Brief Review of the Recently Described Short QT Syndrome and Other Cardiac Channelopathies

There are many diseases related to ion‐channel disorders, so‐called “channelopathies.” Hereditary short QT syndrome is a clinical‐electrocardiographic entity with autosomal‐dominant mode of transmission and it is the most recently described channelopathy. The syndrome may affect infants, children, or young adults with strong positive family background of sudden cardiac death. Short QT syndrome is characterized by short QT and heart‐rate‐corrected QTc intervals. It is frequently associated with tall‐, peaked‐, and narrow‐based T waves that are reminiscent of the typical “desert tent” T waves of hyperkalemia. There is a high tendency for paroxysmal atrial fibrillation due to the heterogeneous abbreviation of action potential duration and refractoriness of atrial myocytes. The arrhythmia can also be induced by programmed electrical stimulation. The safest treatment suggested is an implantable cardioverter defibrillator, though the possibilities of inappropriate shocks have caused some concern, especially in teenagers. The ability of quinidine to prolong the QT interval has the potential to be an effective therapy for patients with short QT syndrome. This is particularly important in developing countries, where the implantable cardioverter‐defibrillator therapy is not always available. Since these patients are at risk of sudden cardiac death from birth, and implantable cardioverter‐defibrillator implantation has a lot of limitations in very young children, the utility of quinidine has to be evaluated further. Clinicians need to be aware of this deadly electrocardiographic (ECG) pattern as it portends a high risk of sudden cardiac death in otherwise healthy subjects with structurally normal hearts.     

Prospective evaluation comparing the effects of enalapril and losartan in left ventricular remodeling after acute myocardial infarction

Background

Previous studies have compared angiotensin receptor blockers and angiotensin-converting enzyme inhibitors in patients with heart failure, but there are few data about the effect of these drugs regarding left ventricular remodeling after myocardial infarction.

Methods

Fifty-two consecutive patients with first anterior wall myocardial infarction within 24 hours of evolution were randomized to receive enalapril (as much as 20 mg; mean, 14.6 mg), or losartan (as much as 50 mg; mean, 48 mg). Left ventricular ejection fraction and ventricular volumes were analyzed in 2 serial radionuclide ventriculograpies, carried out within 4 days after the infarction (mean, 97.4 ± 114.2 hours) and after 6 months (mean, 177.7 ± 16.7 days). Ventriculographies were analyzed by a single blinded observer. Mainly because of the unexpected large SD values obtained, the power of the study to demonstrate equivalence between the groups was only 15.7%.

Results

The differences obtained between the first and the second ventriculographies, for the enalapril and losartan groups, were: for left ventricular ejection fraction, −0.4% ± 6.6% versus −1.1% ± 5.9% (P = . 67; 95% CI, 2.77-4.23); for final systolic volume, 0.07 ± 7.7 mL/m² versus −0.2 ± 6.1mL/m² (P = . 85; 95% CI, −3.57-4.26); for final diastolic volume −0.7 ± 12.1 mL/m² versus −3.6 - 9.9 mL/m² (P = . 34; 95% CI, −3.22-9.17).

Conclusion

This study, although underpowered, suggests that neither enalapril nor losartan was superior as compared with each other for left ventricular remodeling after myocardial infarction; however, powerful evidence of equivalence was not provided.     

Resultados de las 100 primeras colecistectomías por puerto único en un hospital de segundo nivel

Introduction

Despite the excellent results obtained with standard laparoscopic cholecystectomy, the efforts for minimizing the ports needed to reduce postoperative pain, for a quicker recovery and to improve the patient's cosmetics continue. The aim of this study is to report the results of the first 100 cases of single port laparoscopic cholecystectomy performed in a secondary care hospital.

Material and methods

Prospective, observational and unicentric study including 100 patients between January 2010 and April 2012. Inclusion criteria: symptomatic cholelythiasis patients over 16-years of age on whom a single port laparoscopic cholecystectomy was performed. Exclusion criteria: history of acute cholecystitis, pancreatitis or suspected choledocholithiasis, Endoscopic retrograde cholangiopancreatography, BMI > 35 and previous laparotomies. We studied epidemiological, surgical and safety variables.

Results

The mean patient age was 39,89 ± 11,5 years. The mean time of the surgical procedure was 67,94 ± 25,5 min. There were 2 cases of postoperative complications. A non-infected seroma and a biliar leak. In 2 cases the use of an accessory trocar was needed. The mean hospital stay was 1,13 ± 0,8 days. A total of 35% patients were included in the major ambulatory surgery programme.The overall patient satisfaction survey rating showed a high level of cosmetic satisfaction in 100% of patients.

Conclusions

Single port laparoscopic cholecystectomy is a good technique when performed in selected cases by expert surgeons. It is feasible to include the single port laparoscopic cholecystectomy in a major ambulatory surgery programme. We have not had serious complications. There is a high cosmetic satisfaction index with this technique.     

Determination of [11C]PBR28 binding potential in vivo: a first human TSPO blocking study

Positron emission tomography (PET) targeting the 18 kDa translocator protein (TSPO) is used to quantify neuroinflammation. Translocator protein is expressed throughout the brain, and therefore a classical reference region approach cannot be used to estimate binding potential (BP_ND). Here, we used blockade of the TSPO radioligand [¹¹C]PBR28 with the TSPO ligand XBD173, to determine the non-displaceable volume of distribution (V_ND), and hence estimate the BP_ND. A total of 26 healthy volunteers, 16 high-affinity binders (HABs) and 10 mixed affinity binders (MABs) underwent a [¹¹C]PBR28 PET scan with arterial sampling. Six of the HABs received oral XBD173 (10 to 90 mg), 2 hours before a repeat scan. In XBD173-dosed subjects, V_ND was estimated via the occupancy plot. Values of BP_ND for all subjects were calculated using this V_ND estimate. Total volume of distribution (V_T) of MABs (2.94±0.31) was lower than V_T of HABs (4.33±0.29) (P<0.005). There was dose-dependent occupancy of TSPO by XBD173 (ED50=0.34±0.13 mg/kg). The occupancy plot provided a V_ND estimate of 1.98 (1.69, 2.26). Based on these V_ND estimates, BP_ND for HABs is approximately twice that of MABs, consistent with predictions from in vitro data. Our estimates of [¹¹C]PBR28 V_ND and hence BP_ND in the healthy human brain are consistent with in vitro predictions. XBD173 blockade provides a practical means of estimating V_ND for TSPO targeting radioligands.     

Common and specific brain responses to scenic emotional stimuli

Processing of emotions has been an enduring topic of interest in neuroimaging research, but studies have mostly used facial emotional stimuli. The aim of this study was to determine neural networks involved in emotion processing using scenic emotional visual stimuli. One hundred and twenty photographs from the International Affective Picture System (IAPS), including ecological scenes of disgust, fear, happiness, and sadness, were presented to 40 healthy participants while they underwent functional magnetic imaging resonance (fMRI). Afterwards they evaluated the emotional content of the pictures in an offline task. The occipito-temporal cortex and the amygdala–hippocampal complex showed a non-specific emotion-related activation, which was more marked in response to negative emotions than to happiness. The temporo-parietal cortex and the ventral anterior cingulate gyrus showed deactivation, with the former being marked for all emotions except fear and the latter being most marked for disgust. The fusiform gyrus showed activation in response to disgust and deactivation in response to happiness or sadness. Brain regions involved in processing of scenic emotion therefore resemble those reported for facial expressions of emotion in that they respond to a range of different emotions, although there appears to be specificity in the intensity and direction of the response.     

Prodromal Parkinson disease in patients with idiopathic hyposmia

Journal of Neurology - Idiopathic hyposmia (IH) is a prodromal marker of Parkinson disease (PD). However, IH is common in the general population and only a minority will develop PD. Identification...     

Long non‐coding RNAs: biomarkers for acute leukaemia subtypes

Accurate diagnosis of rare inherited anaemias is challenging, requiring a series of complex and expensive laboratory tests. Targeted next‐generation‐sequencing (NGS) has been used to investigate these disorders, but the selection of genes on individual panels has been narrow and the validation strategies used have fallen short of the standards required for clinical use. Clinical‐grade validation of negative results requires the test to distinguish between lack of adequate sequencing reads at the locations of known mutations and a real absence of mutations. To achieve a clinically‐reliable diagnostic test and minimize false‐negative results we developed an open‐source tool (CoverMi) to accurately determine base‐coverage and the ‘discoverability’ of known mutations for every sample. We validated our 33‐gene panel using Sanger sequencing and microarray. Our panel demonstrated 100% specificity and 99·7% sensitivity. We then analysed 57 clinical samples: molecular diagnoses were made in 22/57 (38·6%), corresponding to 32 mutations of which 16 were new. In all cases, accurate molecular diagnosis had a positive impact on clinical management. Using a validated NGS‐based platform for routine molecular diagnosis of previously undiagnosed congenital anaemias is feasible in a clinical diagnostic setting, improves precise diagnosis and enhances management and counselling of the patient and their family.