IGHV-associated methylation signatures more accurately predict clinical outcomes of chronic lymphocytic leukemia patients than IGHV mutation load.

Currently, no molecular biomarker indices are used in standard care to make treatment decisions at diagnosis of chronic lymphocytic leukemia (CLL). We used Infinium MethylationEPIC array data from diagnostic blood samples of 114 CLL patients and developed a procedure to stratify patients based on methylation signatures associated with mutation load of the IGHV gene. This procedure allowed us to predict the time to treatment with a hazard ratio (HR) of 8.34 (95% confidence interval [CI]: 4.54-15.30), as opposed to a HR of 4.35 (95% CI: 2.60-7.28) using IGHV mutation status. Detailed evaluation of 17 cases for which the two classification procedures gave discrepant results showed that these cases were incorrectly classified using IGHV status. Moreover, methylation-based classification stratified patients with different overall survival (HR=1.82; 95% CI: 1.07-3.09), which was not possible using IGHV status. Furthermore, we assessed the performance of the developed classification procedure using published HumanMethylation450 array data for 159 patients for whom information on time to treatment, overall survival and relapse was available. Despite 450K array methylation data not containing all the biomarkers used in our classification procedure, methylation signatures again stratified patients with significantly better accuracy than did IGHV mutation load regarding all available clinical outcomes. Thus, stratification using IGHV-associated methylation signatures may provide better prognostic power than IGHV mutation status.

Effects of post-operative furosemide in adult surgical patients: A systematic review and meta-analysis of randomised clinical trials.

BACKGROUND: Acute kidney injury (AKI) is associated with increased morbidity and mortality and may present as oliguria in the post-operative phase. Diuretics, including furosemide, are commonly used in post-operative patients. Accordingly, we aimed to assess the balance between benefits and harms of furosemide post-operatively in adult surgical patients. METHODS: We conducted a systematic review with meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statements, the Cochrane Handbook and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. We included randomised clinical trials (RCTs) comparing post-operative treatment with furosemide vs no furosemide in adult surgical patients. Risk ratios (RR) with 95% confidence intervals (CI) were estimated by conventional meta-analysis and trial sequential analysis (TSA). RESULTS: Two thousand five hundred and sixty seven records were identified and four trials with 325 patients in total were included. All were adjudicated as having overall high risk of bias. We observed no statistically significant difference between furosemide- vs no furosemide-treated patients in any of the predefined outcome measures, including AKI (RR 1.07, 95% CI 0.43-2.65), all-cause mortality (RR 1.73, 95% CI 0.62-4.80, use of vasopressors post-operatively (RR 1.04, 95% CI 0.74-1.44) or need for renal replacement therapy (RR 3.87, 95% CI 0.44-33.99). TSA highlighted sparse data, and the overall quality of evidence was very low. CONCLUSION: In this systematic review, we found that the quantity and quality of evidence for using furosemide post-operatively in adult surgical patients were very low with no firm evidence for benefit or harm.

Harms associated with taking nalmefene for substance use and impulse control disorders: A systematic review and meta-analysis of randomised controlled trials.

IMPORTANCE: Nalmefene is a newly approved drug for alcohol use disorder, but the risk of harms has not been evaluated from empirical trial evidence. OBJECTIVE: To assess the harm of nalmefene administered to individuals diagnosed with substance use or impulse control disorders by performing a systematic review and meta-analysis of randomised controlled trials. DATA SOURCES: A search was performed in Cochrane Central Register of Controlled Trials (CENTRAL, 2014), MEDLINE via PubMed (1950), EMBASE via Ovid (1974), and Clinicaltrials.gov through December 2014. STUDY SELECTION: This study included only randomised controlled trials with placebo or active controls that administered nalmefene to adult individuals for treating impulse control and/or substance use disorders. Both published and unpublished randomised controlled trials were eligible for inclusion. DATA EXTRACTION AND SYNTHESIS: Internal validity was assessed using the Cochrane risk-of-bias tool. Published information from the trials was supplemented by contact between reviewers and industry sponsor. Data were combined using two meta-approaches in fixed effects models; Peto Odds Ratios and risk differences were reported with 95% confidence intervals (95%CIs). MAIN OUTCOMES AND MEASURES: Number of patients with serious adverse events, including specific psychiatric serious adverse events and withdrawals due to adverse events. RESULTS: Of 20 potentially relevant studies, 15 randomised controlled trials met the inclusion criteria, and 8 of these provided data enabling the meta-analysis. Overall, serious adverse events did not occur more often in the nalmefene group than in the placebo group (Peto Odds Ratio = 0.97 [95% CI 0.64-1.44]; P = 0.86). Risk of psychiatric serious adverse events was slightly elevated, albeit not at a statistically significant level (Peto Odds Ratio = 1.32 [95% CI 0.62, 2.83]; P = 0.47). Withdrawals due to adverse events were significantly more likely to occur with nalmefene compared to placebo (Peto Odds Ratio = 3.22 [95% CI 2.46-4.22]; P<0.001). CONCLUSIONS AND RELEVANCE: The three-fold increased risk of withdrawal from treatment on nalmefene due to adverse events is a matter of safety concern. The nature of these adverse events cannot be elucidated further without access to individual patients data.

Ultrasound-guided single-penetration dual-injection block for leg and foot surgery: a prospective, randomized, double-blind study.

BACKGROUND AND OBJECTIVES: We describe a new approach to blocking the sciatic and saphenous nerves in the proximal thigh (level of the lesser trochanter or immediately below) using a single-penetration dual-injection (SPEDI) technique. The popliteal-sciatic approach necessitates repositioning of the leg exposing the popliteal fossa and an extra injection for the saphenous nerve (SAN) block at the midthigh level. We introduce an alternative, effective, and possibly faster method. METHODS: Sixty patients undergoing leg and foot surgery under general anesthesia were included. We deposited 15 mL of ropivacaine 0.75% around the sciatic nerve (SCN) and 5 mL of ropivacaine 0.75% at the SAN. Patients were randomized to the popliteal-sciatic/saphenous technique or the SPEDI technique. The primary outcome measure was performance time. Positioning time, pain assessment, nausea in the postanesthesia care unit, sufentanil demand, dermatomal anesthesia, and degree of motor blockade were also recorded. RESULTS: Performance time was significantly faster with the SPEDI technique (median time, 110 seconds [range, 57-315 seconds] vs 246 seconds [range, 163-472 seconds]; P < 0.0001). Positioning time was significantly shorter with the SPEDI technique (P < 0.0001). No other statistically significant differences were recorded. CONCLUSIONS: The SPEDI block resulted in significantly faster performance time and reduced positioning time with statistically equal efficacy in relation to pain assessment, nausea, sufentanil demand, dermatomal anesthesia, and motor blockade. The SPEDI block is statistically an equally effective alternative to the traditional popliteal-sciatic/saphenous block combination for leg and foot surgery, but it is faster, requires only 1 skin penetration, and does not require repositioning of the leg.

Cannot ventilate-cannot intubate an infant: surgical tracheotomy or transtracheal cannula?

BACKGROUND: An unanticipated difficult airway is very uncommon in infants. The recommendations for managing the cannot ventilate-cannot intubate (CVCI) situation in infants and small children are based on difficult airway algorithms for adults. These algorithms usually recommend placement of a transtracheal cannula or performing a surgical tracheotomy as a last resort. In this study, we compared the success rate and time used for inserting a transtracheal cannula vs performing a modified surgical tracheotomy in a piglet model. METHODS: We used 10 three-week-old euthanized piglets, weighing eight kilograms each. Thirty physicians had a timed attempt of inserting a transtracheal cannula for jet ventilation. A maximum time of 120 s was allowed. Ten physicians had a timed attempt of performing a modified surgical tracheotomy after a short introduction by an ENT surgeon. The allowed time for this procedure was 240 s. RESULTS: Placement of the transtracheal cannula was successful for eight of 30 physicians. Median time for successful insertion was 68 s. Surgical tracheotomy was successful for 8 of 10 physicians. Median time for successful tracheotomy was 89 s. There was a significantly higher success rate for surgical tracheotomy (P = 0.007). CONCLUSIONS: We found placement of a transtracheal cannula to be significantly less successful than the modified surgical tracheotomy in a piglet model. We question whether placement of a transtracheal cannula should be recommended in infants in a cannot ventilate-cannot intubate situation.

[A 48-year-old woman's survival from a massive verapamil overdose]. / Overlevelse efter massiv verapamiloverdosis hos en 48-årig kvinde.

We present a case report of survival from a massive verapamil overdose. The patient, a 48-year-old female, was admitted 12 hours after suicidal ingestion of 10.08 grams of Isoptin Retard, a sustained release calcium channel blocker. On admittance, the patient had altered mental status, was hypotensive, and ECG showed bradycardia with nodal rhythm. The patient was treated with activated charcoal, colloids, crystalloids, norepinephrine, isoprenalin and epinephrine infusion, high dose glucose-insulin infusion and calcium. The patient was discharged for rehabilitation after two weeks.