Identification of novel susceptibility genes associated with seven autoimmune disorders using whole genome molecular interaction networks.

Convergent evidence from multiple and independent genetics studies implicate a small number of genes that predispose individuals to multiple autoimmune disorders (AuD). These intersecting loci reinforced the hypothesis that disorders with overlapping etiology group into a cluster of closely related genes within a whole genome molecular interaction network. We tested the hypothesis that "biological network proximity" within a whole genome molecular interaction network can be used to inform the search for multigene inheritance. Using a set of nine previously published genome wide association studies (GWAS) of AuD genes, we generated AuD-specific molecular interaction networks to identify networks of associated genes. We show that all nine "seed genes" can be connected within a 35-member network via interactions with 26 connecting genes. We show that this network is more connected than expected by chance, and 13 of the connecting genes showed association with multiple AuD upon GWAS reanalysis. Furthermore, we report association of SNPs in five new genes (IL10RA, DGKA, GRB2, STAT5A, and NFATC2) which were not previously considered as AuD candidates, and show significant association in novel disease samples of Crohn's disease and systemic lupus erythematosus. Furthermore, we show that the connecting genes show no association in four non-AuD GWAS. Finally, we test the connecting genes in psoriasis GWAS, and show association to previously identified loci and report new loci. These findings support the hypothesis that molecular interaction networks can be used to inform the search for multigene disease etiology, especially for disorders with overlapping etiology.

Posterior Inferior Cerebellar Artery Stroke Due to a Severe Right Vertebral Artery Stenosis With a Left Cervical Internal Carotid Artery Dissection: What's Next?

Guidelines for the treatment and management of ischemic strokes triggered by stenosis versus dissection are well established. However, the presence of both entities in the same patient, although rare, poses challenges for short- and long-term treatment. Here, we describe the case of a 55-year-old man who presented to the emergency department with a 72-hour history of headache, dizziness, unbalanced gait, nausea, and two episodes of vomiting. Stroke was initially suspected, but the computerized tomography (CT) scan showed no hemorrhage. His magnetic resonance imaging (MRI) showed right inferior cerebellar acute ischemia in the territory of the right posterior inferior cerebellar artery (PICA), with smaller foci of early acute infarcts in the bilateral inferior cerebellum. Furthermore, magnetic resonance angiography (MRA) and CT angiography revealed right vertebral artery stenosis and left cervical internal carotid artery dissection (ICAD). This clinical report describes a rare case of stroke secondary to vertebral artery stenosis with concomitant carotid artery dissection. The treatment course and evolution are presented.

COVID-19 and Psychiatric Admissions: A Comparative Study of Pre-pandemic and Post-pandemic Psychosis Admissions in a South Florida Emergency Department.

We noticed a subjective increase in psychosis admissions within our emergency department (ED) with the onset of the coronavirus disease 2019 (COVID-19) pandemic. This study aimed to identify trends concerning admissions due to psychosis in the ED before and after the beginning of the COVID-19 pandemic. We analyzed 508 psychiatric admissions through the ED from October 2019 to October 2020, of which 367 cases of psychosis were identified. Statistical analysis was performed using T-tests and Pearson's correlation coefficient. T-testing showed mean psychosis admissions during the pandemic (March 2020 to July 2020) to be greater than admissions occurring during the pre-pandemic period (October 2019 to February 2020) (p = 0.04). Pearson's correlation coefficient identified the relationships between COVID-19 admissions and psychosis admissions during this time as positive (r = 0.5) but did not reach statistical significance (p = 0.06). Therefore, within our time frame, we did see a noted increase in psychosis by 22.9% during the pandemic compared to pre-pandemic times. Current research remains conflicted concerning psychiatric ED admissions during COVID-19, with some stating an increase and others finding a decrease. Our data showed a significant statistical increase in the mean number of psychosis cases when comparing pre-pandemic and pandemic admissions. These findings help add pertinent data to understand how psychosis admissions trended before and during the beginning of the COVID-19 pandemic, specifically in South Miami, Florida. It also provides a foundation for future studies by providing data points concerning mental illness within the vulnerable population of patients served in our community.

A Rare Case of Pancreatic Divisum Presentation.

Pancreatic divisum (PD) is a malformation wherein the majority of affected patients remain asymptomatic or present with complications early in life. Some cases, however, may present in adulthood with recurrent pancreatitis, which makes the diagnosis clinically challenging. Here, we present a rare case of an elderly female with acute-on-chronic epigastric pain secondary to pancreatitis due to PD. During hospitalization, the patient was treated for acute pancreatitis and subsequently discharged with recommendations for corrective surgery. This case is unique particularly due to the older age of onset of symptoms, as well as the lack of exacerbating factors such as drug abuse, alcohol, or obesity. This case highlights the importance of considering PD as a differential diagnosis when managing patients with recurrent pancreatitis regardless of their age.

Course and Treatment of a Rare Neurological Sequelae After COVID-19: Miller Fisher Syndrome.

Reports of COVID-19 infection detailing its symptoms and outcomes point to its effects systemically, including that of the nervous system, such as the rare Miller Fisher syndrome (MFS). In this report, we identified a 43-year-old Caribbean man who arrived in the USA with ataxia and ascending bilateral lower extremity weakness after COVID-19 infection. Before arrival, the patient was diagnosed with Guillain-Barré syndrome (GBS). He was treated with IV methylprednisolone and a round of IV immunoglobulin (IVIG); however, he showed a minimal response. Upon admission to our ED, he had severe tachypnea and flaccid symmetrical quadriparesis combined with areflexia. Moreover, he had begun to exhibit signs of multiple cranial nerve palsies, including ophthalmoplegia and facial diplegia. Additionally, his laboratory cerebrospinal fluid (CSF) analysis was grossly normal. Therefore, he was diagnosed with MFS. Furthermore, he developed acute depression and exhibited signs of mania. The patient was treated with IV methylprednisolone and the second round of a five-day course of IVIG, resulting in marked clinical improvement. This case highlights the need for a multidisciplinary care approach in patients with MFS. It also points to the possible benefit of multiple IVIG rounds in MFS patients who do not improve after the first course.

Isolated Pneumopericardium: A Rare Complication Secondary to COVID-19 Infection.

Pneumopericardium in the setting of COVID-19 is a rare incident. Typically, COVID-19 manifests with respiratory failure, cytokine storm, and gastrointestinal and cardiac symptoms. Chest X-ray (CXR) shows patchy peripheral opacities in bilateral lung fields and computed tomography (CT) shows multifocal ground-glass opacities in a COVID-19 patient. However, CXR is relatively less specific when compared to CT. In this case report, we present a case of isolated pneumopericardium (without pneumomediastinum) in a young female patient with COVID-19 pneumonia. Not only is the mechanism of development of pneumopericardium in COVID-19 patients poorly understood, but it is also considered a bad prognostic factor that leads to mortality.

Third wave COVID-19 delta variant breakthrough infection in a Hispanic-dominant suburb of Miami, Florida: ethical dilemma and vaccination hesitancy.

Background and Aims: The peak of the third wave of COVID-19 infection was in the summer (August-September) of 2021, dominated by the Delta variant. Florida was the epicenter of the third wave with more than 151,449 cases in the first week of August with a positivity rate of 20%. The purpose of this study is to identify the percentage of COVID-19 infection in vaccinated patients in a minority population in south Florida and to elucidate the relationship, if any, between demographics and breakthrough infections, the rate of vaccine hesitancy, as well as the willingness to receive the monoclonal antibody REGEN-COV for the treatment of COVID-19. Methods: This cross-sectional study was performed at the Emergency Department, Larkin Community Hospital Palm Spring Campus, located in Hialeah, the fourth largest city in Florida. Hialeah is dominated (94.7%) by Hispanics and Latinos. This city represents a cross-sectional sample of US cities in general and Florida in specific. We enrolled 127 COVID-19 PCR-positive patients. Results: The infection in vaccinated patients (breakthrough) was found to be about one in three (34%). Despite the high infection rate and mounting death toll, about 73% of our unvaccinated patients answered no to the question 'knowing the consequences of being infected with COVID-19 and the fact that you are positive, would you have chosen to be vaccinated earlier?' However, about 27% of these patients agreed to receive the vaccine and 20.5% received the monoclonal antibody REGEN-COV. Conclusions: Our study revealed that vaccine hesitancy in South Florida continues to be a major challenge, especially with the emergence of mutations including Delta plus and Omicron.

Bell's palsy as a possible complication of mRNA-1273 (Moderna) vaccine against COVID-19.

Introduction: Vero Cell, AstraZeneca, Janssen, mRNA-1273 (Moderna), and Pfizer COVID-19 vaccines have been authorized for emergency use in Nepal. These vacines have been linked to some adverse effects, including fever, myalgia, and headache. Furthermore Bell's Palsy a rare adverse effect was also reported to be associated with the use of mRNA-1273 (Moderna) vaccine in some patients. Case presentation: In this case report we present a 17-year-old female who acquired Bell's Palsy following the administration of mRNA-1273 (Moderna) COVID-19 vaccination. Discussion: The possible etiology of BP that has been suggested is infection by reactivated viruses, such as the varicella-zoster virus (VZV), herpes simplex virus type 1 (HSV-1), human herpesvirus 6, and the Usutu virus, [1] the most accepted hypothesis is the one with reactivation of latent Herpes Simplex Virus type 1 in the geniculate ganglia of the facial nerves, an autoimmune mechanism through the mimicry of host molecules by the antigens of the vaccines. Conclusion: Though the extent of association between the mRNA vaccination and the development of Bell's Palsy has yet to be confirmed, this example highlights the need to closely monitor side effects and repercussions after receiving a new vaccine.

Impact of COVID­19 infection in patients with neurodegenerative diseases with particular focus on Alzheimer's and Parkinson's disease.

Neurodegenerative disorders (NDD) are chronic neurological diseases characterized by loss and/or damage to neurons along with the myelin sheath, and patients are at higher risk of severe infection with the SARS­CoV­2. A comprehensive literature search was performed using relevant terms and inclusion­exclusion criteria. Recent articles, subjects older than 50 years, and articles written in the English language were included, whereas letters to the editor and articles related to pregnant women were excluded from the review study. COVID­19 appears to damage angiotensin­II receptors which cause natural killer cells to lose the ability to clear virus­infected cells, owing to worse outcomes in patients with NDD. COVID­19 can worsen the symptoms of Alzheimer's disease. In addition, COVID­19 worsens drug­responsive motor symptoms in Parkinson's disease (PD) and other symptoms like fatigue and urinary complaints. Vitamin D is essential in decreasing pro­inflammatory and increasing anti­inflammatory cytokines in ongoing COVID­19 infections and reducing angiotensin receptors and, hence, decreasing COVID­19 infection severity. Telemedicine shows promise for patients with NDD but is yet to overcome legal issues and personal barriers. COVID­19 has a significant effect on neurodegenerative conditions, which appears partly to the nature of the NDD and the neuro­invasive capabilities of the SARS­CoV­2. The protective role of vitamin D in patients with NDD further supports this hypothesis. Modifications in current health care, like the telemedicine platform, are required to address the increased risk of serious infection in this population. Further studies will be required to clarify conflicting reports in many fields.

Evidence of Post-COVID-19 Transverse Myelitis Demyelination.

The COVID-19 infection is associated with neurological complications involving both the central and peripheral nervous systems. We present a case of a healthy 36-year-old woman who developed symptoms of transverse myelitis (TM) four weeks following a positive COVID-19 infection. She presented with severe fatigue, bilateral lower extremity ascending tingling, progressive muscle weakness, diminished sensation to pain, temperature and vibration, hyperreflexia, and neurogenic bladder. MRI showed extensive demyelination of the cervical and thoracic spine, and cerebrospinal fluid (CSF) analysis showed mildly elevated protein with normal cell count and no evidence of infection, including negative COVID-19 PCR. The patient was treated with intravenous methylprednisolone dosed daily for five days, and markedly improved and continued to be followed up closely at the office.

Molecular Interaction Network Approach (MINA) identifies association of novel candidate disease genes.

Molecular Interaction Network Approach (MINA) was used to elucidate candidate disease genes. The approach was implemented to identify novel gene association with commonly known autoimmune diseases [1]. In MINA, we evaluated the hypothesis that "network proximity" within a whole genome molecular interaction network can be used to inform the search for multigene inheritance. There are now numerous examples of gene discoveries based upon network proximity between novel and previously identified disease genes (Yin et al., 2017 [2], Wang et al., 2011 [3], and Barrenas et al., 2009 [4]). This study extends the application of interaction networks to the interrogation of Genome Wide Association studies: first, by showing that a group of nine autoimmune diseases (AuD) genes "seed genes", are connected in a highly non-random manner within a whole genome network; and second, by showing that the minimal number of connecting genes required to connect a maximal number of AuD candidate genes are highly enriched as candidate genes for AuD predisposing mutations. The findings imply that a threshold number of candidate genes for any heritable disorder can be used to "seed" a molecular interaction network that •Serves to validate the disease status of closely associated seed genes•Identifies genes that are highly enriched as novel candidate disease genes•Provides a strategy for elucidation of epistatic gene x gene interactions The method could provide a critical toll for understanding the genetic architecture of common traits and disorders.

Diagnostic role of kidney injury molecule-1 in renal cell carcinoma.

Despite rapid advances in diagnostic and therapeutic medicine, renal cell carcinoma (RCC) continues to cause significant morbidity and mortality in patients. While there has been a shift towards earlier detection, approximately 16% of patients present with metastatic disease at the time of diagnosis. Kidney injury molecule-1 (KIM-1) is a glycoprotein that has been shown to be a robust and reliable biomarker of acute proximal tubular injury. As KIM-1 is mainly expressed in RCC derived from the proximal tubules, it is a reliable marker to differentiate between proximal tubular primary RCC and distal nephron primary RCC. Several studies have investigated urinary KIM-1 (uKIM-1) in RCC and demonstrated that it is a sensitive and specific marker for detecting localized RCC, as patients had markedly reduced uKIM-1 levels following nephrectomy, with uKIM-1 levels correlating with tumor size and grade. In addition, levels of KIM-1 present in plasma have also shown utility as a biomarker of RCC with levels being elevated in RCC cases at least 5 years before diagnosis. This review focuses on a progressive understanding of KIM-1 in the diagnosis of RCC using biopsies, urine, and plasma samples, and it will also provide some insight into potential roles of KIM-1 in the growth and spread of RCC.