Myxoid glioneuronal tumor,PDGFRA p.K385‐mutant: clinical,radiologic, and histopathologic features

“Myxoid glioneuronal tumor, PDGFRA p.K385‐mutant” is a recently described tumor entity of the central nervous system with a predilection for origin in the septum pellucidum and a defining dinucleotide mutation at codon 385 of the PDGFRA oncogene replacing lysine with either leucine or isoleucine (p.K385L/I). Clinical outcomes and optimal treatment for this new tumor entity have yet to be defined. Here, we report a comprehensive clinical, radiologic, and histopathologic assessment of eight cases. In addition to its stereotypic location in the septum pellucidum, we identify that this tumor can also occur in the corpus callosum and periventricular white matter of the lateral ventricle. Tumors centered in the septum pellucidum uniformly were associated with obstructive hydrocephalus, whereas tumors centered in the corpus callosum and periventricular white matter did not demonstrate hydrocephalus. While multiple patients were found to have ventricular dissemination or local recurrence/progression, all patients in this series remain alive at last clinical follow‐up despite only biopsy or subtotal resection without adjuvant therapy in most cases. Our study further supports “myxoid glioneuronal tumor, PDGFRA p.K385‐mutant” as a distinct CNS tumor entity and expands the spectrum of clinicopathologic and radiologic features of this neoplasm.     

Evaluation of the Impact of Metabolic Syndrome on Fibrosis in Metabolic Dysfunction-Associated Fatty Liver Disease

Background: Metabolic syndrome (MS) is a condition that consists of several disorders, and the individual impact of these disorders on metabolic dysfunction-associated fatty liver disease (MAFLD) is still not clear in a combined diagnosis of MS. In this study, we aimed to investigate the effect of MS on advanced fibrosis in patients with MAFLD.Methods: We recruited the patients from our gastroenterology out-patient clinic who were being followed up for MAFLD. MAFLD was diagnosed with liver biopsy in all patients. The frequency of MS and other metabolic parameters were also compared between groups with advanced fibrosis and groups in which fibrosis was not as advanced.Results: In total, we enrolled 424 biopsy-proven MAFLD patients to the study. In univariate analysis, individuals with greater age, body mass index (BMI), higher aspartate transaminase (AST), MS, impaired fasting glucose, hypertension, enlarged waist circumference (WC), diabetes mellitus (DM), and women had significantly increased risk for fibrosis. In multivariate analysis, it was found that DM, greater age, higher BMI, and increased AST were seen more commonly in MAFLD patients with advanced fibrosisConclusion: Greater age, a higher BMI, higher AST and a diagnosis of diabetes were more commonly associated with advanced fibrosis. However, DM was found to be the strongest predictive factor of advanced fibrosis in our cohort (OR: 2.495). Multivariate analyses did not indicate a significantly common occurrence of MS in the advanced fibrosis group, despite its important role in MAFLD pathophysiology.     

Complication and cost analysis of transbronchial lung cryobiopsy and awake video-assisted thoracic surgery in diagnosis of interstitial lung disease

Aim and introduction:Diagnosing of interstitial lung disease (ILD) is difficult and expensive. The standard diagnostical approaches to ILD are bronchoalveolar lavage, transbronchial lung biopsy, transbronchial lung cryobiopsy (TBLC) and surgical lung biopsy (SLB). SLB is gold standard for the confident diagnosis of ILD but because of the poor performance of the patients it’s use is limited. We conducted a retrospective study to point out that TBLC plays an important role in diagnosis of ILD and has fewer complications and lower cost than awake video-assisted thoracic surgery (AVATS).Material and methods:132 patients who underwent TBLC and AVATS with a pre-diagnosis of ILD in our hospital between 2015 and 2020 were evaluated retrospectively. Diagnosis rates, complications and costs were recorded.Results:There were no non-diagnostic materials in 44 patients in AVATS arm. Prolonged air leak was observed in 11(25.0%) of the patients, and six of them (13.6%) were discharged with Heimlich Valve (HV). Median length of stay in the hospital was 8 days, while average patient cost was $515.9 (415.2-2662.9) in the AVATS arm. Non-diagnostic material was obtained from 10 (11.3%) of 88 patients in TBLC arm. Six (6.8%) of them had pneumothorax, only one of them required a chest tube. No patient was discharged with HV (p=0.001). Median cost for each patient with a median hospital stay of 2.0 (1.0-21.0) (p<0.001) days was $171.9 (80.8-1493.3) (p<0.001).Discussion:Although TBLC is behind AVATS in terms of diagnostic accuracy, it may be an alternative diagnostic tool in the diagnosis of interstitial lung disease due to its acceptable safety profile and cost-effectiveness.     

Platelet-Derived MRP-14 Induces Monocyte Activation in Patients With Symptomatic Peripheral Artery Disease

Background

Peripheral artery disease (PAD), a diffuse manifestation of atherothrombosis, is a major cardiovascular threat. Although platelets are primary mediators of atherothrombosis, their role in the pathogenesis of PAD remains unclear.

Estimation of COVID-19 vaccine effectiveness against hospitalisation in individuals aged ≥ 65 years using electronic health registries; a pilot study in four EU/EEA countries,October 2021 to March 2022

By employing a common protocol and data from electronic health registries in Denmark, Navarre (Spain), Norway and Portugal, we estimated vaccine effectiveness (VE) against hospitalisation due to COVID-19 in individuals aged ≥ 65 years old, without previous documented infection, between October 2021 and March 2022. VE was higher in 65–79-year-olds compared with ≥ 80-year-olds and in those who received a booster compared with those who were primary vaccinated. VE remained high (ca 80%) between ≥ 12 and < 24 weeks after the first booster administration, and after Omicron became dominant.     

Comparison of Hybrid Capture II,Linear Array,and a Bead-Based Multiplex Genotyping Assay for Detection of Human Papillomavirus in Women with Negative Pap Test Results and Atypical Squamous Cells of Undetermined Significance

Many methods with different levels of analytical sensitivity and clinical specificity have been developed to detect the presence of high-risk (HR) types of the human papillomavirus (HPV) in cervical samples. The Hybrid Capture II (HC-II) assay is broadly used for primary screening. In addition, several HPV genotyping assays, based on PCR methods, display higher sensitivity than the HC-II and are also used in screening programs. We evaluated the performance of three HPV DNA tests, namely, the HC-II, the Linear Array (LA) HPV genotyping assay, and an HPV type-specific E7 PCR bead-based multiplex genotyping assay (TS-MPG) that is a laboratory-developed method for the detection of HPV, in 94 women with atypical squamous cells of undetermined significance (ASC-US) and in cytological samples from 86 women with a negative Pap test. The HPV prevalence with the TS-MPG assay was increased compared to the prevalence with the LA and HC-II assays. The HPV DNA prevalence in women with ASC-US was greater with the TS-MPG assay (46.2%) than with the LA (36.3%) and HC-II (29.7%) assays. The HPV DNA prevalence in the control group was greater with the TS-MPG assay (32.1%) than with the LA assay (10.7%). Two women with ASC-US who were HPV DNA negative by the HC-II and positive by the TS-MPG or/and LA assays had lesions that progressed to low-grade squamous intraepithelial and high-grade squamous intraepithelial lesions. This study shows that the TS-MPG assay exhibited higher analytical sensitivity than the LA and HC-II assays for the detection of HPV DNA, which reduces the potential to incorrectly identify a woman''s HPV infection status.     

Intradural extramedullary leptomeningeal hemangioblastomatosis and paraneoplastic limbic encephalitis diagnosed at autopsy: an unlikely pair

Typical cerebellar or spinal cord hemangioblastoma is often solitary and has a benign clinical course, whereas disseminated hemangioblastomatosis is extremely rare. We report a 75-year-old man with disseminated "leptomeningeal" hemangioblastomatosis and concurrent paraneoplastic limbic encephalitis who died of this disease. The patient presented with gait problems and cognitive deficits, and was diagnosed with a cervical spinal tumor. Surgical resection achieved an apparent gross total resection, but later the patient began experiencing severe cognitive decline. His condition progressively deteriorated during the next few months, and he died 15 months after his initial surgery. Autopsy revealed disseminated extramedullary intradural hemangioblastomatosis with extensive leptomeningeal nodules involving the entire spinal cord, medulla, pons, and midbrain, as well as histologic features of limbic encephalitis. There was no evidence of von Hippel-Lindau disease, and no specific etiology was identified for the dementia. To the best of our knowledge, this is the first case of limbic encephalitis occurring in the setting of disseminated hemangioblastomatosis.     

Emergence of a high-grade sarcoma in a recurrent meningioma: malignant progression or collision tumor?

Anaplastic meningiomas that resemble sarcomas often reveal clues to their meningothelial differentiation or develop in a plausible setting that confirms their meningothelial origin. Malignant mesenchymal neoplasms without obvious evidence of meningothelial differentiation or origin are more likely to be true primary or metastatic sarcomas. Because of their clinical and biological differences, it is important to distinguish anaplastic meningioma from a sarcoma. We present a 67-year-old woman with multiple meningiomas, who developed a high-grade spindle cell tumor 6 months after the resection of a World Health Organization grade I meningioma. It was not clear whether this tumor represented a malignant transformation of meningioma or a primary sarcoma. Malignant transformation of a meningioma is exceptional within this short period and a coexisting sarcoma and meningioma are equally uncommon. Even though these malignant neoplasms are rare in general, they appear to be more prevalent in patients with multiple meningiomas including those with neurofibromatosis type 2.     

Impact of p53 and Ki-67 in predicting recurrence and progression of superficial (pTa and pT1) urothelial cell carcinomas of urinary bladder

In predicting the aggressive behavior of bladder tumors, the histopathological characteristics of grade and invasive stage are of principal importance. However, for predicting tumor recurrence and progression, these are sufficient only to a limited extent, particularly in the case of superficial (pTa and pT1) urothelial cell carcinomas. New prognostic factors are therefore needed to avoid either insufficient or excessive treatment. In this retrospective study, we investigated the prognostic value of the p53 and Ki-67 immunoreactivity indices. The present study included 118 superficial urinary bladder tumors consisting of 58 recurrent and 60 non-recurrent cases. Twenty of the recurrent tumors progressed into a higher grade and/or invasive stage. Paraffin immunohistochemical analysis was carried out using anti-p53 and anti-Ki-67 antibodies on the initial tumor tissues. We concluded that there is a highly significant relationship between the p53 and Ki-67 immunoreactivities and the histological grade and pathological stage of the tumors (P < 0.0001). We observed a significant relationship between the presence of recurrence and progression and the p53 immunoreactivity index (P < 0.01 and P = 0.017, respectively) and Ki-67 immunoreactivity index (P < 0.0001 and P = 0.046, respectively). Positivity for p53 and Ki-67 can demonstrate the risk of recurrence (p53: sensitivity = 76%, specificity = 58%; Ki-67: sensitivity = 86%, specificity = 48%) and progression (p53: sensitivity = 80%, specificity = 46%; Ki-67: sensitivity = 85%, specificity = 36%; ). We believe that both of these immunohistochemical markers can be considered valuable in addition to classical histopathological prognostic parameters for predicting recurrence and progression risks.     

Verbal episodic memory deficits in remitted bipolar patients: A combined behavioural and fMRI study

Background

Episodic memory deficits affect the majority of patients with bipolar disorder (BD).

Aims

The study investigates episodic memory performance through different approaches, including behavioural measures, physiological parameters, and the underlying functional activation patterns with functional neuroimaging (fMRI).

Methods

26 Remitted BD patients and a matched group of healthy controls underwent a verbal episodic memory test together with monitored autonomic response, psychopathological ratings and functional magnetic resonance imaging (fMRI) during the verbal episodic memory test.

Results

Compared to healthy controls, BD patients performed significantly worse during the episodic memory task. The results further indicate that verbal episodic memory deficits in BD are associated with abnormal functional activity patterns in frontal, occipital and limbic regions, and an increase in stress parameters.

Limitations

We aimed to minimise sample heterogeneity by setting clear criteria for remission, based on the scores of a depression (BDI II) and mania scale (BRMAS) and on the DSM IV criteria. However, our patients were not symptom-free and scored higher on BDI II scores than the control group.

Conclusions

The results are of interest for the treatment of cognitive symptoms in BD patients, as persistent cognitive impairment may hamper full rehabilitation.