Comparison of Quantiferon-TB Gold With Tuberculin Skin Test for Detecting Latent Tuberculosis Infection Prior to Liver Transplantation

Screening for latent tuberculosis infection (LTBI) is recommended prior to organ transplantation. The Quantiferon-TB Gold assay (QFT-G) may be more accurate than the tuberculin skin test (TST) in the detection of LTBI. We prospectively compared the results of QFT-G to TST in patients with chronic liver disease awaiting transplantation. Patients were screened for LTBI with both the QFT-G test and a TST. Concordance between test results and predictors of a discordant result were determined. Of the 153 evaluable patients, 37 (24.2%) had a positive TST and 34 (22.2%) had a positive QFT-G. Overall agreement between tests was 85.1% (kappa= 0.60, p < 0.0001). Discordant test results were seen in 12 TST positive/QFT-G negative patients and in 9 TST negative/QFT-G positive patients. Prior BCG vaccination was not associated with discordant test results. Twelve patients (7.8%), all with a negative TST, had an indeterminate result of the QFT-G and this was more likely in patients with a low lymphocyte count (p = 0.01) and a high MELD score (p = 0.001). In patients awaiting liver transplantation, both the TST and QFT-G were comparable for the diagnosis of LTBI with reasonable concordance between tests. Indeterminate QFT-G result was more likely in those with more advanced liver disease.     

The cylindrical titanium mesh cage for treatment of a long bone segmental defect: description of a new technique and report of two cases

This report describes a new technique for treatment of a segmental defect in long bones that uses a cylindrical titanium mesh cage, in combination with cancellous bone allograft and demineralized bone matrix putty (Grafton), stabilized with a statically locked intramedullary nail. Two clinical cases of tibia defects treated with this technique are presented. At the one-year follow-up, radiographically both cases demonstrated excellent limb alignment, stability, and bony healing. Immediate full weight-bearing was initiated in each case, and early limb functional recovery was achieved. Preliminary data suggest that this technique may be a reasonable alternative to currently used methods for management of select long bone segmental defects.     

Sigma-1 receptor and inflammatory pain

Inflammation Research - The sigma-1 receptor (Sig-1R) is a unique ligand-regulated molecular chaperone that interacts with several protein targets such as G protein-coupled receptors and ion...     

Ambulatory blood pressure monitoring over 24 h: A Latin American Society of Hypertension position paper—accessibility,clinical use and cost effectiveness of ABPM in Latin America in year 2020

Accurate office blood pressure measurement remains crucial in the diagnosis and management of hypertension worldwide, including Latin America (LA). Office blood pressure (OBP) measurement is still the leading technique in LA for screening and diagnosis of hypertension, monitoring of treatment, and long‐term follow‐up. Despite this, due to the increasing awareness of the limitations affecting OBP and to the accumulating evidence on the importance of ambulatory BP monitoring (ABPM), as a complement of OBP in the clinical approach to the hypertensive patient, a progressively greater attention has been paid worldwide to the information on daytime and nighttime BP patterns offered by 24‐h ABPM in the diagnostic, prognostic, and therapeutic management of hypertension. In LA countries, most of the Scientific Societies of Hypertension and/or Cardiology have issued guidelines for hypertension care, and most of them include a special section on ABPM. Also, full guidelines on ABPM are available. However, despite the available evidence on the advantages of ABPM for the diagnosis and management of hypertension in LA, availability of ABPM is often restricted to cities with large population, and access to this technology by lower‐income patients is sometimes limited by its excessive cost. The authors hope that this document might stimulate health authorities in each LA Country, as well as in other countries in the world, to regulate ABPM access and to widen the range of patients able to access the benefits of this technique.     

Sigma-1 receptor inhibition reverses acute inflammatory hyperalgesia in mice: role of peripheral sigma-1 receptors

Rationale

Sigma-1 (σ₁) receptor inhibition ameliorates neuropathic pain by inhibiting central sensitization. However, it is unknown whether σ₁ receptor inhibition also decreases inflammatory hyperalgesia, or whether peripheral σ₁ receptors are involved in this process.

Objective

The purpose of this study was to determine the role of σ₁ receptors in carrageenan-induced inflammatory hyperalgesia, particularly at the inflammation site.

Results

The subcutaneous (s.c.) administration of the selective σ₁ antagonists BD-1063 and S1RA to wild-type mice dose-dependently and fully reversed inflammatory mechanical (paw pressure) and thermal (radiant heat) hyperalgesia. These antihyperalgesic effects were abolished by the s.c. administration of the σ₁ agonist PRE-084 and also by the intraplantar (i.pl.) administration of this compound in the inflamed paw, suggesting that blockade of peripheral σ₁ receptors in the inflamed site is involved in the antihyperalgesic effects induced by σ₁ antagonists. In fact, the i.pl. administration of σ₁ antagonists in the inflamed paw (but not in the contralateral paw) was sufficient to completely reverse inflammatory hyperalgesia. σ₁ knockout (σ₁-KO) mice did not develop mechanical hyperalgesia but developed thermal hypersensitivity; however, the s.c. administration of BD-1063 or S1RA had no effect on thermal hyperalgesia in σ₁-KO mice, supporting on-target mechanisms for the effects of both drugs. The antiedematous effects of σ₁ inhibition do not account for the decreased hyperalgesia, since carrageenan-induced edema was unaffected by σ₁ knockout or systemic σ₁ pharmacological antagonism.

Conclusions

σ₁ receptors play a major role in inflammatory hyperalgesia. Targeting σ₁ receptors in the inflamed tissue may be useful for the treatment of inflammatory pain.     

Green alternative cosolvents to N-methyl-2-pyrrolidone in water polyurethane dispersions

N-Methyl-2-pyrrolidone is a toxic dipolar aprotic solvent widely used in the synthesis of polyurethane dispersions (PUD). Since legislation strongly restricts this substance, green alternatives are essential. Dihydrolevoglucosenone and gamma valerolactone demonstrate comparable performance to that of NMP as cosolvent in the synthesis and the film forming process of PUD.

N-Methyl-2-pyrrolidone is a toxic dipolar aprotic solvent widely used in the synthesis of polyurethane dispersions (PUD).

The use of organic solvents in commercial products like coatings or adhesives is being limited due to their toxicity and environmental hazard.^1,2 Aqueous polymeric nanodispersions are suitable alternatives to reduce the use of organic solvents. PUD are extraordinarily interesting due to their equivalent performance to the conventional solvent borne products, but with some additional advantages such as excellent adhesion, tuneable mechanical properties and functionalization, good biocompatibility and potential biodegradability.^3–5These polymeric dispersions are colloidal systems in which polyurethane (PU) particles are dispersed in aqueous media as a continuous phase. Standard polyurethanes are not dispersible in water due to the presence of isocyanates, which are hydrophobic and they also could react with water. Then, polyurethanes dispersible in water need to be modified. Generally, they are obtained by incorporating diol molecules with hydrophilic carboxylic group as internal emulsifier. After synthesising a linear thermoplastic PU prepolymer, the acids groups of the internal emulsifier are neutralized.This hydrophilic isocyanate-terminated prepolymer is subsequently extended with low molecular weight alcohols or amines to obtain the target polyurethane. The dispersion in water can take place in different stages of the process depending mainly on the chain extender used, i.e. before or after chain extension.The most common processes for synthesizing PUD are acetone and prepolymer mixing processes. In acetone process, the polymer synthesis requires acetone to obtain a homogeneous and low viscosity reaction system. However, it has the disadvantage of requiring large amounts of acetone and an extra distillation process for removing this solvent from the waterborne dispersion. This makes the industry to commonly discard this strategy.Nevertheless, in prepolymer mixing process, the medium molecular weight polymer (prepolymer) is prepared through the reaction of di-functional polyols and the internal emulsifier with a molar excess of di-isocyanates. Then, the prepolymer is extended and the dispersion in water is carried out.In this process, around 12–15 wt% of organic solvent, generally N-methyl-2-pyrrolidone (NMP), is used to reduce the viscosity of the mixture.⁶ This organic solvent remains in the dispersion in order to promote the coalescence of nanoparticles and the film formation of coatings or adhesives.⁷ Therefore, any alternative cosolvent to NMP must work as both reaction media and coalesce agent to achieve similar performance and products.NMP is a dipolar aprotic solvent with excellent coalescence capacity, but its use is restricted,⁸i.e., it shall not be placed on the market as a substance on its own or in mixtures in a concentration equal to or greater than 0.3 wt%.^9–11 Hence, there is a pressing need to achieve low toxicity alternative solvents with the suitable polarity profile. Structurally homologues substances with different length of carbon side chain like N-ethyl- or N-butyl-2-pyrrolidone (NEP/NBP)^12,13 have been promoted as alternatives to NMP. However, this was simply an attempt to use the lack of environmental and health data available at the time to keep ahead of legislation.¹⁴In addition, the studies by M. Schmidt using NBP as alternative cosolvent for PUD, an extra cosolvent is need. The coalescence process is not effective enough and extra cosolvent is incorporated in the final product formulation to complete the coalescence of polyurethane nanoparticles and the film forming.¹⁵ This drawback is also the main disadvantage of solvent free PUDs, where the formulation of coatings or adhesive includes additional solvents to achieve proper film forming in the final product.^5,16In this study, two alternative green solvents with improved Health, Environmental and Safety (HES) profile (see detailed information in Table S1 at ESI^†) have been selected. Green solvents studied are: Dihydrole-levoglucosenone (CY) and γ-valerolactone (GVL)^17,18 (Fig. 1).Open in a separate windowFig. 1Molecular structure of cosolvents studied.Dihydrolevoglucosenone (Cyrene, CY) is a biodegradable compound synthesised in a two-step process from waste cellulose.¹⁹ There are evidences that this new substance is an alternative to dipolar aprotic solvents.²⁰ Cyrene is identified as an effective solvent in different chemical applications such as the synthesis of ureas,²¹ the preparation of membranes,²² metal organic frameworks (MOF) synthesis,²³ heteroatom and alkylation reactions, in nucleophilic fluorination reactions²⁰ or in graphene dispersions.²⁴On the other hand, γ-valerolactone (GVL) is a biodegradable substance obtained from lignocellulosic biomass²⁵ that is widely used in food and perfume industries.²⁶ However, new applications as green solvent in chemical industry have been recently reported: crosscoupling reactions (Hiyama reaction),²⁷ synthesis of formamides,²⁸ synthesis of phosphatidylserine²⁹ or the production of 5-hydroxymethylfurfural³⁰ are some outstanding examples as green solvent.Physicochemical properties of these green solvents and NMP are collected in 31 and Hansen parameters have been compared, see Fig. 2 and 32,33 The Reichardt parameter, E^N_T, is extensively used for measuring empirically the polarity of different systems (organic and ionic liquids, switchable-hydrophilicity solvents, polymers, surfaces, etc.). E^N_T values measure preferably the solvent''s dipolarity/polarizability (given by π*) and hydrogen bond donor acidity (given by α).^34,35Physicochemical properties of selected cosolvents

Hyaline‐vascular type Castleman’s disease of the pararenal retroperitoneum: Multidetector CT findings

We describe the case of a 40‐year‐old woman who presented with a pararenal hyaline‐vascular type Castleman’s disease that had an arterial supply from the renal artery and a draining vein as showed by multidetector CT. Identification of the renal artery relationship to the feeding vessel of the mass is critical to prevent potential surgical complications.