[Epidemiological study on the impact of influenza vaccination on the clinical course of patients with COVID-19 and co-infection by both viruses in Gran Canaria, Spain]. / Estudio epidemiológico sobre el impacto de la vacunación antigripal en la evolución clínica de pacientes con COVID-19 y la coinfección por ambos virus en Gran Canaria, España.

OBJECTIVE: To analyze the frequency of influenza and SARS-CoV-2 co-infections, as well as the differences in the course of disease (risk of mortality, hospital and intensive care admissions) in patients infected with the SARS-CoV-2 virus in relation to flu vaccination status in the 2021-2022 season. METHODS: Population-based observational retrospective study in a cohort of 19,850 patients diagnosed with COVID-19 between June 1, 2021 and February 28, 2022 on the island of Gran Canaria. RESULTS: A total of 1,789 patients (9%) diagnosed with COVID-19 had received flu vaccinations. 13,676 people (68.9%) had a full course of COVID-19 vaccinations. In the period between June 1, 2021 and February 28, 2022, 8 cases of flu and COVID-19 coinfection were recorded. Hypertension (18.5%), asthma (12.8%) and diabetes (7.2%) were the most frequent comorbidities. There were 147 deaths (0.7%). Older patients ([OR] 1.11 95% CI 1.09-1.13) and people with cancer ([OR] 4.21 95% CI 2.58-6.89) had a higher risk of dying from COVID-19 (p<0.05). Female sex was noted as a protective factor ([OR] 0.61 95% CI 0.40-0.92). CONCLUSIONS: Old age, male sex and cancer were independent prognostic factors for mortality. Three doses of SARS-CoV-2 vaccines and influenza vaccines were highly effective in preventing COVID-19-related deaths and hospital admissions. These findings suggest that flu vaccination can help control the pandemic.

Hepatic Flow Redistribution is Feasible in Patients with Hepatic Malignancies Undergoing Same-Day Work-Up Angiography and Yttrium-90 Microsphere Radioembolization.

PURPOSE: To assess the feasibility of performing same-day vascular flow redistribution and Yttrium-90 radioembolization (90Y-RE) for hepatic malignancies. MATERIALS AND METHODS: From November 2015 to February 2019, patients undergoing same-day hepatic flow redistribution during work-up angiography, 99mTechnetium-labeled macroaggregated albumin (99mTc-MAA) SPECT/CT and 90Y microsphere-RE, were recruited. Within 18 h following the delivery of 90Y resin microspheres, an 90Y-PET/CT study was performed. According to patients' vascular anatomy, flow redistribution was performed by microcoil embolization of extrahepatic branches (group A), intrahepatic non-tumoral vessels (group B) and intrahepatic tumoral arteries (group C). The accumulation of 99mTc-MAA particles and microspheres in the redistributed areas was qualitatively evaluated using a 5-point visual scale (grade 1 = < 25% accumulation; grade 5 = 100% accumulation). Differences in the distribution of microspheres among groups were assessed with Mann-Whitney U test. RESULTS: Twenty-two patients were treated for primary (n = 17) and secondary (n = 5) hepatic malignancies. The MAA-SPECT/CT showed uptake in all the redistributed areas. Regarding the accumulation of microspheres within the redistributed segments in all the groups, perfusion patterns were classified as 2 in 1 case, 4 in 6 cases and 5 in 15 cases. No statistically significant differences were observed between groups A and B-C (U value = 34, p = 0.32) and between groups B and C (U value = 26, p = 0.7). Mean predicted absorbed doses by the tumoral and normal hepatic tissues were 163.5 ± 131.2 Gy and 60.4 ± 69.3 Gy, respectively. Mean total procedure time (from work-up angiography to 90Y delivery) was 401 ± 0.055 min. CONCLUSION: Performing same-day redistribution of the arterial hepatic flow to the target and 90Y-microsphere delivery is feasible in the treatment of liver tumors. Clinical Trials Registry NCT03380130.

Combined Analysis of Methylation and Gene Expression Profiles in Separate Compartments of Small Bowel Mucosa Identified Celiac Disease Patients' Signatures.

By GWAS studies on celiac disease, gene expression was studied at the level of the whole intestinal mucosa, composed by two different compartments: epithelium and lamina propria. Our aim is to analyse the gene-expression and DNA methylation of candidate genes in each of these compartments. Epithelium was separated from lamina propria in biopsies of CeD patients and CTRs using magnetic beads. Gene-expression was analysed by RT-PC; methylation analysis required bisulfite conversion and NGS. Reverse modulation of gene-expression and methylation in the same cellular compartment was observed for the IL21 and SH2B3 genes in CeD patients relative to CTRs. Bioinformatics analysis highlighted the regulatory elements in the genomic region of SH2B3 that altered methylation levels. The cREL and TNFAIP3 genes showed methylation patterns that were significantly different between CeD patients and CTRs. In CeD, the genes linked to inflammatory processes are up-regulated, whereas the genes involved in the cell adhesion/integrity of the intestinal barrier are down-regulated. These findings suggest a correlation between gene-expression and methylation profile for the IL21 and SH2B3 genes. We identified a "gene-expression phenotype" of CeD and showed that the abnormal response to dietary antigens in CeD might be related not to abnormalities of gene structure but to the regulation of molecular pathways.

Immuno-oncology and interventional oncology: a winning combination. The latest scientific evidence.

OBJECTIVE: Interventional oncology (IO) is an emergent field in interventional radiology that can be considered the fourth pillar of oncology. Interventional oncology has the unique capability to treat malignancy in a loco-regional fashion enabling curative (percutaneous ablation), disease stabilization (intra-arterial chemo/radioembolization), and palliative treatment (such as biliary drainage or nephrostomy). The whole arsenal of IO acts by inducing necrosis and apoptosis, with interactions with the tumour's microenvironment potentially crucial for oncological outcomes. Considering that tumour's microenvironment is a pivotal target for both immuno-oncology and interventional-oncology, the interactions between these two anti-tumour weapons must be investigated to understand their synergy. Interestingly, substantial efforts have been directed to understand which technique combinations are best for specific tumours. This review article summarizes the latest scientific evidence highlighting the future prospective of this winning combination, integrating evidence-reported literature and experience-based perceptions.

The ten commandments of liver ablation: expert discussion and report from Mediterranean Interventional Oncology (MIOLive) congress 2017.

Percutaneous liver ablation has become a cornerstone of the recently developed subspecialty of radiology - that is, interventional oncology. Thermal ablation technology has evolved rapidly during the past decades, with substantial technical and procedural improvements that can help obtain better clinical outcomes and safety profiles. Due to the widespread use of percutaneous ablation, a comprehensive review of the methodologic and technical considerations seems to be mandatory. This article summarizes the expert discussion and report from Mediterranean Interventional Oncology Live Congress (MIOLive 2017) that was held in Rome, Italy, integrating evidence-reported literature and experience-based perceptions, to assist not only residents and fellows who are training in interventional radiology but also practicing colleagues who are approaching to this locoregional treatment.

The ten commandments of chemoembolization: expert discussion and report from Mediterranean Interventional Oncology (MIOLive) congress 2017.

Transarterial therapies in the setting of primary and secondary liver malignancies are becoming an essential part of the oncology landscape. The mechanism of action of c-TACE is the induction of tumor necrosis due to the high concentration of the chemotherapeutic that is delivered only locally and to the embolic effect that causes ischemia and increased dwell time of the chemotherapeutic in the tumor. Recently, DEB-TACE has emerged as a variation of c-TACE with the potential for the selective delivery of large amounts of drugs to the tumor for a prolonged period, thereby decreasing plasma levels of the chemotherapeutic agent and related systemic effects. There is an increasing consensus that compared with conventional lipiodol-based regimen, DEB-TACE offers standardized methodology, is more reproducible and is associated with improved response and significantly better safety profile. Using an easy to access point by point format, this manuscript summarizes the expert discussion from the Mediterranean Interventional Oncology Live Congress (MIOLive 2017) about the role of TACE in the treatment of liver tumors.

Pneumatocele during sorafenib therapy: first report of an unusual complication.

Sorafenib is a multi-kinase inhibitor and a vascular endothelial growth factor (VEGF) inhibitor approved to treat patients with advanced hepatocellular carcinoma, renal cell carcinoma and differentiated thyroid carcinoma. Its most common side effects are asthenia/fatigue, skin toxicity, diarrhea and arterial hypertension. Reported respiratory adverse reactions include dyspnea, cough, pleural effusion and hoarseness. The aim of this report is to describe for the first time the occurrence of pneumatocele in two patients treated with Sorafenib. Patients had no respiratory symptoms and alternative diagnoses were ruled out. Primary tumors were different (liver metastases from a pancreatic neuroendocrine tumor and hepatocellular carcinoma) but both patients had been treated with yttrium 90 radioembolization 9 and 17 months before starting on Sorafenib, respectively. No complications occurred and Sorafenib withdrawal was followed by radiologic improvement.

Hepatocellular carcinoma treatment: ablation and arterial embolization. / Tratamiento del hepatocarcinoma: ablación y embolización arterial.

Percutaneous and endovascular techniques take an important role in the therapeutic management of patients with hepatocarcinoma. Different techniques of percutaneous ablation, especially indicated in tumors up to 2cm diameter offer, at least, similar results to surgical resection. Taking advantage of double hepatic vascularization and exclusive tumor nutrition by the artery, several endovascular techniques of treating the tumor have been developed. Intra-arterial administration of embolizing particles, alone or charged with drug (chemoembolization), will produce ischemia and consequent necrosis with excellent results in selected patients. Certain types of particles may exclusively be carriers of a therapeutic agent when they incorporate a radioisotope that facilitates the direct intratumoral selective irradiation (radioembolization). This technique has demonstrated its efficacy in lesions not susceptible to be treated with other methods and should be considered, together with ablation and chemoembolization, in the therapeutic algorithms of hepatocarcinoma.

The ten commandments of hepatic radioembolization: expert discussion and report from Mediterranean Interventional Oncology (MIOLive) congress 2017.

Microsphere and particle technology represent the next-generation agents that have formed the basis of interventional oncology, an evolving subspecialty of interventional radiology. One of these platforms, yttrium-90 microspheres, is increasingly being used as a treatment modality for primary and secondary liver tumors. Due to the widespread use of radioembolization, a comprehensive review of the methodologic and technical considerations seems to be mandatory. This article summarizes the expert discussion and report from Mediterranean Interventional Oncology Live Congress (MIOLive 2017) that was held in Rome, Italy, integrating evidence-reported literature and experience-based perceptions, to assist not only residents and fellows who are training in interventional radiologists but also practicing colleagues who are approaching to this intra-arterial treatment.

[Ionizing radiation received by patients with osteosarcoma during intra-arterial chemotherapy treatment]. / Radiación ionizante recibida por pruebas de radiología intervencionista durante el tratamiento con quimioterapia intraarterial en pacientes afectos de osteosarcoma.

BACKGROUND: Osteosarcoma paediatric patients are usually treated with intra-arterial chemotherapy (QTia) which is admi-nistered directly to the tumour. This procedure exposes patients to ionizing radiation. Paediatric patients are especially sensitive to this exposure. METHODS: The total amount of ionizing radiation received from QTia administration was quantified in a group of 16 osteo-sarcoma paediatric patients from the Clínica Universidad de Navarra. RESULTS: The median of the total radiation received per patient was 33.4 Gy·cm2 (IQR: 43.33 Gy·cm2), and the median number of procedures performed per subject was 10 (IQR: 6.5). CONCLUSIONS: The study highlights the importance of quantifying the radiation received by a group of children and adoles-cents affected by osteosarcoma during treatment with QTia. Long-term side effects of this radiation should be considered in pae-diatric patients. Currently, there are no previous studies that provide data of the amount of ionizing radiation received through this procedure.

Idiopathic decreased bispectral index during anaesthesia emergence: Possible causes for the phenomenon of paradoxical arousal. / Disminución idiopática del índice biespectral durante la educción anestésica: posibles causas del fenómeno delta paradójico.

In a small percentage of patients, sound, touch and even nociceptive stimulation in the presence of a light anaesthetic depth does not cause an electroencephalogram wave pattern of cortical activation (α, ß waves) as would be expected, but leads to a slowed electroencephalogram pattern instead. We report the case of a patient who on emerging from anaesthesia showed very slowed brain activity on the electroencephalogram and reduced algorithmic value, that lasted approximately 5min coinciding with sound and tactile stimulation. After keeping her under observation for 24h during the postoperative period she did not present any brain disorder that could justify that event.

Efficacy of transjugular intrahepatic portosystemic shunt to prevent total portal vein thrombosis in cirrhotic patients awaiting for liver transplantation.

INTRODUCTION: Complete portal vein thrombosis (PVT) may complicate orthotopic liver transplantation (OLT), increasing its technical difficulty and the transfusion requirements and as well as affecting survival in some cases. Transjugular intrahepatic portosystemic shunt (TIPS) prevents total portal vein occlusion in patients with partial PVT. OBJECTIVE: We aimed to assess the efficacy and safety of TIPS to prevent total portal vein occlusion among patients listed for OLT. PATIENTS AND METHODS: We analyzed the clinical records of 15 consecutive patients with partial PVT who underwent TIPS before OLT. The control group consisted of 8 transplanted patients without TIPS but partial PVT diagnosed before OLT. Portal vein patency at surgery, ischemia time, and transfusion requirements during OLT, and survival thereafter were compared between both groups. The main complications were also compared: mortality after TIPS (from TIPS placement to OLT), intraoperative technical complications, and technical complications during the 6 months after OLT. RESULTS: Clinical characteristics at the time of OLT were similar between the groups. No relevant complications were observed after TIPS; all patients underwent transplantation. One- and 5-year actuarial survival rates were similar in both groups (92% and 85% in TIPS-group versus 100 and 75% in the control group, respectively). No differences in transfusion requirement, duration of ischemia, and frequency of technical complications during and after OLT were observed between the groups. The portal vein was patent at surgery in all TIPS patients and 4 of 8 (50%) in the control group (P = .008). CONCLUSION: TIPS may prevent PVT in liver transplantation candidates with partial PVT.

Response to radioembolization with yttrium-90 resin microspheres may allow surgical treatment with curative intent and prolonged survival in previously unresectable hepatocellular carcinoma.

BACKGROUND: Occasionally, patients with hepatocellular carcinoma (HCC) who receive radioembolization with palliative intent are downstaged for radical treatments. The aim of this study was to describe and analyze the overall survival (OS) in these patients compared with patients of the same baseline stage (UNOS T3), who were not eligible for radical treatment after radioembolization. METHODS: Between September 2003 and August 2010, 118 patients with HCC received radioembolization with yttrium-90 ((90)Y) resin microspheres. Of these, 21 patients with UNOS T3 stage were retrospectively identified and included in this analysis. RESULTS: In total, 6 of 21 patients were downstaged and treated radically between 2 and 35 months post-radioembolization. Three patients were resected, 2 received liver transplantation and 1 was ablated and then resected. Patients treated radically were significantly younger (62 vs. 73 years, p = 0.006) and had higher tumor volume (583 mL vs. 137 mL, p = 0.001) than patients who did not achieve radical treatment. There were no differences between the groups in number of lesions, BCLC stage, previous cirrhosis, activity administered per tumor volume, or median levels of alpha-fetoprotein or total bilirubin. Across the whole series, the median OS was 27.0 months (95% CI 5.0-48.9), varying significantly between those treated radically (OS not reached after a median follow-up of 41.5 months since radical therapy) and those who received palliative treatment only (22.0 months; 95% CI 15.0-30.9). CONCLUSIONS: Radical therapy following tumor downstaging with radioembolization provides the possibility of long-term survival in a select subgroup (UNOS T3 stage) with otherwise limited options.

[Extrahepatic vessels depending on the hepatic artery. Identification and management]. / Vasos extrahepáticos dependientes de la arteria hepática. Identificación y manejo.

Patients with malignant liver tumors, whether primary tumors or metastases, that are not candidates for surgical treatment can benefit from different endovascular treatments with proven efficacy in local control of the disease. Correct treatment requires a careful angiographic technique and precise knowledge about the vascular anatomy afferent to the lesion. Occasionally, lesions considered relapse are actually areas that were untreated because the afferent pedicle was not adequately detected. On the other hand, some of the complications of endovascular treatments are related with material passing into non-hepatic vessels. Knowing the hepatic vascular anatomy and correctly identifying all the extrahepatic vessels will make it possible to perform safer, more efficacious treatments. In this article, we present different representative examples of extrahepatic vessels that originate in the hepatic artery.

A novel double mutation in FUS gene causing sporadic ALS.

It has been shown that mutations in the Fused in Sarcoma gene (FUS) could explain up to 5% of cases with familial amyotrophic lateral sclerosis (ALS). Our mutation analysis of FUS in a Canadian ALS patient of Chinese origin revealed an unusual novel heterozygous double point mutation (R514S/E516V) confirming that exon 15 is a mutation hot-spot. The substitutions are in cis position to each other and affect highly conserved codons in the RGG-rich region of the FUS protein. The absence of clinical signs of ALS in the relatives of the affected carrier could indicate that this mutation is incompletely penetrant or de novo. The pathologic significance of the R514S/E516V mutation was confirmed by immunohistochemistry. FUS-positive cytoplasmic inclusions were noted in a moderate number in neurons and abundantly in glial cells in the motor cortex and the brainstem. Of interest, a significant number of neuronal and glial FUS-positive inclusions were found in the tegmentum of the brainstem. Importantly, some neurons with inclusions showed retention of the normal nuclear FUS immunostaining.

Liver radioembolization using 90Y resin microspheres in elderly patients: tolerance and outcome.

PURPOSE: Yttrium 90 (90Y) microsphere radioembolization (90Y-RE) is an emerging locoregional treatment for liver cancer. The most common complications of 90Y-RE arise from excessive irradiation of nontarget organs (eg, gastrointestinal tract, lung, and nontumoral liver). Patients with advanced age may have substantial comorbidities that can affect their life expectancy, and tolerance to radiation in elderly patients may be altered. The purpose of this study is to evaluate the safety and survival of elderly patients treated with 90Y-RE. MATERIALS AND METHODS: We analyzed 255 patients with liver tumors (primary or metastatic) who were treated with 90Y-RE in our institution from September 2003 to February 2010. We categorized patients as "elderly" if aged ≥ 70 years and "younger" if aged < 70 years. RESULTS: Seventy-three patients (29%) were aged ≥ 70 years. The most frequent liver tumor among elderly patients was hepatocellular carcinoma. Complication rates were similar in both groups: 10.4% of elderly patients and 9.9% of younger patients developed radioembolization-induced liver disease (P = 1.000). Only 1.5% of elderly patients developed gastrointestinal ulceration and no patient in the elderly group developed pneumonitis. The median overall survival of patients with hepatocellular carcinoma was similar in elderly and younger groups (13 months, 95% confidence interval [CI], 10.4-15.5 and 12 months, 95% CI, 4.2-15.7; P = 0.4). In patients with colorectal carcinoma metastatic to the liver, the median overall survival was 10 months (95% CI, 5.2-14.7) for elderly patients and 13 months (95% CI, 7.0-18.9) for younger patients (P = 0.3). The median overall survival of patients with other histologies was 9 months (95% CI, 3.5-14.4) for younger patients and 4 months (95% CI, 2.7-5.2) for elderly patients (P = 0.9). CONCLUSION: Elderly patients did not have more toxicity than younger patients treated with 90Y-RE, and survival was similar for each histology. Elderly patients should be considered for 90Y-RE if they otherwise meet the inclusion criteria applicable to younger patients.

Subtype-specific changes in 5-HT receptor-mediated modulation of C fibre-evoked spinal field potentials are triggered by peripheral nerve injury.

Neurotransmitter serotonin (5-HT) released from descending pain modulation pathways to the dorsal horn is crucial to spinal nociception processing. This study sought to gain insight into the modulatory roles of specific serotonin receptor subtypes in experimentally induced neuropathic pain. In rats subjected to spinal nerve ligation (SNL) surgery, we recorded field potentials evoked in the spinal dorsal horn by C fibre-input, during spinal superfusion with subtype-selective drugs. In neuropathic rats, subtype 5-HT1A agonist 8-OH-DPAT (100 nM) was found to potently depress evoked field potentials, as opposed to 5-HT2A or 5-HT2B subtype agonists TCB-2 (100 nM) or BW 723C86 (1 microM), respectively, which consistently enhanced evoked potentials. All three failed to alter spinal field potentials in sham operated rats. CP 94253 (1 microM), WAY 161503 (1 mM) or SR 57227 (at 1 microM in SNL rats, and 100 microM in sham rats), selective agonists for 5-HT1B, 5-HT2C and 5-HT3 receptors, respectively, significantly depressed evoked field potentials in both animal groups. The 5-HT4 agonist RS 67333 (1 microM) was depressant only in sham operated animals. Only after SNL, spinal superfusion with 5-HT1A- or 5-HT1B receptor-antagonists (S)-WAY 100135 (100 microM) or SB 224289 (100 microM), respectively, disinhibited C fibre-evoked potentials, whereas 5-HT2A or 5-HT2B receptor-antagonists 4F 4PP (100 microM) or SB 204741 (100 microM) depressed evoked potentials, suggesting tonic activity of all four subtypes as a consequence of experimental nerve injury. The present findings reveal profound subtype-specific changes in the functional modulatory activities of spinal serotonin receptors following peripheral nerve injury. In particular, spinal hyperexcitation promoted by receptors 5-HT2A and 5-HT2B is suggested as a novel pathogenic pathway contributing to neuropathic pain.