Microarchitecture of medication-related osteonecrosis of the jaw (MRONJ); a retrospective micro-CT and morphometric analysis

Medication-related osteonecrosis of the jaw (MRONJ) is a severe side effect of antiresorptive (AR) drugs such as bisphosphonates (BP) and denosumab (Dmab). Although several risk factors are described, the etiology of MRONJ is still not fully elucidated. Bone-strengthening is the primary aim of antiresorptive therapy; however, overly increased bone mass and microcrack accumulation are also discussed in MRONJ etiologies. The aim of this study is to evaluate the microarchitecture of jaw bones with micro?computed tomography (micro-CT) in AR-treated patients with or without MRONJ.Human jaw bone samples of AR-treated patients were separated into 11 groups by AR treatment bisphosphonate (BP), denosumab (Dmab), both (M) and control groups. Subgroups were divided according to the clinical localization as AR-exposed vital jaw bone (BP_exp, Dmab_exp, M_exp), osteonecrosis–margin of a sequestrum (BPO_mar, DmabO_mar, MO_mar) and osteonecrosis–sequestrum (BPO_seq, DmabO_seq, MO_seq). Healthy jaw bone (C_HB) and osteoporotic jaw bone (C_OP) represent control groups. Samples underwent retrospective micro-CT and morphometric analysis in representative units by bone volume fraction (BV/TV), bone surface density (BS/BV), trabecular thickness (Tr.Th.), trabecular number (Tr.N.), trabecular space (Tr.Sp.), Euler characteristic for bone connectivity, bone mineral density (BMD) and tissue mineral density (TMD).A total of 141 samples from 78 patients were analyzed. BV/TV of M_exp group (mean: 0.46 ± 0.27) was significantly higher than in the C_OP group (mean: 0.14 ± 0.05; p = 0.0053). Tr.Th. differed significantly between the BP_exp group (mean: 0.32 ± 0.15) and the M_exp group (mean: 0.57 ± 0.20; p = 0.0452) as well as between the BPO_seq group (mean: 0.25 ± 0.10) and the MO_seq group (mean: 0.39 ± 0.18; p = 0.0417). Signs of trabecular thickening and unorganized trabecular microarchitecture from AR-exposed- to sequestrum groups, were analyzed in 3D reconstructions. However, BS/BV, Tr.N., and Tr.Sp. showed no significant differences. Euler characteristic of the BPO_seq group (median: 7.46) doubled compared to that of the BP_exp group (median: 14.97; p = 0.0064). Mineralization parameters BMD and TMD were similar in all groups.Findings show evidence of enhanced bone mass and suspect microarchitecture in some AR-treated jaw bone compared to osteoporotic jaw bone. Despite increased bone mass, some MRONJ samples showed decreased trabecular connectivity by Euler characteristic compared to AR-treated jaw bone. These samples may indicate extensive ossification and ineffective bone mass with superficially higher bone mass without existing or even reduced mechanical stability, indicated by connectivity loss. This result might also suggest a high risk to microcrack accumulation. At some point, possibly some kind of over-ossification could lead to under-nourishment and microarchitectural weakness, creating instability, subsequently increasing vulnerability to MRONJ.     

Functionalities and input methods for recording food intake: A systematic review

BackgroundIncreasing healthcare costs related to lifestyle-related chronic diseases require new solutions. Research on self-management tools is expanding and many new tools are emerging. Recording food intake is a key functionality in many of these tools. Nutrition monitoring is a relevant method to gain an overview of factors influencing health. However, keeping a food diary often constitutes a challenge for a patient, and developing a user-friendly and useful electronic food diary is not straightforward.PurposeTo gain insight into the existing approaches to recording food intake, and to analyze current functionalities and input methods.MethodsWe searched digital libraries, vendor markets and social networks focusing on nutrition. Selection criteria were publications written in English, and patient-oriented tools that offered recording of food intake or nutrition. The system properties that we searched for were types of data, types of terminal, target population, and types of reports and sharing functionalities. We summarized the properties based on their frequency in the reviewed sample.Results31 publications met the selection criteria. The majority of the identified food recording systems (67%) facilitated entry of food type and the consumed quantity of food; 16% of the systems were able to record more than one type of data. The three most frequent target populations were people with obesity, diabetes and overweight. Mobile phones were used as terminals in 35% of the cases, personal computers (PCs) in 29%, and personal digital assistants in 23%. Only 10% supported both PCs and mobile phones. Data sharing was provided by 71% and reports by 51% of the systems. We searched for apps in Google Play and the Apple Store and tested 45 mobile applications that stored food intake data, of which 62% supported recording of types of food, 24% recording of carbohydrate intake and 15% recording of calorie intake. The majority of the mobile applications offered some kind of reports and data sharing, mainly via All of the tested social-network-enabled applications supported access from a personal computer and a mobile phone, search in a food database, reports, graphical presentation, listing of favorite foods, overview of own meals, and entering of consumed food type and quantity.ConclusionThe analyzed apps reflected a variety of approaches to recording food intake and nutrition using different terminals – mostly mobile phones (35%), followed by PCs (29%) and PDAs (23%) for older studies, designed mainly for users with obesity (45%), diabetes mellitus (42%) and overweight (32%), or people who want to stay healthy (10%). The majority of the reviewed applications (67%) offered only input of food type and quantity. All approaches (n = 31), except for two, relied on manual input of data, either by typing or by selecting a food type from a database. The exceptions (n = 2) used a barcode scanning function. Users of mobile phone applications were not limited to data recording, but could view their data on the screen and send it via email. The tested web applications offered similar functionalities for recording food intake. The systems studied provided some degree of personalization: users can access some systems via PCs or mobile phones and they can choose among various types of data input content for recording food intake. Many functions, such as search in a food database, reports, graphical presentation, listing of favorite foods, and overview of the user's own meals, are optimized to simplify the recording process and save time. Data sharing and reports are common features of the reviewed systems. However, none use the user's recorded food history to make suggestions on new nutritional intake, during the food recording process. This may be an area for future research.     

A bipartite signal mediates the transfer of type IV secretion substrates of Bartonella henselae into human cells

Bacterial type IV secretion (T4S) systems mediate the transfer of macromolecular substrates into various target cells, e.g., the conjugative transfer of DNA into bacteria or the transfer of virulence proteins into eukaryotic host cells. The T4S apparatus VirB of the vascular tumor-inducing pathogen Bartonella henselae causes subversion of human endothelial cell (HEC) function. Here we report the identification of multiple protein substrates of VirB, which, upon translocation into HEC, mediate all known VirB-dependent cellular changes. These Bartonella-translocated effector proteins (Beps) A-G are encoded together with the VirB system and the T4S coupling protein VirD4 on a Bartonella-specific pathogenicity island. The Beps display a modular architecture, suggesting an evolution by extensive domain duplication and reshuffling. The C terminus of each Bep harbors at least one copy of the Bep-intracellular delivery domain and a short positively charged tail sequence. This biparte C terminus constitutes a transfer signal that is sufficient to mediate VirB/VirD4-dependent intracellular delivery of reporter protein fusions. The Bep-intracellular delivery domain is also present in conjugative relaxases of bacterial conjugation systems. We exemplarily show that the C terminus of such a conjugative relaxase mediates protein transfer through the Bartonella henselae VirB/VirD4 system into HEC. Conjugative relaxases may thus represent the evolutionary origin of the here defined T4S signal for protein transfer into human cells.     

Employment status at time of first hospitalization for heart failure is associated with a higher risk of death and rehospitalization for heart failure

Aims

Employment status at time of first heart failure (HF) hospitalization may be an indicator of both self‐perceived and objective health status. In this study, we examined the association between employment status and the risk of all‐cause mortality and recurrent HF hospitalization in a nationwide cohort of patients with HF.

Methods and results

We identified all patients of working age (18–60 years) with a first HF hospitalization in the period 1997–2015 in Denmark, categorized according to whether or not they were part of the workforce at time of the index admission. The primary outcome was death from any cause and the secondary outcome was readmission for HF. Cumulative incidence curves, binomial regression and Cox regression models were used to assess outcomes. Of 25 571 patients with a first hospitalization for HF, 15 428 (60%) were part of the workforce at baseline. Patients in the workforce were significantly younger (53 vs. 55 years) more likely to be male (75% vs 64%) and less likely to have diabetes (13% vs 22%) and chronic obstructive pulmonary disease (5% vs 10%) (all P < 0.0001). Not being part of the workforce was associated with a significantly higher risk of death [hazard ratio (HR) 1.59; 95% confidence interval (CI) 1.50–1.68] and rehospitalization for HF (HR 1.09; 95% CI 1.05–1.14), in analyses adjusted for age, sex, co‐morbidities, education level, calendar time, and duration of first HF hospitalization.

Conclusion

Not being part of the workforce at time of first HF hospitalization was independently associated with increased mortality and recurrent HF hospitalization.

     

Predictors of death during 10 years after coronary artery bypass grafting with particular emphasis on age

OBJECTIVES: To describe predictors of death during 10 years of follow-up after coronary artery bypass grafting (CABG); to evaluate whether age interacts with the influence of various predictors on outcome; and to compare the mortality during 10 years after CABG with the mortality in an age- and sex-matched control population. DESIGN: Prospective, observational study. SETTING: Department of Thoracic and Cardiovascular Surgery at Sahlgrenska University Hospital and Scandinavian Heart Centre in G?teborg, Sweden. PARTICIPANTS: All patients from western Sweden who underwent CABG between 1 June 1988 and 1 June 1991 without simultaneous valve surgery and with no previous CABG. MAIN OUTCOME MEASUREMENTS: All-cause mortality during 10 years but more than 30 days after CABG. RESULTS: In all, 2000 patients participated in the survey. The following factors appeared as independent predictors of death: preoperative factors-age, history of congestive heart failure, cerebrovascular disease, history of intermittent claudication, current smoking, degree of left ventricular impairment, valvular disease and duration of angina pectoris; peroperative factors-ventilator time and neurological complications; postoperative factors-arrhythmia, requirement of digitalis and requirement of antidiabetics. There was an interaction between age and history of cerebrovascular disease with a stronger impact on outcome in younger patients. The late (>30 days after CABG) 10-year mortality in the study cohort was 29.6% compared with 25.9% in the control population (P=0.02). CONCLUSION: Among patients who underwent CABG, 13 independent predictors for mortality were found, mainly among preoperative factors but also among peroperative factors, postoperative complications and medication requirement after CABG.