Cardiomyopathies and Genetic Testing in Heart Failure: Role in Defining Phenotype-Targeted Approaches and Management

Cardiomyopathies represent an important cause of heart failure, often affecting young individuals, and have important implications for relatives. Genetic testing for cardiomyopathies is an established care pathway in contemporary cardiology practice. The primary cardiomyopathies where genetic testing is indicated are hypertrophic, dilated, arrhythmogenic, and restrictive cardiomyopathies, with left ventricular noncompaction as a variant phenotype. Early identification and initiation of therapies in patients with inherited cardiomyopathies allow for targeting asymptomatic and presymptomatic patients in stages A and B of the American College of Cardiology/American Heart Association classification of heart failure. The current approach for genetic testing uses gene panel–based testing with the ability to extend to whole-exome and whole-genome sequencing in rare instances. The central components of genetic testing include defining the genetic basis of the diagnosis, providing prognostic information, and the ability to screen and risk-stratify relatives. Genetic testing for cardiomyopathies should be coordinated by a multidisciplinary team including adult and pediatric cardiologists, genetic counsellors, and geneticists, with access to expertise in cardiac imaging and electrophysiology. A pragmatic approach for addressing genetic variants of uncertain significance is important. In this review, we highlight the indications for genetic testing in the various cardiomyopathies, the value of early diagnosis and treatment, family screening, and the care process involved in genetic counselling and testing.     

Rotational thormboelastolmetry guided transfusion practice in living donor liver transplantation,A retrospective comparative study

Introduction

Living donor liver transplantation (LDLT) is a complex surgery with high risk for massive bleeding and blood component transfusion. This retrospective study investigated the effect of adopting ROTEM based transfusion algorithm on blood products transfusion practice among LDLT recipients and the effect of this change on patient outcome.

Prevalence and Predictors of Gastroesophageal Reflux Disease After Laparoscopic Sleeve Gastrectomy

Background and Aims

Laparoscopic sleeve gastrectomy (LSG) might be associated with a new onset or worsening of gastroesophageal reflux disease (GERD). We aim to evaluate the prevalence of post-LSG GERD symptoms and its predictors.

Methods

We included patients who underwent primary LSG at a university hospital from 2009 to 2015. We used the GERD-Health-Related Quality of Life (GERD-HRQL) questionnaire and included questions regarding regurgitation to evaluate symptoms before and after LSG; each item was scored from 1 to 5 based on the symptom severity.

Results

A total of 213 patients (mean age, 36.08 ± 10.22 years; 48.36% were men) were included. The mean preoperative body mass index (BMI) was 47.84 kg/m², mean percent total weight loss was 37.99% (95% CI, 36.64 to 39.34), mean percent excess weight loss was 84.14% (95% CI, 80.91 to 87.36), and the mean percent excess BMI loss was 84.17% (95% CI, 80.94 to 87.41). The mean heartburn score while standing increased (0.71 vs. 1.09, p < 0.01) as well as the score of heartburn requiring a diet change (0.67 vs. 1.16, p < 0.01) post-LSG. The scores for dysphagia, odynophagia, and regurgitation increased. New-onset heartburn was reported in 47.06% of our cohort. Those with high preoperative BMIs were less likely to develop new-onset or worsening symptoms of GERD (odds ratio [OR], 0.97; 95% confidence interval [CI], 0.95–0.99). More severe heartburn symptoms while standing were associated with higher risks of developing or worsening GERD symptoms (OR, 1.22; 95% CI, 1.01–1.47). None of the other variables could predict the development or worsening of the GERD symptoms.

Conclusion

Symptoms of heartburn and regurgitation are common after LSG; however, none of the variables preoperatively could strongly predict patients who would develop new onset or experience worsening of symptoms postoperatively.

     

Visual internal urethrotomy for management of urethral strictures in boys: a comparison of short-term outcome of holmium laser versus cold knife

Purpose

To compare efficacy and safety of visual internal urethrotomy (VIU) using holmium laser (Ho:YAG) (group A) versus cold knife (group B) in children with urethral strictures. It may be the first comparative study on this issue in children.

Methods

This study compared Ho:YAG group, which was evaluated prospectively from January 2014 till January 2016, versus cold knife group, which was a historical control performed from March 2008 till February 2010. Children ≤ 13 years old with urethral strictures ≤ 1.5 cm were included successively. Recurrent cases, congenital obstructions and cases with complete arrest of dye in voiding cystourethrography were excluded. Scar tissue was incised at twelve o’clock. Outcome was compared using Student’s t, Mann–Whitney, Chi-square or Fisher exact tests as appropriate.

Results

Each group included 21 patients. Mean age was 6.27 ± 3.23 (2–13) years old. Mean stricture length was 1.02 versus 1 cm in group A versus B, respectively (p = 0.862). Ten cases of penile/bulbous strictures and another 11 cases of membranous strictures were found in each group. There was no significant difference between both groups in preoperative data. Success rate for initial VIU was 66.7% in group A versus 38% in group B (p = 0.064). This was associated with significantly higher Q_max in group A (mean 16.52 vs 12.09 ml/s; p = 0.03). Success rate after two trials of VIU was 76.2% for group A and 47.61% for group B (p = 0.057). No complications were reported in both groups.

Conclusion

Laser VIU has a higher success rate than cold knife VIU for urethral strictures ≤ 1.5 cm in children with significantly higher Q_max. Both are easy to perform, low invasive and safe.

     

Value of duplex scanning in differentiating embolic from thrombotic arterial occlusion in acute limb ischemia

BackgroundManagement of acute limb ischemia (ALI) is largely based on the etiology of arterial occlusion (embolic vs. thrombotic). To our knowledge, the ability of duplex scanning to differentiate embolic from thrombotic occlusion has not been previously reported.PurposeTo determine the ability of duplex scanning to differentiate embolic from thrombotic acute arterial occlusion.MethodsWe prospectively recruited 97 patients (50.3±19.7 years; 55% males) with 107 nontraumatic ALI in native arteries. All patients underwent surgical revascularization. Preoperative duplex scan detected arterial occlusion in the following arteries: iliac (11), femoral (38), popliteal (38), infrapopliteal (3), subclavian (3), axillary (1), brachial (9), and forearm arteries (4). We measured the arterial diameters at the site of occlusion (d_occl) and at the corresponding contralateral healthy side (d_CONTRA). The difference (Δ) between the two diameters was calculated as d_OCCL?d_CONTRA. Duplex scan was also used to assess the state of the arterial wall whether healthy or atherosclerotic and the presence of calcification or collaterals. According to surgical findings, limbs were classified into embolic (E group=55 limbs) and thrombotic (T group=52 limbs) groups.ResultsBoth groups were comparable regarding age, diabetes, hypertension, smoking, atrial fibrillation, and time of presentation. The status of arterial wall at the site of occlusion and presence of calcification or collaterals were all similar in both groups. Δ in the E group was 0.95±0.92 mm vs. ?0.13±1.02 mm in the T group (P<.001). A value of ≥0.5 mm for Δ had 85% sensitivity and 76% specificity for the diagnosis of embolic occlusion (CI 0.72–0.90, P<.001), whereas a value of less than ?0.5 mm for Δ had 85% sensitivity and 76% specificity for thrombotic occlusion (CI 0.72–0.90, P<.001).ConclusionIn acute arterial occlusion, ≥0.5 mm dilatation or diminution in the occluded artery diameter is a useful duplex sign for diagnosing embolic or thrombotic occlusion, respectively.     

Advances in Peptide-based Human Papillomavirus Therapeutic Vaccines

Cervical cancer is the second leading cause of cancer in women worldwide. Human papillomavirus (HPV) is responsible for all cases of cervical cancer. Commercial prophylactic HPV vaccines are now available, but unfortunately these vaccines have no therapeutic effect against established HPV infections. In order to accelerate the control of cervical cancer and treat established HPV infections, it is necessary to develop therapeutic vaccines to eradicate HPV by generating cell-mediated immunity against HPV infected cells. Two HPV-encoded early proteins, the E6 and E7 oncoproteins, are the preferred targets because they are consistently expressed in virtually all cervical cancer cells and are necessary for the induction and maintenance of HPV-associated disease. A variety of vaccine strategies have been employed targeting immune responses to these proteins. Peptide-based vaccines are a promising strategy for the development of therapeutic HPV vaccines because of their safety, stability, and ease of production. This review summarizes the prospects of peptidebased vaccines for the treatment of established HPV infections. We address the challenges that scientists currently face for developing peptide-based vaccines and explore feasible strategies for improving the potency of the induced immune response with the aim of treating established HPV infections.     

Synthesis and Kinetic Testing of Tetrahydropyrimidine-2-thione and Pyrrole Derivatives as Inhibitors of the Metallo-β-lactamase from Klebsiella pneumonia and Pseudomonas aeruginosa

Metallo‐β‐lactamases (MBLs), produced by an increasing number of bacterial pathogens, facilitate the hydrolysis of many commonly used β‐lactam antibiotics. There are no clinically useful antagonists against MBLs. Two sets of tetrahydropyrimidine‐2‐thione and pyrrole derivatives were synthesized and assayed for their inhibitory effects on the catalytic activity of the IMP‐1 MBL from Pseudomonas aeruginosa and Klebsiella pneumoniae. Nine compounds tested ( 1a , 3b , 5c , 6b , 7a , 8a , 11c , 13a , and 16a ) showed micromolar inhibition constants (K_i values range from ～20–80 μm ). Compounds 1c , 2b , and 15a showed only weak inhibition. In silico docking was employed to investigate the binding mode of each enantiomer of the strongest inhibitor, 5c (K_i = 19 ± 9 μm ), as well as 7a (K_i = 21 ± 10 μm ), the strongest inhibitor of the pyrrole series, in the active site of IMP‐1.     

Dexmedetomidine infusion to facilitate opioid detoxification and withdrawal in a patient with chronic opioid abuse

Many patients are admitted to the intensive care unit (ICU) for acute intoxication, serious complication of overdose, or withdrawal symptoms of illicit drugs. An acute withdrawal of drugs with addiction potential is associated with a sympathetic overactivity leading to marked psychomimetic disturbances. Acute intoxication or withdrawal of such drugs is often associated with life-threatening complications which require ICU admission and necessitate prolonged sedative analgesic medications, weaning from which is often complicated by withdrawal and other psychomimetic symptoms. Dexmedetomidine, an alpha-2 (α(2)) agonist, has been used successfully to facilitate withdrawal and detoxification of various drugs and also to control delirium in ICU patients. Herein, we report a case of a chronic opioid abuse (heroin) patient admitted with acute overdose complications leading to a prolonged ICU course requiring sedative-analgesic medication; the drug withdrawal-related symptoms further complicated the weaning process. Dexmedetomidine infusion was successfully used as a sedative-analgesic to control the withdrawal-related psychomimetic symptoms and to facilitate smooth detoxification and weaning from opioid and other sedatives.