Publications by authors named "Antonio Santoro"

274 Publications

IDH Wild-type Glioblastoma Presenting with Seizure: Clinical Specificity, and Oncologic and Surgical Outcomes.

J Neurol Surg A Cent Eur Neurosurg 2021 Nov 18. Epub 2021 Nov 18.

"Santa Maria Goretti" Hospital, Latina, Italy.

Background:  Glioblastoma (GBM) is the most common and aggressive primary brain neoplasia in adults. Seizure is a common manifestation in GBM. Up to 25 to 60% of patients with GBM have seizures. We aim to summarize all the relevant clinical, surgical, radiologic, and molecular features of a cohort of patients suffering from GBM-related epilepsy and measure the outcome, to understand the possible existence of a clinical/phenotypical specificity of this subgroup of patients.

Methods:  We retrospectively analyzed a cohort of 177 patients affected by isocitrate dehydrogenase wild-type (IDH-WT) GBM; 49 patients presented seizure at onset (SaO) and 128 were seizure free (SF). We investigated the relationship between seizures and other prognostic factors of GBMs.

Results:  A statistically significant association between the location of the lesions in the parietal lobe and seizures was observed. The left side was more commonly affected. Interestingly, there was a statistical relationship between tumors involving the subventricular zone (SVZ) and SaO patients. The tumors were also smaller on average at diagnosis, and generalized SaOs were associated with longer overall survival.

Conclusions:  The typical patient with IDH-WT GBM with SaO is a young (<55 year) male without a history of headache. The lesion is typically small to medium in size and located in the temporoparietal dominant lobe, with a high tendency to involve the SVZ.
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http://dx.doi.org/10.1055/s-0041-1735515DOI Listing
November 2021

Letter to the Editor: "The Neurosurgical Perspective for the 2021 WHO Classification of Tumors of the Central Nervous System: A Missed Opportunity?"

World Neurosurg 2021 Nov;155:203-204

A.U.O. "Policlinico Umberto I", Neurosurgery Division, Human Neurosciences Department, Sapienza University of Rome, Rome, Italy; Division of Neurosurgery, IRCCS "Neuromed", Pozzilli, Italy.

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http://dx.doi.org/10.1016/j.wneu.2021.07.149DOI Listing
November 2021

Lipomatous Meningioma: Clinical-Pathological Findings, Imaging Characterisation and Correlations of a Rare Type of Meningioma.

In Vivo 2021 Nov-Dec;35(6):3031-3037

Department of Human Neurosciences, Division of Neurosurgery, Policlinico Umberto I University Hospital, Sapienza, University of Rome, Rome, Italy.

Lipomatous meningioma (LM) is a form of metaplasia, originating from intracellular lipid bodies accumulation due to metabolic alterations. A comprehensive literature review was performed introducing further elements of evaluation. The parameters utilized were age, sex, location, clinical presentation, imaging features, treatment, and recurrences. Seizure and headache are the primary onsets of symptoms. Further LM clinical features, such as visual disturbances and visual epileptic seizures were examined. Symptoms may occur ten years prior to LM finding and it can resolve completely with the indicated surgery. LM computed tomography imaging analysis reveals hypodense regions due to the presence of fat content. On magnetic resonance imaging, the lesion displays hyperintense signal in T1-T2 with signal loss in the fat-suppression sequences. Immunohistochemically, lipidized meningioma cells are positive for Epithelial-Membrane Antigen, Vimentin, CD99, S-100 protein, and progesterone receptor. The recurrence risk rate of LM is estimated to be around 17%. Precise immune-histological findings have been correlated with imaging features to help with early diagnosis. A defined diagnosis of LM is a crucial factor in the choice of treatment.
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http://dx.doi.org/10.21873/invivo.12598DOI Listing
October 2021

Intermolecular Forces Driving Hexamethylenetetramine Co-Crystal Formation, a DFT and XRD Analysis.

Molecules 2021 Sep 22;26(19). Epub 2021 Sep 22.

Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale F. Stagno d'Alcontres 31, 98166 Messina, Italy.

Interest in co-crystals formation has been constantly growing since their discovery, almost a century ago. Such success is due to the ability to tune the physical-chemical properties of the components in solid state by avoiding a change in their molecular structure. The properties influenced by the co-crystals formation range from an improvement of mechanical features and chemical stability to different solubility. In the scientific research area, the pharmacological field is undoubtedly one of those in which an expansion of the co-crystal knowledge can offer wide benefits. In this work, we described the crystalline structure of hexamethylenetetramine co-crystallized with the isophthalic acid, and we compared it with another co-crystal, showing the same components but different stoichiometry. To give a wider overview on the nature of the interactions behind the observed crystal packing and to rationalize the reasons of its formation, a computational analysis on such structures was carried out.
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http://dx.doi.org/10.3390/molecules26195746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8510214PMC
September 2021

Diffuse Axonal Injury: Clinical Prognostic Factors, Molecular Experimental Models and the Impact of the Trauma Related Oxidative Stress. An Extensive Review Concerning Milestones and Advances.

Int J Mol Sci 2021 Oct 8;22(19). Epub 2021 Oct 8.

Neurosurgery Division, Santa Maria Goretti Hospital, Via Lucia Scaravelli, 04100 Latina, Italy.

Traumatic brain injury (TBI) is a condition burdened by an extremely high rate of morbidity and mortality and can result in an overall disability rate as high as 50% in affected individuals. Therefore, the importance of identifying clinical prognostic factors for diffuse axonal injury (DAI) in (TBI) is commonly recognized as critical. The aim of the present review paper is to evaluate the most recent contributions from the relevant literature in order to understand how each single prognostic factor determinates the severity of the clinical syndrome associated with DAI. The main clinical factors with an important impact on prognosis in case of DAI are glycemia, early GCS, the peripheral oxygen saturation, blood pressure, and time to recover consciousness. In addition, the severity of the lesion, classified on the ground of the cerebral anatomical structures involved after the trauma, has a strong correlation with survival after DAI. In conclusion, modern findings concerning the role of reactive oxygen species (ROS) and oxidative stress in DAI suggest that biomarkers such as GFAP, pNF-H, NF-L, microtubule associated protein tau, Aβ42, S-100β, NSE, AQP4, Drp-1, and NCX represent a possible critical target for future pharmaceutical treatments to prevent the damages caused by DAI.
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http://dx.doi.org/10.3390/ijms221910865DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8509530PMC
October 2021

Post-traumatic intracranial pseudo-aneurysms of posterior circulation: a comprehensive review of an under-diagnosed and rare entity.

Neurosurg Rev 2021 Oct 4. Epub 2021 Oct 4.

Human Neuroscience Department - Neurosurgery Division "Sapienza" University, Roma, Italy.

Traumatic aneurysms are rare and the total number of cases involving the posterior circulation (TIPC) is even smaller. Traumatic brain injury (TBI) may be responsible not only of rupture in brain aneurysm (BrA) pre-existing to trauma, but it has been identified also as a possible pathogenetic cause of TIPC formation in patients not affected by intracranial vascular lesions. A complete literature review was performed of all reported cases regarding rupture of BrA with SAH resulting from TIPC not previously identified at the first radiological screening. A representative case of a left posterior inferior cerebellar artery (PICA) pseudo-aneurysm caused by left vertebral artery's dissection is reported. We show a unique complete collection of all 34 cases. Despite their rarity, TIPCs are associated with a significant morbidity and mortality rate, as high as 40-60%. Of the 22 patients with good neurological status (64.7%), we did not notice a significant correlation with regard to the location of the aneurysm, type of treatment, or clinical onset. Early recognition of a pseudo-aneurysm and adequate treatment seem to be the most important prognostic factor for these patients. Despite their rarity, TIPCs are associated with a significant morbidity and mortality rate. A TIPC should be suspected in case of delayed deterioration in head-injured patient and should be investigated with angiography. Conservative management is worsened by poor prognosis and the goal of treatment is to exclude the aneurysm from circulation with surgical or endovascular methods as soon as possible.
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http://dx.doi.org/10.1007/s10143-021-01657-4DOI Listing
October 2021

Is There a Gender Difference in the Response to onabotulinumtoxinA in Chronic Migraine? Insights from a Real-Life European Multicenter Study on 2879 Patients.

Pain Ther 2021 Dec 26;10(2):1605-1618. Epub 2021 Sep 26.

Neuroscience Section, Department of Applied Clinical Sciences and Biotechnology, University of L'Aquila, Via Vetoio 1 Coppito, 67100, L'Aquila, Italy.

Introduction: Migraine is mostly a female disorder because of its lower prevalence in men. Less than 20% of patients included in the available studies on migraine treatments are men; hence, the evidence on migraine treatments might not apply to men. The aims of the present study were to provide reliable information on the effectiveness of onabotulinumtoxinA (BT-A) for chronic migraine in men and to compare clinical benefits between men and women.

Methods: We performed a pooled patient-level gender-specific analysis of real-life data on BT-A for chronic migraine of patients followed-up to 9 months. We reported the 50% responder rates during each BT-A cycle, defined as percentage of reduction in monthly headache days (MHDs) compared to baseline, along with 75% and 30% responder rates. We also reported the mean decrease in MHDs and in days of acute medication use (DAMs) during each BT-A cycle as compared to baseline. We also evaluated the reasons for stopping the treatment within the third cycle.

Results: We included an overall cohort of 2879 patients, 522 of whom (18.1%) were men. In men, 50% responder rates were 27.7% during the first BT-A cycle, 29.2% during the second, and 35.6% during the third cycle; in women, the corresponding rates were 26.6%, 33.5%, and 41.0%. In the overall cohort, responder rates did not differ between men and women during the first two cycles; during the third cycle, the distribution was different (P < 0.001) mostly because of higher rates of treatment stopping and non-responders in men. In the propensity score matched cohort, the trend was maintained but lost its statistical significance. Both men and women had a significant decrease in MHDs and in DAMs with BT-A treatment (P < 0.001). There were no gender differences in those changes with the only exception of MHD decrease which, during the third cycle, was lower in men than in women (7.4 vs 8.2 days, P = 0.016 in the overall cohort and 9.1 vs 12.5 days, P = 0.009 in the propensity score matched cohort). At the end of follow-up, 152 men and 485 women stopped BT-A treatment (29.1% vs 20.6%; P < 0.001). The relative proportion of patients stopping treatment because of inadequate response (less than 30% decrease in MHDs from baseline) was higher in men than in women (42.8% vs 39.6%), while the proportion of patients stopping because of adverse events was higher in women than in men (5.6% vs 0%; P = 0.031).

Conclusions: Our pooled analysis suggests that the response to BT-A is significant in both men and women with a small gender difference in favor of women. Men tended to stop the treatment more frequently than women. We emphasize the need for more gender-specific data on migraine treatments from randomized controlled trials and observational studies.
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http://dx.doi.org/10.1007/s40122-021-00328-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8586325PMC
December 2021

Improvement of the Collection, Maintenance, and Analysis of Neoplastic Cells from Urine Specimens with the Use of CytoMatrix.

Methods Protoc 2021 Sep 10;4(3). Epub 2021 Sep 10.

Department of Radiological, Oncological and Anatomo-Pathological Sciences, Sapienza University of Rome, 00161 Roma, Italy.

Urine cytology is a non-invasive test used in combination with cystoscopy for screening and follow-up of urothelial carcinoma (UC). Although cytology can be used to efficiently identify high-grade UC, it has a lower accuracy for the diagnosis of low-grade UC or patients with presence of atypical urothelial cells (AUC). For these reasons, ancillary tests have been added to urine cytology in order to improve the accuracy. However, the poor abundance of neoplastic cells in most samples and the absence of a "tissue-like" structure remains a major challenge. We used a novel synthetic support called CytoMatrix which has the property of capturing and storing cells and micro-macro aggregates within its three-dimensional structure. The urine specimens were obtained from 12 patients: 6 with suspected urothelial neoplasia (low- and high-grade) and 6 with AUC or non-neoplastic samples. The first step is the urine samples preparation, through several centrifugation passages; the second step consists in absorbing cells on the CytoMatrix, and in the subsequent formalin fixation, standard processing and paraffin embedding to prepare FFPE-CytoMatrix block. In the final step, sections are consecutively cut, stained with hematoxylin-eosin (H&E), and analyzed via UroVysion FISH and immunohistochemistry (IHC). Using our simple and reliable protocol, we can improve the quality of urine specimens, allowing a better collection, maintenance, and analysis of cells, with the advantage of using ancillary tests to support cytological diagnosis and the advantage of storing cellular material in a FFPE-CytoMatrix block.
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http://dx.doi.org/10.3390/mps4030065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8482097PMC
September 2021

Minimally Invasive Transforaminal Lumbar Interbody Fusion Using Expandable Cages: Increased Risk of Late Postoperative Subsidence Without a Real Improvement of Perioperative Outcomes: A Clinical Monocentric Study.

World Neurosurg 2021 Dec 4;156:e57-e63. Epub 2021 Sep 4.

Human Neurosciences Department, Sapienza University, Rome, Italy; IRCCS Neuromed, Pozzilli, Italy.

Background: Minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) is one of several approaches to lumbar interbody fusion that has proven to be a safe and effective treatment for symptomatic lumbar degenerative disease The clinical outcomes of MIS-TLIF are generally favorable, but there is still controversy regarding its ability to restore sagittal alignment. For this reason, expandable transforaminal lumbar interbody fusion cages have been developed and designed to improve ability to restore disc height and segmental lordosis. The use of expandable cages in transforaminal lumbar interbody fusion has increased drastically; however, it is not clear how effective cage expansion is in regard to disc space lordosis, distraction, and long-term outcome.

Methods: We reviewed a cohort of patients with symptomatic lumbar degenerative disc pathology who underwent MIS-TLIF at our institution. We compared clinical and radiographic outcomes of expandable versus nonexpandable cage use in MIS-TLIF focusing on mean changes in segmental lordosis, disc height, and postoperative complications. The results were compared with other studies reported in the international literature.

Results: Mean change in segmental lordosis was not significantly different between the 2 groups. A significantly higher rate of postoperative subsidence was demonstrated in the expandable cage group.

Conclusion: This study established that expandable cage use in single-level transforaminal lumbar interbody fusion did not reduce the rate of postoperative complications, but rather significantly increased a patient's risk of postoperative subsidence. Expandable cages do not presently demonstrate improved clinical outcomes or improved sagittal alignment compared with static cages.
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http://dx.doi.org/10.1016/j.wneu.2021.08.127DOI Listing
December 2021

Perioperative Glycemia Management in Patients Undergoing Craniotomy for Brain Tumor Resection: A Global Survey of Neuroanesthesiologists' Perceptions and Practices.

World Neurosurg 2021 Nov 1;155:e548-e563. Epub 2021 Sep 1.

Department of Anesthesiology, Critical Care and Pain Medicine, Sapienza University of Rome, Rome, Italy.

Objective: There is a paucity of clinical evidence that guides perioperative glycemia management in patients undergoing craniotomy for brain tumor resection. The purpose of this study was to better understand global perceptions and practices related to glycemia management in these patients.

Methods: Neuroanesthesiologists throughout North America, South America, Europe, and Asia filled out a brief online questionnaire related to their perceptions and practices regarding glycemia management in patients undergoing craniotomy for brain tumor resection.

Results: Over 4 weeks, 435 participants practicing in 34 countries across 6 continents participated in this survey. Although responders in North America were found to perceive a higher risk hyperglycemia compared with those practicing in European (P = 0.024) and South Asian (P = 0.007) countries, responders practicing in South Asian countries (P = 0.030), Middle Eastern countries (P = 0.029), and South American (P = 0.005) countries were more likely than those from North America to remeasure glucose after an initial normal glucose measurement at incision. Responders from North America reported that a higher blood glucose threshold was necessary for them to delay or cancel the surgery compared with responders in Slavic (P < 0.001), European (P = 0.002), South American (P = 0.002), and Asian and Pacific (P < 0.001) countries. Responders from North America were more likely to report that they would delay or cancel the surgery because of a higher blood glucose threshold.

Conclusions: Our survey results suggest that perceptions and practices related to blood glucose management in patients undergoing brain tumor resection are variable. This study highlights the need for stronger clinical evidence and guidelines to help guide decisions for when and how to manage blood glucose derangements in these patients.
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http://dx.doi.org/10.1016/j.wneu.2021.08.092DOI Listing
November 2021

Photoinduced Water Oxidation in Chitosan Nanostructures Containing Covalently Linked Ru Chromophores and Encapsulated Iridium Oxide Nanoparticles.

Chemistry 2021 Aug 21. Epub 2021 Aug 21.

Dipartimento di Scienze Chimiche, Biologiche, Farmaceutiche ed Ambientali, Università di Messina, 98166, Messina, Italy.

The luminophore Ru(bpy) (dcbpy) (bpy=2,2'-bipyridine; dcbpy=4,4'-dicarboxy-2,2'-bipyridine) is covalently linked to a chitosan polymer; crosslinking by tripolyphosphate produced Ru-decorated chitosan fibers (NS-RuCh), with a 20 : 1 ratio between chitosan repeating units and Ru chromophores. The properties of the Ru compound are unperturbed by the chitosan structure, with NS-RuCh exhibiting the typical metal-to-ligand charge-transfer (MLCT) absorption and emission bands of Ru complexes. When crosslinks are made in the presence of IrO nanoparticles, such species are encapsulated within the nanofibers, thus generating the IrO ⊂NS-RuCh system, in which both Ru photosensitizers and IrO water oxidation catalysts are within the nanofiber structures. NS-RuCh and IrO ⊂NS-RuCh have been characterized by dynamic light scattering, scanning electronic microscopy, and energy-dispersive X-ray analysis, which indicated a 2 : 1 ratio between Ru chromophores and IrO species. Photochemical water oxidation has been investigated by using IrO ⊂NS-RuCh as the chromophore/catalyst assembly and persulfate anions as the sacrificial species: photochemical water oxidation yields O with a quantum yield (Φ) of 0.21, definitely higher than the Φ obtained with a similar solution containing separated Ru(bpy) and IrO nanoparticles (0.05) or with respect to that obtained when using NS-RuCh and "free" IrO nanoparticles (0.10). A fast hole-scavenging process (rate constant, 7×10  s ) involving the oxidized photosensitizer and the IrO catalyst within the IrO ⊂NS-RuCh system is behind the improved photochemical quantum yield of IrO ⊂NS-RuCh.
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http://dx.doi.org/10.1002/chem.202102032DOI Listing
August 2021

Rapidly progressive dementia and Parkinsonism as the first symptoms of dural arteriovenous fistula. The Sapienza University experience and comprehensive literature review concerning the clinical course of 102 patients.

Clin Neurol Neurosurg 2021 Sep 22;208:106835. Epub 2021 Jul 22.

A.U.O. "Policlinico Umberto I", Neurosurgery Division, Sapienza University of Rome, Human Neurosciences Department, Via del Policlinico, 155, 00161 Roma, Italy.

Background: Dementia is a chronic loss of neurocognitive function that is progressive and irreversible. Dural arteriovenous fistulas (DAVFs) are acquired lesions that account for 10-15% of intracranial vascular malformations that could present with a rapid decline in neurocognitive function with or without Parkinson-like symptoms and evolve in a rapidly progressive dementia (RPD). Often the DAVFs are not even included in the differential hypotheses of this type of dementia and are not present in any type of diagnostic algorithm for evaluating RPD.

Methods: We performed a systematic review of the international literature and adding the cases coming from our institutional experience and we have collected all the reported cases of DAVFs that debut with ROD identifying the most frequent forms in terms of location and type, reporting the neurological characteristics and the outcome of each patient.

Results: The exact pathogenesis for developing dementia in patients with DAVFs remains largely unknown. The imaging changes and pathologic findings support the hypothesis that the clinical course results from the delivery of excessive volumes of blood flow into a venous system with outflow obstruction and venous congestion. The large variety of clinical manifestations of DAVFs depends on its location but this is not exactly valid for the onset of dementia. It supposed that the highly variable clinical manifestation of DAVFs has been convincingly related to the pattern of venous drainage more than location.

Conclusions: Neurologists and clinicians generally are familiar with the differential diagnoses of slowly progressive neurodegenerative dementias, but the diagnosis of RPD entails a different diagnostic approach. Due to their curable nature, the diagnosis of DAVFs must be suspected when facing a RPD picture, even more so if it is associated with characteristic abnormalities of the hemispheric white matter.
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http://dx.doi.org/10.1016/j.clineuro.2021.106835DOI Listing
September 2021

Microsurgical clipping of Unruptured Intracranial Aneurysms (UIA) by a single surgeon's experience: why we should definitely preserve the neurosurgical skills in our health areas.

J Neurosurg Sci 2021 Aug 3. Epub 2021 Aug 3.

Azienda Ospedaliera Fabrizio Spaziani, Frosinone, Italy -

Background: The long standing comparison between the endovascular and microsurgical treatment is still ongoing. While not any center avails of a neuroendovascular service, and not every aneurysm is suitable for endovascular treatment, the neurovascular technique is slowly disappearing from our territories, whereas in the current Literature, the role of the neurosurgical treatment is being re-appreciated. The objective of this paper is to discuss a single surgeon's clinical and radiological results with the microsurgical management of UIA.

Methods: We retrospectively reviewed the clinical and radiological records of patients treated for UIA, by a single surgeon,in the period ranging between 2015 and 2019. We recorded all the relevant anatomic features of the aneurysm, saliencies of the surgical treatment, such as the need for temporary clipping, intraoperative rupture or postoperative complications. The results of the clinical and radiological follow-up examinations were recorded either.

Results: Fifty-eight patient undergoing microsurgical clipping were included, harboring a total of 65 UIAs. CTA with 3D reconstructions was sufficient to reach a reliable preoperative planning in 46 patients (76%). A total of 94% of the cases were unchanged or neurologically unremarkable at follow-up. The presence of postoperative complications was associated to the neck size and predictor of a longer hospitalizations, as well as longer hospitalizations are associated to the patients' age, size of the aneurysms and surgical times.

Conclusions: According to our experience, we believe that microsurgical clipping plays a critical role in the management of UIA, also on the ground of the encouraging results of the relevant Literature.
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http://dx.doi.org/10.23736/S0390-5616.21.05366-2DOI Listing
August 2021

Histone-deacetylase 8 drives the immune response and the growth of glioma.

Glia 2021 Nov 26;69(11):2682-2698. Epub 2021 Jul 26.

Department of Physiology and Pharmacology, Sapienza University, Rome, Italy.

Many epigenetic modifications occur in glioma, in particular the histone-deacetylase class proteins play a pivotal role in glioma development, driving the proliferation rate and the invasiveness of tumor cells, and modulating the tumor microenvironment. In this study, we evaluated the role of the histone deacetylase HDAC8 in the regulation of the immune response in glioma and tumor growth. We found that inhibition of HDAC8 by the specific inhibitor PCI-34051 reduces tumor volume in glioma mouse models. We reported that HDAC8 modulates the viability and the migration of human and murine glioma cells. Interestingly, HDAC8 inhibition increases the acetylation of alpha-tubulin, suggesting this epigenetic modification controls glioma migration. Furthermore, we identify HDAC8 as a key molecule that supports a poorly immunogenic tumor microenvironment, modulating microglial phenotype and regulating the gene transcription of NKG2D ligands that trigger the Natural Killer cell-mediated cytotoxicity of tumor cells. Altogether, these results identify HDAC8 as a key actor in glioma growth and tumor microenvironment, and pave the way to a better knowledge of the molecular mechanisms of immune escape in glioma.
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http://dx.doi.org/10.1002/glia.24065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8457175PMC
November 2021

COVID-19 incidence and mortality in non-dialysis chronic kidney disease patients.

PLoS One 2021 9;16(7):e0254525. Epub 2021 Jul 9.

Local Healthcare Authority of Romagna (AUSL Romagna), Ravenna, Italy.

Many studies reported a higher risk of COVID-19 disease among patients on dialysis or with kidney transplantation, and the poor outcome of COVID-19 in these patients. Patients in conservative management for chronic kidney disease (CKD) have received attention only recently, therefore less is known about how COVID-19 affects this population. The aim of this study was to provide evidence on COVID-19 incidence and mortality in CKD patients followed up in an integrated healthcare program and in the population living in the same catchment area. The study population included CKD patients recruited in the Emilia-Romagna Prevention of Progressive Renal Insufficiency (PIRP) project, followed up in the 4 nephrology units (Ravenna, Forlì, Cesena and Rimini) of the Romagna Local Health Authority (Italy) and alive at 1.01.2020. We estimated the incidence of COVID-19, its related mortality and the excess mortality within this PIRP cohort as of 31.07.2020. COVID-19 incidence in CKD patients was 4.09% (193/4,716 patients), while in the general population it was 0.46% (5,195/1,125,574). The crude mortality rate among CKD patients with COVID-19 was 44.6% (86/193), compared to 4.7% (215/4,523) in CKD patients without COVID-19. The excess mortality of March-April 2020 was +69.8% than the average mortality of March-April 2015-19 in the PIRP cohort. In a cohort mostly including regularly followed up CKD patients, the incidence of COVID-19 among CKD patients was strongly related to the spread of the infection in the community, while its lethality is associated with the underlying kidney condition and comorbidities. COVID-19 related mortality was about ten times higher than that of CKD patients without COVID. For this reason, it is urgent to offer a direct protection to CKD patients by prioritizing their vaccination.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0254525PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270438PMC
July 2021

Calcifediol supplementation in adults on hemodialysis: a randomized controlled trial.

J Nephrol 2021 Jun 26. Epub 2021 Jun 26.

Faculty of Medicine and Health, Sydney School of Public Health, University of Sydney, Sydney, Australia.

Background: Vitamin D deficiency is associated with increased risks of mortality in people with chronic kidney disease. The benefits and harm of vitamin D supplementation on cardiovascular outcomes and mortality are unknown. We aimed to assess the effectiveness of calcifediol in reducing mortality in patients with vitamin D insufficiency on hemodialysis compared to no additional therapy.

Methods: A phase III, multicenter, randomized, open-label trial was conducted including 284 adults with vitamin D insufficiency undergoing hemodialysis who were randomly assigned to receive oral calcifediol or standard care for 24 months.

Results: Two hundred eighty-four participants were enrolled (143 assigned to the calcifediol group and 141 to the no additional therapy group). The primary outcome (mortality) occurred in 34 and 31 participants in the calcifediol and control group, respectively [hazard ratio (HR) 1.03; 95% confidence interval (CI) 0.63-1.67]. Calcifediol had no detectable effects on cardiovascular death (HR 1.06; 95% CI 0.41-2.74), non-cardiovascular death (HR 1.13; 95% CI 0.62-2.04), nonfatal myocardial infarction (HR 0.20; 95% CI 0.02-1.67) or nonfatal stroke (HR could not be estimated). The incidence of hypercalcemia and hyperphosphatemia was similar between groups. None of the participants underwent parathyroidectomy.

Conclusions: In adults treated with hemodialysis and who had vitamin D insufficiency, calcifediol supplementation for 24 months had inconclusive effects on mortality and cardiovascular outcomes.

Trial Registration Number: NCT01457001.
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http://dx.doi.org/10.1007/s40620-021-01104-zDOI Listing
June 2021

Association between hyperkalemia, RAASi non-adherence and outcomes in chronic kidney disease.

J Nephrol 2021 Jun 11. Epub 2021 Jun 11.

CliCon S.r.l. Health, Economics and Outcomes Research, Bologna, Italy.

Background: Hyperkalemia is relatively frequent in CKD patients treated with renin-angiotensin-aldosterone-system inhibitors (RAASi).

Aim: The aim of the present study was to estimate the increased risk of cardiovascular events and mortality due to sub-optimal adherence to RAASi in CKD patients with hyperkalemia.

Methods: An observational retrospective cohort study was conducted, based on administrative and laboratory databases of five Local Health Units. Adult patients discharged from the hospital with a diagnosis of CKD, who were prescribed RAASi between January 2010 and December 2017, were included. We evaluated the appearance of documented episodes of hyperkalemia, RAASi therapy adherence and the effects of these two variables on cardiovascular events, death and dialysis inception for study patients.

Results: Of the 9241 selected patients, 4451 met all the criteria for study inclusion. Among them, 1071 had at least one documented episode of hyperkalemia, while 3380 did not. After propensity score matching based on several variables we obtained 2 groups of patients. The appearance of hyperkalemia caused treatment discontinuation in 21.8% of patients previously on RAASi therapy, and sub-optimal adherence (proportion of days covered  < 80%) in 33.6% of them. Non-adherence to RAASi therapy among hyperkalemia patients was associated with a higher risk of cardiovascular events (hazard ratio [HR] 1.45, confidence interval [CI] 1.02-2.08; p < 0.05). Moreover, in non-adherent hyperkalemia patients, the risk of death increased by 126% (HR 2.26, CI 1.62-3.15; p < 0.001) compared with adherent patients.

Conclusions: In a large cohort of CKD patients treated with RAASi, we observed that following hyperkalemia onset, non-adherence to RAASi medication can result in an increased risk of cardiovascular events and death.
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http://dx.doi.org/10.1007/s40620-021-01070-6DOI Listing
June 2021

Treatment of ischemic stroke is an opportunity for the revival of neurovascular surgery.

J Neurosurg Sci 2021 Jun 10. Epub 2021 Jun 10.

Department of Neurosurgery, Policlinico Umberto I - Sapienza Università di Roma, Roma, Italy.

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http://dx.doi.org/10.23736/S0390-5616.21.05459-XDOI Listing
June 2021

Dorsal epidural "Spindle Cell Lipoma" in a pregnant female.

Surg Neurol Int 2021 14;12:162. Epub 2021 Apr 14.

Department of Neurosurgery, Sapienza University, Rome, Italy.

Background: Spindle cell lipoma (SCL) constitutes just 1.5% of all lipomatous tumors. They typically occur in the upper back and shoulders. Here, we report a 37-year-old female presenting with a SCL in the dorsal epidural thoracic spine, during her 9 month of pregnancy.

Case Description: A 37-year-old female presented with a subacute (2 months) progressive paraparesis during her month of pregnancy. The MR showed a dorsal epidural mass at the D8 level. Following a cesarean section, the patient underwent a laminectomy for tumor excision. Microscopically, the lesion proved to be a SCL. At 5-year follow-up, there was no tumor recurrence.

Conclusion: SCL represents a variant of benign lipomas that may occur in the dorsal thoracic spine. Gross total excision may be followed by a benign clinical course without recurrence or malignant degeneration. Very atypical SCLs need closer follow-up to avoid the misdiagnosis of liposarcoma.
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http://dx.doi.org/10.25259/SNI_128_2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088489PMC
April 2021

Early Management of OnabotulinumtoxinA Treatment in Chronic Migraine: Insights from a Real-Life European Multicenter Study.

Pain Ther 2021 Jun 28;10(1):637-650. Epub 2021 Mar 28.

Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, Sant'Andrea Hospital, Sapienza University, 00189, Rome, RM, Italy.

Introduction: OnabotulinumtoxinA (BT-A) quarterly was the first treatment approved specifically for chronic migraine (CM). It is unclear whether three cycles are better than two to assess early BT-A response.

Methods: We performed a retrospective analysis on real-life prospectively collected data in 16 European headache centers. All the centers provided data on patients treated with BT-A for CM over the first three cycles of treatment. For each treatment cycle we defined patients as "good responders" if reporting a ≥ 50% reduction in monthly headache days compared with the three months before starting BT-A, "partial responders" if reporting a 30-49% reduction in monthly headache days, and "non-responders" if reporting a < 30% reduction in monthly headache days or stopping the treatment before the third cycle.

Results: We included 2879 patients. Seven hundred and eighty-four (64.6%) of the 1213 patients reporting a good response during the first and/or the second cycle had a good response during the third cycle; 309 (49.3%) of the 627 patients reporting a partial response (but no good response) during the first and/or the second cycle had a good response during the third cycle; only 65 (6.3%) of the 1039 patients who did not respond during both the first two cycles achieved a good response during the third cycle. Multivariate analyses showed that partial or good response during the first or the second cycle were independently associated with good response during the third cycle.

Conclusions: Our data suggest that patients with CM responding to BT-A during the first two cycles will likely benefit from the third cycle of treatment, while the probability that non-responders to the first two cycles start responding during the third cycle is low. These results can help guide the individual decision to stop or continue treatment after the second cycle in patients who have not responded to the first two cycles.
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http://dx.doi.org/10.1007/s40122-021-00253-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8119503PMC
June 2021

A new device for bone cranial flap fixation: Technical note and surgical remarks. A multicentric experience.

Surg Neurol Int 2021 23;12:74. Epub 2021 Feb 23.

Department of Neurosurgery, Sapienza University of Rome, Roma.

Background: Fixation of bone flaps after craniotomy is a routine part of every neurosurgical procedure. The ideal fixation device should be safe, reliable, biologically inert, easy to use, and inexpensive and should not produce artifacts on neuroimaging. The authors describe a new device that meets these criteria.

Methods: This is an observational, multicentric, and case series study of 56 patients who underwent a craniotomy and were subject to cranial bone flap fixation with the NT cranial small fixation system. A case-control group in whom titanium miniplates and screws were implanted was collected. All patients underwent CT scans of the head with 3D reconstruction at day 1 and day 90 postoperatively to evaluate bone flap position and fusion.

Results: A total of 140 NT cranial small were implanted in 56 patients (mean age 44.2, range 22-63 years). The new device has shown stronger fixation qualities with optimal bone flap fusion and good cosmetic features. No surgical or relevant postsurgical follow-up complications have been associated with the device.

Conclusion: Although this is a preliminary report in a relatively small number of patients, NT cranial small provides a safe, reliable, and easily applied postoperative cranial bone flap fixation system.
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http://dx.doi.org/10.25259/SNI_819_2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982122PMC
February 2021

Presentation and outcome of chronic kidney disease in Italian and immigrant citizens: results from the Emilia-Romagna PIRP project.

J Nephrol 2021 Feb 17. Epub 2021 Feb 17.

Specialty School of Nephrology, University of Bologna, Via Albertoni 15, 40138, Bologna, Italy.

Introduction: In recent decades, high income countries (HIC) have been exposed to huge human migratory flows. Consistent with this influx, there has been a dramatic increase in the number of chronic kidney disease (CKD) patients in the immigrant population. In Italy, comparisons between Italian and immigrant CKD patients are still lacking, thus we aimed to describe the baseline clinical characteristics and the main outcomes of CKD patients who immigrated to Italy and reside in the Emilia Romagna region.

Methods: This is a retrospective cohort study based on CKD patients from the Prevenzione Insufficienza Renale Progressiva (PIRP) project, which included 963 (3.1%) immigrants among the 30,702 patients seen by nephrologists between April 1st, 2004 and June 30th, 2020. We sub-divided the immigrants into seven groups based on their area of origin, and compared their baseline characteristics, CKD progression and time to end-stage kidney disease (ESKD) to those of Italian CKD patients.

Results: At presentation, Italian subjects were on average older (73.1 years) and had less preserved kidney function (eGFR 34.3 ml/min), while South and East Asians had the highest proportion of diabetes and obesity (approximately 45% and 30%, respectively). At 4-year follow-up, about 20% of patients from South Asia, Eastern Europe and Arab Countries were diagnosed with ESKD, compared to only 11% of Italians and Latin Americans.

Conclusions: We found important differences between Italian and immigrant CKD patients, as well as among immigrant subgroups. First clinical encounters with nephrologists revealed that immigrants had varied patterns of clinical presentation and of nephropathy. During follow-up, immigrants showed faster kidney function decline which led to a higher risk of disease evolution and progression towards ESKD.
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http://dx.doi.org/10.1007/s40620-021-00984-5DOI Listing
February 2021

Updates on hemodialysis techniques with a common denominator: The personalization of the dialytic therapy.

Semin Dial 2021 05 16;34(3):183-195. Epub 2021 Feb 16.

Department of Organ Failures and Transplantations, Policlinico S.Orsola-Malpighi- Bologna, Italy.

Hemodialysis (HD) is a life-saving therapy for patients with end-stage renal disease. In dialyzed patients, the prevalence of multi-morbidity is rising driven by various factors, such as the population aging, the incomplete correction of uremia, and the side effects of the dialysis therapy itself. Each dialyzed patient has their own specific clinical and biochemical problems. It is therefore unthinkable that the same dialysis procedure can be able to meet the needs of every patient on chronic dialysis. We have very sophisticated dialysis machines and different dialysis techniques and procedures beyond conventional HD, such as hemodiafiltration (HDF) with pre- and post-dilution, acetate-free biofiltration (AFB), hemofiltration (HF), and expanded HD. Each of these techniques has its own specific characteristics. To solve some intradialytic clinical issues, such as arterial hypotension and arrhythmias, we have biofeedback systems with automatic regulation of the blood volume, body temperature, arterial pressure, as well as potassium profiling techniques in the dialysis bath. New technical innovations, such as citrate-containing dialysate or heparin-coated membranes, could reduce the risk of bleeding. To better address to patient needs, the strengths and weaknesses of each of these systems must be well-known, in order to have a personalized dialysis prescription for each patient.
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http://dx.doi.org/10.1111/sdi.12956DOI Listing
May 2021

Moon landing in the operating room: neurosurgery in the covid-19 era.

Br J Neurosurg 2021 Feb 10. Epub 2021 Feb 10.

Department of Neurosurgery Policlinico Umberto I, University of Rome, Roma, Italia.

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http://dx.doi.org/10.1080/02688697.2021.1879014DOI Listing
February 2021

Outcome Features Analysis in Intramedullary Tumors of the Cervicomedullary Junction: A Surgical Series.

J Neurol Surg A Cent Eur Neurosurg 2021 May 4;82(3):225-231. Epub 2021 Feb 4.

Department of Neurology and Psychiatry, Endovascular Neurosurgery/Interventional Neuroradiology, "Sapienza" University of Rome, Rome, Italy.

Object:  The aim of this study is to investigate the impact of surgery for different cervicomedullary lesions on symptomatic pattern expression and postoperative outcome. We focused on specific outcome features of the early and late postoperative assessments. The former relies on surgery-related transient and permanent morbidity and feasibility of radicality in eloquent areas, whereas the latter on long-term course in lower grade tumors and benign tumorlike lesions (cavernomas, etc.).

Material And Methods:  We retrospectively analyzed 28 cases of intramedullary tumors of the cervicomedullary junction surgically treated at our institution between 1990 and 2018. All cases were stratified for gender, histology, macroscopic appearance, location, surgical approach, and presence of a plane of dissection (POD). Mean follow-up was 5.6 years and it was performed via periodic magnetic resonance imaging (MRI) and functional assessments (Karnofsky Performance Scale [KPS] and modified McCormick [MC] grading system).

Results:  In all, 78.5% were low-grade tumors (or benign lesions) and 21.5% were high-grade tumors. Sixty-one percent underwent median suboccipital approach, 18% a posterolateral approach, and 21% a posterior cervical approach. Gross total resection was achieved in 54% of cases, near-total resection (>90%) in 14%, and subtotal resection (50-90%) in 32% of cases. Early postoperative morbidity was 25%, but late functional evaluation in 79% of the patients showed KPS > 70 and MC grade I; only 21% of cases showed KPS < 70 and MC grades II and III at late follow-up. Mean overall survival was 7 years in low-grade tumors or cavernomas and 11.7 months in high-grade tumors. Progression-free survival at the end of follow-up was 71% (evaluated mainly on low-grade tumors).

Conclusions:  The surgical goal should be to achieve maximal cytoreduction and minimal postoperative neurologic damage. Functional outcome is influenced by the presence of a POD, radicality, histology, preoperative status, and employment of advanced neuroimaging planning and intraoperative monitoring.
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http://dx.doi.org/10.1055/s-0040-1719080DOI Listing
May 2021

Do Secondary Electrostatic Interactions Influence Multiple Dihydrogen Bonds? AA-DD Array on an Amine-Borane Aza-Coronand: Theoretical Studies and Synthesis.

Chemphyschem 2021 03 10;22(6):593-605. Epub 2021 Feb 10.

Department of chemical, biological, pharmaceutical and environmental sciences, University of Messina, Viale F. Stagno d'Alcontres 31, 98166, Messina, Italy.

Hydrogen bond plays a key role in a wide range of inorganic, organic, as well as biological systems. The understanding on how the chemical environment can affect this kind of interaction is crucial to predict its binding strength and consequently the robustness and the dynamic properties of many supramolecular systems. In this paper a new donor-acceptor complex was synthesized and characterized by SCXRD, showing for the first time in an organic system an AA-DD pattern of a particular hydrogen interaction, called dihydrogen bond. Over 250 functionals were computationally evaluated to select the best method to reproduce the binding interaction geometry of this new pattern. Moreover, a new vector force model was used to split the contribution of primary and secondary electrostatic interactions (SEIs), in order to evaluate how the latter one can modify the binding strength of this unusual hydrogen-hydrogen interaction.
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http://dx.doi.org/10.1002/cphc.202000906DOI Listing
March 2021

Entrapment of the temporal horn: case series and systematic review of literature.

J Neurosurg Sci 2021 Oct 9;65(5):532-540. Epub 2020 Dec 9.

Section of Neurosurgery, Department of Neurological Sciences, Sapienza University, Rome, Italy.

Introduction: Entrapment of the temporal horn (ETH) is a form of focal, obstructive hydrocephalus. Etiology and clinical presentation are diversified. Though known since 1947, standard treatment has not yet been defined. The objective of our study was to perform a systematic review on ETH.

Evidence Acquisition: Data from patients treated at our Institution from 2008 to 2019 were retrospectively collected and analyzed. A systematic PRISMA review of literature was also performed using PubMed and Google Scholar. The following search terms were used: "temporal horn entrapment" [All Fields] OR "trapped temporal horn" [All Fields].

Evidence Synthesis: One hundred and twenty-one cases (mean age 41 years; M/F ratio: 1/1) were analyzed. In 65 (vs. 56) cases (53.7% vs. 46.3%), ETH was not surgery related. Headache was the most common symptom (42%). "Major" treatments were ventriculoperitoneal/ventriculoatrial shunt (42 cases, 34.7%), and endoscopic ventriculocisternostomy (12 cases, 9.9%). In the first group, no perioperative complications were found, 39 patients (92.9%) had a favorable outcome, three patients (7.1%) died for the underlying disease, four cases (9.5%) went through revision; also considering the cases in which another procedure was performed as definitive treatment, there were six shunt failures (13.6%). In the second group, one case (8.3%) developed a deep intracerebral hemorrhage, 11 cases (91.6%) had a favorable long-term outcome, one case (8.3%) had a favorable short-term outcome; also considering the cases in which another procedure was performed as definitive treatment, there were six endoscopic ventriculocisternostomy failures (37.5%).

Conclusions: Described as uncommon, ETH is probably underestimated. Early diagnosis and appropriate treatment are critical. VP shunt is still the most commonly performed treatment. Further randomized clinical trials are, however, needed to establish the gold standard.
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http://dx.doi.org/10.23736/S0390-5616.20.05111-5DOI Listing
October 2021

Trigeminal Neuralgia Secondary to Intracranial Neoplastic Lesions: a Case Series and Comprehensive Review.

J Neurol Surg A Cent Eur Neurosurg 2021 Mar 8;82(2):118-124. Epub 2020 Dec 8.

Department of Neurology and Psychiatry, Neurosurgery, Sapienza University of Rome, Rome, Italy.

It is known that intracranial tumors may trigger trigeminal neuralgia (TN) in some patients although the exact prevalence and occurrence is not completely defined yet. In the present study, we present a case series of patients with brain tumor and a clinical diagnosis of TN as the first and main manifestation of the disease. A retrospective analysis was performed involving patients diagnosed with brain tumor whose exclusive clinical feature our department focused on was TN. In addition, a review of all published cases was performed. From January 2017 to November 2018, 718 patients with brain tumor were admitted to our department, 17 of which suffered of TN, of which 8 patients presented with at least another neurologic symptom and 9 patients presented with TN alone, with typical symptoms of stubbing electric pain in 6 cases. In our series, we found that 2.3% of patients admitted for brain tumors had TN. In 0.8% of cases, TN was the main clinical symptom. The prevalence of tumor lesion in patients with facial neuropathic pain is not defined, but it is a well-known recognized initial symptom; however, early cerebral magnetic resonance imaging (MRI) is not yet strongly recommended in patients with newly diagnosed trigeminal neuralgia. The purpose of this article is, especially in unusual cases, to show that the application of such MR techniques and preoperative evaluation may contribute to diagnosis, indication, and surgery planning.
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http://dx.doi.org/10.1055/s-0040-1718708DOI Listing
March 2021

First-in-man craniectomy and asportation of solitary cerebellar metastasis in COVID-19 patient: A case report.

Int J Surg Case Rep 2020 21;77:753-758. Epub 2020 Nov 21.

Department of Human Neurosciences, Division of Neurosurgery, Policlinico Umberto I University Hospital, Sapienza University of Rome, Rome, Italy.

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak has an impact on the delivery of neurosurgical care, and it is changing the perioperative practice worldwide. We present the first case in the literature of craniectomy procedure and asportation of a solitary cerebellar metastasis of the oesophagus squamous carcinoma in a 77 years old woman COVID-19 positive. In these particular circumstances, we show that adequate healthcare resources and risk assessments are essential in the management of COVID-19 patients referred to emergency surgery.

Presentation Of Case: The case here presented was treated in 2019 for squamous carcinoma of the oesophagus. In April 2020, she presented a deterioration of her clinical picture consisting of dysphagia, abdominal pain, hyposthenia and ataxia. A Head CT scan was performed, which showed the presence of a solitary cerebellar metastasis. Her associated SARS-CoV-2 positivity status represented the principal clinical concern throughout her hospitalisation.

Discussion: The patient underwent a suboccipital craniectomy procedure with metastasis asportation. She tested positive for SARS-CoV-2 in the pre- and post-operative phases, but she was not admitted to the intensive care unit because she did not present any respiratory complications. Her vital parameters and inflammation indexes fell within the reference ranges, and she was kept in isolation for 16 days in our neurosurgical unit following strict COVID-19 measures. She was asymptomatic and not treated for any of the specific and non-specific symptoms of COVID-19.

Conclusion: This is the first case reported of solitary cerebellar metastasis of oesophagus carcinoma operated on a COVID-19 positive patient. It shows that asymptomatic COVID-19 positive patients can undergo major emergency surgeries without the risk of infecting the operating team if adequate Personal Protection Equipment (PPE) is used. The patient remained asymptomatic and did not develop the disease's active phase despite undergoing a stressful event such as a major emergency neurosurgical procedure. In the current crisis, a prophylactic COVID-19 screening test can identify asymptomatic patients undergoing major emergency surgery and adequate resource planning and Personal Protective Equipment (PPE) for healthcare workers can minimise the effect of the COVID-19 pandemic.
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http://dx.doi.org/10.1016/j.ijscr.2020.11.102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7679517PMC
November 2020
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