A new concept of the pathogenesis of oral mucous cysts based on a study of 200 cases.

A new hypothesis regarding the pathogenesis of mucous cysts of the oral mucosa is proposed. Based upon a histological study of 188 mucous cysts without epithelial lining out of a total of 200 cysts it is claimed that some cysts may not develop in any of the hitherto described ways as intraductal "mucous retention cysts" or extraductal "mucous extravasation cysts" or from destruction of acini due to the pressure of mucous caused by duct obstruction. It is suggested that some of the cysts, that are found to have developed intraglandularly, are caused by traumatic destruction of a large amount of glandular acini ("parenchymal destruction cysts") and continuous secretion from the remaining acini. The mucus from the disintegrated cells forms a pool, which in time is surrounded by a connective tissue capsule that contains remnants of parenchyma from the affected lobule. This parenchyma degenerates, and eventually the cyst shows the same histological picture as the "mucous extravasation cyst". It is argued that the presence of a feeder duct does not necessarily indicate an extravasation cyst, but may be seen in the "parenchymal destruction cysts" as well. Of the 188 cysts examined 20 (11 per cent) were found to develop intraglandularly, and 36 (19 per cent) were considered probably to have developed intraglandularly.     

Mechanisms of cytolysin‐induced cell damage – a role for auto‐ and paracrine signalling

Cytolysins inflict cell damage by forming pores in the plasma membrane. The Na⁺ conductivity of these pores results in an ion influx that exceeds the capacity of the Na⁺/K⁺‐pump to extrude Na⁺. This net load of intracellular osmolytes results in swelling and eventual lysis of the attacked cell. Many nucleated cells have the capacity to reduce the potential damage of pore‐forming proteins, whereas erythrocytes have been regarded as essentially defenceless against cytolysin‐induced cell damage. This review addresses how autocrine/paracrine signalling and the cells intrinsic volume regulation markedly influence the fate of the cell after membrane insertion of cytolysins. Moreover, it regards the various steps that may explain the relative large degree of diversity between cell types and species as well as highlights some of the current gaps in the mechanistic understanding of cytolysin‐induced cell injury.     

Poor patient-reported outcome after shoulder replacement in young patients with cuff-tear arthropathy: a matched-pair analysis from the Danish Shoulder Arthroplasty Registry

Background and purpose — Reverse shoulder arthroplasty (RSA) has become the treatment of choice for cuff-tear arthropathy. There are, however, concerns about the longevity and the outcome of an eventual revision procedure. Thus, resurfacing hemiarthroplasty (RHA) with extended articular surface has been suggested for younger patients. We compared the patient-reported outcome of these arthroplasty designs for cuff-tear arthropathy.

Patients and methods — We included patients operated on because of cuff-tear arthropathy and reported to the Danish Shoulder Arthroplasty Registry (DSR) from January 1, 2006 to December 31, 2013. 117 RHA cases were matched by age and sex with 233 RSA controls. 34 of the RHAs were conventional and 67 were RHAs with extended articular surface. The Western Ontario Osteoarthritis of the Shoulder (WOOS) Index at 1 year was used as primary outcome. The score was converted to a percentage of a maximum score. Revision, defined as removal or exchange of any component or the addition of a glenoid component, was used as secondary outcome.

Results — Median WOOS was 49 (30–81) for RHA and 77 (50–92) for RSA (p < 0.001). For patients younger than 65 years, median WOOS was 58 (44–80) after RHA, similar to the 54 after RSA (37–85). For patients older than 65 years, median WOOS was 48 (28–82) after RHA and 79 (55–92) after RSA (p < 0.001).

Interpretation — In all patients RSA had a clinically and statistically better patient-reported outcome than RHA. However, in patients younger than 65 years the functional outcome was similar and poor for either arthroplasty type. The optimal treatment of CTA in young patients remains a challenge.     

Dealing with substantial heterogeneity in Cochrane reviews. Cross-sectional study

Background  

Dealing with heterogeneity in meta-analyses is often tricky, and there is only limited advice for authors on what to do. We investigated how authors addressed different degrees of heterogeneity, in particular whether they used a fixed effect model, which assumes that all the included studies are estimating the same true effect, or a random effects model where this is not assumed.     

A Randomized Trial Investigating the Pharmacokinetics,Pharmacodynamics, and Safety of Subcutaneous Semaglutide Once-Weekly in Healthy Male Japanese and Caucasian Subjects

Introduction

Semaglutide is a glucagon-like peptide-1 analogue for once-weekly subcutaneous treatment of type 2 diabetes. This trial compared the pharmacokinetics, pharmacodynamics, and safety of semaglutide in Japanese and Caucasian subjects.

Methods

In this single-center, double-blind, parallel-group, 13-week trial, 44 healthy male subjects (22 Japanese, 22 Caucasian) were randomized within each race to semaglutide 0.5 mg (n = 8), 1.0 mg (n = 8), placebo 0.5 mg (n = 3) or 1.0 mg (n = 3). The primary endpoint was semaglutide exposure at steady state [area under the curve (AUC_0–168h)].

Results

Steady-state exposure of semaglutide was similar for both populations: AUC_0–168h estimated race ratio (ERR), Japanese/Caucasian: 0.5 mg, 1.06; 1.0 mg, 0.99; maximum concentration (C_max) ERR: 0.5 mg, 1.06; 1.0 mg, 1.02. Exposure after the first dose (0.25 mg) was slightly higher in Japanese versus Caucasian subjects (AUC_0–168h ERR 1.11; C_max ERR 1.14). Dose-dependent increases in AUC_0–168h and C_max occurred in both populations. Accumulation was as expected, based on the half-life (t_1/2, ~ 1 week) and dosing interval of semaglutide. Significant body weight reductions were observed with semaglutide 0.5 mg and 1.0 mg in Japanese (both p ≤ 0.05) and Caucasian (both p ≤ 0.05) subjects versus placebo. No new safety issues were identified.

Conclusions

The pharmacokinetic, pharmacodynamic, and safety profiles of semaglutide were similar in Japanese and Caucasian subjects, suggesting that no dose adjustment is required for the clinical use of semaglutide in Japanese subjects.

Funding

Novo Nordisk A/S, Denmark.

Trial registration

ClinicalTrials.gov identifier NCT02146079. Japanese trial registration number JapicCTI-142550.

     

1- and 7-year risk of cardiac events in relation to Holter monitoring in patients admitted with chest pain in whom AMI is not confirmed

The prognostic value of ventricular premature beats (VPBs) was evaluated in 198 patients with chest pain (non-AMI patients) in whom the diagnosis of acute myocardial infarction was ruled out after admission to hospital. VPBs were registered at the time of discharge during a 24-hour Holter monitoring. The amount of cardiac events (CEs) were analyzed after 1 and 7 years follow-up. After 1 year, CEs were seen in 9% of the non-acute myocardial infarction (AMI) patients. After 7 years, 51 CEs (20 nonfatal AMIs and 31 cardiac deaths) had occurred (25%). After 1 year, only pairs of VPBs were associated with an increased risk of CEs. CEs were seen in 25% of the patients with pairs of VPBs and in 6% of the patients without pairs (p<0.01). The occurrence of CEs after 7 years was related to the presence of pairs of VPBs and multiform VPBs. Fifty-five percent of the patients with pairs of VPBs had CEs during the long-term follow-up, compared with 22.5% without pairs (p<0.0005). CE was seen in 48.9% of the patients with multiform VPBs, compared with 19.0% without multiform VPBs (p< 0.0001). Thus, Holter monitoring seems to be of better value for predicting long-term prognosis than for predicting short-term prognosis in non-AMI patients. The presence of multiform VPBs or pairs of VPBs is strongly associated with an increased risk of CE after 7 years. Non-AMI patients with pairs of VPBs or multiform VPBs should be considered as high-risk patients.Presented at The 35th World Congress, International College of Angiology, Copenhagen, Denmark, July 1993