The Gastric and Intestinal Microbiome: Role of Proton Pump Inhibitors.

PURPOSE OF REVIEW: The discovery of Helicobacter pylori and other organisms colonizing the stomach and the intestines has shed some light on the importance of microbiome in maintaining overall health and developing pathological conditions when alterations in biodiversity are present. The gastric acidity plays a crucial role in filtering out bacteria and preventing development of enteric infections. In this article, we discuss the physiology of gastric acid secretion and bacterial contribution to the composition of gastric and intestinal barriers and review the current literature on the role of proton pump inhibitors (PPIs) in the microbial biodiversity of the gastrointestinal tract. RECENT FINDINGS: Culture-independent techniques, such as 16S rRNA sequencing, have revolutionized our understanding of the microbial biodiversity in the gastrointestinal tract. Luminal and mucosa-associated microbial populations are not identical. Streptococcus is overrepresented in the biopsies of patients with antral gastritis and may also be responsible for the development of peptic ulcer disease. The use of PPIs favors relative streptococcal abundance irrespective of H. pylori status and may explain the persistence of dyspeptic symptoms in patients on PPI therapy. Increased risk of enteric infections has also been seen in patients taking PPIs. The overuse of PPIs leads to significant shift of the gastrointestinal microbiome towards a less healthy state. With the advent of PPIs, many studies have demonstrated the significant changes in the microbial composition of both gastric and intestinal microbiota. Although they are considered relatively safe over-the-counter medications, PPIs in many cases are over- and even inappropriately used. Future studies assessing the safety of PPIs and their role in the development of microbiome changes should be encouraged.

Carotid-Cavernous Fistula in a Patient With Unilateral Periorbital Swelling and Proptosis Initially Attributed to Possible Immunoglobulin G4-Related (IgG4-Related) Disease.

The differential diagnosis for proptosis and periorbital swelling is broad and includes infectious, malignant, vascular, and rheumatologic etiologies. In this study, we report a case of carotid-cavernous fistula as the cause of acute-onset unilateral proptosis and periorbital swelling of the right eye in a 44-year-old female patient whose symptoms were initially attributed to possible immunoglobulin G4-related disease (IgG4-RD). The patient initially received antibiotics for presumed cellulitis and steroid treatment for a possible autoimmune cause, however; her autoimmune work-up was negative. Radiologic imaging later confirmed that she had a direct spontaneous carotid-cavernous fistula. She experienced significant improvement in her symptoms and vision after embolization treatment. Due to the risk that a carotid-cavernous fistula will progress quickly and cause neurological damage, this is a key diagnosis that should not be missed in patients with acute-onset periorbital and visual symptoms. Rheumatologists should include this condition in the differential for any patient who presents with periorbital swelling and vision disturbances.

"I Can't Move My Arms and Legs": A Rare Cause of Hypokalemia-Induced Quadriparesis.

Hypokalemia is a relatively common electrolyte abnormality in hospitalized patients. Severe hypokalemia (<2.5 mEq/L) can lead to profound muscle weakness or paralysis, especially in the setting of acute onset of hypokalemia. Multiple mechanisms of hypokalemia have been described, such as decreased potassium intake, increased losses, and increased transcellular shift of potassium. Drugs can rarely cause hypokalemia by one of the above-mentioned mechanisms. Here, we report a case of cocaine use leading to severe hypokalemia manifesting as quadriparesis. The aggressive repletion of potassium led to a complete resolution of muscular weakness.

Systemic Sclerosis: Current State and Survival After Lung Transplantation.

Systemic sclerosis (SSc) is an autoimmune disorder characterized by the involvement of skin and internal organs. With the introduction of angiotensin-converting enzyme inhibitors (ACEIs), scleroderma renal crisis (SRC) is no longer considered a leading cause of death in affected patients. In fact, pulmonary manifestations [interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH)] are currently the major cause of death in patients with SSc. Historically, many centers have been reluctant to offer lung transplantation to patients with SSc due to multiple extrapulmonary manifestations and the assumption of poor post-transplant survival. The purpose of this review is to highlight the recent advances in the evaluation and management of patients with pulmonary manifestations of SSc. We also engage in a systematic literature review to assess all the available data on the survival of patients with SSc after lung transplantation.

Severe acute respiratory syndrome coronavirus 2-induced acute aortic occlusion: a case report.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 infection can lead to a constellation of viral and immune symptoms called coronavirus disease 2019. Emerging literature increasingly supports the premise that severe acute respiratory syndrome coronavirus 2 promotes a prothrombotic milieu. However, to date there have been no reports of acute aortic occlusion, itself a rare phenomenon. We report a case of fatal acute aortic occlusion in a patient with coronavirus disease 2019. CASE REPORT: A 59-year-old Caucasian male with past medical history of peripheral vascular disease presented to the emergency department for evaluation of shortness of breath, fevers, and dry cough. His symptoms started 5-7 days prior to the emergency department visit, and he received antibiotics in the outpatient setting without any effect. He was found to be febrile, tachypneic, and hypoxemic. He was placed on supplemental oxygen via a non-rebreather mask. Chest X-ray showed multifocal opacifications. Intravenous antibiotics for possible pneumonia were initiated. Hydroxychloroquine was initiated to cover possible coronavirus disease 2019 pneumonia. During the hospitalization, the patient became progressively hypoxemic, for which he was placed on bilevel positive airway pressure. D-dimer, ferritin, lactate dehydrogenase, and C-reactive protein were all elevated. Severe acute respiratory syndrome coronavirus 2 reverse transcription polymerase chain reaction was positive. On day 3, the patient was upgraded to the intensive care unit. Soon after he was intubated, he developed a mottled appearance of skin, which extended from his bilateral feet up to the level of the subumbilical plane. Bedside ultrasound revealed an absence of flow from the mid-aorta to both common iliac arteries. The patient was evaluated emergently by vascular surgery. After a discussion with the family, it was decided to proceed with comfort-directed care, and the patient died later that day. DISCUSSION: Viral infections have been identified as a source of prothrombotic states due to direct injury of vascular tissue and inflammatory cascades. Severe acute respiratory syndrome coronavirus 2 appears to follow a similar pattern, with numerous institutions identifying elevated levels of thrombotic complications. We believe that healthcare providers should be aware of both venous and arterial thrombotic complications associated with coronavirus disease 2019, including possible fatal outcome.

Behavioral Deficits and Brain α-Synuclein and Phosphorylated Serine-129 α-Synuclein in Male and Female Mice Overexpressing Human α-Synuclein.

BACKGROUND: Alpha-synuclein (α-syn) is involved in pathology of Parkinson's disease, and 90% of α-syn in Lewy bodies is phosphorylated at serine 129 (pS129 α-syn). OBJECTIVE: To assess behavior impairments and brain levels of α-syn and pS129 α-syn in mice overexpressing human α-syn under Thy1 promoter (Thy1-α-syn) and wild type (wt) littermates. METHODS: Motor and non-motor behaviors were monitored, brain human α-syn levels measured by ELISA, and α-syn and pS129 α-syn mapped by immunohistochemistry. RESULTS: Male and female wt littermates did not show differences in the behavioral tests. Male Thy1-α-syn mice displayed more severe impairments than female counterparts in cotton nesting, pole tests, adhesive removal, finding buried food, and marble burying. Concentrations of human α-syn in the olfactory regions, cortex, nigrostriatal system, and dorsal medulla were significantly increased in Thy1-α-syn mice, higher in males than females. Immunoreactivity of α-syn was not simply increased in Thy1-α-syn mice but had altered localization in somas and fibers in a few brain areas. Abundant pS129 α-syn existed in many brain areas of Thy1-α-syn mice, while there was none or only a small amount in a few brain regions of wt mice. The substantia nigra, olfactory regions, amygdala, lateral parabrachial nucleus, and dorsal vagal complex displayed different distribution patterns between wt and transgenic mice, but not between sexes. CONCLUSION: The severer abnormal behaviors in male than female Thy1-α-syn mice may be related to higher brain levels of human α-syn, in the absence of sex differences in the altered brain immunoreactivity patterns of α-syn and pS129 α-syn.

Hamman-Rich Syndrome: A Diagnosis of Exclusion in the COVID-19 Pandemic.

Hamman-Rich syndrome is a rapidly progressive interstitial lung disease with acute respiratory distress syndrome physiology. It carries a grave prognosis and a high early mortality rate. It is often distinguished from other similar pulmonary pathologies based on the clinical course, laboratory findings, bronchoalveolar lavage testing, and pathology report. We detail a 77-year-old lady with no prior pulmonary disease, smoking history, or occupational and environmental exposures present to the emergency department found to be in acute hypoxic respiratory failure with impressive progressive radiographic findings. The presumptive diagnosis of Hamman-Rich syndrome was made based on a combination of factors after ruling out other similar clinical entities, especially in the setting of an ongoing COVID-19 pandemic.

Peritonsillar Phlegmon: An Addition to the Spectrum of COVID-19.

The coronavirus disease 2019 (COVID-19) epidemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first reported in December 2019 in Wuhan, China, then declared to be a pandemic associated with substantial morbidity and mortality. It has shown to exhibit a vast array of symptoms, among which fever, shortness of breath, and cough are the most commonly reported. Lymphadenopathy and tonsillar enlargement is a less common finding reported with this infection. This case describes a patient with tonsillar inflammation which was complicated by peritonsillar phlegmon, with negative throat culture and positive COVID-19 test, suggesting a COVID-19-related etiology of the disease. After the literature search, to the best of our knowledge, this is the first reported case of COVID-related peritonsillar inflammation and phlegmon formation.

A Rare Presentation of Coronavirus Disease 2019 (COVID-19) Induced Viral Myositis With Subsequent Rhabdomyolysis.

A 38-year-old gentleman with no significant past medical history but had recent COVID-19 exposure presented to the hospital with the chief complaints of fever, shortness of breath, and generalized myalgia. He was unfortunately found to be severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive. Laboratory findings showed creatine kinase (CK) >42,670 U/L along with elevated inflammatory markers and unremarkable creatinine, cardiac troponin level. The cause of his rhabdomyolysis was discovered to be due to COVID-19 as he had no evidence of other viral infections, strenuous exercise, seizure, or other nontraumatic exertional etiologies. He received aggressive fluid resuscitation while we trended his CK levels along with other inflammatory markers throughout his hospitalization course. His diffuse myalgia improved with treatments, and he was found to maintain stable hemodynamics and was subsequently discharged home.

Rhabdomyosarcoma from uterus to heart.

Rhabdomyosarcoma (RMS) is a malignant soft tissue tumor of the pediatric population which is  rarely seen in adults. Metastatic rhabdomyosarcoma is even rarer. We present an unusual case of a 49 year old female presenting with palpitations and uterine bleeding. An Echo-cardiogram revealed a large oval mass on the posterior mitral leaflet and a Computerized Tomography (CT) scan of the abdomen revealed a uterine growth. Surgical excision of the cardiac mass was done and histological analysis of cardiac lesion confirmed it to be rhabdomyosarcoma with a primary source in the uterus. The patient became asymptomatic from a cardiac standpoint after excision of the mass and was scheduled for chemo/radiation therapy for the primary uterine malignancy. Metastatic cardiac rhabdomyosarcoma can be confused with a myxoma or any other primary or secondary cardiac tumors resulting in delayed diagnosis. However, its aggressive nature makes it a life-threatening tumor that requires an early diagnosis to prevent fatal consequences.

Efficacy of Allopurinol in Cardiovascular Diseases: A Systematic Review and Meta-Analysis.

BACKGROUND: Given current evidence, the use of allopurinol for the prevention of major cardiovascular events (acute cardiovascular syndrome (ACS) or cardiovascular mortality) in patients undergoing coronary artery bypass graft (CABG), after index ACS or heart failure remains unknown. METHODS: Multiple databases were queried to identify studies comparing the efficacy of allopurinol in patients undergoing CABG, after ACS or heart failure. The unadjusted odds ratio (OR) was calculated using a random effect model. RESULTS: A total of nine studies comprising 850 patients (allopurinol 480, control 370) were identified. The pooled OR of periprocedural ACS (OR: 0.25, 95% confidence interval (CI): 0.06 - 0.96, P = 0.05) and cardiovascular mortality (OR: 0.22, 95% CI: 0.07 - 0.71, P = 0.01) was significantly lower in patients receiving allopurinol during CABG compared to patients in the control group. The overall number needed to treat (NNT) to prevent one ACS event was 11 (95% CI: 7 - 28), while the NNT to prevent one death was 24 (95% CI: 13 - 247). By contrast, the odds of cardiovascular mortality in the allopurinol group were not significantly different from the control group in patients on long-term allopurinol after ACS or heart failure (OR: 0.33, 95% CI: 0.01 - 8.21, P = 0.50) and (OR: 1.12, 95% CI: 0.39 - 3.20, P = 0.83), respectively. Similarly, the use of allopurinol did not reduce the odds of recurrent ACS events at 2 years (OR: 0.32, 95% CI: 0.03 - 3.18, P = 0.33). CONCLUSIONS: Periprocedural use of allopurinol might be associated with a significant reduction in the odds of ACS and cardiovascular mortality in patients undergoing CABG. Allopurinol, however, offers no long-term benefits in terms of secondary prevention of ACS or mortality. Larger scale studies are needed to validate our findings.

Comparative accuracy of non-invasive imaging versus right heart catheterization for the diagnosis of pulmonary hypertension: A systematic review and meta-analysis.

BACKGROUND: Right heart catheterization (RHC) is the gold-standard in the diagnosis of pulmonary hypertension (PH) but at the cost of procedure-related complications. We sought to determine the comparative accuracy of RHC versus non-invasive imaging techniques such as computed tomography (CT), magnetic resonance imaging (MRI), and transthoracic echocardiography (TTE). METHODS: Pulmonary hypertension was defined as a mean pulmonary artery pressure (mPAP) of>20 mmHg. Multiple databases were queried for relevant articles. Raw data were pooled using a bivariate model to calculate the measures of diagnostic accuracy and to estimate Hierarchical Summary Receiver Operating Characteristic (HSROC) on Stata 13. RESULTS: A total of 51 studies with a total patient population of 3947 were selected. The pooled sensitivity and specificity of MRI for diagnosing PH was 0.92(95% confidence interval (CI) 0.88-0.96) and 0.86 (95% CI, 0.77-0.95), respectively. The net sensitivities for CT scan and TTE were 0.79 (95% CI 0.72-0.89) and 0.85 (95% CI 0.83-0.91), respectively. The overall specificity was 0.82 (0.76-0.92) for the CT scan and 0.71 (95% CI 0.61-0.84) for TTE. The diagnostic odds ratio (DOR) for MRI was 124 (95% CI 36-433) compared to 30 (95% CI 11-78) and 24 (95% 11-38) for CT scan and TTE, respectively. Chi-squared (x2) test showed moderate heterogeneity on the test for equality of sensitivities and specificities. CONCLUSIONS: MRI has the highest sensitivity and specificity compared to CT and TTE. MRI can potentially serve as a surrogate technique to RHC for the diagnosis of PH.

Falling for a Diagnosis: West Nile Myelitis without Encephalitis.

Poliovirus has been eradicated in the US for 40 years. Its sequelae, poliomyelitis, a syndrome characterized by fever, meningitis, and flaccid paralysis, is a rare entity. Other viruses have been implicated in poliomyelitis-like syndromes since the elimination of poliovirus. West Nile virus (WNV), since its westward migration in 1999, has recently been found to be a causative agent of fever, encephalitis, and acute flaccid paralysis. We present the case of a male who presented to the hospital for fever and experienced a subsequent fall, without any symptoms of encephalitis, diagnosed with WNV infection.

Endobronchial Hamartoma as a Rare Cause of Recurrent Respiratory Symptoms: Case Report and Literature Review.

Most of the endobronchial lesions are malignant in origin. In rare instances, benign lesions occupying the endobronchial tree can mimic malignant neoplasms on conventional imaging tests. We present a case of a middle-aged male patient who was admitted to our hospital with recurrent hemoptysis concerning for lung cancer on computed tomography (CT) of the chest. Biopsy of the mass obtained via bronchoscopy revealed a benign lesion most consistent with lipomatous hamartoma, which is known to constitute only 10% of all pulmonary hamartomas. We also present the data of a comprehensive literature review of the epidemiology, clinical symptoms, diagnosis, treatment, and prognosis of patients with endobronchial hamartomas.

Multiple Beneficial Effects of Ghrelin Agonist, HM01 on Homeostasis Alterations in 6-Hydroxydopamine Model of Parkinson's Disease in Male Rats.

Background and objective: Developing therapy for non-motor symptoms of Parkinson's disease (PD) is important for improving patients' quality of life. Previously, we reported that the ghrelin receptor agonist, HM01 normalized the decreased 4-h fecal output and levodopa-inhibited gastric emptying in 6-OHDA rats, and activated selective areas in brain and spinal cord. In this study, we evaluated whether chronic HM01 treatment influences motor functions and/or has beneficial effects on non-motor symptoms including alterations of body weight and composition, defecation, feeding and water intake in 6-OHDA rats. Methods: Male rats were microinjected unilaterally into the medial forebrain bundle with either vehicle or 6-OHDA. Three weeks later, we assessed basal body weight, and 24-h fecal output (pellets, weight, dry weight and water content), water intake and food intake (ingested and spillage). Then, HM01 (3 mg/kg) or vehicle was given per gavage daily for 10-12 days and the same parameters were re-assessed daily. Motor behavior (stepping and rotations tests), body composition were monitored before and after the HM01 treatment. Results: 6-OHDA rats showed motor deficits in rotation test induced by apomorphine and stepping test. They also displayed a significant reduction in body weight, water consumption, fecal weight and water content and an increase in food spillage compared to vehicle microinjected rats. Daily oral treatment of HM01 did not modify motor alterations compared to vehicle but significantly increased the body weight, fat mass, and 24-h fecal weight, fecal water content, food and water intake in 6-OHDA rats, while HM01 had no significant effect in vehicle microinjected rats. Fecal weight and water content were both correlated with water intake, but not with food intake. Fat mass, but not body weight, was correlated with food intake. HM01 effects were significant after 24 h and remained similar during the treatment. Conclusions: Chronic treatment with ghrelin agonist, HM01 improved several non-motor symptoms in the rat PD model induced by 6-OHDA lesion including the decrease in body weight, water consumption, fecal weight and water content, and increased food intake while not improving the motor deficits. These findings provide pre-clinical evidence of potential benefits of ghrelin agonists to alleviate non-motor symptoms in PD patients.

The Use of High-dose Insulin Infusion and Lipid Emulsion Therapy in Concurrent Beta-blocker and Calcium Channel Blocker Overdose.

Patients admitted with the presumed coingestion of beta-blockers (BBs) and calcium channel blockers (CCBs) should be initially managed in accordance with standardized resuscitation protocols (the airway, breathing, and circulation (ABC) approach). Additionally, more specific interventions should be promptly attempted. Intravenous glucagon and calcium salts have long been used in the treatment of BB and CCB toxicities. We present a case of a severe, concurrent BB and CCB toxicity resulting in cardiovascular collapse refractory to vasopressors. The administration of high-dose insulin (HDI) and lipid emulsion therapy (LET) resulted in a significant improvement in hemodynamics with an overall favorable outcome in the patient.

Autoimmune atrophic gastritis: current perspectives.

At present there is no universally accepted classification for gastritis. The first successful classification (The Sydney System) that is still commonly used by medical professionals was first introduced by Misiewicz et al in Sydney in 1990. In fact, it was the first detailed classification after the discovery of Helicobacter pylori by Warren and Marshall in 1982. In 1994, the Updated Sydney System was proposed during the International Workshop on the Histopathology of Gastritis followed by the publication in The American Journal of Surgical Pathology by Dixon et al. Using the new classification, distinction between atrophic and nonatrophic gastritis was revised, and the visual scale grading was incorporated. According to the Updated Sydney System Classification, atrophic gastritis is categorized into multifocal (H. pylori, environmental factors, specific diet) and corpus-predominant (autoimmune). Since metaplasia is a key histological characteristic in patients with atrophic gastritis, it has been recommended to use the word "metaplastic" in both variants of atrophic gastritis: autoimmune metaplastic atrophic gastritis (AMAG) and environmental metaplastic atrophic gastritis. Although there are many overlaps in the course of the disease and distinction between those two entities may be challenging, the aim of this review article was to describe the etiology, epidemiology, pathogenesis, diagnosis, clinical manifestations and treatment in patients with AMAG. However, it is important to mention that H. pylori is the most common etiologic factor for the development of gastritis in the world.