Inhaled amikacin for pneumonia treatment and dissemination prevention: an experimental model of severe monolateral Pseudomonas aeruginosa pneumonia.

BACKGROUND: Pseudomonas aeruginosa pneumonia is commonly treated with systemic antibiotics to ensure adequate treatment of multidrug resistant (MDR) bacteria. However, intravenous (IV) antibiotics often achieve suboptimal pulmonary concentrations. We therefore aimed to evaluate the effect of inhaled amikacin (AMK) plus IV meropenem (MEM) on bactericidal efficacy in a swine model of monolateral MDR P. aeruginosa pneumonia. METHODS: We ventilated 18 pigs with monolateral MDR P. aeruginosa pneumonia for up to 102 h. At 24 h after the bacterial challenge, the animals were randomized to receive 72 h of treatment with either inhaled saline (control), IV MEM only, or IV-MEM plus inhaled AMK (MEM + AMK). We dosed IV MEM at 25 mg/kg every 8 h and inhaled AMK at 400 mg every 12 h. The primary outcomes were the P. aeruginosa burden and histopathological injury in lung tissue. Secondary outcomes included the P. aeruginosa burden in tracheal secretions and bronchoalveolar lavage fluid, the development of antibiotic resistance, the antibiotic distribution, and the levels of inflammatory markers. RESULTS: The median (25-75th percentile) P. aeruginosa lung burden for animals in the control, MEM only, and MEM + AMK groups was 2.91 (1.75-5.69), 0.72 (0.12-3.35), and 0.90 (0-4.55) log10 CFU/g (p = 0.009). Inhaled therapy had no effect on preventing dissemination compared to systemic monotherapy, but it did have significantly higher bactericidal efficacy in tracheal secretions only. Remarkably, the minimum inhibitory concentration of MEM increased to > 32 mg/L after 72-h exposure to monotherapy in 83% of animals, while the addition of AMK prevented this increase (p = 0.037). Adjunctive therapy also slightly affected interleukin-1ß downregulation. Despite finding high AMK concentrations in pulmonary samples, we found no paired differences in the epithelial lining fluid concentration between infected and non-infected lungs. Finally, a non-significant trend was observed for higher amikacin penetration in low-affected lung areas. CONCLUSIONS: In a swine model of monolateral MDR P. aeruginosa pneumonia, resistant to the inhaled AMK and susceptible to the IV antibiotic, the use of AMK as an adjuvant treatment offered no benefits for either the colonization of pulmonary tissue or the prevention of pathogen dissemination. However, inhaled AMK improved bacterial eradication in the proximal airways and hindered antibiotic resistance.

Role of Biodegradable Stents as Part of Treatment of Biliary Strictures after Pediatric and Adult Liver Transplantation: An Observational Single-Center Study.

This brief report presents the results of 20 adult and pediatric patients treated with the use of biodegradable SX-Ella biliary stents placed by means of a transhepatic approach for the treatment of benign biliary strictures after liver transplantation. Stent insertions were always feasible (100%), and only 1 case of acute pancreatitis was observed (5%). The overall clinical success rate of the procedure, including anastomotic and nonanastomotic strictures, was 75%, and was higher in the anastomotic stricture group (81.25%) than in the nonanastomotic stricture group (50%).

Detection of early portal hypertension with routine data and liver stiffness in patients with asymptomatic liver disease: a prospective study.

BACKGROUND & AIMS: Detecting portal hypertension (PH) before the development of varices is important for prognosis and for designing interventional studies. None of the available strategies is used in practice. We evaluated a sequential screening-diagnostic strategy based on clinical data and transient elastography (TE) to detect PH in asymptomatic outpatients with liver disease. METHODS: Consecutive patients with chronic liver disease and no previous diagnosis of PH were screened by TE. Patients with liver stiffness (LS) ⩾ 13.6 kPa were further evaluated by endoscopy and hepatic venous pressure gradient (HVPG). For analysis, patients were classified in 3 groups: group A, platelets ⩾ 150,000/mm(3), normal abdominal ultrasound; group B, platelets <150,000/mm(3), normal ultrasound; group C, platelets <150,000/mm(3), abnormal ultrasound (splenomegaly, nodular liver surface). RESULTS: 250 patients were evaluated (69% group A, 20% group B, 11% group C). In 9% elastography was non-valid. LS ⩾ 13.6 was found in 54 patients (8% A, 43% B, and 81% C, p<0.001). Endoscopy was performed in 49 of these: 20% had small varices, 0% high-risk varices. No patients from group A had varices, and 90% with varices belonged to group C. HVPG was obtained in 40 patients: 93% had PH (HVPG >5 mmHg) and 65% clinically significant PH (CSPH, HVPG ⩾ 10). Only 3 patients, all from group A, had HVPG <5. All patients from groups B and C with LS ⩾ 13.6 had PH. The LS 25 cut-off was excellent at ruling-in CSPH. CONCLUSIONS: A simple strategy based on routine clinical data and TE could be useful to detect early PH among asymptomatic patients with chronic liver disease.

Long-term follow-up of hemodynamic responders to pharmacological therapy after variceal bleeding.

UNLABELLED: Although it is assumed that hemodynamic responders to pharmacological therapy after a variceal hemorrhage are adequately protected from rebleeding, there is no evidence that either this response or its protective effect extend beyond the usual 2-year follow-up featured in available studies. We aimed to assess the maintenance of hemodynamic response and its impact on outcomes in a large cohort of hemodynamic responders during a long follow-up. One hundred three patients with cirrhosis admitted with acute variceal bleeding between 2001 and 2010 were prospectively evaluated. The hepatic venous pressure gradient (HVPG) was determined 5 days after the bleeding and repeated 5-7 days after maximal tolerated doses of nadolol and nitrates. Hemodynamic responders (HVPG ≤ 12 mm Hg or ≥ 20% decrease from baseline) were maintained on drugs and followed up with annual HVPG measurements. Forty-eight patients (47%) were hemodynamic responders. The median follow-up was 48 months (range, 2-108 months). Long-term HVPG evaluations could not be performed in eight patients (four deaths, two rebleedings, two follow-ups <1 year). Among the remaining 40 patients, hemodynamic response was maintained in 26 (65%) and lost in 14 (35%). There were no baseline differences between the two subgroups. However, 100% of alcoholic patients who remained abstinent maintained long-term response, compared with 36% of nonabstinent alcoholics and 50% of patients with viral cirrhosis. Patients with loss of hemodynamic response rebled more during follow-up and showed a higher incidence of death or liver transplantation. CONCLUSIONS: After variceal bleeding, long-term maintenance of hemodynamic response to drug therapy is mainly restricted to patients with alcoholic cirrhosis who remain abstinent. The loss of this long-term response carries worse clinical outcomes.

Adding banding ligation is effective as rescue therapy to prevent variceal rebleeding in haemodynamic non-responders to pharmacological therapy.

BACKGROUND: It is unknown which is the best therapy to treat haemodynamic non-responders to pharmacological therapy after variceal bleeding. AIM: To evaluate the efficacy of adding banding ligation to drugs to prevent variceal rebleeding in haemodynamic non-responders to drugs. METHODS: Fifty-three cirrhotic patients with variceal bleeding underwent a hepatic venous pressure gradient (HVPG) measurement 5 days after the episode. Nadolol and nitrates were then titrated to maximum tolerated doses. A second HVPG was taken 14 days later. Responders (HVPG ≤12 mm Hg or ≥20% decrease from baseline) were maintained on drugs and non-responders had banding ligation added to drugs. RESULTS: Mean follow-up was 28 months. In 5 patients the second HVPG could not be performed because of early rebleeding. The remaining 48 patients were classified as responders (n=24) and non-responders (n=24), who had banding added. No baseline differences were observed between groups. Variceal rebleeding occurred in 12% of the 48 patients whose haemodynamic response was assessed. Responders on drug therapy presented a 16% rebleeding rate, whilst non-responders rescued with banding showed an 8% rebleeding rate. Rebleeding-related mortality was not different between groups. CONCLUSION: In a HVPG-guided strategy, adding banding ligation to drugs is an effective rescue strategy to prevent rebleeding in haemodynamic non-responders to drug therapy.

Successful embolization of a spontaneous mesocaval shunt using the Amplatzer Vascular Plug II.

A 48-year-old man with alcoholic liver cirrhosis and hepatic encephalopathy was found to have a large, spontaneous mesocaval shunt. The shunt was successfully occluded with the use of an Amplatzer Vascular Plug. To our knowledge, this is the first report of the use of this device to embolize a mesocaval shunt involving the superior mesenteric vein.

Hemodynamic response-guided therapy for prevention of variceal rebleeding: an uncontrolled pilot study.

The clinical usefulness of assessing hemodynamic response to drug therapy in the prophylaxis of variceal rebleeding is unknown. An open-labeled, uncontrolled pilot trial was performed to evaluate the feasibility and efficacy of using the hemodynamic response to pharmacological treatment to guide therapy in this setting. Fifty patients with acute variceal bleeding underwent a hepatic venous pressure gradient (HVPG) measurement 5 days after the episode. Nadolol and nitrates were initiated, and a second HVPG was measured 15 days later. Responder patients (> or =20% decrease in HVPG from baseline) were maintained on drugs, partial responders (> or =10% and <20%) had banding ligation added to the drugs, and nonresponders (<10%) received a transjugular intrahepatic portal-systemic shunt (TIPS). Mean follow-up was 22 months. Eight patients (16%) did not receive the second HVPG, 6 of them because of early variceal rebleeding. Of the other 42 patients, 24 were classified as responders (57%); 10 as partial responders (24%), who had banding added; and 8 as nonresponders (19%), who received a TIPS. Patients with cirrhosis of viral etiology compared to alcoholic cirrhosis tended to present more early rebleedings, less response to drugs and needed more TIPS. Variceal rebleeding occurred in 22% of all patients but only in 12% of patients whose hemodynamic response was assessed. The 3 therapeutic groups were not different. In conclusion, using hemodynamic response to pharmacological treatment to guide therapy in secondary prophylaxis to prevent variceal bleeding is feasible and effectively protects patients from rebleeding. In this context, viral cirrhosis seems to present a worse outcome than alcoholic cirrhosis.

Lesión traumática de la arteria epigástrica inferior: una causa de inestabilidad hemodinámica diferida en fractura de pelvis rotacionalmente inestable / Traumatic lesion of the inferior epigastric artery: a cause of delayed hemodynamic instability in a rotationally unstable fracture of the pelvis

Se presenta un paciente politraumatizado con fractura de pelvis rotacionalmente inestable pero vertical y posteriormente estable, que se inició con inestabilidad hemodinámica diferida, secundaria a hemorragia retroperitoneal por ruptura de la rama púbica de la arteria epigástrica inferior derecha. Se destaca la utilidad de la tomografía computarizada (TC) en la detección de sangrado activo, la arteriografía en la localización precisa del vaso lesionado, y el tratamiento con éxito mediante embolización selectiva con microcoils y alcohol polivinilo

We present a case of a patient suffering multiple trauma with rotationally unstable but vertically and posteriorly stable fracture of the pelvis who presented delayed hemodynamic instability secondary to retroperitoneal hemorrhage due to rupture of the pubic branch of the right inferior epigastric artery. We emphasize the usefulness of computed tomography (CT) in the detection of active bleeding, of arteriography in the precise localization of the injured vessel, and the successful treatment by selective embolization using microcoils and polyvinyl alcohol