Heart failure in the patient with diabetes: Epidemiology,aetiology, prognosis,therapy and the effect of glucose-lowering medications

In people with type 2 diabetes the frequency of heart failure (HF) is increased and mortality from HF is higher than with non-diabetic HF. The increased frequency of HF is attributable to the cardiotoxic tetrad of ischaemic heart disease, left ventricular hypertrophy, diabetic cardiomyopathy and an extracellular volume expansion resistant to atrial natriuretic peptides. Activation of the renin-angiotensin-aldosterone system and sympathetic nervous systems results in cardiac remodelling, which worsens cardiac function. Reversal of remodelling can be achieved, and cardiac function improved in people with HF with reduced ejection fraction (HFrEF) by treatment with angiotensin-converting enzyme inhibitors and β-blockers. However, with HF with preserved ejection fraction (HFpEF), only therapy for the underlying risk factors helps. Blockers of mineralocorticoid receptors may be beneficial in both HFrEF and HFpEF. Glucose-lowering drugs can have a negative effect (insulin, sulphonylureas, dipeptidyl peptidase-4 inhibitors and thiazolidinediones), a neutral effect (α-glucosidase inhibitors and glucagon-like peptide-1 receptor agonists) or a positive effect (sodium-glucose co-transporter-2 inhibitors and metformin).     

Learning curves of novice anesthesiology residents performing simulated fibreoptic upper airway endoscopy

Background

In various medical and surgical specialties, it is essential to acquire fibreoptic upper airway endoscopy skills for successful endotracheal intubation, especially when faced with a difficult airway. The aim of our study was to evaluate the learning curves of residents performing fibreoptic upper airway endoscopy in the simulation environment.

Methods

Following a standardized video and practice session, 16 residents newly enrolled in the anesthesiology program performed nasal fibreoptic endoscopy of the upper airway (endpoint being the carina) on a high fidelity simulator. Weekly 20-min sessions continued for a period of one month. Each attempt was designated as either a “success” or a “failure” based on the study participant’s ability or inability to visualize the carina in ≤60 sec and with ≤five collisions with the simulated mucosal wall. Proficiency was attained when the downward graphical trend of the cumulative sum (CUSUM) analysis crossed two adjacent boundary lines, i.e., an acceptable failure rate was reached.

Results

The residents’ mean number of attempts at fibreoptic airway endoscopy was 47 (9) with a range of 32–64. Time to visualization of the carina was 51 (36) sec. Three classical patterns of CUSUM trends were observed: proficient (n = 7); not proficient with a downward (improvement) trend (n = 3); and not proficient with an upward (worsening) trend (n = 6). The number of attempts at which proficiency was achieved varied from 27 to 58.

Conclusion

There is a large variation in the learning curves of residents performing fibreoptic upper airway endoscopy. The training for fibreoptic airway endoscopy should be tailored to the needs of each individual.     

Amino acid immunoreactivity in normal human retina and after brachytherapy

We localised amino acids in the mid‐peripheral aged human retina and a retina that had undergone radiation treatment 10 years earlier. The distribution pattern of glutamate, γ‐amino butyric acid (GABA), glycine, glutamine and taurine, reflected patterns established in the primate retina. The retina that had undergone radiation exposure displayed both anatomical and neurochemical remodelling. The proximal retina comprised around 40 to 45 per cent of the total retina and neuronal kinesis and aberrant neuronal projections were also present. Amino acid neurochemistry was strikingly different with Müller cells displaying GABA loading, glycinergic neurons displaced and displaying a very high level of glycine labelling. We conclude that radiation exposure triggered these changes in the human retina and likely reflects general remodelling of structure and function following ischaemic damage to endothelial cells.     

Indoleamine-2,3-dioxygenase modulation of allergic immune responses

Induction of immunologic tolerance is highly desirable in the treatment and prevention of allergy and other immune disease states in which the immune response to foreign or self antigens has become overactive. Indoleamine-2, 3-dioxygenase (IDO), an enzyme classically known for its role in the tryptophan degradation pathway, has recently emerged as an important immunomodulator of T-cell function and inducer of tolerance. The induced expression of IDO by dendritic cells may suppress T-cell responses and promote tolerance either through direct effects on T cells (mediated by tryptophan depletion or tryptophan metabolites) or through effects of IDO on the dendritic cell. In addition to the potential role of IDO in promoting tolerance in pregnancy, transplantation, and autoimmunity, its role in modulating allergic responses has more recently been investigated, raising the possibility that IDO and its metabolites may be novel targets for immunomodulation in allergy and asthma.     

Epidemiology of heart failure and left ventricular dysfunction after acute myocardial infarction

The development of heart failure and/or left ventricular systolic dysfunction has long been regarded as an ominous complication, significantly increasing the morbidity and short- and long-term mortality of survivors of acute myocardial infarction. Although the incidence of heart failure after myocardial infarction has fallen over the last few decades, it remains common, complicating up to 45% of infarcts. Moreover, up to 60% of myocardial infarcts will result in left ventricular systolic dysfunction, depending on the exact definition used. Those at greatest risk of developing heart failure are the elderly, females, and those with prior myocardial infarction. Advances in the management of acute myocardial infarction have led to reduced in-hospital mortality (even when complicated by heart failure), but longerterm mortality remains high in these patients.     

Is the Anatomical Protrusion on the Posterior Hypopharyngeal Wall Associated with Cadavers of Only the Elderly?

Cricopharyngeal bars are commonly seen on a barium swallow radiologic examination and represent the failure of the cricopharyngeus to relax. Traditionally, the bars have been considered as functional or physiologic protrusions. Recently, anatomical cricopharyngeal protrusion has been found in about 30% of cadavers of the elderly, suggesting that such a structural change may become a physical barrier that affects the normal deglutition in a living person. This suggests that such a radiographic finding should be carefully considered when interpreting radiologic and manometrical examinations and managing dysphagia of the elderly. However, the finding of the anatomical cricopharyngeal protrusion was based on the observation of cadavers of the elderly (mean age = 77 years). The aim of this study was to further investigate whether such an anatomical cricopharyngeal protrusion exists in cadavers of other ages. Using the dissection method, we examined 63 human cadavers that were divided into three age groups: young adult (6 females and 10 males, age = 16–24 years old), adult (8 females and 23 males, age = 25–64 years old), and early elderly (5 females and 11 males, age = 65–69 years old). We found that 57 of the 63 cadavers had a smooth mucosal surface on the posterior hypopharyngeal and upper esophageal wall. A slightly thickened posterior muscular wall was observed at the cricoid level in six cadavers (five from the adult group and one from the early elderly group), but its boundary was not clearly identified. Taking the previous reports together, our results suggest that an anatomical cricopharyngeal protrusion is closely associated with the aging process.