Medición automática de la zona avascular foveal de ojos sanos en angiografía por tomografía de coherencia óptica de dominio espectral Heidelberg

PurposeTo develop and evaluate an automated method to measure the foveal avascular zone (FAZ) area in healthy eyes on Heidelberg Spectralis Optical Coherence Tomography Angiography (HS-OCTA). This method is referred to as the modified Kanno-Saitama macro (mKSM) which is an evolution of the Kanno-Saitama macro (KSM) approach.MethodsThis cross-sectional study included 29 eyes of 25 healthy volunteers who underwent HS-OCTA at the macular area twice at the same time. Regardless of the quality of the images, all of them were included. Macular data on the superficial vascular plexus, intermediate capillary plexus (ICP) and deep capillary plexus were processed by mKSM. The FAZ area was measured twice automatically using the mKSM and KSM and twice manually by two independent examiners.ResultsFrom 174 images, KSM could not measure correctly 31% while mKSM could successfully measure all of them. Intrascan intraclass coefficient ranged from 0.948 to 0.993 for manual measurements and was 1 for mKSM method. Despite that the difference between human examiners is smaller than between human examiners and mKSM according to Bland-Altman plots, the scatterplots show a strong correlation between human and automatic measurements. The best results are obtained in ICP.ConclusionsWith mKSM, the automated determination of the FAZ area in HS-OCTA is feasible and less human-dependent. It solves the inability of KSM to measure the FAZ area in suboptimal quality images which are frequent in daily clinical practice. Therefore, the mKSM processing could contribute to our understanding of the three vascular plexuses.     

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.     

Dorsal Root Ganglion Stimulation for the Management of Intractable Painful Polyneuropathy: A Prospective Pilot Study

Objectives: Dorsal root ganglion stimulation (DRGS) is a promising neurostimulation modality in the treatment of painful polyneuropathy. The aim of this prospective pilot study was to investigate the effect of DRGS on pain intensity in patients with intractable painful polyneuropathy.Materials and Methods: Nine patients with chronic, intractable painful polyneuropathy in the lower limbs were recruited. In each subject, between two and four DRGS leads were placed at the level of the L5 and S1 dorsal root ganglion. If trial stimulation was successful, a definitive implantable pulse generator (IPG) was implanted. Pain intensity was scored using an 11-point numeric rating scale (NRS) and reported as median and interquartile range (IQR), and compared to baseline values using the Wilcoxon signed-rank test. Additionally, patients’ global impression of change (PGIC), pain extent, presence of neuropathic pain, physical functioning, quality of life, and mood were assessed.Results: Eight out of nine patients had a successful trial phase, of which seven received an IPG. Daytime pain decreased from a median (IQR) NRS score of 7.0 (5.9–8.3) to 2.0 (1.0–3.5) and 3.0 (1.6–4.9) in the first week and at six months after implantation, respectively. Similar effects were observed for night time and peak pain scores.Conclusions: The results of this study suggest that DRGS significantly reduces both pain intensity and PGIC in patients with intractable painful polyneuropathy in the lower extremities. Large-scale clinical trials are needed to prove the efficacy of DRGS in intractable painful polyneuropathy.     

Repertoire of Rearranged Immunoglobulin Heavy Chain Genes in Russian Patients With B-Cell Lymphoproliferative Diseases

IntroductionImmunoglobulin heavy chain variable region (IGHV) repertoire narrowing could be an evidence for the involvement of a limited set of antigens in the development of lymphomas. For chronic lymphocytic leukemia (CLL) the existence of more than 200 subgroups of tumor IGHV antigen-binding sites, so called “stereotypical” antigen receptors (SAR) has been shown. For others lymphomas the possibility of SARs is also suggested. The aim of this study is to compare the tumor IGHVs and possible SARs in various B-cell malignancies in Russia and other countries.Materials and MethodsThe study included samples of 1800 CLL patients, 52 patients with mantle cell lymphoma, 48 patients with hairy cell lymphoma and 37 patients with splenic marginal cell lymphoma. The nucleotide sequences of the IGHV genes were determined according to ERIC protocol.ResultsIn CLL most common IGHV genes were IGHV1-69, IGHV1-2, IGHV3-30 and IGHV4-34. The most common SARs were CLL#1, CLL#6, CLL#2, CLL#3. In MCL the most common genes were IGHV4-34, IGHV3-21, IGHV3-23. In 5 MCL patients CDR3 sequences were identified matching definitions of a stereotyped. In the half of SMZL patients was identified gene IGHV1-2. Other IGHV genes were much less common. Two pairs of SMZL patients have motives similar to each other. In HCL IGHV repertoire was the most variable, no trends for antigen receptor stereotypy were observed. It was found that SARs are highly disease-specific both at the level of nucleotide and amino acid sequences.ConclusionOur results suggest that antigens crucial for the pathogenesis of B-cell malignancies could be disease-specific. Further studies on extended samples of non-CLL patients concerning the role of SARs in pathogenesis of these diseases may also contribute to the development of new diagnostic and prognostic markers.     

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.     

Diabetic macular ischaemia- a new therapeutic target?

Diabetic macular ischaemia (DMI) is traditionally defined and graded based on the angiographic evidence of an enlarged and irregular foveal avascular zone. However, these anatomical changes are not surrogate markers for visual impairment. We postulate that there are vascular phenotypes of DMI based on the relative perfusion deficits of various retinal capillary plexuses and choriocapillaris. This review highlights several mechanistic pathways, including the role of hypoxia and the complex relation between neurons, glia, and microvasculature. The current animal models are reviewed, with shortcomings noted. Therefore, utilising the advancing technology of optical coherence tomography angiography (OCTA) to identify the reversible DMI phenotypes may be the key to successful therapeutic interventions for DMI. However, there is a need to standardise the nomenclature of OCTA perfusion status. Visual acuity is not an ideal endpoint for DMI clinical trials. New trial endpoints that represent disease progression need to be developed before irreversible vision loss in patients with DMI. Natural history studies are required to determine the course of each vascular and neuronal parameter to define the DMI phenotypes. These DMI phenotypes may also partly explain the development and recurrence of diabetic macular oedema. It is also currently unclear where and how DMI fits into the diabetic retinopathy severity scales, further highlighting the need to better define the progression of diabetic retinopathy and DMI based on both multimodal imaging and visual function. Finally, we discuss a complete set of proposed therapeutic pathways for DMI, including cell-based therapies that may provide restorative potential.