Motivation for and adherence to growth hormone replacement therapy in adults with hypopituitarism: the patients‘ perspective

Pituitary - While reasons for non-adherence in children requiring growth hormone (GH) replacement (GH-Rx) are well researched, few studies have investigated adherence in adult GH deficient...     

Epidemiology,pathophysiology and contemporary management of cardiogenic shock – a position statement from the Heart Failure Association of the European Society of Cardiology

Cardiogenic shock (CS) is a complex multifactorial clinical syndrome with extremely high mortality, developing as a continuum, and progressing from the initial insult (underlying cause) to the subsequent occurrence of organ failure and death. There is a large spectrum of CS presentations resulting from the interaction between an acute cardiac insult and a patient's underlying cardiac and overall medical condition. Phenotyping patients with CS may have clinical impact on management because classification would support initiation of appropriate therapies. CS management should consider appropriate organization of the health care services, and therapies must be given to the appropriately selected patients, in a timely manner, whilst avoiding iatrogenic harm. Although several consensus‐driven algorithms have been proposed, CS management remains challenging and substantial investments in research and development have not yielded proof of efficacy and safety for most of the therapies tested, and outcome in this condition remains poor. Future studies should consider the identification of the new pathophysiological targets, and high‐quality translational research should facilitate incorporation of more targeted interventions in clinical research protocols, aimed to improve individual patient outcomes. Designing outcome clinical trials in CS remains particularly challenging in this critical and very costly scenario in cardiology, but information from these trials is imperiously needed to better inform the guidelines and clinical practice. The goal of this review is to summarize the current knowledge concerning the definition, epidemiology, underlying causes, pathophysiology and management of CS based on important lessons from clinical trials and registries, with a focus on improving in‐hospital management.     

Characterisation of ecto- and endoparasites in domestic cats from Tirana,Albania

During 2008 to 2011, faecal samples, ear swabs, and ectoparasites obtained by full body search and total body comb were collected from 252 cats originating from the greater Tirana area. Faecal samples were examined using the McMaster and Baermann techniques, and a subset of 58 samples was tested for Giardia-specific antigen using a coproantigen enzyme-linked immunosorbent assay (ELISA). The ear swabs were examined for the presence of parasitic mites. Overall, almost 93 % of the cats were identified harbouring one or more parasites: 59.1 % (95 % confidence interval (CI), 53.0–65.0) and 86.9 % (95 % CI, 82.7–91.1) of the cats tested positive for ecto- or endoparasites, respectively; 53.2 % of the cats had evidence for concomitant ectoparasite infestation and endoparasite infection. For ectoparasite infestation, prevalence was 52.0 % for total fleas (Ctenocephalides felis, 51.2 %; Ctenocephalides canis, 2.0 %; and Leptopsylla segnis, 0.4 %), 8.3 % each for Felicola subrostratus and Otodectes cynotis and 4.0 % for Rhipicephalus sanguineus sensu lato. The most prevalent endoparasites were Toxocara ascarids (48.0 %), followed by Aelurostrongylus lungworms (39.7 %), Capillaria spp. (31.7 %), hookworms (32.9 %), dipylidiid cestodes (27.8 %), Cystoisospora spp. (23.4 %) and taeniid cestodes (2.0 %). One animal was found shedding Pseudamphistomum truncatum eggs. Giardia-specific antigen was detected in 29.3 % of the 58 cats tested. Mixed infections with up to six endoparasites concurrently (excluding Giardia) and mixed infestations with two or three species of ectoparasites were recorded in 73.1 and 22.8 % of the parasite-positive cats, respectively. Cats ≤9 months of age were more frequently tested (p?Toxocara and Cystoisospora infections than cats >9 months while these cats tested more often (p?Aelurostrongylus-positive compared with the younger cats. The prevalence of infestation with ectoparasites did not differ between the cats of these two age groups. Given the impact that some of the parasites may have upon animal health as well as the zoonotic potential of some of them, measures should be taken to minimise the transmission of these parasites.     

Altered GPM6A/M6 Dosage Impairs Cognition and Causes Phenotypes Responsive to Cholesterol in Human and Drosophila

Glycoprotein M6A (GPM6A) is a neuronal transmembrane protein of the PLP/DM20 (proteolipid protein) family that associates with cholesterol‐rich lipid rafts and promotes filopodia formation. We identified a de novo duplication of the GPM6A gene in a patient with learning disability and behavioral anomalies. Expression analysis in blood lymphocytes showed increased GPM6A levels. An increase of patient‐derived lymphoblastoid cells carrying membrane protrusions supports a functional effect of this duplication. To study the consequences of GPM6A dosage alterations in an intact nervous system, we employed Drosophila melanogaster as a model organism. We found that knockdown of Drosophila M6, the sole member of the PLP family in flies, in the wing, and whole organism causes malformation and lethality, respectively. These phenotypes as well as the protrusions of patient‐derived lymphoblastoid cells with increased GPM6A levels can be alleviated by cholesterol supplementation. Notably, overexpression as well as loss of M6 in neurons specifically compromises long‐term memory in the courtship conditioning paradigm. Our findings thus indicate a critical role of correct GPM6A/M6 levels for cognitive function and support a role of the GPM6A duplication for the patient's phenotype. Together with other recent findings, this study highlights compromised cholesterol homeostasis as a recurrent feature in cognitive phenotypes.     

Skin and Adhesive Issues With Continuous Glucose Monitors: A Sticky Situation

Background:The purpose of this article is to describe challenges associated with successful use of continuous glucose monitoring (CGM) by young children with type 1 diabetes (T1D) and to detail the techniques and products used to improve the duration of sensor wear.Methods:The DirecNet Study Group conducted 2 studies in 169 children with T1D between the ages of 1 and 9 years who were instructed to wear a CGM device daily. Problems related to skin irritation and sensor adhesiveness in these young children presented challenges to daily use of the CGM. Study coordinators instituted a variety of techniques using commercially available products to attempt to overcome these problems.Results:Three primary factors that contributed to reduced CGM use were identified: the limited body surface area in smaller children, ambient temperature and humidity, as well as the type and duration of physical activity. Using supplemental products to minimize the impact of these factors resulted in improved adherence and reduced skin irritation.Conclusion:Achieving satisfactory adhesion of the CGM sensor and transmitter may involve finding the right supplemental product or combination of products through trial and error. Optimizing adhesion and minimizing skin irritation can significantly improve duration of use and tolerability of CGM devices by young children.     

Conservative management of post-intubation tracheal tears—report of three cases

Iatrogenic tracheal rupture is a rare complication after intubation. We present three patients with tracheal tears. In all of these patients, a common finding was a lesion of the posterior tracheal wall with postoperative subcutaneous and emphysema as the first clinical sign of the rupture. Diagnosis and follow-up were based on clinical and endoscopic findings and chest computed tomography (CT) scans. In our cases with progressive subcutaneous and mediastinal emphysema or dyspnea, we performed a tracheotomy and bypassed the lesion with a tracheostomy tube to avoid an increase in air leakage into the mediastinum. Under broad-spectrum antibiotic therapy, no mediastinitis occurred and all patients survived without sequelae. Closure of tracheostomy was scheduled for 1-2 months after tracheal injury. Analysis of surgical and anesthesiological procedures revealed no abnormalities and the accumulation of tracheal injuries was considered as accidental. We found that in clinically stable patients with spontaneous breathing and with no mediastinitis, a conservative management of tracheal tears is a safe procedure.     

Synthesis and biological evaluation of heteroalicyclic cyanoguanidines at histamine receptors

Recent studies on histamine receptor (HR) subtypes identified imidazolyl butyl cyanoguanidines, like UR‐PI376, as highly potent agonists at the human histamine H₄ receptor (hH₄R). While imidazole‐containing compounds display drawbacks in pharmacokinetics, we studied the possibility of replacing the heteroaromatic cycle by nonaromatic six‐membered heterocycles (piperidine, morpholine, thiomorpholine, and N‐methylpiperazine) as potential bioisosteres. Beyond that, this approach should give more information about the indispensability of the aromatic ring as a basic head group. Besides these changes, a variation of the spacer length (C₃–C₅) connecting the heterocycle and the cyanoguanidine moiety has been made to possibly trigger the selectivity towards the respective HRs. Investigations in radioligand‐binding assays exhibited only very weak activity at the hH₁R and hH₃R, while nearly all compounds were inactive at the hH₂R and hH₄R. In the case of piperidine‐containing compounds, moderate affinities at the hH₃R over the single‐digit micromolar range were detected.