Early treatment with inhaled antibiotics postpones next occurrence of Achromobacter in cystic fibrosis

ObjectivesIn this nationwide retrospective study, we analysed species distribution, antimicrobial susceptibility and time to next occurrence of Achromobacter in Danish cystic fibrosis (CF) patients from 2000 to 2011.MethodsThirty-four primary isolates were identified to species level and subjected to antimicrobial susceptibility testing. Effectiveness of early antimicrobial treatment was assessed by a Kaplan–Meier estimation of time to recurrence.ResultsAchromobacter xylosoxidans accounted for 13 (38%) of the isolates, and an unnamed species accounted for 11 (32%) of the isolates. Meropenem, piperacillin–tazobactam and trimethoprim–sulfamethoxazole were highly active against chemotherapy-naïve Achromobacter, while ceftazidime, colistin and tobramycin were judged adequate for inhalation therapy. Fifty-five percent of 25 patients treated with inhaled ceftazidime, colistin, or tobramycin remained free of Achromobacter three years after acquisition, in contrast to 17% of 22 patients who did not receive inhaled antibiotics (P < 0.01).ConclusionsEarly treatment with inhaled antibiotics may prevent or postpone chronic infection with Achromobacter in CF patients.     

Charlson Co‐morbidity Index and albumin significantly associated with fracture risk in peritoneal dialysis patients

Published literature on fracture in dialysis patients seldom addressed the effect of co‐morbidity and malnutrition. In this study, we reported the incidence and risk factors for fracture in peritoneal dialysis patients. Peritoneal dialysis patients who had fractures between 2006 and 2011 were recruited. Demographic data, details of fracture, Charlson Co‐morbidity Index (CCI) and biochemical parameters were also collected. Non‐fracture controls, matched for age, gender and duration of dialysis, were also recruited at ratio 1:1 for fracture risk analysis. The incidence of fracture was 1 in 37 patient‐years. The commonest site of fracture was neck of femur (n = 16, 55.2%). Twenty‐four patients (82.8%) developed fracture after slip and fall injury. Eight out of 17 self‐ambulatory patients (47.1%) became non‐ambulatory after fracture. Infection was the commonest complication during hospitalization. Univariant analysis demonstrated high CCI (P = 0.001), hypoalbuminaemia (P < 0.001), loss of self autonomy (P = 0.006) and non‐ambulatory state (P = 0.011) significantly associated with increased fracture risk. However, only CCI (odds ratio (OR) 1.373, P = 0.028) and albumin (OR 0.893, P = 0.025) increased fracture risk significantly on multivariant analysis. Bone profile and parathyroid hormone were not significant risk factors. To conclude, fracture associated with adverse outcome in peritoneal dialysis patients. High CCI score and hypoalbuminaemia significantly increase risk of fracture.     

Carry-over of host nutrients during sampling enhances undesired growth of Staphylococcus aureus in liquid Amies transport medium

Optimal transportation of bacteria is important for accurate clinical interpretation, quantitative assays, and microbiome studies. A transport medium should ideally keep the bacteria alive without supporting growth or altering the relative proportions of the constituent species. We investigated the effect of nasal mucus and mucin on the growth and survival of two Staphylococcus aureus strains in liquid Amies transport medium at room temperature and 4?°C for 14?days. The study showed that the presence of nasal mucus in microbiological samples stimulated undesired S. aureus growth at room temperature in a dose-dependent manner. These findings underscore that microbiological samples from humans and animals should be stored at 4?°C until analysis to avoid undesired S. aureus growth.     

Clues for early detection of autoimmune Addison's disease – myths and realities

Background

Early detection of autoimmune Addison's disease (AAD ) is important as delay in diagnosis may result in a life‐threatening adrenal crisis and death. The classical clinical picture of untreated AAD is well‐described, but methodical investigations are scarce.

Objective

Perform a retrospective audit of patient records with the aim of identifying biochemical markers for early diagnosis of AAD .

Material and Methods

A multicentre retrospective study including 272 patients diagnosed with AAD at hospitals in Norway and Sweden during 1978–2016. Scrutiny of medical records provided patient data and laboratory values.

Results

Low sodium occurred in 207 of 247 (84%), but only one‐third had elevated potassium. Other common nonendocrine tests were largely normal. TSH was elevated in 79 of 153 patients, and hypoglycaemia was found in 10%. Thirty‐three per cent were diagnosed subsequent to adrenal crisis, in whom electrolyte disturbances were significantly more pronounced (P < 0.001). Serum cortisol was consistently decreased (median 62 nmol L^?1 [1–668]) and significantly lower in individuals with adrenal crisis (38 nmol L^?1 [2–442]) than in those without (81 nmol L^?1 [1–668], P < 0.001).

Conclusion

The most consistent biochemical finding of untreated AAD was low sodium independent of the degree of glucocorticoid deficiency. Half of the patients had elevated TSH levels. Only a minority presented with marked hyperkalaemia or other nonhormonal abnormalities. Thus, unexplained low sodium and/or elevated TSH should prompt consideration of an undiagnosed AAD , and on clinical suspicion bring about assay of cortisol and ACTH . Presence of 21‐hydroxylase autoantibodies confirms autoimmune aetiology. Anticipating additional abnormalities in routine blood tests may delay diagnosis.

     

Oxidative metabolism of the human eosinophil

We have compared the oxidative metabolism of human eosinophils (80%-90% purity) to that of neutrophils. Hexose monophosphate (HMP) shunt activity of eosinophils was higher than that of neutrophils under either resting or phagocytizing conditions. Eosinophil HMP shunt activity also was stimulated by phorbol myristate acetate, a membrane- active agent. Eosinophils showed a marked incorporation of 125I into trichloroacetic acid-insoluble material under resting conditions, which increased markedly during phagocytosis. Eosinophils likewise showed a greater reduction of nitroblue tetrazolium dye during phagocytosis than did neutrophils. Measurement of other parameters of oxidative metabolism indicated that eosinophils generated superoxide anion following phagocytosis and also elicited a burst of chemiluminescence similar to that observed during phagocytosis by neutrophils. Measurement of NADPH oxidase activity demonstrated that this enzyme was 3-6 times more active in fractions isolated from eosinophils than in corresponding fractions isolated from neutrophils; this was observed over a range of substrate concentrations. The eosinophil enzyme sedimented differently than the neutrophil enzyme with differential centrifugation; neither showed sedimentation characteristics of peroxidase. These data indicate that eosinophils possess a similar, although in some ways more potent, oxidative burst than neutrophils and are consistent with a role for NADPH oxidase in the initiation of that burst.     

Antagonism of the interleukin 4 receptor α promotes TH1-signalling among T cells from patients with atopic dermatitis after stimulation

Atopic dermatitis (AD) is a chronic and relapsing inflammatory skin disease. Molecular characterization of AD shows an underlying inflammation with tissue infiltration of T helper (T_H) 2 cells and increased IL-4 and IL-13. The multifaceted roles of IL-4 and IL-13 in allergic disease development make IL-4Rα an attractive target for treatment strategies, and a neutralizing monoclonal antibody which antagonizes the effects of both IL-4 and IL-13 by blocking the interaction site found in the IL-4 receptor subunit α (IL-4Rα) has been successfully used to treat patients with moderate-to-severe AD. To elucidate the effects of IL-4Rα blockade on the cellular level, we used flow cytometry to examine cytokine production after antigen stimulation in human T cells from patients with AD (n = 12) and healthy controls (n = 6). The cells were stimulated with and without a neutralizing monoclonal antibody against IL-4Rα. Our results indicate that blocking IL-4Rα prohibits IL-4 signalling and IL-13 signalling and thereby T_H2 differentiation followed by an upregulation of interferon-γ-producing cells.     

Deforestation reduces fruit and vegetable consumption in rural Tanzania

Strategies to improve food and nutrition security continue to promote increasing food via agricultural intensification. Little (if any) consideration is given to the role of natural landscapes such as forests in meeting nutrition goals, despite a growing body of literature that shows that having access to these landscapes can improve people’s diets, particularly in rural areas of low- and middle-income countries. In this study, we tested whether deforestation over a 5-y period (2008–2013) affected people’s dietary quality in rural Tanzania using a modeling approach that combined two-way fixed-effects regression analysis with covariate balancing generalized propensity score (CBGPS) weighting which allowed for causal inferences to be made. We found that, over the 5 y, deforestation caused a reduction in household fruit and vegetable consumption and thus vitamin A adequacy of diets. The average household member experienced a reduction in fruit and vegetable consumption of 14 g⋅d⁻¹, which represented a substantial proportion (11%) of average daily intake. Conversely, we found that forest fragmentation over the survey period led to an increase in consumption of these foods and dietary vitamin A adequacy. This study finds a causal link between deforestation and people’s dietary quality, and the results have important implications for policy makers given that forests are largely overlooked in strategies to improve nutrition, but offer potential “win–wins” in terms of meeting nutrition goals as well as conservation and environmental goals.

The challenge of achieving food and nutrition security for the worlds’ growing population while also minimizing and reversing damage to the natural environment is unprecedented. The dominant narrative on how to achieve food and nutrition security continues to be centered on intensifying agricultural production to produce more food (1–3). While agricultural intensification is undoubtedly a key reason we have kept pace with food demands and ended hunger for millions of people over the past decades, it has led to a preoccupation with dietary energy (calories), and thus the production of staple grains which provide the majority of calories globally (4, 5). The focus on staple foods has resulted in dietary quality and diversity being overlooked, despite the fact that far more people suffer from micronutrient deficiency than undernourishment (6–8). Likewise, agricultural intensification is a leading driver of environmental degradation (9–11). There has been much research in recent years examining the impact of different diets on land use (12–15), but less attention has been given to the reverse of this relationship: How do landscapes affect diets? A growing body of literature has examined this relationship with a focus on the linkages between forests and diets in low- and middle-income countries. This relatively new field of research has important implications for strategies to achieve food and nutrition security worldwide, particularly for rural areas in low- and middle-income countries where there are strong connections between livelihoods and landscapes, and undernourishment is most prevalent.Forests provide critical ecosystem services that benefit human populations in several ways, such as the provision of food and fiber, and climate and water regulation (16), with an estimated 1.5 billion forest-proximate people worldwide (i.e., living within 5 km of a forest) (17). Forests can improve people’s diets via four key pathways (18, 19). The most direct way is via the provision of wild forest foods, which most often include fruits, vegetables, mushrooms, and animal products (i.e., bushmeat and insects), all of which tend to be high in essential micronutrients (20–22). The second pathway is via income generation from the sale of forest foods and other nontimber forest products (NTFPs), which can improve livelihoods and facilitate the purchase of nutritious foods from markets (23, 24). The third pathway is via the flow of ecosystem services from forests into surrounding agricultural landscapes (e.g., forests can contribute to soil formation and nutrient cycling, and increase pollination) which can increase and/or diversify production (25). The final pathway is the provision of fuelwood for cooking, which is a key (but often overlooked) pathway that can improve nutrition by facilitating the preparation of a range of foods, particularly those with long cooking times (26, 27).The majority of studies have found a positive relationship between living near (having access to) forests and several measures of diet, nutrition, and food security outcomes. Most studies use metrics of diet quality such as dietary diversity scores or consumption of certain nutritious food groups. Very few studies have examined more detailed measures of dietary quality such as energy and nutrient intakes (28–30), and only one study has examined these in relation to forest cover using multivariate regression (31). Moreover, the majority of studies examine the relationship between forests and diet quality at a single point in time. Two studies have examined the relationship between diets and previous forest loss (32, 33), but no studies, to date, have used longitudinal data to understand concurrent changes in forests and diets over time. In this sense, most studies have only been able to identify associations between forests and diets as opposed to causal relationships. Furthermore, only one study, to date, has examined how the spatial arrangement of forests (as opposed to just forest amount) can affect people’s diets (34), finding that forest configuration may be as important as forest amount for dietary quality.This study aimed to advance the current knowledge on the forest–diet relationship in three main ways:

• 1)By using panel data and a rigorous estimation method which combines covariate balancing generalized propensity score (CBGPS) weighting with two-way fixed-effects regression, we were able to test the causal impact of forest changes on diets, which no studies, to our knowledge, have done. We were also able to explore the causal mechanisms by which forest cover change is hypothesized to affect people’s diets (the direct consumption pathway, the income pathway, and the ecosystem services pathway).
• 2)Most existing studies rely on measures such as dietary diversity scores and consumption of nutritious food groups as proxies for overall diet quality. In addition to these, we also quantified household energy and nutrient adequacy levels in order to gain a better understanding of how forests can affect people’s diets.
• 3)We considered not just forest amount but also the spatial arrangement of forests in relation to diet quality, which only one study has done, to date (34). Thus, this study aimed to extend this research to examine whether changes in forest configuration [in terms of fragmentation (35)] were related to people’s dietary quality.

     

No influence of OPG and its ligands, RANKL and TRAIL, on proliferation and regulation of the calcification process in primary human vascular smooth muscle cells

The aim of this study was to examine the effects of the OPG-RANKL-TRAIL system on proliferation, regulation of calcification-associated genes and calcification of human vascular smooth muscle cells (HVSMCs). Small interfering (si)RNA-mediated knockdown of OPG was followed by treatment of HVSMCs with recombinant RANKL or TRAIL. Regulation of a calcification-associated gene set was assayed by pathway analysis of microarray results. The lack of OPG in HVSMCs or treatment with RANKL or TRAIL did not affect proliferation of HVSMCs. In addition, OPG, RANKL or TRAIL did not modify the regulation of a calcification-associated gene set. Finally, in the long term calcification assay, we found that cells isolated from seven different human donors showed a great variability in the response to RANKL and insulin. However, overall RANKL and/or insulin did not affect the development of calcification of HVSMCs. These studies indicate that OPG knockdown does not alter the calcification process in HVSMCs.     

Annular and subvalvular dynamics after extracellular matrix mitral tube graft implantation in pigs

 Open in a separate windowOBJECTIVESEntire mitral valve reconstruction with an extracellular matrix tube graft is a potential candidate to overcome the current limitations of mechanical and bioprosthetic valves. However, clinical data have raised concern with respect to patch failure. The aim of our study was to evaluate the impact of extracellular matrix mitral tube graft implantation on mitral annular and subvalvular regional dynamics in pigs.METHODSA modified tube graft design made of 2-ply extracellular matrix was used (CorMatrix^®; Cardiovascular Inc., Alpharetta, GA, USA). The reconstructions were performed in an acute 80-kg porcine model (N = 8), where each pig acted as its own control. Haemodynamics were assessed with Mikro-Tip pressure catheters and mitral annular and subvalvular geometry and dynamics with sonomicrometry.RESULTSCatheter-based peak left atrial pressure and pressure difference across the mitral and aortic valves in the reconstructions were comparable to the values seen in the native mitral valves. Also comparable were maximum mitral annular area (755 ± 100 mm²), maximum septal-lateral distance (29.7 ± 1.7 mm), maximum commissure–commissure distance (35.0 ± 3.4 mm), end-systolic annular height-to-commissural width ratio (10.2 ± 1.0%) and end-diastolic interpapillary muscle distance (27.7 ± 3.3 mm). Systolic expansion of the mitral annulus was, however, observed after reconstruction.CONCLUSIONSThe reconstructed mitral valves were fully functional without regurgitation, obstruction or stenosis. The reconstructed mitral annular and subvalvular geometry and subvalvular dynamics were found in the same range to those in the native mitral valve. A regional annular ballooning effect occurred that might predispose to patch failure. However, the greatest risk was found at the papillary muscle attachments.