Effects of a multifactorial ecosustainable isocaloric diet on liver fat in patients with type 2 diabetes: randomized clinical trial.

INTRODUCTION: Treatment options for non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes (T2D) are still a matter of debate. We compared the effects of a diet including different components versus a proven beneficial diet rich in monounsaturated fatty acids (MUFAs) on liver fat in T2D. RESEARCH DESIGN AND METHODS: According to a parallel design, 49 individuals with T2D, overweight/obese, with high waist circumference, 35-75 years-old, in satisfactory blood glucose control with diet or drugs not affecting liver fat content, were randomly assigned to an 8-week isocaloric intervention with a MUFA diet (n=26) or a multifactorial diet rich in fiber, MUFA, n-6 and n-3 polyunsaturated fatty acids, polyphenols, and vitamins D, E, and C (n=23). Before and after the intervention, liver fat content was evaluated by proton magnetic resonance spectroscopy (1H-MRS). 1H-MRS complete data were available for n=21 (MUFA diet) and n=18 (multifactorial diet) participants. RESULTS: Adherence to dietary interventions was optimal. No significant differences between groups in body weight reduction, plasma glycated hemoglobin, insulin, glucose, lipids and liver enzymes were observed. Liver fat significantly decreased after both the multifactorial diet (9.18%±7.78% vs 5.22%±4.80%, p=0.003) and the MUFA diet (9.47%±8.89% vs 8.07%±8.52%, p=0.027) with a statistically significant difference between changes either in absolute terms (-4.0%±4.5% vs -1.4%±2.7%, p=0.035) or percent (-40%±33% vs -19%±25%, p=0.030). CONCLUSIONS: An isocaloric multifactorial diet including several beneficial dietary components induced a clinically relevant reduction of liver fat in patients with T2D, more pronounced than that induced by simply replacing saturated fat with MUFA. This suggests that the 'optimal diet' for NAFLD treatment in T2D should be based on synergic actions of different dietary components on multiple pathophysiological pathways. TRIAL REGISTRATION NUMBER: NCT03380416.

Preventive skin analgesia with lidocaine patch for management of post-thoracotomy pain: Results of a randomized, double blind, placebo controlled study.

BACKGROUND: To evaluate whether pre-emptive skin analgesia using a lidocaine patch 5% would improve the effects of systemic morphine analgesia for controlling acute post-thoracotomy pain. METHODS: This was a double-blind, placebo controlled, prospective study. Patients were randomly assigned to receive lidocaine 5% patch (lidocaine group) or a placebo (placebo group) three days before thoracotomy. Postoperative analgesia was induced in all cases with intravenous morphine analgesia. The intergroup differences were assessed in order to evaluate whether the lidocaine patch 5% would have effects on pain intensity when at rest and after coughing (primary end-point) on morphine consumption, on the recovery of respiratory function, and on peripheral painful pathways measured with N2 and P2 laser-evoked potential (secondary end-points). RESULTS: A total of 90 patients were randomized, of whom 45 were allocated to the lidocaine group and 45 to the placebo group. Lidocaine compared with the placebo group showed a significant reduction in pain intensity both at rest (P = 0.013) and after coughing (P = 0.015), and in total morphine consumption (P = 0.001); and also showed a better recovery of flow expiratory volume in one second (P = 0.025) and of forced vital capacity (P = 0.037). The placebo group compared with the lidocaine group presented a reduction in amplitude of N2 (P = 0.001) and P2 (P = 0.03), and an increase in the latency of N2 (P = 0.023) and P2 (P = 0.025) laser-evoked potential. CONCLUSIONS: The preventive skin analgesia with lidocaine patch 5% seems to be a valid adjunct to intravenous morphine analgesia for controlling post-thoracotomy pain. However, our initial results should be corroborated/confirmed by larger studies.

Resection of esophageal diverticulum through uniportal video-assisted thoracoscopic surgery.

Open surgery remains the standard strategy for management of esophageal diverticulum in symptomatic patients. However, in the last years an increasing number of minimally invasive approaches have been proposed for this issue in order to reduce the surgical trauma and favor a fast return to daily activity. Herein, we describe a novel technique as uniportal video-assisted thoracoscopic surgery (VATS) for performing resection of esophageal diverticulum. This procedure was successfully carried out in three consecutive patients with giant mid-esophageal diverticulum (mean size: 6.5±0.5 cm). The mean post-operative time was 121±10 minutes. The chest drain was removed 48 hours later in all cases and the mean length of hospital stay was 9±1 days. No intraoperative neither postoperative complications were found in all patients but one. He had a small fistula 15 days later that was successfully treated with stent insertion. No recurrence of diverticulum was seen in all cases. Uniportal VATS is a feasible procedure that in theory could reduce the surgical trauma compared to standard open approach. However, future prospective studies should corroborate our impression before it can be recommended as acceptable therapy.

Biological Functions of Interferon ß-1a Are Enhanced By Deamidation.

Human type I Interferons (IFN-ß, IFN-ɛ, IFN-κ, IFN-ω, and 12 subtypes of IFN-α) are a family of pleiotropic cytokines with antiviral, antiproliferative, and immunomodulatory activities. They signal through the same cell surface receptors, IFNAR1 and IFNAR2, yet evoking markedly differential potency. One differentiating factor of IFN-ß from other type I interferons is the presence of a consensus sequence (NG) for deamidation. Comparing almost completely deamidated IFN-ß-1a with untreated IFN-ß-1a, this present study reports the increased activities in 3 in-vitro bioassays testing the antiviral, antiproliferative, and immunomodulatory properties, respectively, of the molecule. Deamidated IFN-ß-1a has the potential to improve current therapies in multiple sclerosis, and its ability to potentiate the MHC-Class I expression suggests a clinical benefit in diseases where the downmodulation of the MHC-class I expression plays a role (eg, in immuno-oncology combination therapies or antiviral agents). The present study on IFN-ß deamidation adds a new prospective on deamidation as part of a posttranslational modification code that allows the modulation of the biological properties of proteins. Moreover, it underlines the unique IFN-ß-1a properties that differentiate this molecule from other members of the type I interferon family.

Efficacy of wound analgesia for controlling post-thoracotomy pain: a randomized double-blind study†.

OBJECTIVES: Continuous wound infusion of local anaesthetics has been successfully applied for postoperative pain control in several procedures but, surprisingly, it is underused in thoracic surgery. We aimed to investigate the effects of wound analgesia associated with systemic patient-controlled analgesia in patients undergoing lung cancer resection with muscle-sparing thoracotomy. METHODS: Sixty consecutive patients undergoing lung cancer resection via standard muscle-sparing thoracotomy were randomized into two groups (wound analgesia and placebo groups). Bupivacaine in the wound group and free-saline solution in the placebo group were injected using a multiholed catheter connected to an elastomeric pump inserted at the end of operation between the pericostal sutures and the serratus muscle and removed 48 h after. The inter-group differences were assessed by the following criteria: (i) level of cytokines [IL-6, IL-10 and tumour necrosis factor-alpha (TNF-alpha)]; (ii) pain on a visual analogue scale at rest and after coughing; (iii) recovery of respiratory functions (flow expiratory volume in 1 s % and forced vital capacity %) and (iv) narcotic medication consumption at different time points of the postoperative course. RESULTS: Five out of a total of 60 patients were excluded from the final analysis. Thus, the wound and placebo groups comprised 27 and 28 patients, respectively. The wound group compared with the placebo group had a significant decrease of IL-6 (P < 0.001), IL-10 (P < 0.001) and TNF-alpha (P < 0.001) blood concentration levels, pain scores at rest (P < 0.001) and after coughing (P = 0.01), and a reduction of additional morphine intake (P = 0.03) and Ketorolac (P = 0.01) during the entire postoperative course. The recovery of the flow expiratory volume in one second % (P = 0.01) and the forced vital capacity % (P = 0.02) was also better in the wound than in the placebo group. CONCLUSIONS: Our data prove that wound analgesia is an effective, easy and safe procedure. It significantly reduces systemic inflammatory markers, pain scores and opioid intake; and accelerates the recovery of respiratory function. Catheter placement does not require particular manoeuvres by the surgeon nor does the elastomeric pump need any adjustment or care by physicians or nurses.

Correlation between matrix metalloproteinase 9 and 18F-2-fluoro-2-deoxyglucose-positron emission tomography as diagnostic markers of lung cancer.

OBJECTIVES: This study was conducted to evaluate the diagnostic role of matrix metalloproteinase 9 (MMP9) measured in bronchoalveolar lavage (BAL), serum and tissue samples of patients with indeterminate lung lesions and its correlation with F-18-2-fluoro-2-deoxyglucose-positron emission tomography ((18)FDG-PET) findings in diagnostic work. METHODS: MMP9 levels (ng/ml) in serum and BAL were analysed using enzyme-linked immunosorbent assay in 60 consecutive patients with lung mass. (18)FDG-PET was performed on all patients and a standard uptake value (SUV) threshold of 2.5 was used to differentiate benign from malignant lesions. In tissue samples of resectable patients, MMP9 expression was also revealed by immunohistochemical staining. RESULTS: Twenty patients had benign disease and 40 patients had malignant lesions, of which 7 (17.5%) were classified as Stage I, 18 (45%) as Stage II, 7 (17.5%) as Stage III and 8 (20%) as Stage IV. MMP9 levels in serum were significantly higher in malignant than in benign lesions (673 ± 182 versus 309 ± 96, respectively, P < 0.0001), and were significantly higher in patients with metastatic disease than in patients of other stage groups; no significant difference was found between different histological types. MMP9 levels in BAL were higher in malignant than in benign lesions (502 ± 137 versus 325 ± 118, respectively, P = 0.001); no significant differences were found between different stages or histological groups. In patients with malignant lesions, MMP9 levels in BAL were inversely correlated with FEV(1) (volume that has been exhaled at the end of the first second of forced expiration) and FVC (forced vital capacity of maximally forced expiratory effort) values. In patients with SUV > 2.5, MMP9 levels in serum and BAL had a sensitivity, specificity, positive predictive value and negative predictive value of 73, 100, 100 and 81% (cut-off point of 601; area under the curve (AUC): 0.7) and 94, 100, 100 and 83% (cut-off point of 745; AUC: 0.9), respectively. In patients with SUV < 2.5, MMP9 levels in serum and BAL had a sensitivity, specificity, positive predictive value and negative predictive value of 94, 100, 100 and 75% (cut-off point of 240; AUC: 0.9) and 70, 100, 100 and 73% (cut-off point of 321; AUC: 0.7), respectively. Of the 26 tumour samples, 9 (34%) showed positive immunohistochemical staining for MMP9. CONCLUSIONS: The measurement of MMP9 levels helps to differentiate benign from malignant lung mass. Its use in combination with PET study adds further information to the diagnosis work-up of lesions to select patients who may or may not benefit from additional invasive procedures.

Characterisation of a novel growth hormone variant comprising a thioether link between Cys182 and Cys189.

A novel variant of recombinant human growth hormone (r-hGH), isolated from biopharmaceutical preparations produced in E. coli, was identified and characterised. This variant contains a nonreducible thioether bridge near the C terminus between Cys182 and Cys189 and was characterised using various analytical techniques. As previous work by Cunningham and Wells (1993) highlighted the involvement of several residues in this part of the sequence in the binding and affinity of the molecule to its receptor, the presence of this modified intramolecular link may have important implications with regard to the biological behaviour of the molecule. Furthermore, as the conversion of a disulfide into a thioether was previously reported for a therapeutic monoclonal antibody (Tous et al., 2005), this may imply that disulfide bridges located in this part of the molecule have a generic susceptibility to thioether formation. This in turn is relevant to the biopharmaceutical industry for monitoring the integrity of disulfide bridges near the protein C terminus. The present study exhibits a state of the art physicochemical investigation for the unequivocal elucidation of a novel structure involving peptide mapping with mass spectrometry and de novo peptide sequencing. Changes in the higher order structure of the molecule were highlighted by near UV circular dichroism and molecular modelling.