thromboembolism including acute coronary syndrome related prosthetic heart valve thrombosis, acute pulmonary embolism and acute renal embolism who were treated with low-dose (25 mg) and slow infusion (6 hours) of t-PA. We evaluated mainly in-hospital safety and also effectiveness.Total treatment episodes was 1.66±0.88 (1-4) times.Results All thromboembolic events have been successfully treated with low-dose (25 mg) and slow infusion (6 hours) of t-PA. The success criteria were clinically improvement and radiologically lysis. None of the patients had ischemic stroke, intracranial hemorrhage, embolism (peripheral and recurrence of coronary artery embolism), bleeding requiring transfusion. The most frequent in-hospital complication was a gum bleeding without need for transfusion (two patients).Conclusions In our case series low-dose (25 mg) and slow infusion (6 hours) of t-PA have been performed successfully for thromboembolic events including acute coronary syndrome related prosthetic heart valve thrombosis, pulmonary embolism and renal embolism in patients with in the intensive care unit. Safety is promising and if efficacy will be proved; this method may be a valuable alternative to standard fibrinolytic regimen.