Post-Coronavirus Disease Autoimmunity-associated Morvan's Syndrome.

A lot of autoimmune conditions have been found to be associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There are multiple cases of autoimmune and autoinflammatory diseases reported after the coronavirus disease 2019 (COVID-19) pandemic. Autoimmune neurological presentations have also been reported but are very rare. Morvan's syndrome is a life-threatening autoimmune disease and is very rare. Morvan's syndrome is classically characterized by neuromyotonia, dysautonomia, insomnia, and neuropsychiatric symptoms. Leucine-rich glioma-inactivated protein 1 (LGI1) and contactin-associated protein 2 (CASPR2) autoimmunity has also been associated with Morvan's syndrome. We hereby report an interesting case of a male patient in his 40s, who had a history of COVID-19 infection, following which he had bilateral lower-limb weakness and pain, with profuse sweating, and was later diagnosed as a case of SARS-CoV-2-associated Morvan's syndrome.

Withaferin A mitigates metastatic traits in human oral squamous cell carcinoma caused by aberrant claudin-1 expression.

Abnormal expression of claudin-1 (CLDN1) has important roles in carcinogenesis and metastasis in various cancers. The role of CLDN1 in human oral squamous cell carcinoma (OSCC) remains unknown. Here, we report the functional role of CLDN1 in metastasis of human OSCC, as a potential target regulated by withaferin A. From gene expression profiling with microarray technology, we found that the majority of notable differentially expressed genes were classified into migration/invasion category. Withaferin A impaired the motility of human OSCC cells in vitro and suppressed metastatic nodule formation in an in vivo metastasis model, both associated with reduced CLDN1. CLDN1 overexpression enhanced metastatic nodule formation in vivo, resulting in severe metastatic lesions in lung tissue. Moreover, CLDN1 expression was positively correlated to lymphatic metastasis in OSCC patients. The impaired motility of human OSCC cells upon withaferin A treatment was restored by CLDN1 overexpression. Furthermore, upregulation of let-7a induced by withaferin A was inversely correlated to CLDN1 expression. Overall, these give us an insight into the function of CLDN1 for prognosis and treatment of human OSCC, substantiating further investigation into the use of withaferin A as good anti-metastatic drug candidate.

A novel technique to manage transcatheter aortic valve embolization.

We report a case of a 69-year-old male who was planned for a transcatheter aortic valve replacement (TAVR) with a 26 mm Sapien 3 Valve (Edwards Lifesciences, Irvine, California) for the treatment of symptomatic severe aortic stenosis. During rapid ventricular pacing and implantation of the TAVR valve, there was a loss of pacing capture and subsequent embolization of the valve into the aortic arch. Retrieval of the embolized valve was attempted unsuccessfully using several techniques. Finally, by using a 34 mm Evolut R Valve (Medtronic, Minneapolis, Minnesota), we were able to secure the embolized valve in the transverse segment of the aortic arch without compromising the branch vessels. To our knowledge, this is the first reported case of using a valve-in-valve approach to fixate an embolized valve in the transverse aorta.

SOX7 blocks vasculogenic mimicry in oral squamous cell carcinoma.

BACKGROUND: Vasculogenic mimicry (VM) is the formation of an alternative circulatory system by aggressive tumor cells. The characteristics of VM and its underlying mechanism in oral squamous cell carcinoma (OSCC) remain unclear. This study aims to determine the relationship between VM in OSCC tissues and clinical outcomes and to investigate the biological role of SOX7 in VM in OSCC cells. METHODS: CD31/PAS staining was performed to evaluate VM in OSCC tissue. The relationships between VM and clinicopathological variables, and VM and SOX7 levels were analyzed. The correlation between SOX7 levels and cancer cohorts was investigated using in silico analysis. VM formation assay was performed to observe VM in vitro. To investigate the role of SOX7 in VM formation, SOX7 was transiently over-expressed in SCC-9 cells. VM-modulating genes were identified by Western blotting. RESULTS: We found a positive correlation between VM and lymph node metastasis and patient survival in OSCC (p = 0.003). In silico analysis from The Cancer Genome Atlas and Gene Expression Omnibus database showed that down-regulation of SOX7 expression was significantly correlated with OSCC patients (p = 0.0187) and lymph node metastasis (p = 0.0017). We also found that the presence of VM in OSCC tissue was inversely associated with SOX7 expression (p = 0.020). We observed that overexpression of SOX7 impaired VM formation by reducing the expression of VE-cadherin, thereby inhibiting cell migration and invasion. CONCLUSION: These results suggest that SOX7 plays an important role in the regulation of VM formation and may inhibit OSCC metastasis.

Pancreatitis with normal lipase and amylase in setting of end-stage renal disease.

Pancreatitis with normal lipase and amylase level is a rare phenomenon. This is especially true in patient with end-stage renal disease as lipase and amylase are renally excreted. Literature review reveals previous case report of pancreatitis with normal lipase and amylase level, however, none of them occurred in the setting of end-stage renal disease. Our case is the first such reported case of pancreatitis in such setting. Here we report a 30year old male with past medical history of end-stage renal disease who presented in emergency department with acute abdominal pain. Laboratory work up revealed normal lipase and amylase level. However, radiological work up was consistent with pancreatitis. This case report highlight the importance of taking the overall clinical picture rather than laboratory work up to rule in or rule out the diagnosis of pancreatitis. Furthermore, this should also serve an important reminder for clinicians to further investigate where clinical suspicion for pancreatitis is high.

Bilateral bifid ureter with unilateral renal vasculature variations.

During routine dissection of 82-year-old female cadaver with no known unfavorable medical history, we observed bilateral bifid ureter and variation in arterial supply of left kidney only. Careful examination revealed that there were bifid ureters on both sides enclosed in single facial sheath. It was also observed that both the ureter have different pattern of origin. On the right side, both the ureters were seen to be emerging from the hilum, one below another and joined together at the brim of the lesser pelvis just before crossing the right external iliac artery. Right kidney was supplied by single renal artery lying anterior to both the ureters. On the left side one ureter emerged from the hilum while the second one exited the kidney from a prominent lobule present below the inferior pole.

Fault in Our Genes: A Case of Pulmonary Thromboembolism in Young.

Methylenetetrahydrofolate reductase (MTHFR) enzyme is one of the key enzymes involved in the metabolism of folate. Mutations in this enzyme can lead to a procoagulant state. We present a case of a 20-year-old male with no known comorbidities, who presented with fever and hemoptysis and was diagnosed as a case of pulmonary embolism. He was found to have a homozygous mutation in the MTHFR gene that was responsible for his disease state. He was started on unfractionated heparin infusion and underwent catheter-directed thrombolysis. He showed marked improvement in his condition and was discharged on oral anticoagulants with an advice to follow-up.

RésuméL'enzyme méthylènetétrahydrofolate réductase (MTHFR) est l'une des enzymes clés impliquées dans le métabolisme du folate. Les mutations de cette enzyme peuvent conduire à un état procoagulant. Nous présentons le cas d'un homme de 20 ans sans comorbidités connues, qui s'est présenté avec de la fièvre et une hémoptysie et a été diagnostiqué comme un cas d'embolie pulmonaire. Il s'est avéré qu'il présentait une mutation homozygote du gène MTHFR responsable de son état pathologique. Il a commencé une perfusion d'héparine non fractionnée et a subi une thrombolyse dirigée par cathéter. Il a montré une nette amélioration de son état et a été libéré sous anticoagulants oraux avec un conseil de suivi.

A Study of Neurological Involvement in Dengue and Chikungunya Infection.

INTRODUCTION: Chikungunya virus (CHIKV) and dengue fever have been reported for recent epidemics worldwide, with varied clinical involvement. Chikungunya was first reported to affect the nervous system in the 1960s. The clinical profile of dengue with multi-organ involvement is varied with reported involvement of the central nervous system in some. AIM: The aim of this study was to study the frequency and pattern of neurological involvement in patients admitted with dengue and chikungunya in a tertiary care hospital. MATERIALS AND METHODS: Patients admitted with confirmed chikungunya and dengue were evaluated clinically and investigations were enrolled in the study. Patients with preexisting neurological issues, obvious metabolic, vascular, or septic causes for neurological involvement were excluded from the study. RESULTS: A total of 309 patients with chikungunya were included in the study. Out of these, 11 (3.56%) patients were found to have neurological involvement. The most common presentations were altered sensorium (100%) followed by headache (81.81%). The relative risk of mortality in patients with neurological involvement due to chikungunya was 7.96. A total of 443 patients with dengue fever were enrolled in the study. Out of these, 5 (1.10%) patients were found to have neurological involvement. The most common presentations were altered sensorium and headache (100%), followed by vomiting (80%). The relative risk of mortality in patients with neurological involvement due to dengue was 5.15. CONCLUSION: The recent epidemic of chikungunya and dengue virus infections was associated with various neurological complications. Neurological involvement of chikungunya and dengue was identified to be a bad prognostic factor with significantly higher mortality. LIMITATIONS: This is a single center study, involving only the patients admitted to the hospital. Furthermore, being an observational study, follow-up could not be done to look for neurological sequelae.

Résumé Introduction:le virus du chikungunya (CHIKV) et la dengue ont été signalés pour des épidémies récentes dans le monde, avec une implication clinique variée. Chikungunya a d'abord affecté le système nerveux dans les années 1960. Le profil clinique de la dengue avec une implication multi-organes est varié avec l'implication rapportée du système nerveux central dans certains.Objectif:Le but de cette étude était d'étudier la fréquence et le schéma d'implication neurologique chez les patients admis avec de la dengue et le chikungunya dans un hôpital de soins tertiaires.Matériaux et méthodes:patients Admis avec le chikungunya et la dengue confirmés ont été évalués cliniquement et les enquêtes ont été inscrites à l'étude. Les patients présentant des problèmes neurologiques préexistants, des causes métaboliques, vasculaires ou septiques évidentes de participation neurologique ont été exclues de l'étude.Résultats:Un total de 309 patients atteints de chikungunya ont été inclus dans l'étude. Parmi ceux-ci, 11 (3,56%) patients se sont révélés avoir une atteinte neurologique. Les présentations les plus courantes ont été modifiées du sensorium (100%) suivie de maux de tête (81,81%). Le risque relatif de mortalité chez les patients présentant une atteinte neurologique due au chikungunya était de 7,96. Au total, 443 patients atteints de dengue ont été inscrits à l'étude. Parmi ceux-ci, 5 (1,10%) patients se sont révélés avoir une atteinte neurologique. Les présentations les plus courantes ont été modifiées du sensorium et des maux de tête (100%), suivis par des vomissements (80%). Le risque relatif de mortalité chez les patients présentant une atteinte neurologique due à la dengue était de 5,15.Conclusion:L'épidémie récente des infections du chikungunya et du virus de la dengue a été associée à diverses complications neurologiques. L'atteinte neurologique du chikungunya et de la dengue a été identifiée comme étant un mauvais facteur pronostique avec une mortalité significativement plus élevée.Limites:Il s'agit d'une étude centrale unique, impliquant uniquement les patients admis à l'hôpital. De plus, étant une étude observationnelle, le suivi n'a pas pu être fait pour rechercher des séquelles neurologiques.

High prevalence of respiratory ciliary dysfunction in congenital heart disease patients with heterotaxy.

BACKGROUND: Patients with congenital heart disease (CHD) and heterotaxy show high postsurgical morbidity/mortality, with some developing respiratory complications. Although this finding is often attributed to the CHD, airway clearance and left-right patterning both require motile cilia function. Thus, airway ciliary dysfunction (CD) similar to that of primary ciliary dyskinesia (PCD) may contribute to increased respiratory complications in heterotaxy patients. METHODS AND RESULTS: We assessed 43 CHD patients with heterotaxy for airway CD. Videomicrocopy was used to examine ciliary motion in nasal tissue, and nasal nitric oxide (nNO) was measured; nNO level is typically low with PCD. Eighteen patients exhibited CD characterized by abnormal ciliary motion and nNO levels below or near the PCD cutoff values. Patients with CD aged >6 years show increased respiratory symptoms similar to those seen in PCD. Sequencing of all 14 known PCD genes in 13 heterotaxy patients with CD, 12 without CD, 10 PCD disease controls, and 13 healthy controls yielded 0.769, 0.417, 1.0, and 0.077 novel variants per patient, respectively. One heterotaxy patient with CD had the PCD causing DNAI1 founder mutation. Another with hyperkinetic ciliary beat had 2 mutations in DNAH11, the only PCD gene known to cause hyperkinetic beat. Among PCD patients, 2 had known PCD causing CCDC39 and CCDC40 mutations. CONCLUSIONS: Our studies show that CHD patients with heterotaxy have substantial risk for CD and increased respiratory disease. Heterotaxy patients with CD were enriched for mutations in PCD genes. Future studies are needed to assess the potential benefit of prescreening and prophylactically treating heterotaxy patients for CD.

Targeting tumor-intrinsic PD-L1 suppresses the progression and aggressiveness of head and neck cancer by inhibiting GSK3ß-dependent Snail degradation.

PURPOSE: PD-L1 is an immune checkpoint protein that allows cells to evade T-cell-mediated immune responses. Herein, we uncover a tumor-intrinsic mechanism of PD-L1 that is responsible for the progression and aggressiveness of HNC and reveal that the extracts of a brown alga can target the tumor-intrinsic signaling pathway of PD-L1. METHODS: The biological functions of PD-L1 in the proliferation and aggressiveness of HNC cells in vitro were examined by metabolic activity, clonogenic, tumorigenicity, wound healing, migration, and invasion assays. The clinical importance of PD-L1 in the prognosis of patients with HNC was analyzed by immunohistochemistry. The relationship between PD-L1 and EMT was confirmed via western blotting, qPCR, and immunocytochemistry. RESULTS: Through our in silico approach, we found that PD-L1 was upregulated in HNC and was correlated with an unfavorable clinical outcome in patients with HNC. PD-L1 was crucial for promoting tumor growth, both in vitro and in vivo. High expression of PD-L1 was closely correlated with LN metastasis in OSCC. PD-L1 facilitated the cytoskeletal reorganization and aggressiveness of HNC cells. Moreover, PD-L1 enhanced the EMT of HNC cells by regulating the Snail/vimentin axis. Consistently, MEIO suppressed the PD-L1/Snail/vimentin axis, thereby inhibiting the aggressiveness of HNC cells. Inhibition of PD-L1 induced by PD-L1 silencing or MEIO treatment caused Snail degradation through a GSK3ß-dependent mechanism. The tumor-intrinsic function of PD-L1 could be attributed to the regulation of the GSK3ß/Snail/vimentin axis. CONCLUSION: The discovery of MEIO targeting the tumor-intrinsic function of PD-L1 may prove particularly valuable for the development of novel and effective anticancer drug candidates for HNCs overexpressing PD-L1.

Severe Aortic Stenosis: More Than an Imaging Diagnosis.

The definition of severe aortic stenosis has undergone significant change casting a wider net to avoid missing patients who could benefit from valve replacement. The presence or absence of symptoms remains the key decision-making element; however, individuals presently undergoing evaluation are older, more likely asymptomatic, and have lower gradients. Due to numerous potential measurement errors, attention to detail when performing diagnostic testing and understanding their limitations are necessary to render appropriate treatment. Exercise testing adds useful information for individuals with severe aortic stenosis felt to be asymptomatic. Dobutamine echocardiography, in low flow-low gradient aortic stenosis, distinguishes between a myopathic and valvular cause of left ventricular dysfunction. Evaluation of patients when normotensive minimizes measurement errors. The amount of aortic valve calcification adds useful information when the degree of aortic stenosis is uncertain. A good history and physical integrated with high-quality imaging data allows for appropriate clinical treatment decisions for patients with aortic stenosis. The goal is simultaneously to provide aortic valve replacement for patients in need while avoiding overdiagnosis and performance of unnecessary procedures.

Effect of PAIP1 on the metastatic potential and prognostic significance in oral squamous cell carcinoma.

Poly Adenylate Binding Protein Interacting protein 1 (PAIP1) plays a critical role in translation initiation and is associated with the several cancer types. However, its function and clinical significance have not yet been described in oral squamous cell carcinoma (OSCC) and its associated features like lymph node metastasis (LNM). Here, we used the data available from Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), and Clinical Proteomic Tumor Analysis Consortium (CPTAC) to analyze PAIP1 expression in oral cancer. The publicly available data suggests that PAIP1 mRNA and protein levels were increased in OSCC. The high PAIP1 expression was more evident in samples with advanced stage, LNM, and worse pattern of invasion. Moreover, the in vitro experiments revealed that PAIP1 knockdown attenuated colony forming, the aggressiveness of OSCC cell lines, decreasing MMP9 activity and SRC phosphorylation. Importantly, we found a correlation between PAIP1 and pSRC through the analysis of the IHC scores and CPTAC data in patient samples. Our findings suggest that PAIP1 could be an independent prognostic factor in OSCC with LNM and a suitable therapeutic target to improve OSCC patient outcomes.

Methanol extract of Sedum oryzifolium and its constituent, trehalose, impede the invasiveness of oral squamous cell carcinoma cell lines via downregulation of Slug.

BACKGROUND: Sedum species are reported to possess diverse pharmacological activities in various solid tumors. However, the anticancer functions of Sedum orizyfolium and its constituents have never been determined in human cancers. PURPOSE: The present study focused on addressing the inhibition efficacy of the methanol extract of S. orizyfolium (MESO) and its constituents and the molecular mechanism underlying invasion and epithelial-to-mesenchymal transition (EMT) in oral squamous cell carcinoma (OSCC) cell lines. STUDY DESIGN/METHODS: After MESO treatment, a wound-healing assay, an invasion assay, and immunocytochemistry were performed in OSCC cell lines, coupled with in silico analysis and immunohistochemistry in OSCC patient samples, to investigate the role of the EMT transcription factor Slug. Trehalose, an active component of MESO, was identified through gas chromatography-mass spectrometry. RESULTS: Among the methanol extracts of 18 various wild plants from South Korea, MESO exhibited the highest anticancer functionality in OSCC cells by downregulating Slug expression. In silico analysis and immunohistochemistry indicated that elevated Slug levels are remarkably associated with tumor progression and invasion in patients with OSCC, suggesting that changes in Slug expression alter EMT progression and invasion in OSCC. Notably, treatment with trehalose, a sugar component of MESO, inhibited invasiveness and Slug expression in OSCC cells. CONCLUSION: Cumulatively, this study highlighted the beneficial role of MESO and trehalose in the inhibition of invasiveness of OSCC cells via suppression of Slug expression and suggested a new design for potential chemotherapeutic drugs against OSCC.

Co-existing tuberculosis and malignant mesothelioma with multiple sites venous thrombosis: a case report.

BACKGROUND: Tuberculosis is endemic in India and almost 40 % of the Indian population is infected with tubercle bacilli. Tuberculosis being a great mimicker of infectious as well as non infectious diseases and recent rise of multi drug resistant and extended drug resistant cases have made diagnosis and management more difficult. To the best of our knowledge there have been no reported cases of tuberculosis coexisting with malignant peritoneal mesothelioma leading to multiple site venous thrombosis. CASE PRESENTATION: Forty five year old male, belonging to Indian/Aryan ethnicity presented with cough, breathlessness and fever for 7 months with past history of pulmonary tuberculosis. On examination he was found to have pleural effusion for which he received anti-tuberculosis therapy empirically. Later his condition deteriorated and on further examination he was found to have ascites, multiple site venous thrombosis and pyothorax which was found positive for acid fast bacilli. Despite anti-tuberculosis therapy he did not improve and was suspected to be a multidrug resistant case. Later on computed tomography peritoneal nodule was detected and on biopsy revealed malignant mesothelioma. CONCLUSION: In a diagnosed case of tuberculosis with clinical findings compatible with it but not responding to anti tubercular therapy, underlying secondary co-existing pathology should be explored.

The enigmatic psalterium: a review and anatomic study with relevance to callosotomy procedures.

BACKGROUND: Recalcitrant seizures after callosotomy procedures are challenging to treat. One commissure, the psalterium, has received little attention. OBJECTIVE: To review the literature on this structure, and with dissection, better elucidate its morphology and relationships. METHODS: Twenty adult cadaver brains underwent microsurgical dissection of the psalterium. Measurements included the size and distance from the splenium of the corpus callosum and posterior border of the hippocampus tail. Observations included the relationships between the psalterium and the vein of Galen and the fiber direction within this structure. RESULTS: The psalterium was identified in all specimens. It intimately contacted the undersurface of the splenium superiorly and the velum interpositum inferiorly. It was always in the midline. Just posterior to the psalterium, the internal cerebral veins were found leaving the velum interpositum to drain into the vein of Galen. In most specimens, the psalterium fibers traveled in the same plane as the commissural fibers of the splenium. Mean width of the psalterium was 11 mm; mean length was 13 mm. Average thickness in the midline was 1.4 mm, and at the lateral edges, it was generally thicker as it joined the fornix with an average of 2 mm. In 30%, efferents from the hippocampus were arranged in the form of a sheet bilaterally rather than the normal bundle-like formation forming the posterior crura. CONCLUSION: Better understanding of the commissures of the human brain, including the psalterium, might help the neurosurgeon during procedures near this structure.

Standardizing nasal nitric oxide measurement as a test for primary ciliary dyskinesia.

RATIONALE: Several studies suggest that nasal nitric oxide (nNO) measurement could be a test for primary ciliary dyskinesia (PCD), but the procedure and interpretation have not been standardized. OBJECTIVES: To use a standard protocol for measuring nNO to establish a disease-specific cutoff value at one site, and then validate at six other sites. METHODS: At the lead site, nNO was prospectively measured in individuals later confirmed to have PCD by ciliary ultrastructural defects (n = 143) or DNAH11 mutations (n = 6); and in 78 healthy and 146 disease control subjects, including individuals with asthma (n = 37), cystic fibrosis (n = 77), and chronic obstructive pulmonary disease (n = 32). A disease-specific cutoff value was determined, using generalized estimating equations (GEEs). Six other sites prospectively measured nNO in 155 consecutive individuals enrolled for evaluation for possible PCD. MEASUREMENTS AND MAIN RESULTS: At the lead site, nNO values in PCD (mean ± standard deviation, 20.7 ± 24.1 nl/min; range, 1.5-207.3 nl/min) only rarely overlapped with the nNO values of healthy control subjects (304.6 ± 118.8; 125.5-867.0 nl/min), asthma (267.8 ± 103.2; 125.0-589.7 nl/min), or chronic obstructive pulmonary disease (223.7 ± 87.1; 109.7-449.1 nl/min); however, there was overlap with cystic fibrosis (134.0 ± 73.5; 15.6-386.1 nl/min). The disease-specific nNO cutoff value was defined at 77 nl/minute (sensitivity, 0.98; specificity, >0.999). At six other sites, this cutoff identified 70 of the 71 (98.6%) participants with confirmed PCD. CONCLUSIONS: Using a standardized protocol in multicenter studies, nNO measurement accurately identifies individuals with PCD, and supports its usefulness as a test to support the clinical diagnosis of PCD.