Molecular mimicry in the post-COVID-19 signs and symptoms of neurovegetative disorders?

Many individuals who have severe forms of COVID-19 experience a suite of neurovegetative signs and symptoms (eg, tachycardia) after their recovery, suggesting that the imbalance of the sympathetic-parasympathetic activity of the autonomic nervous system1 could continue for many weeks or months after respiratory symptoms stop. Moreover, a reduction of the parasympathetic tone could have a role in restricting the cholinergic anti-inflammatory pathway, thus favouring hyperinflammation and cytokine storm in the most severe phases of the disease. As reported by Guglielmo Lucchese in The Lancet Microbe,2 SARS-CoV-2 can damage the nervous system via an indirect mechanism, resulting in a high prevalence of autoantibodies, mainly against unknown autoantigens in the brain, in cerebrospinal fluid from patients with neurological complications.2 The cause of low vagal tone and SARS-CoV-2 has not yet been investigated sufficiently and here we would like to share some original data supporting the putative role of molecular mimicry as the culprit of COVID-19 pathogenesis, including the post-COVID-19 neurovegetative syndrome.2, 3, 4, 5 Using methods that have been previously described,3 we looked specifically at the human proteins expressed in vagal nuclei and ganglia. As shown in the appendix (pp 1–2), we found that 22 of these proteins share peptides that could putatively generate a T-cell or B-cell driven autoimmune response. The location and function of these proteins are described in the appendix (pp 3–24). Fibres of the vagal nerve originate from four nuclei located in the medulla oblongata—ie, the dorsal motor nucleus, the nucleus ambiguus, the solitary nucleus, and, to a lesser extent, the spinal trigeminal nucleus. These fibres contribute to the somatic and visceral motricity, somatic and visceral sensibility, and the sense of taste. The visceral motor inputs originate specifically from the dorsal motor nucleus and nucleus ambiguus and are directed towards the heart, the airways, and the gastrointestinal system. Moreover, the vagal visceral innervation includes two sensory ganglia of the peripheral nervous system—the nodose ganglion and the jugular ganglion. In particular, peripheral fibres of the neurons of the nodose ganglion not only innervate the taste buds on the epiglottis, the chemoreceptors of the aortic bodies, and baroreceptors in the aortic arch, but they also provide sensory innervation to the circulatory, respiratory, and gastrointestinal systems. An impairment of the vagal innervation of the heart can lead to tachycardia at rest, which is often seen by clinicians during physical examination of patients who have recovered from a severe form of COVID-19.1 We found that the dorsal motor nucleus, nucleus ambiguus, nodose ganglion, and jugular ganglion can all host neurons presenting proteins with epitopes in common with SARS-CoV-2 proteins, and the peptide TGRLQSL is embedded in one immunoreactive linear epitope that has already been experimentally validated in the human host (Immune Epitope Database and Analysis Resource identification number 36724) to be able to generate an autoimmune response. We share our findings to prompt further studies assessing whether severe forms of COVID-19 could produce transitory or permanent damage in some vagal structure and whether this can, in turn, be responsible for the low vagal tone and the related clinical signs and symptoms

Cooled tip radiofrequency ablation of benign thyroid nodules: preliminary experience with two different devices

Background: Thyroid nodules are very common in general population. Even if benign, they may require a treatment in case of symptoms or cosmetic concerns. In the last years, minimally invasive treatments alternative to surgery have been developed, in particular ultrasound (US) guided radiofrequency ablation (RFA). Methods: Twenty-four patients (9 males; 15 females; mean age 57.9 years) were treated and divided in two groups (A and B) according to the RFA needle used (18 gauge needle, AMICA; 17 gauge needle, COVIDIEN). Nodules and patients characteristics, together with procedural data were registered pretreatment and at 1-month follow-up. US visibility of the needle, volume of the nodules, symptoms and cosmetic concerns, complications were registered. Results: Visibility of the needle was not significantly different in the two groups (P=0.0787). At 1 month the mean volume of the nodules dropped from 37.1 to 25 mL in group A and from 23.2 to 15.4 mL in group B; shrinkage rate (36.9% and 39.5%, respectively) was not significantly different (P=0.3137). Symptoms decreased from 3.1 to 1.4 in group A and from 4 to 1.6 in group B: no significant differences in reductions were observed (P=0.3305). Cosmetic score decreased from 3.7 to 3.4 in group A and from 3.9 to 3.6 in group B: no significant differences in reductions were observed (P=0.96). Total complication rate (18.2% in group A vs. 23.1% in group B) did not showed significant differences (P=0.5049). Conclusions: The two systems used in our study resulted equivalent in terms of US needle visibility, efficacy, symptom/cosmetic relief, safety. More patients and a longer follow-up are necessary to confirm our results

Percutaneous Application of High Power Microwave Ablation With 150 W for the Treatment of Tumors in Lung, Liver, and Kidney: A Preliminary Experience

Objective: The aim of this study is to evaluate the feasibility, safety, and short-term effectiveness of a high-power (150 W) microwave ablation (MWA) device for tumor ablation in the lung, liver, and kidney. Methods: Between December 2021 and June 2022, patients underwent high-power MWA for liver, lung, and kidney tumors. A retrospective observational study was conducted in accordance with the Declaration of Helsinki. The MWA system utilized a 150-W, 2.45-GHz microwave generator (Emprint™ HP Ablation System, Medtronic). The study assessed technical success, safety, and effectiveness, considering pre- and post-treatment diameter and volume, lesion location, biopsy and/or cone beam computed tomography (CBCT) usage, MWA ablation time, MWA power, and dose-area product (DAP). Results: From December 2021 to June 2022, 16 patients were enrolled for high-power MWA. Treated lesions included hepatocellular carcinoma (10), liver metastasis from colon cancer (1), liver metastasis from pancreatic cancer (1), squamous cell lung carcinoma (2), renal cell carcinoma (1), and renal oncocytoma (1). Technical success rate was 100%. One grade 1 complication (6.25%) was reported according to CIRSE classification. Overall effectiveness was 92.8%. Pre- and post-treatment mean diameters for liver lesions were 19.9 mm and 37.5 mm, respectively; for kidney lesions, 34 mm and 35 mm; for lung lesions, 29.5 mm and 31.5 mm. Pre- and post-treatment mean volumes for liver lesions were 3.4 ml and 24 ml, respectively; for kidney lesions, 8.2 ml and 20.5 ml; for lung lesions, 10.2 ml and 32.7 ml. The mean ablation time was 48 minutes for liver, 42.5 minutes for lung, and 42.5 minutes for renal ablation. The mean DAP for all procedures was 40.83 Gcm2. Conclusion: This preliminary study demonstrates the feasibility, safety, and effectiveness of the new 150 W MWA device. Additionally, it shows reduced ablation times for large lesions

Cooled radiofrequency ablation technology for painful bone tumors

Bone metastases are a common cause of cancer-related debilitating pain, especially when -localized in the vertebral column and not responsive to standard treatment. In such cases, various treatment options are available; among these is Radiofrequency, whose role has been rapidly growing over the past few years. In this study, we used the innovative Osteocool RF Ablation System (Medtronic) on a patient with a painful bone metastasis localized in the 5th lumbar vertebra, with encouraging results. The radiofrequency ablation of bone metastases with palliative aim represents an excellent treatment option, as it is a minimally invasive and safe procedure, and can be repeated multiple times

Expression of telomeric repeat binding factor-1 in astroglial brain tumors

OBJECTIVE: In human somatic cells, telomeres shorten with successive cell divisions, resulting in progressive genomic instability, altered gene expression, and cell death. Recently, telomere-specific deoxyribonucleic acid-binding proteins, such as telomeric repeat binding factor-1 (TRF1), have been proposed as candidates for the role of molecules regulating telomerase activity, and they have been suggested to play key roles in the maintenance of telomere function. The present study was designed to assess TRF1 expression in human astroglial brain tumors and to speculate on the clinical implications of its expression. METHODS: Twenty flash-frozen surgical specimens obtained from adult patients who underwent craniotomy for microsurgical tumor resection, histologically verified as World Health Organization Grade II to IV astrocytomas, were used. Expression of TRF1 in astrocytomas of different grades was studied by means of both immunohistochemical and Western blotting analysis. The correlation between the extent of TRF1 expression and histological grading, performance status, and length of survival of patients underwent statistical analyses. RESULTS: TRF1 was expressed in all tumor samples. The level of its expression was variable, decreasing from low-grade through high-grade astrocytomas (P 0.0032). TRF1 expression correlated with the patient’s length of survival (P 0.001) and performance status (P 0.001) and proved to be an independent indicator of length of survival. CONCLUSION: Our findings suggest that the loss of TRF1 expression capability, as a result of down-regulation of TRF1 expression in malignant gliomas cells, may play a role in the malignant progression of astroglial brain tumors

Percutaneous High Frequency Microwave Ablation of Uterine Fibroids : Systematic Review

Uterine fibroids are the most common benign pelvic tumor of the female genital tract and tend to increase with age; they cause menorrhagia, dysmenorrhea, pelvic pressure symptoms, back pain, and subfertility. Currently, the management is based mainly on medical or surgical approaches. The nonsurgical and minimally invasive therapies are emerging approaches that to the state of the art include uterine artery embolization (UAE), image-guided thermal ablation techniques like magnetic resonance-guided focused ultrasound surgery (MRgFUS) or radiofrequency ablation (RF), and percutaneous microwave ablation (PMWA). The purpose of the present review is to describe feasibility results and safety of PMWA according to largest studies available in current literature. Moreover technical aspects of the procedure were analyzed providing important data on large scale about potential efficacy of PMWA in clinical setting. However larger studies with international registries and randomized, prospective trials are still needed to better demonstrate the expanding benefits of PMWA in the management of uterine fibroids.Uterine fibroids are the most common benign pelvic tumor of the female genital tract and tend to increase with age; they cause menorrhagia, dysmenorrhea, pelvic pressure symptoms, back pain, and subfertility. Currently, the management is based mainly on medical or surgical approaches. The nonsurgical and minimally invasive therapies are emerging approaches that to the state of the art include uterine artery embolization (UAE), image-guided thermal ablation techniques like magnetic resonance-guided focused ultrasound surgery (MRgFUS) or radiofrequency ablation (RF), and percutaneous microwave ablation (PMWA). The purpose of the present review is to describe feasibility results and safety of PMWA according to largest studies available in current literature. Moreover technical aspects of the procedure were analyzed providing important data on large scale about potential efficacy of PMWA in clinical setting. However larger studies with international registries and randomized, prospective trials are still needed to better demonstrate the expanding benefits of PMWA in the management of uterine fibroids

Peptide receptor radionuclide therapy for aggressive pituitary tumors: a monocentric experience

In aggressive pituitary tumors (PT) showing local invasion or growth/recurrence despite multimodal conventional treatment, temozolomide (TMZ) is considered a further therapeutic option, while little data are available on peptide receptor radionuclide therapy (PRRT). We analyzed PRRT effectiveness, safety and long-term outcome in three patients with aggressive PT, also reviewing the current literature. Patient #1 (F, giant prolactinoma) received five cycles (total dose 37 GBq) of 111In-DTPA-octreotide over 23 months, after unsuccessful surgery and long-term dopamine-agonist treatment. Patient #2 (M, giant prolactinoma) underwent two cycles (12.6 GBq) of 177Lu-DOTATOC after multiple surgeries, radiosurgery and TMZ. In patient #3 (F, non-functioning PT), five cycles (29.8 GBq) of 177Lu-DOTATOC followed five surgeries, radiotherapy and TMZ. Eleven more cases of PRRT-treated aggressive PT emerged from literature. Patient #1 showed tumor shrinkage and visual/neurological amelioration over 8-year follow-up, while the other PTs continued to grow causing blindness and neuro-cognitive disorders (patient #2) or monolateral amaurosis (patient #3). No adverse effects were reported. Including the patients from literature, 4/13 presented tumor shrinkage and clinical/biochemical improvement after PRRT. Response did not correlate with patients’ gender or age, neither with used radionuclide/peptide, but PRRT failure was significantly associated with previous TMZ treatment. Overall, adverse effects occurred only in two patients. PRRT was successful in 1/3 of patients with aggressive PT, and in 4/5 of those not previously treated with TMZ, representing a safe option after unsuccessful multimodal treatment. However, at present, considering the few data, PRRT should be considered only in an experimental setting

Predicting the Fibroid-Migratory Impact of UAE: Role of Pre-embolization MRI Characteristics.

AIM: To investigate potential factors on MR imaging that could be used to predict migration of uterine fibroids post-UAE. METHODS AND MATERIALS: We retrospectively reviewed patients referred for UAE having pre-procedural and 6 months post-procedural MRI, at a tertiary centre, over a 1-year period. Pre- and post-UAE images were reviewed in 64 women by two radiologists to identify the sub-type, dimensions, and infarction rate of each dominant fibroid. The shortest distance between the fibroid and the endometrial wall was measured to determine intramural fibroid movement. Paired sample T tests and two-sample T tests were used to compare between pre- and post-embolization variations and between migrated and non-migrated intramural fibroids, respectively. After preliminary results suggested potential predictors of intramural fibroids migration, we tested our findings against the non-dominant intramural fibroids in the same patients. RESULTS: Review of images revealed 35 dominant intramural fibroids, of which eight migrated to become submucosal fibroids, while five were either partially or completely expelled. These 13 migrated fibroids had a shorter pre-procedural minimum endometrial distance (range 1-2.4 mm) and greater maximum fibroid diameter (range 5.1-18.1 cm), when compared to non-migrating fibroids. On image reassessment, the migrated non-dominant intramural fibroids had a minimum endometrial distance and maximum fibroid diameter within the same range. CONCLUSION: Intramural fibroids with a minimum endometrial distance less than 2.4 mm and a maximum fibroid diameter greater than 5.1 cm have a high likelihood of migrating towards the endometrial cavity after UAE

The management of pediatric severe traumatic brain injury: Italian guidelines

Introduction: the aim of the work was to update the “guidelines for the Management of severe traumatic Brain Injury” published in 2012, to reflect the new available evidence, and develop the Italian national guideline for the management of severe pediatric head injuries to reduce variation in practice and ensure optimal care to patients. eViDeNce acQUisitioN: MeDliNe and eMBase were searched from January 2009 to october 2017. inclusion criteria were english language, pediatric populations (0-18 years) or mixed populations (pediatric/adult) with available age subgroup analyses. the guideline development process was started by the Promoting group that composed a multidisciplinary panel of experts, with the representatives of the Scientific Societies, the independent expert specialists and a representative of the Patient associations. the panel selected the clinical questions, discussed the evidence and formulated the text of the recommendations. the documentarists of the University of Florence oversaw the bibliographic research strategy. a group of literature reviewers evaluated the selected literature and compiled the table of evidence for each clinical question. EVIDENCE SYNTHESIS: The search strategies identified 4254 articles. We selected 3227 abstract (first screening) and, finally included 67 articles (second screening) to update the guideline. This Italian update includes 25 evidence-based recommendations and 5 research recommendations. coNclUsioNs: in recent years, progress has been made on the understanding of severe pediatric brain injury, as well as on that concerning all major traumatic pathology. this has led to a progressive improvement in the clinical outcome, although the quantity and quality of evidence remains particularly low