Treatment of meningiomas involving the optic canal with endoscopic transnasal decompression of the optic nerve.

BACKGROUND: Management of patients with optic nerve sheath meningiomas (ONSM) is controversial and the treatment strategy in this patient group is still up for discussion. Transnasal endoscopic orbital and optic nerve decompression aims to reduce the pressure in the orbit and on the optic nerve and thereby prevent vision loss. This article presents material from seven cases of transnasal endoscopic orbital decompressions. METHODS: The study design is a retrospective cohort study. The aim was to include all patients with a meningioma residing along the nerve sheath and who were operated using endoscopic transnasal decompression of the orbit and if needed the optic canal at Odense University Hospital. Data from the medical records were collected and pre- and postoperative eye examinations were compared. In addition, it was recorded whether there were complications to the procedure and whether additional treatments were given. RESULTS: In total, four women and three men were included in the study. Four out of seven patients experienced improvement in vision after the operation. One patient experienced unchanged vision and two patients experienced deterioration of vision after surgery. CONCLUSIONS: The current report of seven patients with ONSM shows promising results for this surgical procedure as four out of seven patients experienced improvement in their vision at follow-up examinations. The two patients, who experienced deterioration of vision, already had severely reduced vision pre-operatively, which indicates that surgery should be considered before the vision becomes significantly reduced.

Prevalence of Medical Payment Products Promoted on US Hospitals' Websites.

This cross-sectional study examines the prevalence of hospital-promoted medical payment products (MPPs) by whether hospitals offered any MPP or an interest-bearing MPP.

PDP type brain tumor in association with multiple endocrine neoplasia type 1.

Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant syndrome caused by inactivating pathogenic variants in the tumor suppressor gene menin 1 on chromosome 11q13 (Falchetti et al., 2009). The syndrome is characterized by neoplasia in two or more endocrine glands and has a high degree of penetrance. Pathogenic germline multiple neoplasia type 1 variants primarily result in neoplasia affecting the parathyroid glands, the pancreatic islet cells, and the anterior pituitary in combination. Primary hyperparathyroidism is the most common pathological manifestation of the syndrome, followed by pancreatic neuroendocrine tumors. Important genetic confirmation has been provided showing that ependymoma should be considered as a neoplasm that can occur in patients with MEN1 (Kato et al., 1996; Cuevas-Ocampo et al., 2017). The biphasic histopathological tumor entity shown in the present case we name Pleomorphic Xanthoastocytoma grade 3 differential pathology (PDP) in association with Multiple Endocrine Neoplasia type 1. This MEN1 associated tumor subtype is an extension of the findings on MEN1 associated ependymoma, where we show that the clinical phenotype itself may potentially be triggered by a frameshift germline pathogenic variant for the MEN1 gene, in combination with cyclin-dependent kinase inhibitor 1B gene germline variant and cyclin dependent kinase inhibitor 2A somatic deletion downstream of menin.

Repeated immunization with ATRA-containing liposomal adjuvant transdifferentiates Th17 cells to a Tr1-like phenotype.

In many autoimmune diseases, autoantigen-specific Th17 cells play a pivotal role in disease pathogenesis. Th17 cells can transdifferentiate into other T cell subsets in inflammatory conditions, however, there have been no attempts to target Th17 cell plasticity using vaccines. We investigated if autoantigen-specific Th17 cells could be specifically targeted using a therapeutic vaccine approach, where antigen was formulated in all-trans retinoic acid (ATRA)-containing liposomes, permitting co-delivery of antigen and ATRA to the same target cell. Whilst ATRA was previously found to broadly reduce Th17 responses, we found that antigen formulated in ATRA-containing cationic liposomes only inhibited Th17 cells in an antigen-specific manner and not when combined with an irrelevant antigen. Furthermore, this approach shifted existing Th17 cells away from IL-17A expression and transcriptomic analysis of sorted Th17 lineage cells from IL-17 fate reporter mice revealed a shift of antigen-specific Th17 cells to exTh17 cells, expressing functional markers associated with T cell regulation and tolerance. In the experimental autoimmune encephalomyelitis (EAE) mouse model of MS, vaccination with myelin-specific (MOG) antigen in ATRA-containing liposomes reduced Th17 responses and alleviated disease. This highlights the potential of therapeutic vaccination for changing the phenotype of existing Th17 cells in the context of immune mediated diseases.

Factors that influence Asian American college students use of mental health services: A systematic mixed studies review.

WHAT IS KNOWN ON THE SUBJECT?: Only 8.6% Asian Americans (AAs) report seeking mental health services compared to nearly 18% of the general population. There is a stigma against seeking mental health services among AAs. Mental illness is thought to be caused by a lack of harmony of emotions or evil spirits leading to delay in treatment among AAs. WHAT THE PAPER ADDS TO EXISTING KNOWLEDGE?: Asian students are hesitant to use mental health services because they are balancing their desire to be part of the two cultures. Concepts used to define culture were found to have overlapping aspects of how researchers operationally define them, and few studies examined a combination of these concepts as a means of examining interactions between the concepts. AA emerging adults feel pressure through personal stigma from elders to 'save face' by keeping their problems to themselves or within the family to maintain a positive reputation for the family. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: The overlap of conceptual definitions to understand cultural beliefs and values affecting measurement have complicated the interpretation of the research. Future research should include a multidimensional operationalization of culture that includes acculturation, ethnic identity, personal stigma and their effect on mental health help-seeking attitudes. Differences between South Asian and East Asian philosophical and cultural perspectives could influence access to mental health services; therefore, future studies should consider sampling that would allow for comparison of the groups. Understanding the factors that influence mental health help-seeking behaviours can determine intervention strategies to improve AA emerging adult mental health. ABSTRACT: INTRODUCTION: Only 8.6% of Asian Americans (AA) sought mental health services compared to 18% of United States population. AA college students report higher levels of mental health concerns compared to White students. AIM: The purpose of this systematic review was to identify the factors that influence AA students' mental health help-seeking behaviours. METHOD: Employing a data-based convergent synthesis design. The Mixed Methods Appraisal Tool (MMAT) was used to assess the quality of the sample. Inclusion criteria were peer-reviewed studies published in English, focused on AA college students' mental health seeking attitudes in United States. RESULTS: The final sample was forty-four studies. Four themes emerged: acculturation, ethnic identity, racism and stigma. There were discrepant findings regarding how acculturation affects mental health help-seeking attitudes. Several studies included more than one theme in their analyses. The different concepts included across studies make it difficult to compare the findings. DISCUSSION: There is some overlap between acculturation and ethnic identity that could affect the analysis in studies where both concepts are included. Personal stigma negatively influences mental health help-seeking attitudes. IMPLICATIONS FOR PRACTICE: Defining culture to include acculturation, ethnic identity, personal stigma can help in understanding their effect on mental health help-seeking attitudes.

Facile iodine-promoted synthesis of bis(1-imidazo[1,5-a]pyridyl)arylmethanes and exploration of applications.

A practical strategy for the iodine-promoted synthesis of bis(1-imidazo[1,5-a]pyridyl)arylmethane and its derivatives has been developed. These compounds exhibit high cytotoxicity toward various cancer cell lines and moreover they are promising ligands for the Cu-catalysed synthesis of quinolines.

Rheumatic disease patient decision-making about COVID-19 vaccination: a qualitative analysis.

BACKGROUND: Although patients with rheumatic and musculoskeletal diseases (RMDs) are at increased risk for adverse outcomes of COVID-19 illness compared to healthy controls, they also have lower rates of willingness to be vaccinated. Previous research has identified reasons for vaccine hesitancy among patients with RMDs (such as concerns about side effects and flares), but little is known about what these reasons mean in the context of patients' lives, or how vaccine decision making is experienced from a patient perspective. Our objective was to describe decision-making about COVID-19 vaccination among RMD patients. METHODS: Participants in a RMD registry were invited to complete monthly online surveys regarding COVID-19 vaccination from March-June 2021. We qualitatively analyzed comments from two open-ended survey questions reporting general experiences with vaccination and side effects. Comments were coded for attitudes towards COVID-19 vaccination, vaccine access, rheumatologic medication management around vaccination, and vaccine side effects. Themes were identified for the process and context of COVID-19 vaccine decisions, patient motivations for receiving or avoiding vaccination, and consistency of peri-vaccine medication management with current ACR guidelines. RESULTS: We analyzed 710 comments from 537 respondents. Commenting respondents had a mean age of 64 years, were 87% female, 94% white, and 93% received/intended to receive ≥ 1 dose of a COVID-19 vaccine. Desire for protection and a return to normal routines motivated some commenters to get vaccinated, while concerns about vaccine side effects motivated others to delay or avoid vaccination. Several commenters reported disease flares following vaccination. Some commenters did not consult their providers about vaccination and failed to withhold immunomodulatory medications during vaccination, while others withheld medications more conservatively than recommended by current ACR guidelines, either on their own or directed by their provider. CONCLUSIONS: While most commenters were vaccine-accepting, challenges to COVID-19 vaccine uptake in the RMD population may include fears of side effects, including worsened RMD symptoms, and perceptions that vaccination is unnecessary. Addressing these concerns and beliefs may be critical for promoting vaccination in this population.

The treatment of acute lymphoblastic leukemia in Jehovah's Witnesses and patients who cannot accept blood products.

Jehovah's Witnesses cannot accept blood products based upon religious beliefs, and when they present with acute leukemia, the ideal treatment strategy can be controversial. We present six cases of Jehovah's Witnesses with acute lymphoblastic leukemia and show that complete remission can be achieved without using anthracycline in 83% (5/6) of patients. We also report, for the first time in this population, that the use of agents with novel mechanisms of action, such as blinatumomab and nelarabine, is associated with minimal myelosuppression and can produce durable responses, with 2 of 6 patients still alive in CR3 at 4.9 and 6.6 years.

Combination venetoclax and selinexor effective in relapsed refractory multiple myeloma with translocation t(11;14).

Patients with multiple myeloma-bearing translocation t(11;14) have recently been shown to benefit from the apoptosis-inducing drug venetoclax; however, the drug lacks FDA approval in multiple myeloma thus far due to a potential safety signal in the overall patient population. Selinexor is an inhibitor of nuclear export that is FDA-approved for patients with multiple myeloma refractory to multiple lines of therapy. Here, we report that in four patients with multiple myeloma with t(11;14), the concomitant administration of venetoclax and selinexor was safe and associated with disease response. Moreover, the combination was synergistic in t(11;14) multiple myeloma cell lines and caused decreased levels of Cyclin D1 (which is overexpressed due to the CCND1-IGH fusion) when given in combination as compared to single agents. These data suggest that the combination of venetoclax and selinexor is effective and t(11;14) may serve as a therapeutic marker for response and target for future clinical trials.

Genome Sequences of Microbacterium foliorum Phages Anseraureola, Pondwater, and Yasuo.

Anseraureola, Pondwater, and Yasuo are bacteriophages with siphovirus morphology that infect Microbacterium foliorum NRRL B-24224. They were isolated from soil collected in Amherst, Massachusetts, and have genome lengths between 17,362 bp and 17,453 bp. These phages each contain 25 predicted protein-coding genes and are assigned to phage cluster EE.

Association of ictal imaging changes in status epilepticus and neurological deterioration.

OBJECTIVE: In patients with status epilepticus (SE), the clinical significance of ictal changes on magnetic resonance imaging (MRI) is insufficiently understood. We here studied whether the presence of ictal MRI changes was associated with neurological deterioration at discharge. METHODS: The retrospective cohort comprised all identifiable patients treated at Odense University Hospital in the period 2008-2017. All amenable MRIs were systemically screened for ictal changes. Patient demographics, electroencephalography, seizure characteristics, treatment, and SE duration were assessed. Neurological status was estimated before and after SE. The predefined endpoint was the association of neurological deterioration and ictal MRI changes. RESULTS: Of 261 eligible patients, 101 received at least one MRI during SE or within 7 days after cessation; 43.6% (44/101) had SE due to non- or less brain-damaging etiologies. Patients who received MRI had a longer duration of SE, less frequently had a history of epilepsy, and were more likely to have SE due to unknown causes. Basic characteristics (including electroencephalographic features defined by the Salzburg criteria) did not differ between patients with (n = 20) and without (n = 81) ictal MRI changes. Timing of MRI was important; postictal changes were rare within the first 24 h and hardly seen >5 days after cessation of SE. Ictal MRI changes were associated with a higher risk of neurological deterioration at discharge irrespective of etiology. Furthermore, they were associated with a longer duration of SE and higher long-term mortality that reached statistical significance in patients with non- or less brain-damaging etiologies. SIGNIFICANCE: In this retrospective cohort, ictal changes on MRI were associated with a higher risk of neurological deterioration at discharge and, possibly, with a longer duration of SE and poorer survival.

Cu-catalyzed Synthesis of Quinolines by Dehydrogenative Reaction of 2-Aminobenzyl Alcohol and Ketones: A Combined Experimental and Computational Study.

Quinoline derivatives are important moieties in bioactive molecules and advanced materials. However, an efficient strategy to synthesize quinoline derivatives remains challenging. Herein, we describe an efficient and practical method for the synthesis of quinolines by Cu-catalyzed cyclization of 2-amino benzyl alcohol with ketones (or secondary alcohols) via an acceptorless dehydrogenation pathway. Interestingly, a range of highly functionalized quinolines is prepared in good yields using low catalyst loading under relatively mild conditions. Furthermore, density functional theory (DFT) calculations are carried out to investigate mechanistic insights for the acceptorless dehydrogenation pathway.

[Amphetamine-induced toxic encephalopathy].

In this case report, a 40-year-old woman presented with altered mentation, central facial palsy and hemiparesis. Acute CT scan showed several hypodense, rounded areas in both hemispheres. Urine toxicology tested positive for amphetamine. Subsequent cerebral MRI had hyperintense T2-weighted fluid-attenuated inverse recovery (FLAIR) lesions in both hemispheres, indicating demyelinating disease. A biopsy was made from one of the lesions. The final diagnosis was toxic encephalopathy.

A prospective, one-year follow-up study of patients newly diagnosed with neurosarcoidosis.

METHODS: Twenty patients with newly diagnosed neurosarcoidosis were examined for multiple outcomes in an observational cohort study with 12-month follow-up. RESULTS: The patients' contrast-enhancing lesions on MRI scans reduced during treatment (p < 0.0001). The mean modified Rankin Score improved from 3.0 to 1.8 (p < 0.0001), and 75% of patients experienced clinically important improvement. Patients improved on the Symbol Digit Modalities Test (p < 0.0001) and on SF-36 Physical (p = 0.003) and Mental Component Summary scores (p = 0.03). Proportions of patients with substantial fatigue (75%) and high depression score (35%) were unchanged. CONCLUSIONS: 12-month immunosuppression improved several outcomes, and 75% of patients experienced clinically important improvement.

N-Oleoyl dopamine induces IL-10 via central nervous system TRPV1 and improves endotoxemia and sepsis outcomes.

BACKGROUND: The transient receptor potential vanilloid 1 (TRPV1) participates in thermosensation and inflammatory pain, but its immunomodulatory mechanisms remain enigmatic. N-Oleoyl dopamine (OLDA), an endovanilloid and endocannabinoid, is a TRPV1 agonist that is produced in the central nervous system and the peripheral nervous system. We studied the anti-inflammatory effects and TRPV1-dependent mechanisms of OLDA in models of inflammation and sepsis. METHODS: Mice were challenged intratracheally or intravenously with LPS, or intratracheally with S. aureus to induce pneumonia and sepsis, and then were treated intravenously with OLDA. Endpoints included plasma cytokines, leukocyte activation marker expression, mouse sepsis scores, lung histopathology, and bacterial counts. The role of TRPV1 in the effects of OLDA was determined using Trpv1-/- mice, and mice with TRPV1 knockdown pan-neuronally, in peripheral nervous system neurons, or in myeloid cells. Circulating monocytes/macrophages were depleted using clodronate to determine their role in the anti-inflammatory effects of OLDA in endotoxemic mice. Levels of exogenous OLDA, and of endovanilloids and endocannabinoids, at baseline and in endotoxemic mice, were determined by LC-MS/MS. RESULTS: OLDA administration caused an early anti-inflammatory response in endotoxemic and septic mice with high serum levels of IL-10 and decreased levels of pro-inflammatory cytokines. OLDA also reduced lung injury and improved mouse sepsis scores. Blood and lung bacterial counts were comparable between OLDA- and carrier-treated mice with S. aureus pneumonia. OLDA's effects were reversed in mice with pan-neuronal TRPV1 knockdown, but not with TRPV1 knockdown in peripheral nervous system neurons or myeloid cells. Depletion of monocytes/macrophages reversed the IL-10 upregulation by OLDA in endotoxemic mice. Brain and blood levels of endovanilloids and endocannabinoids were increased in endotoxemic mice. CONCLUSIONS: OLDA has strong anti-inflammatory actions in mice with endotoxemia or S. aureus pneumonia. Prior studies focused on the role of peripheral nervous system TRPV1 in modulating inflammation and pneumonia. Our results suggest that TRPV1-expressing central nervous system neurons also regulate inflammatory responses to endotoxemia and infection. Our study reveals a neuro-immune reflex that during acute inflammation is engaged proximally by OLDA acting on neuronal TRPV1, and through a multicellular network that requires circulating monocytes/macrophages, leads to the systemic production of IL-10.

Phenotypic manifestations in FLNA-related periventricular nodular heterotopia: a case report and review of the literature.

Periventricular nodular heterotopia (PVNH) is an X-linked disease caused by loss-of-function variants in the filamin A (FLNA) gene. FLNA-PVNH is a heterogeneous disorder, and the phenotype is associated with neurological and non-neurological features including cardiovascular, gastrointestinal, pulmonary, haematological, cutaneous and skeletal manifestations. No clear definition of the FLNA-PVNH phenotype has been established, but the patients are predominantly females with seizures, cardiovascular manifestations, and normal intelligence or mild intellectual disability. Herein, we describe a PVNH patient diagnosed with a novel heterozygous missense variant in FLNA after an atypical presentation of deep vein thrombosis and thrombocytopenia. Clinical evaluation found hypermobility, cardiovascular and skin manifestations. Moreover, we conducted a literature review of 186 FLNA-PVNH patients to describe the phenotypic spectrum. In conclusion, our patient highlights the importance of thorough clinical evaluation to identify manifestations in this very heterogeneous disorder. The phenotypic review may guide clinicians in the assessment and follow-up of FLNA-PVNH patients.

Endonasal Endoscopic Approach for Minimally Invasive Orbital Decompression in Nonthyroid Proptosis-A Scoping Review.

OBJECTIVE: The endoscopic endonasal approach (EEA) was originally performed to treat thyroid orbitopathy and proptosis. Since then, this approach also has been used to treat other causes of proptosis. This review systematically identifies surgical outcome and complication rates in patients without thyroid proptosis who underwent endoscopic endonasal orbital decompression. METHODS: Databases were searched using the following search terms: orbital disease, surgical decompression, and endoscopic endonasal approach. Two independent reviewers screened all abstracts and titles for relevance and all articles passing this screen were subjected to full-text review. To assess risk of bias, we used ROBINS-I (Risk Of Bias in Non-randomized Studies-of Interventions). RESULTS: Eight studies with a total of 74 patients with nonthyroid proptosis were included. Pre- and postoperative eye examination was performed in all studies, but the extent of examination was varying. With a mean age of 35.7 years, most patients were adolescent, and most pathologies induced unilateral proptosis Complications to EEA for orbital decompression were transient diplopia (5 patients/6.8%), transient facial dysesthesia (2 patients/2.7%), ptosis (1 patient/1.4%), infarction (1 patient/1.4%), sinus obstruction (1 patient/1.4%), and enophtalmos (1 patient/1.4%). The authors reported successful reduction of proptosis in all but 2 patients (97.2%), and only 2 authors reported a need for secondary decompression. CONCLUSIONS: Medial orbital decompression using EEA is a feasible approach for orbital decompression in patients with nonthyroid proptosis. While being comparable in primary outcome to transorbital approaches, the EEA seems superior in terms of complication rates.

Th1/Th17 T cell Tissue-Resident Immunity Increases Protection, But Is Not Required in a Vaccine Strategy Against Genital Infection With Chlamydia trachomatis.

The requirement for vaccine-induced tissue-resident immunity for protection against one or repeated infections with Chlamydia trachomatis (C.t.) is still not fully resolved. In this study, our aim was to investigate to which degree tissue-resident Th1/Th17 T cells in the genital tract (GT) could add to the protection mediated by circulating immunity. Out of several mucosal vaccine strategies, a strategy termed SIM (for simultaneous intrauterine and parenteral immunization with CAF01 adjuvanted CTH522), was superior in generating genital tract tissue-resident Th1/Th17 T cell immunity. This led to a faster and stronger local CD4 T cell response post infection, consisting of multifunctional IFNγ/TNFα-producing Th1 T cells and IFNγ/TNFα/IL-17-producing Th17 T cells, and a faster recruitment of innate immune cells. Post infection, SIM animals showed an additional significant reduction in bacterial levels compared to mice having received only a parenteral vaccine. Nevertheless, the parenteral strategy reduced bacterial levels by 75%, and interestingly, post infection, these mice generated their own vaccine-derived genital tract tissue-resident memory Th1/Th17 T cells, which upon a subsequent infection showed as fast an activation in the genital tract, as observed in SIM mice. Furthermore, in contrast to after the first infection, both groups of mice now showed a similar infection-induced boost in local vaginal IgA and IgG titers. Thus, vaccine-induced resident immunity, generated pre-infection, led to an advantage in the response against the first infection, but not the second infection, suggesting that a parenteral vaccine strategy is a suitable vaccine strategy against infections with Chlamydia trachomatis.