Fungal infections and antifungal prophylaxis in pediatric cardiac extracorporeal life support Gardner, Aaron H., MD; Prodhan, Parthak, MD; Stovall, Stephanie H., MD ...
Journal of thoracic and cardiovascular surgery/The Journal of thoracic and cardiovascular surgery/The journal of thoracic and cardiovascular surgery,
03/2012, Letnik:
143, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Objective Infections acquired by children during extracorporeal membrane oxygenation (ECMO) increase mortality. Our aim was to evaluate the effectiveness of prophylactic fluconazole on the incidence ...of fungal infections and to assess whether hospital-acquired fungal infection is associated with increased in-hospital mortality in pediatric cardiac patients requiring ECMO. Methods We retrospectively reviewed a prospectively maintained database and collected data on all hospital-acquired infections in patients supported for cardiac indications at a tertiary children’s hospital from 1989 to 2008. Results ECMO was deployed 801 times in 767 patients. After exclusion criteria were applied, 261 pediatric patients supported for cardiac indications were studied. Fungal infection (blood, urine, or surgical site) occurred in 12% (31/261) of patients, 9 (7%) of 127 patients receiving fluconazole prophylaxis versus 22 (16.4%) of 134 without antifungal prophylaxis ( P = .02). Using a multivariable logistic regression model, the absence of fluconazole prophylaxis was associated with an increased risk of fungal infection (odds ratio OR = 2.8; 95% confidence intervals CI, 1.2, 6.7; P = .016). In a multivariable logistic regression model for in-hospital mortality, the presence of fungal infection was associated with increased odds (OR = 3.8; 95% CI, 1.5, 9.6; P = .005) of in-hospital mortality among cardiac patients requiring ECMO, and the absence of antifungal prophylaxis showed a trend toward the same (OR = 1.6; 95% CI, 0.96, 2.8; P = .072). Conclusions Children with cardiac disease supported with ECMO who acquire fungal infections have increased mortality. Routine fluconazole prophylaxis is associated with lower rates of fungal infections in these patients.
Summary Background In the Medical Research Council (MRC) COIN trial, the epidermal growth factor receptor (EGFR)-targeted antibody cetuximab was added to standard chemotherapy in first-line treatment ...of advanced colorectal cancer with the aim of assessing effect on overall survival. Methods In this randomised controlled trial, patients who were fit for but had not received previous chemotherapy for advanced colorectal cancer were randomly assigned to oxaliplatin and fluoropyrimidine chemotherapy (arm A), the same combination plus cetuximab (arm B), or intermittent chemotherapy (arm C). The choice of fluoropyrimidine therapy (capecitabine or infused fluouroracil plus leucovorin) was decided before randomisation. Randomisation was done centrally (via telephone) by the MRC Clinical Trials Unit using minimisation. Treatment allocation was not masked. The comparison of arms A and C is described in a companion paper. Here, we present the comparison of arm A and B, for which the primary outcome was overall survival in patients with KRAS wild-type tumours. Analysis was by intention to treat. Further analyses with respect to NRAS, BRAF , and EGFR status were done. The trial is registered, ISRCTN27286448. Findings 1630 patients were randomly assigned to treatment groups (815 to standard therapy and 815 to addition of cetuximab). Tumour samples from 1316 (81%) patients were used for somatic molecular analyses; 565 (43%) had KRAS mutations. In patients with KRAS wild-type tumours (arm A, n=367; arm B, n=362), overall survival did not differ between treatment groups (median survival 17·9 months IQR 10·3–29·2 in the control group vs 17·0 months 9·4–30·1 in the cetuximab group; HR 1·04, 95% CI 0·87–1·23, p=0·67). Similarly, there was no effect on progression-free survival (8·6 months IQR 5·0–12·5 in the control group vs 8·6 months 5·1–13·8 in the cetuximab group; HR 0·96, 0·82–1·12, p=0·60). Overall response rate increased from 57% (n=209) with chemotherapy alone to 64% (n=232) with addition of cetuximab (p=0·049). Grade 3 and higher skin and gastrointestinal toxic effects were increased with cetuximab (14 vs 114 and 67 vs 97 patients in the control group vs the cetuximab group with KRAS wild-type tumours, respectively). Overall survival differs by somatic mutation status irrespective of treatment received: BRAF mutant, 8·8 months (IQR 4·5–27·4); KRAS mutant, 14·4 months (8·5–24·0); all wild-type, 20·1 months (11·5–31·7). Interpretation This trial has not confirmed a benefit of addition of cetuximab to oxaliplatin-based chemotherapy in first-line treatment of patients with advanced colorectal cancer. Cetuximab increases response rate, with no evidence of benefit in progression-free or overall survival in KRAS wild-type patients or even in patients selected by additional mutational analysis of their tumours. The use of cetuximab in combination with oxaliplatin and capecitabine in first-line chemotherapy in patients with widespread metastases cannot be recommended. Funding Cancer Research UK, Cancer Research Wales, UK Medical Research Council, Merck KGgA.
Summary Background When cure is impossible, cancer treatment should focus on both length and quality of life. Maximisation of time without toxic effects could be one effective strategy to achieve ...both of these goals. The COIN trial assessed preplanned treatment holidays in advanced colorectal cancer to achieve this aim. Methods COIN was a randomised controlled trial in patients with previously untreated advanced colorectal cancer. Patients received either continuous oxaliplatin and fluoropyrimidine combination (arm A), continuous chemotherapy plus cetuximab (arm B), or intermittent (arm C) chemotherapy. In arms A and B, treatment continued until development of progressive disease, cumulative toxic effects, or the patient chose to stop. In arm C, patients who had not progressed at their 12-week scan started a chemotherapy-free interval until evidence of disease progression, when the same treatment was restarted. Randomisation was done centrally (via telephone) by the MRC Clinical Trials Unit using minimisation. Treatment allocation was not masked. The comparison of arms A and B is described in a companion paper. Here, we compare arms A and C, with the primary objective of establishing whether overall survival on intermittent therapy was non-inferior to that on continuous therapy, with a predefined non-inferiority boundary of 1·162. Intention-to-treat (ITT) and per-protocol analyses were done. This trial is registered, ISRCTN27286448. Findings 1630 patients were randomly assigned to treatment groups (815 to continuous and 815 to intermittent therapy). Median survival in the ITT population (n=815 in both groups) was 15·8 months (IQR 9·4–26·1) in arm A and 14·4 months (8·0–24·7) in arm C (hazard ratio HR 1·084, 80% CI 1·008–1·165). In the per-protocol population (arm A, n=467; arm C, n=511), median survival was 19·6 months (13·0–28·1) in arm A and 18·0 months (12·1–29·3) in arm C (HR 1·087, 0·986–1·198). The upper limits of CIs for HRs in both analyses were greater than the predefined non-inferiority boundary. Preplanned subgroup analyses in the per-protocol population showed that a raised baseline platelet count, defined as 400 000 per μL or higher (271 28% of 978 patients), was associated with poor survival with intermittent chemotherapy: the HR for comparison of arm C and arm A in patients with a normal platelet count was 0·96 (95% CI 0·80–1·15, p=0·66), versus 1·54 (1·17–2·03, p=0·0018) in patients with a raised platelet count (p=0·0027 for interaction). In the per-protocol population, more patients on continuous than on intermittent treatment had grade 3 or worse haematological toxic effects (72 15% vs 60 12%), whereas nausea and vomiting were more common on intermittent treatment (11 2% vs 43 8%). Grade 3 or worse peripheral neuropathy (126 27% vs 25 5%) and hand–foot syndrome (21 4% vs 15 3%) were more frequent on continuous than on intermittent treatment. Interpretation Although this trial did not show non-inferiority of intermittent compared with continuous chemotherapy for advanced colorectal cancer in terms of overall survival, chemotherapy-free intervals remain a treatment option for some patients with advanced colorectal cancer, offering reduced time on chemotherapy, reduced cumulative toxic effects, and improved quality of life. Subgroup analyses suggest that patients with normal baseline platelet counts could gain the benefits of intermittent chemotherapy without detriment in survival, whereas those with raised baseline platelet counts have impaired survival and quality of life with intermittent chemotherapy and should not receive a treatment break. Funding Cancer Research UK.
Objective The objective of the study was to examine the effect of selective fetoscopic laser photocoagulation (SFLP) vs serial amnioreduction (AR) on perinatal mortality in severe twin-twin ...transfusion syndrome (TTTS). Study Design This was a 5 year multicenter, prospective, randomized controlled trial. The primary outcome variable was 30 day postnatal survival of donors and recipients. Results There was no statistically significant difference in 30-day postnatal survival between SFLP or AR treatment for donors at 55% (11 of 20) vs 55% (11 of 20) ( P = 1.0, odds ratio OR 1, 95% confidence interval CI 0.242 to 4.14) or recipients at 30% (6 of 20) vs 45% (9 of 20) ( P = .51, OR 1.88, 95% CI 0.44 to 8.64). There was no difference in 30 day survival of 1 or both twins on a per-pregnancy basis between AR at 75% (15 of 20) and SFLP at 65% (13 of 20) ( P = .73, OR 1.62, 95% CI 0.34 to 8.09). Overall survival (newborns divided by the number of fetuses treated) was not statistically significant for AR at 60% (24 of 40) vs SFLP 45% (18 of 40) ( P = .18, OR 2.01, 95% CI 0.76 to 5.44). There was a statistically significant increase in fetal recipient mortality in the SFLP arm at 70% (14 of 20) vs the AR arm at 35% (7 of 20) ( P = .25, OR 5.31, 95% CI 1.19 to 27.6). This was offset by increased recipient neonatal mortality of 30% (6 of 20) in the AR arm. Echocardiographic abnormality in recipient twin Cardiovascular Profile Score is the most significant predictor of recipient mortality ( P = .055, OR 3.025/point) by logistic regression analysis. Conclusion The outcome of the trial did not conclusively determine whether AR or SFLP is a superior treatment modality. TTTS cardiomyopathy appears to be an important factor in recipient survival in TTTS.
Update on Burkitt Lymphoma Dunleavy, Kieron; Little, Richard F; Wilson, Wyndham H
Hematology/oncology clinics of North America,
12/2016, Letnik:
30, Številka:
6
Journal Article
Recenzirano
Because of its rarity and high curability, progress in advancing therapeutics in Burkitt lymphoma (BL) has been difficult. Over recent years, several new mutations that cooperate with MYC have been ...identified, and this has paved the way for testing novel agents in the disease. One of the challenges of most standard approaches typically used is severe treatment-related toxicity that often leads to discontinuation of therapy. To that point, there has been recent success developing intermediate intensity approaches that are well tolerated in all patient groups and maintain high cure rates in a multicenter setting.
The burden of chronic obstructive pulmonary disease (COPD) in the USA continues to grow. Although progress has been made in the the development of diagnostics, therapeutics, and care guidelines, ...whether patients' quality of life is improved will ultimately depend on the actual implementation of care and an individual patient's access to that care. In this Commission, we summarise expert opinion from key stakeholders-patients, caregivers, and medical professionals, as well as representatives from health systems, insurance companies, and industry-to understand barriers to care delivery and propose potential solutions. Health care in the USA is delivered through a patchwork of provider networks, with a wide variation in access to care depending on a patient's insurance, geographical location, and socioeconomic status. Furthermore, Medicare's complicated coverage and reimbursement structure pose unique challenges for patients with chronic respiratory disease who might need access to several types of services. Throughout this Commission, recurring themes include poor guideline implementation among health-care providers and poor patient access to key treatments such as affordable maintenance drugs and pulmonary rehabilitation. Although much attention has recently been focused on the reduction of hospital readmissions for COPD exacerbations, health systems in the USA struggle to meet these goals, and methods to reduce readmissions have not been proven. There are no easy solutions, but engaging patients and innovative thinkers in the development of solutions is crucial. Financial incentives might be important in raising engagement of providers and health systems. Lowering co-pays for maintenance drugs could result in improved adherence and, ultimately, decreased overall health-care spending. Given the substantial geographical diversity, health systems will need to find their own solutions to improve care coordination and integration, until better data for interventions that are universally effective become available.
Abstract Background Inflammation is associated with progression of chronic heart failure (HF). Few data exist on high-sensitivity C-reactive protein (hsCRP) levels and their importance in acute HF. ...Methods and Results In this biomarker substudy of the ASCEND-HF trial, we measured hsCRP levels at admission (n = 794), 48–72 hours (n = 677), and 30 days (n = 581) and evaluated their association with outcomes. Levels of hsCRP were considerably elevated at admission (median 12.6 mg/L, interquartile range IQR 5.23–30.5) and 48–72 hours (median 11.0 mg/L, IQR 4.87–29.9) and declined only at 30 days (median 4.7 mg/L, IQR 1.83–13.1). Admission hsCRP was not associated with dyspnea improvement at 6 hours (74.1%) and 24 hours (86.2%), in-hospital death or worsening HF (n = 37; 4.7%), 30-day mortality or HF readmission (death: n = 25 3.2%; combined death and HF readmission: n = 95 12.0%), or 180-day mortality (n = 96; 12.1%). Hospital stay (median 5 days, IQR 3–7) was longer among patients with higher admission hsCRP levels (0.57 days per log2 -hsCRP in adjusted models; 95% confidence interval CI 0.33–0.81; P < .001). Levels of hsCRP at 48–72 hours did not predict 30-day mortality or HF readmission and were only marginally associated with 180-day mortality. However, higher hsCRP at 30 days among survivors was associated with higher 180-day mortality in models including admission hsCRP (adjusted hazard ratio HR per log2 -hsCRP: 1.23; 95% CI 1.04–1.45; P = .016). Patients with an hsCRP increase at day 30, defined as >10% increase over baseline value, had higher 180-day mortality risk compared with those with unchanged or decreased 30-day hsCRP (HR 2.29, 95% CI 1.16–4.52; P = .017). Conclusions Levels of hsCRP are elevated among patients with acute HF. Increasing levels at 30 days after discharge are associated with higher 180-day mortality.
To determine the incidence and risk factors for postoperative acute respiratory distress syndrome (ARDS) in a large cohort of bleomycin-exposed patients undergoing surgery with general endotracheal ...anesthesia.
From a Mayo Clinic cancer registry, we identified patients who had received systemic bleomycin and then underwent a major surgical procedure that required more than 1 hour of general anesthesia from January 1, 2000, through August 30, 2012. Heart, lung, and liver transplantations were excluded. Postoperative ARDS (within 7 days after surgery) was defined according to the Berlin criteria.
We identified 316 patients who underwent 541 major surgical procedures. Only 7 patients met the criteria for postoperative ARDS; all were white men, and 6 were current or former smokers. On univariate analysis, we observed an increased risk of postoperative ARDS in patients who were current or former smokers. Furthermore, significantly greater crystalloid and colloid administration was found in patients with postoperative ARDS. We also observed a trend toward longer surgical duration and red blood cell transfusion in patients with postoperative ARDS, although this finding was not significant. Intraoperative fraction of inspired oxygen was not associated with postoperative ARDS. In bleomycin-exposed patients, the incidence of postoperative ARDS after major surgery with general anesthesia is approximately 1.3% (95% CI, 0.6%-2.6%). For first major procedures after bleomycin therapy, the incidence is 1.9% (95% CI, 0.9%-4.1%).
The risk of postoperative ARDS in patients exposed to systemic bleomycin appears to be lower than expected. Smoking status may be an important factor that modifies the risk of postoperative ARDS in these patients.
Abstract Background context After spinal fusion surgery, postoperative management often includes imaging with either computed tomography (CT) or magnetic resonance imaging (MRI) to assess the spinal ...canal and nerve roots. The metallic implants used in the fusion can cause artifact that interferes with this imaging, reducing their diagnostic value. Stainless steel is known to produce large amounts of artifact, whereas titanium is known to produce significantly less. Other alloys such as vitallium are now being used in spinal implants, but their comparison to titanium and stainless steel has not been well documented in the orthopedic literature. Titanium is a desirable metal because of its light weight and lower production of artifact on imaging, although it is not as stiff as stainless steel. Vitallium is proposed as a replacement for titanium because it has stiffness similar to stainless steel, while still being as light as titanium. Purpose The purpose of this study was to compare the amount of artifact produced on MRI and CT by three types of spinal implants: stainless steel, titanium, and vitallium. Study design A prospective experimental design was used to compare three types of spinal implants used in posterior spinal fusion surgery. Outcome measures The resulting images were evaluated by a radiologist to measure the amount of artifact (in millimeters) and by an orthopedic surgeon to assess the diagnostic quality (on a Likert scale). Methods A porcine torso was used for repeated MRI and CT scans before and after implantation with pedicle screws and rods made of the three metals being studied. Results Images produced after the insertion of vitallium rods and titanium screws as well as those with titanium rods and screws were found to have less artifact and a better overall diagnostic quality than those produced with stainless steel implants. Overall, there was not a difference between the amount of artifact in the spinal images with vitallium and titanium rods, with the exception of a few trials that showed small but statistically significant differences between the two metals, where titanium had slightly better images. Conclusions If vitallium rods are used in posterior spinal surgery in place of implants made of titanium or stainless steel, any postoperative imaging of the spine using MRI or CT should have amounts of artifact that are similar to titanium and better than stainless steel.
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