Novel Therapies for Celiac Disease: A Clinical Review Article.

Celiac disease is emerging as an autoimmune disorder with increasing prevalence and incidence. The mean age of presentation is also increasing with the passage of time. The delay in diagnosis is partly attributable to the asymptomatic state in which most patients present. The diagnosis of the disease is primarily based on biopsy, but serology can also be included for possible screening purposes. Although the primary management strategy is to eliminate gluten from the diet of such patients; however, compliance with the diet and follow-up to detect healing might be difficult to maintain. Therefore, there is a need to investigate further management therapies that can be easily administered and monitored. The aim of the review is to discuss the epidemiology, clinical presentation, and novel therapies being investigated for celiac disease.

Role of Fecal Microbiota Transplantation in Managing Clostridium Difficile Infection and Inflammatory Bowel Disease: A Narrative Review.

Fecal microbiota transplantation (FMT) has been emerging as an alternate treatment modality in the management of patients with dysbiosis by restoring abnormal gut microbiota composition through the transplantation of normal fecal microbiota from healthy donors. This technique has lately gained a lot of attention in the treatment of recurrent or refractory Clostridium difficile infection (CDI) owing to its high success rates combined with its favorable safety profile. FMT has also been attracting the interest of clinicians as a new treatment option for inflammatory bowel diseases (IBD). Here, we reviewed most of the recent advancements in the use of FMT for CDI as well as its use in the treatment of IBD.

Diagnostic Modalities Used in Diagnosing Gastroparesis: A Clinical Review.

Gastroparesis is associated with abnormal gastric motility characterized by delayed gastric emptying without any obvious mechanical gastric outlet obstruction or blockage. Gastroparesis is associated with significant morbidity and mortality. It is pertinent to make a timely diagnosis of gastroparesis so that prompt treatment can be initiated. The purpose of this clinical review article is to help the internist and the primary care providers to get a better idea of various diagnostic modalities used in diagnosing gastroparesis. We have also discussed the advantages and disadvantages of various diagnostic modalities based on the latest evidence.

A Case Report of Wernicke's Encephalopathy Disguised As Limbic Encephalitis: A Clinical Puzzle.

Wernicke's encephalopathy (WE) is the presence of neurological symptoms in the central nervous system caused by thiamine (Vitamin B1) deficiency. It is an acute clinical condition characterized by confusion, ataxia, and ophthalmoplegia triad. WE is most commonly observed in chronic alcohol users, while it can also present in non-alcoholics. We present a 33-year-old man with alcohol-induced WE who presented with altered mental status and fever. His initial diagnosis was skewed towards bacterial meningitis and limbic encephalitis, but MRI findings were consistent with WE. The patient responded promptly to intravenous (IV) thiamine infusion, and his mental status changed significantly. Repeat EEG in 15 days shows complete recovery with normal brain wave activity. Untreated WE is a significant cause of permanent neurological morbidity and mortality, easily preventable. High suspicion of WE should always be entertained, especially when patients have a known history of alcohol use. Early initiation of IV thiamine could prevent the consequences. Hence, it is essential to raise awareness of WE to take measures without delay and reduce mortality and morbidity with an improved prognosis.

Mechanisms and management of prothrombotic state in COVID-19 disease.

The novel severe acute respiratory syndrome viral disease outbreak due to SARS-CoV-2 is a rapidly evolving disease and represents one of the greatest medical challenges in recent times. It is believed that SARS-CoV-2 has migrated from bats to an intermediate host and then to humans. This article aims at the mechanism and management of prothrombotic state in COVID-19 positive patients. We tried to present how the SARS-CoV-2 virus can induce thromboembolic events and the incidence of these thromboembolic events. We also tried to depict anticoagulation management in these patients as well as postdischarge plan and follow-up. Invasion of type 2 pneumocytes by the SARS-CoV-2 virus is critical in the course of illness because it results in activation of immune cells leading to elevation of cytokines. The subsequent activation of T cells and macrophages infiltrates the infected myocardial cells causing direct myocardiocyte toxicity and development of arrhythmia. Hypoxia or hypotension during the clinical course causes a mismatch between myocyte oxygen supply and workload demand resulting in cardiac distress. SARS-CoV-2 affects endothelial cells and pericytes that lead to severe micro and macrovascular dysfunction, and together with oxygen supply-demand mismatch, immune hyperresponsivity can potentially cause destabilization and plaque rupture causing acute coronary syndromes. Other mechanisms of injury include myocarditis, pericarditis, stress cardiomyopathy, vasculitis, and DIC (Disseminated intravascular coagulation)/microthrombi. SARS-CoV-2 enters the cells by the Spike protein S whose surface unit, S1, binds to the ACE2 receptor on the host cell. The type II transmembrane serine proteases TMPRSS2 and histone acetyltransferases (HAT) are host cell proteases that are recruited by the virus to cleave ACE2 surface protein S which facilitates the viral entry. Therefore, TMPRSS2 and HAT could be targeted for potential drugs against SARS-CoV-2. SARS-CoV-2 uses an RNA-dependent RNA polymerase for proliferation, which is targeted by remdesivir that is currently approved for emergency use by Food and Drug Administration (FDA). We need to adopt a multifaceted approach when combating SARS-CoV-2 because it presents several challenges including medical, psychological, socioeconomic, and ethical. COVID-19 is the biggest calamity during the 21st century, we need to have a keen understanding of its pathophysiology and clinical implications for the development of preventive measures and therapeutic modalities.

PPAR-γ activation enhances myelination and neurological recovery in premature rabbits with intraventricular hemorrhage.

Intraventricular hemorrhage (IVH) results in periventricular inflammation, hypomyelination of the white matter, and hydrocephalus in premature infants. No effective therapy exists to prevent these disorders. Peroxisome proliferator activated receptor-γ (PPAR-γ) agonists reduce inflammation, alleviate free radical generation, and enhance microglial phagocytosis, promoting clearance of debris and red blood cells. We hypothesized that activation of PPAR-γ would enhance myelination, reduce hydrocephalus, and promote neurological recovery in newborns with IVH. These hypotheses were tested in a preterm rabbit model of IVH; autopsy brain samples from premature infants with and without IVH were analyzed. We found that IVH augmented PPAR-γ expression in microglia of both preterm human infants and rabbit kits. The treatment with PPAR-γ agonist or PPAR-γ overexpression by adenovirus delivery further elevated PPAR-γ levels in microglia, reduced proinflammatory cytokines, increased microglial phagocytosis, and improved oligodendrocyte progenitor cell (OPC) maturation in kits with IVH. Transcriptomic analyses of OPCs identified previously unrecognized PPAR-γ-induced genes for purinergic signaling, cyclic adenosine monophosphate generation, and antioxidant production, which would reprogram these progenitors toward promoting myelination. RNA-sequencing analyses of microglia revealed PPAR-γ-triggered down-regulation of several proinflammatory genes and transcripts having roles in Parkinson's disease and amyotrophic lateral sclerosis, contributing to neurological recovery in kits with IVH. Accordingly, PPAR-γ activation enhanced myelination and neurological function in kits with IVH. This also enhanced microglial phagocytosis of red blood cells but did not reduce hydrocephalus. Treatment with PPAR-γ agonist might enhance myelination and neurological recovery in premature infants with IVH.

Digital Ischemia as an Initial Presentation in a COVID-19-Positive Patient Without Any Significant Respiratory Symptoms.

Coronavirus disease 2019 (COVID-19) is an evolving situation worldwide, which is associated with a broad range of symptoms from pneumonia/acute respiratory distress syndrome (ARDS) to multiorgan failure. So far, we have also encountered several patients with coagulopathy, including pulmonary embolism and deep vein thrombosis. A few cases of limb ischemia related to COVID-19 have been reported as well, but most of them involve critically ill patients. In this report, we discuss a case of COVID-19 in a patient who presented with right thumb ischemia without any significant respiratory symptoms.

A Rare Case of Acute Pericarditis Due to SARS-CoV-2 Managed With Aspirin and Colchicine.

SARS-CoV-2 infection presents with predominant respiratory illness. Cardiac injury has been reported in patients with SARS-CoV-2 infection. The spectrum of cardiac involvement ranges from pericarditis to myocarditis. Acute pericarditis attributed to SARS-CoV-2 is rare. A 68-year-old male with co-morbid condition of hypertension and arthritis presented with chest tightness, cough and exertional shortness of breath for five days. He was tachycardic at the time of presentation and cardiac auscultation was positive for pericardial rub. His room air oxygen saturation was 95%. Chest imaging studies revealed bilateral infiltrate. His electrocardiogram showed ST elevation with diffusely elevated J point in lead II, III, aVF and V4-V6. Echocardiogram was unrevealing for pericardial effusion and left ventricular ejection fraction was normal. Serial troponin level did not reveal a rising trend. The nasopharyngeal swab was positive for SARS-CoV-2 RNA. Nonsteroidal anti-inflammatory drugs (NSAIDs) use in SARS-CoV-2 positive patient is debatable. The patient had acute pericarditis due to SARS-CoV-2 and it was treated with high dose aspirin with colchicine. Acute pericarditis is a rare complication of SARS-CoV-2 infection and can be managed with aspirin and colchicine.