Glioneuronal tumor with ATRX alteration, kinase fusion and anaplastic features (GTAKA): a molecularly distinct brain tumor type with recurrent NTRK gene fusions.

Glioneuronal tumors are a heterogenous group of CNS neoplasms that can be challenging to accurately diagnose. Molecular methods are highly useful in classifying these tumors-distinguishing precise classes from their histological mimics and identifying previously unrecognized types of tumors. Using an unsupervised visualization approach of DNA methylation data, we identified a novel group of tumors (n = 20) that formed a cluster separate from all established CNS tumor types. Molecular analyses revealed ATRX alterations (in 16/16 cases by DNA sequencing and/or immunohistochemistry) as well as potentially targetable gene fusions involving receptor tyrosine-kinases (RTK; mostly NTRK1-3) in all of these tumors (16/16; 100%). In addition, copy number profiling showed homozygous deletions of CDKN2A/B in 55% of cases. Histological and immunohistochemical investigations revealed glioneuronal tumors with isomorphic, round and often condensed nuclei, perinuclear clearing, high mitotic activity and microvascular proliferation. Tumors were mainly located supratentorially (84%) and occurred in patients with a median age of 19 years. Survival data were limited (n = 18) but point towards a more aggressive biology as compared to other glioneuronal tumors (median progression-free survival 12.5 months). Given their molecular characteristics in addition to anaplastic features, we suggest the term glioneuronal tumor with ATRX alteration, kinase fusion and anaplastic features (GTAKA) to describe these tumors. In summary, our findings highlight a novel type of glioneuronal tumor driven by different RTK fusions accompanied by recurrent alterations in ATRX and homozygous deletions of CDKN2A/B. Targeted approaches such as NTRK inhibition might represent a therapeutic option for patients suffering from these tumors.

Accessory nerve schwannoma extending into the fourth ventricle: case report and review of literature.

Accessory nerve schwannoma is a rare entity in patients presenting with cranial nerve (CN) deficits. Most of these tumours arise from the cisternal segment of the eleventh CN and extend caudally. Herein, we report the third case of an accessory schwannoma extending cranially into the fourth ventricle. A 61-year-old female presented with a history of variable headaches. Cerebral magnetic resonance imaging (cMRI) revealed a large inhomogeneous contrast-enhancing lesion at the craniocervical junction extending through the foramen of Magendi and concomitant hydrocephalus due to obstruction of the foramina of Luschkae. Microsurgical tumour resection was performed in the half-sitting position. Intraoperatively, the tumour arose from a vestigial fascicle of the spinal accessory nerve. At three month follow-up, neither radiological tumour recurrence nor neurological deficits were observed.

Iran's Approach to COVID-19: Evolving Treatment Protocols and Ongoing Clinical Trials.

The coronavirus disease 2019 (COVID-19) pandemic is challenging the health care systems around the world and compelling them to timely share their strategies, tactics and experiences. Since mid-January, a huge volume of instructions has been released by Iran's Ministry of Health and Medical Education (MOHME) covering diverse aspects of disease control and prevention. In this study, we aimed to review the instructions published either before or after COVID-19's transmission to Iran to depict the clinical approach and therapeutics used in Iran to battle the current pandemic. We retrospectively gathered and critically reviewed all official situation reports, guidelines, guidance, flowcharts, protocols, recommendations and advice released by Iranian scientific, or administrative arms of action against COVID-19. The ongoing clinical trials approved by MOHME and registered to the Iranian Registry of Clinical Trials (IRCT) have been reviewed as well. Our study resulted in the following mainstays of Iran's approach to COVID-19: (i) active clinical screening; preferably on-line or on-phone, (ii) management of limited paraclinical resources; by using them as diagnostic tools rather than epidemiological, (iii) a trend toward outpatient care of mild-to-moderate cases; either confirmed or suspicious, with active scheduled follow-up, and (iv) avoidance of pharmacotherapy, as far as possible. The therapeutic and administrative instructions are still being actively updated with some recommendations different from the previous ones. Nevertheless, a common approach in the background could be detected, It seems that the instructions are conceptually in line with the first "National Guideline for 2019-nCoV" published on 20 January 2020. The screening has mainly been clinically oriented rather than being based on laboratory tests and MOHME seems to be following the approach of "early detection of symptomatic cases followed by early source control."

Therapeutic duplication of anticoagulants: a retrospective study of frequency and consequences in a tertiary referral hospital.

BACKGROUND: Anticoagulants are commonly prescribed in medical practices and could be of significant harm in the case of medication errors. We conducted a retrospective observational study to determine the frequency and consequences of the therapeutic duplication of anticoagulants (TDA). As a secondary objective, we aimed to determine the characteristics of the population in which TDA occurs. METHODS: We conducted a retrospective observational study among admitted patients who concomitantly received at least two anticoagulants from August 2017 to August 2018. RESULTS: A total of 107 patients with TDA are included in the research. The patients with TDA have a mean age of 73. The TDA population has a high rate of associated comorbidities with 69% of patients having arterial hypertonia, 40% with chronic kidney disease, 26% with a history of malignancy, and 20.5% with a history of stroke. More than 65% of patients were under anticoagulation before admission, mostly due to atrial fibrillation. The TDA occurred in more than 95% of cases in the first week or the last week of hospitalization. Patients had a high risk of bleeding prior to the TDA-event with about 62.5% of TDA patients having a HAS-BLED score at least 3. A total of 8 patients showed a significant Hemoglobin (Hb)-drop of at least 10 g/L within 24 h after TDA-event. Two patients had a new or worsened hematuria following TDA-event. CONCLUSION: TDA occurred in 0.8% of patients who were under anticoagulation and in 6.7% of patients who received direct oral anticoagulants (DOACs). TDA led in about 7.4% of cases to hemoglobin-relevant bleeding. The old patients with significant comorbidities and a high HAS-BLED score were mainly affected. The female gender and presence of anemia independently predicted the occurrence of bleeding following TDA.

Respiratory Distress in Postanesthesia Care Unit: First Presentation of Coronavirus Disease 2019 in a 17-Year-Old Girl: A Case Report.

A 17-year-old healthy girl underwent an uneventful esthetic septorhinoplasty. She was easily extubated and transferred to the postanesthesia care unit (PACU) with oxygen saturation (SpO2) of 96%. About 30 minutes after arrival in the PACU, she developed dyspnea with SpO2 of 84% and promptly received oxygen with bilevel positive airway pressure in conjunction with low-dose corticosteroid. The subsequent chest computed tomography (CT) revealed bilateral patchy infiltrates similar to the radiologic findings of Coronavirus Disease 2019 (COVID-19). Finally, a reverse transcriptase polymerase chain reaction (RT-PCR) of a pharyngeal specimen confirmed the diagnosis of COVID-19.

Redefinition of tumor capsule: Rho-dependent clustering of cancer-associated fibroblasts in favor of tensional homeostasis.

Fibroblasts are the most frequent cells of the connective tissues. Having the ability to sense and respond to mechanical stimuli in addition to the biochemical ones makes them crucial for such a composite-like and tension-preserving tissue. Over the last decade, the investigation of the role of these cells in tumor progression was a hot topic of research in tumor biology. Literatures almost unanimously describe the re-education of stromal fibroblasts by tumor cells in favor of tumor progression, which resulted in the birth of a new nomenclature, the cancer-associated fibroblasts. On the other hand, some studies reported anti-tumor roles for these cells. Herein, author suggests that the previously described pro-migratory and pro-contractile contexts, which respectively results in divergent and convergent distribution of fibroblasts by changing Rho-Rac1 balance, could be applied for cancer-associated fibroblasts as well. Based on this proposed concept, stromal fibroblasts could represent different roles, either pro-tumor or anti-tumor, during the course of tumor progression. In the earlier phases, they tend to assemble along tumor-stroma interface in the form of tumor capsules in order to resist tumor growth and to maintain tensional homeostasis in stroma. But in later phases, after being chronically subjected to tumor-induced chemical and mechanical stimuli, they will gradually lose their substantial abilities to oppose tumor expansion and, in contrary, will promote tumorigenesis. In summary, this paper redefines tumor capsule from chemical and mechanical standpoints as Rho-dependent clustering of cancer-associated fibroblasts in favor of tensional homeostasis. Furthermore, it proposes that stromal fibroblasts will undergo some irreversible epigenetic changes in Rac1- and Rho-related proteins through tumor-stroma crosstalk, which irreversibly diminish their ability of capsule formation. Finally, the author discusses the possible researches helping us to assess the proposed concept and its clinical implications.

Demyelination with preferential MAG loss: A complex message from MS paraffin blocks.

Multiple sclerosis (MS) is generally considered to be a demyelinating autoimmune disorder. However, neuropathological examinations of MS lesions do not support this concept. Demyelination with preferential loss of myelin-associated glycoprotein (MAG) is a common finding in MS tissues and has been reported by several groups. As MAG is located in ad-axonal myelin layers and is not accessible to infiltrating immune cells, demyelination with preferred loss of MAG may be suggestive of a primary oligodendrocytopathy in MS. Moreover, it has been shown that oligodendrocytopathy may precede the infiltration of inflammatory cells at the lesion site. In this paper, we review studies of neuropathology of MS tissues that reported this type of demyelination and then we discuss three emerging explanations that are trying to interpret this mismatched observation.

Pilocytic Astrocytoma of Fornix Mimicking a Colloid Cyst: Report of 2 Cases and Review of the Literature.

BACKGROUND: Colloid cyst is a gelatin-containing cyst in the brain almost always found in the third ventricle. The specific shape and location of these cysts, a round well-delineated mass in the rostral part of the third ventricle adjacent to the foramen of Monro, on imaging are the main findings for diagnosis. Several masses of the third ventricle masquerading colloid cysts on images have been reported. Based on different surgical approaches, preoperative misdiagnosis of colloid cyst may have great impact on prognosis. METHODS: We report 2 cases that presented with severe headache and hydrocephalus, and their preoperative images were highly indicative of colloid cyst. RESULTS: Histopathologic investigations after tumor resection showed pilocytic astrocytoma of fornix in both cases. CONCLUSIONS: Fifteen cases of colloid cyst misdiagnosis with other masses have been reported thus far; among them, 2 cases were pilocytic astrocytoma. In this study we report 2 other cases. Furthermore, we discuss additional clues helping to differentiate pilocytic astrocytoma from colloid cyst on images.

Congenital Absence of the Posterior Element of C1, C2, and C3 Along with Bilateral Absence of C4 Pedicles: Case Report and Review of the Literature.

BACKGROUND: Abnormalities of the posterior arch of vertebrae are rare conditions that may incidentally be found on neck radiographs. We report a case and present a comprehensive review of the literature. CASE DESCRIPTION: A 10-year-old boy presented with intermittent paresthesia in the lower extremities, mild neck pain, and episodes of drop attacks following neck flexion. Radiologic investigations depicted a complete absence of the posterior element of C1, C2, and C3 along with bilateral absence of C4 pedicles. CONCLUSIONS: The diagnosis of posterior arch abnormalities is of high-level of importance because of resultant neurologic defects. To the best of our knowledge, no case of this type has been reported in literature thus far.

Posterior reversible encephalopathy syndrome in a patient with mixed connective tissue disease: a case report.

BACKGROUND: Posterior reversible encephalopathy is a syndrome highly associated with hypertension and cytotoxic therapy. The syndrome typically presents with headache, visual abnormality, seizures and characteristic vasogenic edema on magnetic resonance imaging. The entity warrants a prompt diagnosis to avoid deteriorating consequences. CASE PRESENTATION: In this report, we describe a 15-year-old Iranian boy who was diagnosed with mixed connective tissue disease, and cyclophosphamide pulse therapy was administered. Three days after the second pulse of cyclophosphamide, when he was receiving prednisolone and hydroxycholoroquine, our patient developed generalized tonic-clonic seizures. Magnetic resonance imaging findings showed high signal intensities in the posterior areas of his brain. After 8 days, the brain magnetic resonance imaging abnormalities were resolved following the control of his blood pressure and antiepileptic treatment. These observations have been indicative of posterior reversible encephalopathy syndrome. Nevertheless, our patient developed uncontrollable respiratory distress and eventually died. CONCLUSIONS: To the best of our knowledge, this case is the first report of posterior reversible encephalopathy syndrome in a patient with mixed connective tissue disease. As the patient developed posterior reversible encephalopathy syndrome 3 days after cyclophosphamide pulse therapy to reduce the disease activity, it is hard to accurately determine whether posterior reversible encephalopathy syndrome in this case is a complication of cyclophosphamide or a condition that resulted from the mixed connective tissue disease flare-up.

Bilateral Choroid Plexus Metastasis from Papillary Thyroid Carcinoma: Case Report and Review of the Literature.

BACKGROUND: Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. It has an indolent clinical course and favorable prognosis. Brain metastasis is uncommon and complicates about 0.1%-5% of PTCs. Metastasis to the choroid plexus of the lateral ventricles has been reported in 7 cases of thyroid malignancies, all of which were unilateral. METHODS: We report a case of a 52-year-old woman with a history of PTC who presented with severe headache, nausea and vomiting, right hemiparesis, and speech disturbance. Imaging studies depicted lesions in both lateral ventricles. RESULTS: The patient underwent microsurgical tumor resection. Histopathologic examination revealed choroid plexus metastasis from PTC. CONCLUSIONS: Metastases to the choroid plexus from extracranial tumors are very rare, with only a few cases reported thus far. A demographic analysis of these cases suggests there may be a tropism of some extracranial carcinomas, such as renal cell carcinoma, for choroid plexus, especially in the lateral ventricles. We report the eighth case of choroid plexus metastasis, but it is the first bilateral one arising from thyroid cancer.

Naloxone induces frequent jumping after chronic morphine and methamphetamine co-administration in rats.

Combined use of an opioid with a psychostimulant is popular among drug abusers. Such "polydrug use" may increase drug effects or attenuate adverse effects of either drug alone. We proposed that a combination of methamphetamine (meth) and morphine may change physical opioid withdrawal symptoms. Adult male rats were chronically injected with cumulative subcutaneous (s.c.) doses of morphine, meth or a combination of both drugs within five days. On day six, a challenge dose of the same drug was injected. Two hours later, precipitated withdrawal symptoms were scored within 30 minutes after naloxone (1mg/kg, i.p.) injection. Both frequency and incidence of jumping significantly increased in combined treated animals (P<0.05). The sole emergent symptom in combined treated animals was digging which we consider as another escaping behavior in addition to jumping. Our findings imply that combined use of meth and morphine may exacerbate averseness of morphine withdrawal which may cause more intense opioid dependence.