Drezotomía en el tratamiento del dolor por desaferentización: revisión de resultados y análisis de factores predictores de éxito

Background and objectivesThe treatment of deafferentation pain by spinal DREZotomy is a proven therapeutic option in the literature. In recent years, use of DREZotomy has been relegated to second place due to the emergence of neuromodulation therapies. The objectives of this study are to demonstrate that DREZotomy continues to be an effective and safe treatment and to analyse predictive factors for success.Patients and methodsA retrospective study was conducted of all patients treated in our department with spinal DREZotomy from 1998 to 2018. Bulbar DREZotomy procedures were excluded. A visual analogue scale (VAS) and the reduction of routine medication were used as outcome variables. Demographic, clinical and operative variables were analysed as predictive factors for success.ResultsA total of 27 patients (51.9% female) with a mean age of 53.7 years underwent DREZotomy. The main cause of pain was brachial plexus injury (BPI) (55.6%) followed by neoplasms (18.5%). The mean time of pain evolution was 8.4 years with a mean intensity of 8.7 according to the VAS, even though 63% of the patients had previously received neurostimulation therapy. Favourable outcome (≥ 50% pain reduction in the VAS) was observed in 77.8% of patients during the postoperative period and remained in 59.3% of patients after 22 months average follow-up (mean reduction of 4.9 points). This allowed for a reduction in routine analgesic treatment in 70.4% of them. DREZotomy in BPI-related pain presented a significantly higher success rate (93%) than the other pathologies (41.7%) (p = .001). No association was observed between outcome and age, gender, DREZ technique, duration of pain or previous neurostimulation therapies. There were six neurological complications, four post-operative transient neurological deficits and two permanent deficits.ConclusionDorsal root entry zone surgery is effective and safe for treating patients with deafferentation pain, especially after brachial plexus injury. It can be considered an alternative treatment after failed neurostimulation techniques for pain control. However, its indication should be considered as the first therapeutic option after medical therapy failure due to its good long-term results.     

High expression of HVEM is associated with improved prognosis in intrahepatic cholangiocarcinoma

Herpesvirus entry mediator (HVEM) displays dual signals in T-cell activation according to the ligands and intracytoplasmic effectors it interacts with. High HVEM expression may play an immunosuppressive role in several malignancies. The present study investigated the clinical impact of HVEM on intrahepatic cholangiocarcinoma (ICC), including its prognostic value, and association with clinicopathological features and immune status. The clinical data of 102 consecutive patients with ICC who underwent surgical treatment from January 2012 to December 2017 were collected. The expression of HVEM and different types of tumor-infiltrating lymphocytes (TILs) were investigated in ICC tissue samples by immunohistochemical staining. HVEM expression was detected in the tumor tissues of 92 (90.2%) patients with ICC. Patients with high HVEM expression were more likely to have increased peripheral blood lymphocyte (PBL) concentrations (P=0.031), decreased CEA (P=0.036), low TNM stage (P=0.043) and high frequencies of small-duct histological type (P=0.021) and BAP1 retained expression (P=0.010). Survival analysis showed that high HVEM expression was a favorable independent predictor of overall postoperative survival (P=0.034, hazard ratio=0.486, 95% confidence interval=0.249–0.945). In addition, no significant association of HVEM expression with CD4⁺ (P=0.512), CD8⁺ (P=0.750) or CD45RO⁺ (P=0.078) TILs was identified in the ICC tissues. These results indicate that HVEM may serve as a favorable prognostic marker for ICC. Furthermore, co-stimulatory signals from HVEM may play a dominant role in the progression of ICCs, which can be explained by an increase in the number of PBLs rather than a change in the number of TILs. However, the function of the HVEM network in ICC progression is complex and requires further study.     

Comparative Outcome Analysis of N-Butyl Cyanoacrylate Embolization of the False Lumen Versus Thoracic Endovascular Aortic Repair in Aortic Dissection

PurposeTo evaluate the feasibility, safety, and effectiveness of N-butyl cyanoacrylate (NBCA) embolization for the treatment of aortic dissection.Materials and MethodsIn this single-center retrospective study conducted from February 2003 to June 2019, NBCA embolization of an aortic false lumen was attempted in 12 patients (median age, 59 y; range, 41–68 y) and thoracic endovascular aortic repair (TEVAR) was performed in 53 patients (median age, 59 y; range, 37–70 y) for aortic dissection with one or more indications of persisting pain, malperfusion, rupture or impending rupture, maximal aortic diameter ≥ 55 mm, and/or rapid aortic enlargement. The main exclusion criterion for embolization was the presence of fast blood flow in the aortic false lumen on aortography. The efficacy of NBCA embolization and TEVAR was compared by evaluating technical and clinical outcomes, repeat intervention–free survival (RFS), and overall survival (OS).ResultsTechnical success was achieved in 11 of the 12 patients treated with NBCA embolization (91.7%), and clinical success was achieved in 9 of these 11 (81.8%). No significant difference was found between embolization and TEVAR in clinical success rates (embolization, 81.8%; TEVAR, 84.9%; P = .409) or procedure-related complications (embolization, 1 patient [8.3%]; TEVAR, 4 patients [7.5%]; P = .701). In addition, embolization showed comparable 5-y RFS (embolization, 82.5% ± 9.3; TEVAR, 85.5% ± 4.8; P = .641) and 5-y OS (embolization, 100%; TEVAR, 95.4% ± 3.2; P = .744) rates to TEVAR.ConclusionsNBCA embolization of the false lumen in aortic dissection seems to be a safe and effective treatment modality for the closure of false lumen in selected patients.     

Risk sharing in managed entry agreements—A review of the Swedish experience

BackgroundIn 2014 managed entry agreements (MEA) between Swedish health care payers (county councils), the reimbursement authority (the Dental and Pharmaceutical Benefits Agency (TLV)) and pharmaceutical companies were introduced to facilitate early and equal access to treatments. MEAs complement the value-based pricing system for out-patient drugs and enables stake-holders to negotiate risk-sharing agreements.AimThe aim of the study was to review existing agreements, describe the type of uncertainty dealt with, and to analyze incentives created using the literature on performance-based reimbursement schemes in Sweden.MethodA document review of all agreements made in the period January 2015 to August 2019 was conducted, classifying agreements by the type of uncertainty dealt with.ResultsAgreements were made for 56 products during the studied time period (45 ongoing), mainly in the fields of hepatitis C (n = 10) and oncology (n = 14). Uncertainties addressed in ongoing agreements included size of treated population (10), treatment duration (13), and effectiveness (9). The mechanism for risk-sharing was limited to refunds based on patient numbers, duration or just flat-rate refunds. The estimated refund in 2018 was 50 % of total sales.DiscussionThis review show that the main driver behind risk sharing in Sweden so far have seem to be affordability rather than managing uncertainty.     

Inactivated influenza vaccine formulated with single-stranded RNA-based adjuvant confers mucosal immunity and cross-protection against influenza virus infection

Influenza vaccination is considered the most valuable means to prevent and control seasonal influenza infections, which causes various clinical symptoms, ranging from mild cough and fever to even death. Among various influenza vaccine types, the inactivated subunit type is known to provide improved safety with reduced reactogenicity. However, there are some drawbacks associated with inactivated subunit type vaccines, with the main ones being its low immunogenicity and the induction of Th2-biased immune responses. In this study, we investigated the role of a single-stranded RNA (ssRNA) derived from the intergenic region in the internal ribosome entry site of the Cricket paralysis virus as an adjuvant rather than the universal vaccine for a seasonal inactivated subunit influenza vaccine. The ssRNA adjuvant stimulated not only well-balanced cellular (indicated by IgG2a, IFN-γ, IL-2, and TNF-α) and humoral (indicated by IgG1 and IL-4) immune responses but also a mucosal immune response (indicated by IgA), a key protector against respiratory virus infections. It also increases the HI titer, the surrogate marker of influenza vaccine efficacy. Furthermore, ssRNA adjuvant confers cross-protective immune responses against heterologous influenza virus infection while promoting enhanced viral clearance. Moreover, ssRNA adjuvant increases the number of memory CD4⁺ and CD8⁺ T cells, which can be expected to induce long-term immune responses. Therefore, this ssRNA-adjuvanted seasonal inactivated subunit influenza vaccine might be the best influenza vaccine generating robust humoral and cellular immune responses and conferring cross-protective and long-term immunity.     

Telling stories out of school: Experiencing the paramedic's oral traditions and role dissonance

Role dissonance is an uncomfortable experience for graduate paramedics, and some blame their university education for the problem. For paramedics the conflict is between identifying as a rescuer and acting largely as a care giver. With vocational pathways into so many uniformed professions closing down in preference for graduate entrants, young new professionals have to negotiate a rapidly changing work culture. Their older colleagues may be challenged and threatened by the new order. For paramedics the problem is compounded by the newness of its place in the tertiary landscape. Since 9/11 young people have been increasingly attracted to rescue roles. Yet in Australia there is increasing need and scope for health workers in remote and aging populations, a preference not immediately attractive to young people hoping for a more heroic future. While the near professions such as nursing have established their discourses around culture, role and pedagogy, paramedics is still trying to chisel its identity. The myths of paramedic glories past tend to add to the confusion of graduates. Due to a lack of empirical studies of non-clinical aspects of paramedicine, a bricolage methodology was used to refresh data from two discrete qualitative research projects conducted in 2011. Both projects had originally been interested in optimal paramedic preceptorship before and after graduation, but neither had explored the implicit theme which revealed the role of rescue experiences in paramedic culture and identity. The bricolage included a new search of literature from near professions and applied new theoretical frameworks to the analysis of the extant data, to demonstrate how storytelling as an element of paramedic collegiality perpetuates rescue stories that are then used to define paramedic work.     

Herpesvirus entry mediator (HVEM) attenuates signals mediated by the lymphotoxin β receptor (LTβR) in human cells stimulated by the shared ligand LIGHT

Signals mediated by members of the tumor necrosis factor receptor superfamily modulate a network of diverse processes including initiation of inflammatory responses and altering cell fate between pathways favoring survival and death. Although such pathways have been well-described for the TNF-α receptor, less is known about signaling induced by the TNF superfamily member LIGHT and how it is differentially altered by expression of its two receptors LTβR and HVEM in the same cell. We used cell lines with different relative expression of HVEM and LTβR to show that LIGHT-induced signals mediated by these receptors were associated with altered TRAF2 stability and RelA nuclear translocation. Production of the inflammatory chemokine CXCL10 was primarily mediated by LTβR. Higher expression of HVEM was associated with cell survival, while unopposed LTβR signaling favored pathways leading to apoptosis. Importantly, restoring HVEM expression in cells with low endogenous expression recapitulated the phenotype of cells with higher endogenous expression. Together, our data provide evidence that relative expression of HVEM and LTβR modulates canonical NF-κB and pro-apoptotic signals stimulated by LIGHT.