Reply to the letter to the editor “chronic disseminated candidiasis” by Kenneth Rolston

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State-of-the-artery: periadventitial adipose tissue (tunica adiposa)

Traditional view considers that the arterial wall is composed of three concentric tissue coats (tunicae): intima, media, and adventitia. However, large- and medium-sized arteries, where usually atherosclerosis develops, are consistently surrounded by periadventitial adipose tissue (PAAT). Here we update growing information about PAAT, and  conceptualize it as the fourth coat of arterial wall, that is, tunica adiposa (in brief, adiposa, like intima, media, adventitia). Recent evidence has revealed that adipose tissue expresses not only metabolic, but also secretory (endo- and paracrine) phenotype, producing/releasing a large number of signaling proteins collectively termed adipokines. Through paracrine ("vasocrine") way, adiposa-derived mediators may contribute to various arterial functions such as contraction-relaxation, smooth muscle cell growth, inflammation, hemostasis, and innervation, hence to "outside-in" signaling pathway of atherogenesis.Biomedical Reviews 2009; 20: 41-44

Pegfilgrastim in primary prophylaxis of febrile neutropenia following frontline bendamustine plus rituximab treatment in patients with indolent non-Hodgkin lymphoma: a single center, real-life experience

In this prospective study, the impact of granulocyte colony-stimulating factors (G-2 CSF) administered during induction treatment with bendamustine plus rituximab for indolent non- Hodgkin Llymphoma (NHL) was evaluated by comparing patients who received secondary prophylaxis with filgrastim (control group) versus. patients who received pegfilgrastim as primary prophylaxis (peg-group). The primary endpoint was the incidence rate of febrile neutropenia (FN)- related chemotherapy disruptions (regarding dose-dense and/or dose-intensity of schedule). The Ssecondary endpoint included days of hospitalization due to FN, and G-CSF-related side effects (grade ≥3 WHO toxicity criteria) in each group

A Frontline Approach With Peripherally Inserted Versus Centrally Inserted Central Venous Catheters for Remission Induction Chemotherapy Phase of Acute Myeloid Leukemia: A Randomized Comparison

BACKGROUND: The incidence of peripherally inserted central catheter (PICC)-related adverse events has been uncertain in the setting of acute myeloid leukemia (AML) compared with the incidence of centrally inserted central catheter (CICC) adverse events. PATIENTS AND METHODS: We conducted a monocentric, randomized trial of patients with previously untreated AML. Of the 93 patients, 46 had received a PICC and 47 had received a CICC as frontline intravascular device. Thereafter, all patients underwent intensive chemotherapy for hematologic remission induction. The primary endpoint was catheter-related (CR)-bloodstream infection (BSI) and venous thrombosis (VT) rate. The secondary endpoints catheter malfunction, catheter removal, and patient overall survival. RESULTS: The CR-BSI and CR-VT rate in the PICC and CICC groups was 13% and 49%, respectively, with a difference of 36 percentage points (relative risk for CR-BSI or CR-VT, 0.266; P = .0003). The CR-BSI incidence was 1.4 and 7.8 per 1000 catheters daily in the PICC and CICC groups, respectively. Among the CR thromboses, the symptomatic VT rate was 2.1% in the PICC group and 10.6% in the CICC group. In the CICC group, 16 of the 47 patients (34%) had the catheter removed for BSI (n = 5), septic thrombophlebitis (n = 4), VT (n = 2), or malfunction (n = 5) a median of 7 days after insertion. In the PICC group, only 6 of the 46 patients (13%) required catheter removal for VT (n = 2) or malfunction (n = 4). At a median follow-up of 30 days, 6 patients in the CICC group died of CR complications versus none of the patients in the PICC group (P = .012). Using PICCs, the reduction in BSI and symptomatic VT decreased mortality from CR infection and venous thromboembolism. In contrast, the CICC approach led to early catheter removal mostly for difficult-to-treat infectious pathogens. CONCLUSION: Our data have confirmed that BSI and symptomatic VT are the major complications affecting frontline central intravascular device-related morbidity in the leukemia setting. The use of a PICC is safer than that of a CICC and maintains the effectiveness for patients with AML undergoing chemotherapy, with an approximate fourfold lower combined risk of infection or thrombosis at 30 days

The adipose tissue: a new member of the diffuse neuroendocrine system?

Adipose tissue is a sophisticated module, consisting of adipocytes and non-adipocyte cellular elements including stromal, vascular, nerve and immune cells. There is at present evidence that sharing of ligands and their receptors constitutes a molecular language of the human's body, which is also the case for adipose tissue and hypothalamus-pituitary gland. Historically, Nikolai Kulchitsky's identification of the enterochromaffin cell in 1897 formed the basis for the subsequent delineation of the diffuse neuroendocrine system (DNES) by Friedrich Feyrter in 1938. In DNES paradigm, the secretion of hormones, neuropeptides and neurotrophic factors is executed by cells disseminated throughout the body, for example, Kulchitsky (enterochromaffin) cells, testicular Leydig cells, and hepatic stellate cells. Here we propose that the adipose tissue might be a new member of DNES. Today (dnes, in Bulgarian), adipose tissue is "getting nervous" indeed: (i) synthesizes neuropeptides, neurotrophic factors, neurotransmitters, hypothalamic hormones/releasing factors and their receptors, (ii) like brain expresses endocannabinoids and amyloid precursor protein and, for steroidogenesis, the enzyme aromatase (P450arom), (iii) adipocytes may originate from the neural crest cells, and (iv) adipose-derived stem cells may differentiate into neuronal cells. Further molecular profiling of adipose tissue may provide new biological insights on its neuroendocrine potential. Overall this may frame a novel field of study, neuroadipobiology; its development and clinical application may contribute to the improvement of human's health.Adipobiology 2009; 1: 87-93

Reduction of De Novo Lipogenesis Mediates Beneficial Effects of Isoenergetic Diets on Fatty Liver: Mechanistic Insights from the MEDEA Randomized Clinical Trial

Background: Non‐alcoholic liver steatosis (NAS) results from an imbalance between hepatic lipid storage, disposal, and partitioning. A multifactorial diet high in fiber, monounsaturated fatty acids (MUFAs), n‐6 and n‐3 polyunsaturated fatty acids (PUFAs), polyphenols, and vitamins D, E, and C reduces NAS in people with type 2 diabetes (T2D) by 40% compared to a MUFA‐rich diet. We evaluated whether dietary effects on NAS are mediated by changes in hepatic de novo lipogenesis (DNL), stearoyl‐CoA desaturase (SCD1) activity, and/or β‐ oxidation.; Methods: According to a randomized parallel group study design, 37 individuals with T2D completed an 8‐week isocaloric intervention with a MUFA diet (n = 20) or multifactorial diet (n = 17). Before and after the intervention, liver fat content was evaluated by proton magnetic resonance spectroscopy, serum triglyceride fatty acid concentrations measured by gas chromatography, plasma β‐hydroxybutyrate by enzymatic method, and DNL and SCD‐1 activity assessed by calculating the palmitic acid/linoleic acid (C16:0/C18:2 n6) and palmitoleic acid/palmitic acid (C16:1/C16:0) ratios, respectively; Results: Compared to baseline, mean ± SD DNL significantly decreased after the multifactorial diet (2.2 ± 0.8 vs.1.5 ± 0.5, p = 0.0001) but did not change after the MUFA diet (1.9 ± 1.1 vs. 1.9 ± 0.9, p = 0.949), with a significant difference between the two interventions (p = 0.004). The mean SCD‐1 activity also decreased after the multifactorial diet (0.13 ± 0.05 vs. 0.10 ± 0.03; p = 0.001), but with no significant difference between interventions (p = 0.205). Fasting plasma β‐hydroxybutyrate concentrations did not change significantly after the MUFA or multifactorial diet. Changes in the DNL index significantly and positively correlated with changes in liver fat (r = 0.426; p = 0.009). Conclusions: A diet rich in multiple beneficial dietary components (fiber, polyphenols, MUFAs, PUFAs, and other antioxidants) compared to a diet rich only in MUFAs further reduces liver fat accumulation through the inhibition of DNL. Registered under ClinicalTrials.gov no. NCT03380416