The prevalence and clinical characteristics of glucose metabolism disorders in patients with liver cirrhosis. A prospective study

Aims. To define the prevalence and clinical characteristics of glucose metabolism disorders (GMD) in patients with compensated liver cirrhosis (LC).Material and methods. Fasting plasma glucose (FPG) levels were measured to 130 patients with clinically stable LC. Oral glucose tolerance tests (OGTT) and fasting plasma insulin determinations were performed to patients with normal FPG. Insulin resistance (IR) was calculated with HOMA2-IR index. GMD were classified according to FPG and OGTT tests results and to the chronologic relation between diagnosis of diabetes mellitus (DM) and LC as follows: type-2 DM (T2DM), hepatogenous diabetes (HD) and impaired glucose tolerance. Patients from all groups were compared.Results. The prevalence of GMD were as follows: T2DM in 25 patients (19.2%, 95% CI 12.5-25.9), HD in 28 (21.5%, 95% CI 14.5-28.5) and IGT in 36 (38.5%, 95% CI 30.1-46.7). The total of patients with GMD was 79.2% (95% CI 72.3-86.1). In 41% of cases GMD were subclinical and 48.7% of patients had IR. Patients with T2DM had a higher number of variables with significant differences compared with the other groups (more marked compared to the patients without GMD). The only differences between the patients with T2DM and HD were hypercreatininemia: 1.14 ± 0.53 vs. 0.84 ± 0.22 mg/dL (p = 0.005) and family history of DM: 8 (32%) vs. 2 (7%) (p = 0.02).Conclusion. Almost 80% of patients with compensated LC had GMD. Half of them were subclinical. The patients with T2DM had marked clinical differences compared to patients from the other groups, particularly renal impairment.     

Microglial activation and expression of immune‐related genes in a rat ex vivo nervous system model after infection with Listeria monocytogenes

A wide variety of microorganisms has previously been identified as causes of brain infection. Among them, Listeria monocytogenes has a particular tropism for the central nervous system. To gain knowledge about the immune response elicited by L. monocytogenes in the brain, we used a rat ex vivo organotypic nervous system culture as a model for Listeria infection. Scanning electron microscopy (SEM) revealed that activated microglial cells showing a typical amoeboid morphology are quickly recruited to the surface of the explants after the infection. After bacterial engulfment, these cells appear to act as Trojan horses, releasing the engulfed bacteria inside the brain tissue. We describe cycles of microglial phagocytosis, necrotic cell death and the subsequent removal of cell debris for the first time. Furthermore, we used this ex vivo model to assess the expression profiles of immune relevant genes up to 24 h postinfection by means of q‐PCR‐arrays, finding that a number of inflammation‐promoting genes are upregulated. Shortly after infection by L. monocytogenes, upregulated genes were those that encoded molecules involved in Th1 responses, being the Ccl2 chemokine and members of the interleukin1‐β family the most abundant immunomodulatory signals expressed. After 5 h of infection, L. monocytogenes caused a substantial increase in the expression of TLR1 and TLR2 genes, as well as in several downstream genes of the TLR signaling pathways. © 2013 Wiley Periodicals, Inc.     

Inhaled phage therapy: a promising and challenging approach to treat bacterial respiratory infections

Introduction: Bacterial respiratory tract infections (RTIs) are increasingly difficult to treat due to evolving antibiotic resistance. In this context, bacteriophages (or phages) are part of the foreseen alternatives or combination therapies. Delivering phages through the airways seems more relevant to accumulate these natural antibacterial viruses in proximity to their bacterial host, within the infectious site.

Areas covered: This review addresses the potential of phage therapy to treat RTIs and discusses preclinical and clinical results of phages administration in this context. Recent phage formulation and aerosolization attempts are also reviewed, raising technical challenges to achieve efficient pulmonary deposition via inhalation.

Expert opinion: Overall, the inhalation of phages as antibacterial treatment seems both clinically relevant and technically feasible. Several crucial points still need to be investigated, such as phage product pharmacokinetics and immunogenicity. Furthermore, given phage-specific features, appropriate regulatory and manufacturing guidelines will need to be defined. Finally, randomized controlled clinical trials should be carried out to establish phage therapy’s clinical positioning in the antimicrobial arsenal against RTIs.     

Sentinel Lymph Node Biopsy Versus Axillary Dissection in Node-Negative Early-Stage Breast Cancer: 15-Year Follow-Up Update of a Randomized Clinical Trial

Background

Sentinel lymph node biopsy (SLNB) allows for staging of the axillary node status in early-stage breast cancer (BC) patients and avoiding complete axillary lymph node dissection (ALND) when the sentinel lymph node (SLN) is proven to be free of disease. In a previous randomized trial we compared SLNB followed by ALND (ALND arm) with SLNB followed by ALND only if the SLN presented metastasis (SLNB arm). At a mid-term of ≈ 6 years median follow-up, the two strategies appeared to ensure similar survival and locoregional control. We have revised these previous findings and update the results following a 15-year observation period.

Methods

Patients were randomly assigned to either the ALND or SLNB arm. The main endpoints were event-free survival (EFS), overall survival (OS), and axillary disease recurrence. EFS and OS were assessed using Kaplan–Meier analysis and the log-rank test.

Results

The ALND and SLNB arms included 115 and 110 patients, respectively. At 14.3 years median follow-up, 39 primary BC-related recurrences occurred, 22 (19 %) of which occurred in the ALND arm and 17 (16 %) occurred in the SLNB arm (p = 0.519). No axillary relapse developed in the SLNB arm, while two were observed in the ALND arm. OS (82.0 vs. 78.8 %) and EFS (72.8 vs. 72.9 %) were not statistically different between the ALND and SLNB arms (p = 0.502 and 0.953, respectively).

Conclusions

SLNB is a safe and efficacious component of the surgical treatment of early-stage BC patients. In the long-term, SLNB is equivalent to ALND in terms of locoregional nodal disease control and survival in this subset of patients.

     

Elevated inflammatory markers in response to prolonged sleep restriction are associated with increased pain experience in healthy volunteers

CONTEXT: Sleep disturbances, pain, and inflammation co-occur in various medical conditions, but their interrelationships are poorly understood. OBJECTIVE: We investigated the effects of reduced sleep duration (by approximately 50%) to 4 h/night across 10 days, on peripherally circulating inflammatory mediators. In addition, we tested the prediction that degree of inflammation is quantitatively related to the extent to which pain is increased in response to prolonged sleep restriction. DESIGN: Randomized, 16 day controlled in-laboratory study conducted in GCRC. METHODS: Eighteen volunteers were randomly assigned to either 12 days of sleeping 8 h/night or 4 h/night. Participants rated mood and pain symptoms throughout experimental days. Urine was collected and blood was drawn frequently on the baseline day and after the 10th experimental day for 25 hours. OUTCOME MEASURES: Levels of plasma interleukin (IL)-6, serum C-reactive protein (CRP), plasma soluble tumor necrosis factor receptor p55 (sTNF-R p55), urinary levels of prostaglandin (PG) metabolites D2 and E2, subjective assessment of pain and tiredness-fatigue. RESULTS: IL-6 levels were elevated in the 4-h sleep condition over the 8-h sleep condition (P <0.05). CRP levels showed the same trend as IL-6, but did not differ significantly between groups (P = 0.11). Levels of sTNF-R p55 were unchanged in both groups. PG E2 and 11beta-F2alpha metabolite increased in 4-h sleepers, but did not differ significantly from the 8-h sleepers. Elevated IL-6 levels were strongly associated with increased pain ratings in response to sleep restriction (r = 0.67, P <0.01), and this association could not be explained by elevations in tiredness-fatigue. CONCLUSION: Insufficient sleep quantity may facilitate and/or exacerbate pain through elevations of IL-6. In disorders where sleep disturbances are common, insufficient sleep quantity itself may establish and maintain its co-occurrence with pain and increased inflammation.     

Nutritional screening and dietitian consultation rates in a geriatric evaluation and management unit

Aim

Nutritional screening may not always lead to intervention. The present study aimed to determine: (i) the rate of nutritional screening in hospitalised older adults; (ii) whether nutritional screening led to dietitian consultation and (iii) factors associated with malnutrition.

Methods

In this prospective study of patients aged ≥70 years admitted to a Geriatric Evaluation and Management Unit (GEMU), malnutrition was screened for using the Mini Nutritional Assessment Short Form (MNA‐SF) and identified using the Mini Nutritional Assessment (MNA).

Results

Of the 172 patients participating in the study, 53 (30.8%) patients were malnourished, and 84 (48.8%) were at risk of malnutrition. Mean (SD) age was 85.2 (6.4 years), with 131 patients (76.2%) female. Nutritional screening was performed for all patients; however, it was incomplete in 59 (34.3%) because of omission of the anthropometric measurement. Overall, 62 (36.0%) of the total number of patients were seen by the dietitian, which included 26 (49%) of malnourished patients, 27 (32%) of at‐risk patients and 9 (26%) of the well‐nourished patients. No patients lost >1% of body weight during GEMU stay. Malnourished patients were more likely to be frail, have poor appetite, depression, and have lower levels of: albumin, cognition, physical function, grip strength and quality of life.

Conclusions

The full benefits of nutritional screening by MNA‐SF may not be realised if it does not result in malnourished patients receiving a dietitian consultation. However, it is possible that enrichment of the foodservice with high protein/high‐energy options minimised patient weight loss in the GEMU.     

Multifunctional magnetic-responsive hydrogels to engineer tendon-to-bone interface

Photocrosslinkable magnetic hydrogels are attracting great interest for tissue engineering strategies due to their versatility and multifunctionality, including their remote controllability ex vivo, thus enabling engineering complex tissue interfaces. This study reports the development of a photocrosslinkable magnetic responsive hydrogel made of methacrylated chondroitin sulfate (MA-CS) enriched with platelet lysate (PL) with tunable features, envisioning their application in tendon-to-bone interface. MA-CS coated iron-based magnetic nanoparticles were incorporated to provide magnetic responsiveness to the hydrogel. Osteogenically differentiated adipose-derived stem cells and/or tendon-derived cells were encapsulated within the hydrogel, proliferating and expressing bone- and tendon-related markers. External magnetic field (EMF) application modulated the swelling, degradation and release of PL-derived growth factors, and impacted both cell morphology and the expression and synthesis of tendon- and bone-like matrix with a more evident effect in co-cultures. Overall, the developed magnetic responsive hydrogel represents a potential cell carrier system for interfacial tissue engineering with EMF-controlled properties.