Reperfusion therapy in renal dysfunction patients presenting with STEMI: Which is better in the Tunisian context?

BackgroundPatients with renal insufficiency experience worse prognosis after STEMI. Current guidelines do not clearly draw specific strategies for renal dysfunction (RD) patients, and most clinical trials exclude them from the study population.Aim of the studyTo compare primary PCI (PPCI) and thrombolysis (using Strepokinase) results as well as in-hospital mortality after successful reperfusion between patients with or without RD.MethodsFrom January 1995 to October 2011, 1388 patients admitted for STEMI were enrolled in the MIRAMI (MonastIR’s Acute Myocardial Infarction) registry. Two reperfusion groups were identified: PPCI (315 patients) and thrombolysis (379 patients). Patients who underwent rescue PCI were excluded. Due to lacking clearance data, we used a serum creatinine level >130μmol/l to define RD patients. We compared in each reperfusion group: (1) The success of revascularization (TIMI III flow restoring with <20% residual stenosis after PPCI, pain relief with ST regression >50% 60min after thrombolysis) and (2) the in-hospital mortality rate after reperfusion success between the RD patients (RD+) and normal renal function patients (RD−).ResultsNinety patients (13%) had RD, 50% of which underwent PPCI, and 50% received thrombolytics. Among RD+ and RD- groups, baseline characteristics were similar between the two reperfusion groups.In the PPCI group, although TIMI flow was similar before angioplasty (p=0.82), TIMI III restoring was significantly lower in the RD+ group (78.6% vs 91.8%, p=0.013). Suboptimal result was also higher in the RD+ group (13.6% vs 2.7%, p<0.001), but ST regression after TIMI III achievement was similar in the 2 groups (p=0.43) reflecting probably no microvascular damage.In the thrombolysis group, successful reperfusion was also significantly lower when RD exists (58% vs 74%, p=0.03).After successful reperfusion, in-hospital mortality is higher among RD+ patients in the PPCI group (33.3% vs 4.3%, p<0.001), whereas it is similar after successful thrombolysis (2.6% vs 0%, p=0.42).ConclusionRD reduces either PPCI or thrombolysis success, with no proven microvascular damage after PPCI. In-hospital prognosis is however worse in RD group only after successful PPCI, but not after successful Streptokinase thrombolysis

Cetuximab plus chronomodulated irinotecan, 5-fluorouracil, leucovorin and oxaliplatin as neoadjuvant chemotherapy in colorectal liver metastases: POCHER trial

Background:We assessed the effectiveness of cetuximab plus chronomodulated irinotecan, 5-fluorouracil (5-FU), leucovorin (FA) and oxaliplatin (L-OHP) (chrono-IFLO) administered as neoadjuvant chemotherapy to increase the resectability of colorectal liver metastases.Methods:This was a phase II prospective trial with rate of liver metastases resection as primary end point. Forty-three patients with unresectable metastases were enroled: 9 with metastases &gt;5 cm; 29 with multinodular (4) disease; 1 with hilar location; 4 with extrahepatic lung disease. Treatment consisted of cetuximab at day 1 plus chronomodulated irinotecan 5-FU, FA and L-OHP for 2-6 days every 2 weeks. After the first 17 patients, doses were reduced for irinotecan to 110 mg m 2, 5-FU to 550 mg m 2 per day and L-OHP to 15 mg m 2 per day.Results:Macroscopically complete resections were performed in 26 out of 43 patients (60%) after a median of 6 (range 3-15) cycles. Partial response was noticed in 34 patients (79%). Median overall survival was 37 months (95% CI: 21-53 months), with a 2-year survival of 68% in the entire population, 80.6% in resected patients and 47.1% in unresected patients (P=0.01). Grade 3/4 diarrhoea occurred in 93% and 36% of patients before and after dose reduction.Conclusion:Cetuximab plus chrono-IFLO achieved 60% complete resectability of colorectal liver metastases. © 2010 Cancer Research UK All rights reserved

Circadian and chemotherapy-related changes in urinary modified nucleosides excretion in patients with metastatic colorectal cancer

Urinary levels of modified nucleosides reflect nucleic acids turnover and can serve as non-invasive biomarkers for monitoring tumour circadian dynamics, and treatment responses in patients with metastatic colorectal cancer. In 39 patients, median overnight urinary excretion of LC-HRMS determinations of pseudouridine, was ~ tenfold as large as those of 1-methylguanosine, 1-methyladenosine, or 4-acetylcytidine, and ~ 100-fold as large as those of adenosine and cytidine. An increase in any nucleoside excretion after chemotherapy anticipated plasma carcinoembryonic antigen progression 1–2 months later and was associated with poor survival. Ten fractionated urines were collected over 2-days in 29 patients. The median value of the rhythm-adjusted mean of urinary nucleoside excretion varied from 64.3 for pseudouridine down to 0.61 for cytidine. The rhythm amplitudes relative to the 24-h mean of 6 nucleoside excretions were associated with rest duration, supporting a tight link between nucleosides turnover and the rest-activity rhythm. Moreover, the amplitude of the 1-methylguanosine rhythm was correlated with the rest-activity dichotomy index, a significant predictor of survival outcome in prior studies. In conclusion, urinary excretion dynamics of modified nucleosides appeared useful for the characterization of the circadian control of cellular proliferation and for tracking early responses to treatments in colorectal cancer patients

Multi-centre phase II clinical trial of yttrium-90 resin microspheres alone in unresectable, chemotherapy refractory colorectal liver metastases

Background:This multi-centre phase II clinical trial is the first prospective evaluation of radioembolisation of patients with colorectal liver metastases (mCRC) who failed previous oxaliplatin-and irinotecan-based systemic chemotherapy regimens.Methods:Eligible patients had adequate hepatic, haemopoietic and renal function, and an absence of major hepatic vascular anomalies and hepato-pulmonary shunting. Gastroduodenal and right gastric arteries were embolised before hepatic arterial administration of yttrium-90 resin microspheres (median activity, 1.7 GBq; range, 0.9-2.2).Results:Of 50 eligible patients, 38 (76%) had received 654 lines of chemotherapy. Most presented with synchronous disease (72%), <4 hepatic metastases (58%), 25-50% replacement of total liver volume (60%) and bilateral spread (70%). Early and intermediate (<48 h) WHO G1-2 adverse events (mostly fever and pain) were observed in 16 and 22% of patients respectively. Two died due to renal failure at 40 days or liver failure at 60 days respectively. By intention-to-treat analysis using Response Evaluation Criteria in Solid Tumours, 1 patient (2%) had a complete response, 11 (22%) partial response, 12 (24%) stable disease, 22 (44%) progressive disease; 4 (8%) were non-evaluable. Median overall survival was 12.6 months (95% CI, 7.0-18.3); 2-year survival was 19.6%.Conclusion: Radioembolisation produced meaningful response and disease stabilisation in patients with advanced, unresectable and chemorefractory mCRC. \ua9 2010 Cancer Research UK All rights reserved

Emergent balloon mitral valvotomy in pregnant women presenting with refractory pulmonary edema

Mitral stenosis is the most common valvular heart lesion found in pregnancy. When severe, it leads to significant risk of mortality for both mother and fetus, since the hemodynamic adaptations to pregnancy are badly tolerated. Many pregnant women with mitral stenosis present in a critically ill condition. The role of balloon mitral valvotomy (BMV) in such patients is ill-defined. Objectives: We sought to evaluate the feasibility, efficacy and safety of emergent BMV in pregnant patients with refractory pulmonary edema and to determine maternal and fetal outcome. Methods: Of 88 patients undergoing BMV during pregnancy from January 1990 to December 2011 in Cardiology A Department of Monastir Hospital, 28 women were in New York Heart Association functional class IV and underwent emergent BMV. During the procedure, radiation exposure was minimized by means of total abdominal and pelvic shielding. Results: The mothers’s mean age at the time of BMV was 28.86 ± 5.7 (range 19–43) years, and the gestation period was 30 ± 5.1 (range 20 –39) weeks. Ten patients were primiparas. Mitral valve (MV) was assessed using the Wilkins score which averaged 7.4 ± 1.8 (range 4–14). Fluoroscopy time was 7.8 ± 1.9 min. The BMV procedure was successful in 25 (89.3%) patients with a dramatic improvement in patient symptoms. The mitral valve area increased from 0.8 ± 0.2 cm2 to 2.2 ± 0.42 cm2 (p < 0.0001). The mitral valve pressure gradient decreased from 22.2 ± 9.3 to 5.7 ± 4 mmHg (p < 0.0001). The left atrial pressure decreased from 29.4 ± 9.3 to 15.4 ± 7.3 mmHg (p < 0.0001). The pulmonary artery pressure decreased from 58.8 ± 21.1 to 37.2 ± 14.3 mmHg (p < 0.0001). One patient developed severe mitral regurgitation and required urgent mitral valve replacement. There was no maternal mortality or significant foetal morbidity. Pregnancy was uneventful in all patients, all babies were born at full term by spontaneous vaginal delivery in 24 cases (85.7%) and by cesarian section for obstetrical reasons in 4 (14.3%), with no obvious malformations (4 of them were twin babies). None of the babies needed intensive care monitoring. The average Apgar scores at 1 min were 8.6 ± 1. The mean birth weight was 3.1 Kilograms (Kg) ranged from 1.9 to 3.8 kg. Conclusion: During pregnancy, emergent BMV is safe and feasible in patients with symptomatic mitral stenosis and severe pulmonary edema. There is marked symptomatic relief, along with excellent maternal and fetal outcomes