Evaluating primary intra-arterial chemotherapy versus intravenous plus intra-arterial chemotherapy for advanced intraocular retinoblastoma.

PURPOSE: Although intra-arterial chemotherapy (IAC) is commonly used for treating intraocular retinoblastoma, it is not a systemic therapy. We aimed to investigate whether the addition of intravenous chemotherapy (IVC) before IAC administration had any effects (whether beneficial or adverse) on patient outcomes. METHODS: This multicenter retrospective cohort study included 213 patients with advanced intraocular retinoblastoma who received IVC plus IAC (n = 103) or IAC alone (n = 110) between April 2009 and January 2017. Eyes were grouped according to the International Intraocular Retinoblastoma Classification. Kaplan-Meier and Cox regression analyses were performed to compare survival outcomes between the two groups. Moreover, details regarding enucleation were recorded. RESULTS: The 3-year ocular survival rates were 62% in the IVC plus IAC group and 68% in the IAC group (hazard ratio (HR) 0.88, 95% confidence interval (CI) 0.55-1.43, P = 0.61). Moreover, the corresponding 3-year overall survival rates were 97% and 93%, respectively (HR 1.56, 95% CI 0.41-5.90, P = 0.51), while the 3-year event-free survival rates were 76% and 72%, respectively (HR 0.96, 95% CI 0.56-1.65, P = 0.89). CONCLUSIONS: Within a 3-year follow-up period, IVC plus IAC produced no additional benefit over primary IAC for treating advanced intraocular retinoblastoma in terms of local tumor control and extending survival. Longer follow-up periods are required to assess long-term efficacy.

Intraosseous compared to intravenous drug resuscitation in out-of-hospital cardiac arrest.

AIMS: Although the intraosseous (IO) route is increasingly used for vascular access in out-of-hospital cardiac arrest (OHCA), little is known about its comparative effectiveness relative to intravenous (IV) access. We evaluated clinical outcomes following OHCA comparing drug administration via IO versus IV routes. METHODS: This retrospective cohort study evaluated Emergency Medical Services (EMS)-treated adults with atraumatic OHCA in a large metropolitan EMS system between 9/1/2012-12/31/2014. Access was classified as IO or IV based on the route of first EMS drug administration. Study endpoints were survival to hospital discharge, return of spontaneous circulation (ROSC) and survival to hospital admission. RESULTS: Among 2164 adults with OHCA, 1800 met eligibility criteria, 1525 of whom were treated via IV and 275 principally via tibial-IO routes. Compared to IV, IO-treated patients were younger, more often women, had unwitnessed OHCA, a non-cardiac aetiology, and presented with non-shockable rhythms. IO versus IV-treated patients were less likely to survive to hospital discharge (14.9% vs 22.8%, p=0.003), achieve ROSC (43.6% vs 55.5%, p<0.001) or be hospitalized (38.5% vs 50.0% p<0.001). In multivariable adjusted analyses, IO treatment was not associated with survival to discharge (odds ratio (OR) (95% confidence interval) 0.81 (0.55, 1.21), p=0.31), but was associated with a lower likelihood of ROSC (OR=0.67 (0.50, 0.88), p=0.004) and survival to hospitalization (OR=0.68 (0.51, 0.91), p=0.009). CONCLUSION: Though not independently associated with survival to discharge, principally tibial IO versus IV treatment was associated with a lower likelihood of ROSC and hospitalization. How routes of vascular access influence clinical outcomes after OHCA merits additional study.

Effects of different types of fluid resuscitation for hemorrhagic shock on splanchnic organ microcirculation and renal reactive oxygen species formation.

INTRODUCTION: Fluid resuscitation is an indispensable procedure in the acute management of hemorrhagic shock for restoring tissue perfusion, particularly microcirculation in splanchnic organs. Resuscitation fluids include crystalloids, hypertonic saline (HTS), and synthetic colloids, and their selection affects the recovery of microcirculatory blood flow and reactive oxygen species (ROS) formation, which is often evident in the kidney, following reperfusion. In this study, the effects of acute resuscitation with 0.9% saline (NS), 3% HTS, 4% succinylated gelatin (GEL), and 6% hydroxyethyl starch (HES) 130/0.4 were compared in a hemorrhagic shock rat model to analyze restoration of microcirculation among various splanchnic organs and the gracilis muscle and reperfusion-induced renal ROS formation. METHODS: A total of 96 male Wistar rats were subjected to sham operation (sham group), hemorrhagic shock (control group), and resuscitation with NS, HTS, GEL and HES. Two hours after resuscitation, changes in the mean arterial pressure (MAP), serum lactate level and the microcirculatory blood flow among various splanchnic organs, namely the liver, kidney, and intestine (mucosa, serosal muscular layer, and Peyer's patch), and the gracilis muscle, were compared using laser speckle contrast imaging. Renal ROS formation after reperfusion was investigated using an enhanced in vivo chemiluminescence (CL) method. RESULTS: Microcirculatory blood flow was less severely affected by hemorrhaging in the liver and gracilis muscle. Impairment of microcirculation in the kidney was restored in all resuscitation groups. Resuscitation in the NS group failed to restore intestinal microcirculation. Resuscitation in the HTS, GEL, and HES groups restored intestinal microcirculatory blood flow. By comparison, fluid resuscitation restored hemorrhagic shock-induced hypotension and decreased lactatemia in all resuscitation groups. Reperfusion-induced in vivo renal ROS formation was significantly higher in the GEL and HES groups than in the other groups. CONCLUSION: Although fluid resuscitation with NS restored the MAP and decreased lactatemia following hemorrhagic shock, intestinal microcirculation was restored only by other volume expanders, namely 3% HTS, GEL, and HES. However, reperfusion-induced renal ROS formation was significantly higher when synthetic colloids were used.

Impact of the use of propofol remifentanil goal-directed sedation adapted by nurses on the time to extubation in mechanically ventilated ICU patients: the experience of a French ICU.

AIM: Inappropriate sedation could prolong the duration of mechanical ventilation. The present "before-after" study assessed the impact of a goal-directed sedation using an algorithm with a combination of propofol and remifentanil on the time to extubation. METHODS: During 16 months, ICU-patients requiring sedation greater than 24 h were prospectively studied. In the first eight months, sedation was achieved using continuous infusions of a benzodiazepine (flunitrazepam or midazolam) and an opioid (fentanyl or sufentanil). In the following eight months, sedation using a propofol-remifentanil combination was given and adapted by the nurses according to the Ramsay score and a pain scale. The main endpoint was the time to extubation (from the cessation of sedation to extubation). The secondary endpoints were the duration of mechanical ventilation, the length of ICU stay, the ICU mortality rate, the need of vasopressive support, the occurrence of self-extubations and Ventilator-Associated Pneumonia (VAP). RESULTS: Forty-six and 39 patients were included in the first and second periods, respectively. The durations of sedation were similar. The time to extubation was shorter in the second period (10 versus 92h, p<0.0001). The duration of mechanical ventilation, the length of stay in ICU, the mortality rate, the need for vasopressor support and the occurrence of VAP were similar. Five self-extubations occurred in the second period versus one in the first one (p=0.02). CONCLUSION: Sedation with adapted infusions of propofol and remifentanil according to the Ramsay score and a pain scale decreases the time to extubation in ICU patients requiring sedation longer than 24h but increases the rate of self-extubations.

Safety in iron management.

Intravenous (IV) iron therapy has become an integral part of hemodialysis management during the past several decades, and the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative guidelines recognize that most patients undergoing hemodialysis will require IV iron therapy on a regular basis to reach target hemoglobin (Hgb) levels. There now are three IV iron compounds available in the United States: iron dextran, sodium ferric gluconate, and iron sucrose. Although all have been proven effective for increasing Hgb/hematocrit levels, recent data show differences in their relative safety profiles. During the past two decades, more than 30 deaths have been attributed to the use of IV iron dextran. The two newer compounds available in the United States, sodium ferric gluconate and iron sucrose, have more favorable safety profiles, with the largest prospective safety comparison to date showing sodium ferric gluconate to be similar to placebo in the incidence of serious anaphylactoid-type reactions. This article reviews safety data surrounding the IV iron therapies.

Retrospective analysis of the safety of Herceptin immunotherapy in metastatic breast cancer.

Approximately 25,000 patients have been treated to date with the humanized anti-HER2 monoclonal antibody, Herceptin. This therapy has proved effective and well tolerated in patients with HER2-positive metastatic breast cancer; adverse events were generally infusion-related fever and chills of mild-to-moderate severity. Cardiotoxicity and infusion-related reactions emerged as the two main safety concerns with the use of Herceptin. Retrospective analysis revealed a higher incidence of heart failure when Herceptin was combined with anthracyclines than that expected with anthracyclines alone. Age, anthracycline exposure and cardiac risk factors were found to be predictors of cardiac adverse events. Patients experiencing cardiac dysfunction responded well to standard cardiac medication and the majority improved. Cardiac function should be monitored regularly and Herceptin should be discontinued if significant heart failure develops unless the benefits for an individual patient outweigh the risks. Of 25,000 patients, 74 (0.3%) were reported to have experienced a serious infusion-related reaction. The majority occurred during or shortly after the first infusion and were characterized by respiratory symptoms. Most patients were successfully treated; a total of 33 patients continued Herceptin therapy with no recurrence of infusion reactions. Although the benefit to risk ratio of Herceptin remains favorable, physicians must be vigilant and aggressive in managing cardiotoxicity and infusion-related reactions.