Trans-cricoid thyroid injection of local anaesthesia: a serious complication.

Transcricothyroid membrane (CTM) injection of local anaesthesia is widely used during bronchoscopic procedures. It is an effective way of delivering topical anaesthesia, and has been shown to reduce patient discomfort, improve clinician satisfaction and reduce overall sedation requirements. Risks from this procedure are uncommon and usually minor. Localisation of the CTM is usually performed clinically by palpation of anatomical landmarks and can vary depending on clinician skillset and experience. Clinical identification may be less accurate compared with ultrasound guidance in identifying puncture site, however, ultrasound is not always readily available and seldom used for this purpose. This case describes a rare complication following attempted local anaesthetic infiltration into the cricothyroid space, after clinical identification of puncture site. An obstructive fluid-filled mass formed around the site of injection on the right vocal cord; resulting in airway compromise, abandonment of procedure and subsequent intubation.

Is Bigger Really Better? Comparison of Ultraportable Handheld Ultrasound with Standard Point-of-Care Ultrasound for Evaluating Safe Site Identification and Image Quality prior to Pleurocentesis.

BACKGROUND: Pleural effusions remain a common medical problem which often requires diagnostic pleurocentesis to determine the underlying cause. Pleurocentesis is a frequently performed procedure worldwide with improved safety using ultrasound (US) technology. OBJECTIVES: This prospective, single-center study evaluated the use of an ultraportable handheld (UPHH) US compared with standard point-of-care (SPOC) US in determining a safe site for pleurocentesis. In addition, US image quality and factors impacting on image quality were assessed using both UPHH and SPOC US. METHODS: Paired US assessments were performed by thoracic physicians using UPHH and SPOC US on patients with unilateral pleural effusions to determine a safe site for pleurocentesis (defined as >2 cm of pleural fluid, >2 cm from a solid organ/diaphragm, and <7 cm chest wall depth). Distance measurements for key structures and image quality scores (using a 5-point Likert rating scale) were obtained at the time of US assessment. Factors affecting image quality were analyzed using univariate analysis. RESULTS: In 52 of the 54 included patients (96.3%), UPHH US was able to identify a safe site for pleurocentesis. Distance measurements between UPHH and SPOC US were not statistically different (all <0.5 cm with values of p > 0.05), but image quality was reduced in UPHH compared with SPOC US by 1 point on a 5-point Likert rating scale (p < 0.002). Increasing body mass index was associated with a reduction in image quality in both UPHH and SPOC US (all p < 0.01). CONCLUSIONS: Although image quality was lower in UPHH than SPOC US, a safe site was found in 96.3% of patients, which suggests that UPHH US may be a useful tool for diagnostic pleuro-centesis when SPOC US is not available (http://www.anzctr.org.au/, Australia New Zealand Clinical Trials Registry, No. ACTRN12618001592235).

Predictors of long-term mortality with cardiac resynchronization therapy in mild heart failure patients with left bundle branch block.

BACKGROUND: Cardiac resynchronization therapy (CRT) is highly beneficial in patients with heart failure (HF) and left bundle branch block (LBBB); however, up to 30% of patients in this selected group are nonresponders. HYPOTHESIS: We hypothesized that clinical and echocardiographic variables can be used to develop a simple mortality risk stratification score in CRT. METHODS: Best-subsets proportional-hazards regression analysis was used to develop a simple clinical risk score for all-cause mortality in 756 patients with LBBB allocated to the CRT with defibrillator (CRT-D) group enrolled in the multicenter automatic defibrillator implantation trial with cardiac resynchronization therapy. The score was used to assess the mortality risk within the CRT-D group and the associations with mortality reduction with CRT-D vs implantable cardioverter defibrillator (ICD) in each risk category. RESULTS: Four clinical variables comprised the risk score: age ≥ 65, creatinine ≥ 1.4 mg/dL, history of coronary artery bypass graft, and left ventricular ejection fraction (LVEF) < 26%. Every 1 point increase in the score was associated with 2-fold increased mortality within the CRT-D arm (P < 0.001). CRT-D was associated with mortality reduction as compared with ICD only in patients with moderate risk: score 0 (HR = 0.80, P = 0.615), score 1 (HR = 0.54, P = 0.019), score 2 (HR = 0.54, P = 0.016), score 3-4 risk factors (HR = 1.08, P = 0.811); however, the device by score interaction was not significant (P = 0.306). The score was also significantly predictive of left ventricular reverse remodeling (P < 0.001). CONCLUSIONS: Four clinical variables can be used for improved mortality risk stratification in mild HF patients with LBBB implanted with CRT-D.

Clinical presentation at first heart failure hospitalization does not predict recurrent heart failure admission.

AIMS: There are limited data on whether clinical presentation at first heart failure (HF) hospitalization predicts recurrent HF events. We aimed to assess predictors of recurrent HF hospitalizations in mild HF patients with an implantable cardioverter defibrillator or cardiac resynchronization therapy with defibrillator. METHODS AND RESULTS: Data on HF hospitalizations were prospectively collected for patients enrolled in MADIT-CRT. Predictors of recurrent HF hospitalization (HF2) after the first HF hospitalization were assessed using Cox proportional hazards regression models including baseline covariates and clinical presentation or management at first HF hospitalization. There were 193 patients with first HF hospitalization, and 156 patients with recurrent HF events. Recurrent HF rate after the first HF hospitalization was 43% at 1 year, 52% at 2 years, and 55% at 2.5 years. Clinical signs and symptoms, medical treatment, or clinical management of HF at first HF admission was not predictive for HF2. Baseline covariates predicting recurrent HF hospitalization included prior HF hospitalization (HR = 1.59, 95% CI: 1.15-2.20, P = 0.005), digitalis therapy (HR = 1.58, 95% CI: 1.13-2.20, P = 0.008), and left ventricular end-diastolic volume >240 mL (HR = 1.62, 95% CI: 1.17-2.25, P = 0.004). CONCLUSIONS: Recurrent HF events are frequent following the first HF hospitalization in patients with implanted implantable cardioverter defibrillator or cardiac resynchronization therapy with defibrillator. Neither clinical presentation nor clinical management during first HF admission was predictive of recurrent HF. Prior HF hospitalization, digitalis therapy, and left ventricular end-diastolic volume at enrolment predicted recurrent HF hospitalization, and these covariates could be used as surrogate markers for identifying a high-risk cohort.

Thermodynamics and kinetics of adaptive binding in the malachite green RNA aptamer.

Adaptive binding, the ability of molecules to fold themselves around the structure of a ligand and thereby incorporating it into their three-dimensional fold, is a key feature of most RNA aptamers. The malachite green aptamer (MGA) has been shown to bind several closely related triphenyl dyes with planar and nonplanar structures in this manner. Competitive binding studies using isothermal titration calorimetry and stopped flow kinetics have been conducted with the aim of understanding the adaptive nature of RNA-ligand interaction. The results of these studies reveal that binding of one ligand can reduce the ability of the aptamer pocket to adapt to another ligand, even if this second ligand has a significantly higher affinity to the free aptamer. A similar effect is observed in the presence of Mg(2+) ions which stabilize the binding pocket in a more ligand bound-like conformation.

Combined assessment of sex- and mutation-specific information for risk stratification in type 1 long QT syndrome.

BACKGROUND: Men and women with type 1 long QT syndrome (LQT1) exhibit time-dependent differences in the risk for cardiac events. OBJECTIVE: We hypothesized that sex-specific risk for LQT1 is related to the location and function of the disease-causing mutation in the KCNQ1 gene. METHODS: The risk for life-threatening cardiac events (comprising aborted cardiac arrest [ACA] or sudden cardiac death [SCD]) from birth through age 40 years was assessed among 1051 individuals with LQT1 (450 men and 601 women) by the location and function of the LQT1-causing mutation (prespecified as mutations in the intracellular domains linking the membrane-spanning segments [ie, S2-S3 and S4-S5 cytoplasmic loops] involved in adrenergic channel regulation vs other mutations). RESULTS: Multivariate analysis showed that during childhood (age group: 0-13 years) men had >2-fold (P < .003) increased risk for ACA/SCD than did women, whereas after the onset of adolescence the risk for ACA/SCD was similar between men and women (hazard ratio = 0.89 [P = .64]). The presence of cytoplasmic-loop mutations was associated with a 2.7-fold (P < .001) increased risk for ACA/SCD among women, but it did not affect the risk among men (hazard ratio 1.37; P = .26). Time-dependent syncope was associated with a more pronounced risk-increase among men than among women (hazard ratio 4.73 [P < .001] and 2.43 [P = .02], respectively), whereas a prolonged corrected QT interval (≥ 500 ms) was associated with a higher risk among women than among men. CONCLUSION: Our findings suggest that the combined assessment of clinical and mutation location/functional data can be used to identify sex-specific risk factors for life-threatening events for patients with LQT1.

Entropy and Mg2+ control ligand affinity and specificity in the malachite green binding RNA aptamer.

The binding of small molecule targets by RNA aptamers provides an excellent model to study the versatility of RNA function. The malachite green aptamer binds and recognizes its ligand via stacking and electrostatic interactions. The binding of the aptamer to its original selection target and three related molecules was determined by isothermal titration calorimetry, equilibrium dialysis, and fluorescence titration. The results reveal that the entropy of complex formation plays a large role in determining binding affinity and ligand specificity. These data combined with previous structural studies show that metal ions are required to stabilize the complexes with non-native ligands whereas the complex with the original selection target is stable at low salt and in the absence of divalent metal ions.

Mutation and gender-specific risk in type 2 long QT syndrome: implications for risk stratification for life-threatening cardiac events in patients with long QT syndrome.

BACKGROUND: Men and women with type 2 long QT syndrome (LQT2) exhibit time-dependent differences in the risk for cardiac events. We hypothesized that data regarding the location of the disease-causing mutation in the KCNH2 channel may affect gender-specific risk in LQT2. OBJECTIVE: This study sought to risk-stratify LQT2 patients for life-threatening cardiac events based on clinical and genetic information. METHODS: The risk for life-threatening cardiac events from birth through age 40 years (comprising aborted cardiac arrest [ACA] or sudden cardiac death [SCD]) was assessed among 1,166 LQT2 male (n = 490) and female (n = 676) patients by the location of the LQTS-causing mutation in the KCNH2 channel (prespecified in the primary analysis as pore-loop vs. non-pore-loop). RESULTS: During follow-up, the cumulative probability of life-threatening cardiac events years was significantly higher among LQT2 women (26%) as compared with men (14%; P <.001). Multivariate analysis showed that the risk for life-threatening cardiac events was not significantly different between women with and without pore-loop mutations (hazard ratio 1.20; P =.33). In contrast, men with pore-loop mutations displayed a significant >2-fold higher risk of a first ACA or SCD as compared with those with non-pore-loop mutations (hazard ratio 2.18; P = .01). Consistently, women experienced a high rate of life-threatening events regardless of mutation location (pore-loop: 35%, non-pore-loop: 23%), whereas in men the rate of ACA or SCD was high among those with pore-loop mutations (28%) and relatively low among those with non-pore-loop mutations (8%). CONCLUSION: Combined assessment of clinical and mutation-specific data can be used for improved risk stratification for life-threatening cardiac events in LQT2.

A two-year follow-up study and prospective evaluation of the DSM-IV axis V.

A six-month cohort of general adult psychiatric inpatients was followed for up to two years to evaluate outcome and contrast the validity of DSM-IV measures of adaptive functioning-the Global Assessment of Functioning (GAF), the Social and Occupational Functioning Assessment Scale (SOFAS), and the Global Assessment of Relational Functioning Scale (GARF). Detailed data, including quality-of-life ratings and DSM-IV axis I and V codes, were collected by interview and self-report questionnaires for 53 study participants. Patients' retrospective ratings of the care they received were not predictive of outcome. Adaptive functioning at discharge was predictive of both severity of illness and social functioning at follow-up. The SOFAS had the strongest concurrent and predictive validity, the latter both for length of initial inpatient stay and two-year outcome.