Metastatic Squamous Cell Carcinoma of the Lung Disclosed From Constipation Workup.

A palpable rectal mass associated with gastrointestinal (GI) symptoms immediately raises concern for colorectal cancer, but rarely can represent distant metastatic disease. The incidence of symptomatic colorectal metastasis from a primary lung cancer without any pulmonary symptom is extremely rare. We report a rare case of constipation as the presenting symptom in a patient ultimately found to have metastatic squamous cell carcinoma of the lung. A rectal mass was readily palpable on examination, illustrating the importance of digital rectal examination. In addition, GI clinicians should maintain a high index of suspicion when evaluating patients at risk of non-GI malignancies.

Hydroxychloroquine and Cardiotoxicity.

Hydroxychloroquine (HCQ) has been used for rheumatological diseases such as systemic lupus erythematous and rheumatoid arthritis and demonstrated to improve clinical symptoms and reduce long-term sequelae. The drug is metabolized in the liver, is primarily excreted through the kidney, and works by modulating major histocompatibility complex (MHC) and various cytokines, suppressing the immune system in the process. Prolonged administration and high dosages of HCQ have been associate with cardiotoxic effects such as bradycardia, tachycardia, QT prolongation, atrioventricular block, and cardiomyopathy. Common cardiac biopsy findings of HCQ-induced toxicity are enlarged and vacuolated cells on light microscopy along with the presence of myelinoid and curvilinear bodies on transmission electron microscopy. HCQ cardiotoxicity is not very well recognized, and there are no current guidelines for routine cardiac function monitoring from either rheumatology or cardiology societies.

Cardiovascular Manifestations of Systemic Sclerosis: An Overview of Pathophysiology, Screening Modalities, and Treatment Options.

Systemic sclerosis, previously known as scleroderma, is a heterogeneous, systemic disease that is defined by its 3 pathological hallmarks: the production of autoantibodies, small vessel vasculopathy, and fibroblast dysfunction, leading to an increased deposition of extracellular matrix. We conducted a review of the available literature that covers the cardiovascular manifestations of SSc: electrical conduction abnormalities, pulmonary hypertension, pericardial disease, and atherosclerosis. Within each major category, we will discuss the definition, diagnostics, and available treatment options. Increased mortality from cardiovascular complications necessitates early screening and management. Annual screening with noninvasive modalities is encouraged. The current management of each complication generally follows the management algorithms of patients regardless of SSc status and is dependent on the severity of the patient's clinical presentation.

Effectiveness of cross-linked human acellular dermal matrix in primary and revision augmentation rhinoplasty.

BACKGROUND: Among the materials used for dorsal augmentation rhinoplasty (DAR), cross-linked human acellular dermal matrix (ADM) has been claimed for its low risk of infection and extrusion. The aim of this study was to compare the effectiveness of ADM in subjects undergoing primary versus revision dorsal augmentation rhinoplasties. METHODS: Using a retrospective cohort study design, the investigators enrolled a cohort set of DAR patients operated by a single surgeon during a 65-month interval. The predictor variable was the treatment group (primary or revision DAR). The main outcome variables were postoperative changes with regard to the degree of augmentation (ratio of the dorsal height [DH] and radix height [RH] to the nasal length) and patients' and surgeons' satisfaction with the aesthetic and functional results. Other study variables were grouped into the following categories: demographic, surgical, and pathological. Descriptive, uni-, and bivariate statistics were computed using P ≤ 0.05 as a cutoff value. RESULTS: The study cohort comprised 145 subjects (75.2% with primary DAR; 39.3% females) with a mean age of 30.7 ±â€¯9.4 years (range, 19-58). DAR was linked to the significant changes in DH and RH in both the treatment groups. Comparison of the two groups revealed that there was no significant difference in DH and RH between both the groups. Surgeons' and patients' satisfaction rates were comparable between the two surgery groups, neither of which experienced serious complications. Microscopic findings of the removed ADM showed abundant collagen tissue with newly formed vessels without signs of foreign body reaction. CONCLUSION: Despite significant differences in patient characteristics (age; number of osteotomy, tip plasty, and hump reduction surgeries), the results of this study suggest that ADM can be used in both primary and revision DAR, with minimal complications.

Anticoagulation for Atrial Fibrillation: A Review of Current Literature and Views.

Atrial fibrillation is a common supraventricular tachyarrhythmia with uncoordinated atrial activation and ineffective atrial contraction. This leads to an increased risk of atrial thrombi, most commonly in the left atrial appendage, and increased risks of embolic strokes and/or peripheral thromboembolism. It is associated with significant morbidity and mortality. To meet the concerns of thrombi and stroke, anticoagulation has been the mainstay for prevention and treatment thereof. Historically, anticoagulation involved the use of aspirin or vitamin K antagonists, mainly warfarin. Since early 2010s, direct oral anticoagulants (DOACs) including dabigatran, rivaroxaban, apixaban, and edoxaban have been introduced and approved for anticoagulation of atrial fibrillation. DOACs demonstrated a dramatic reduction in the rate of intracranial hemorrhage as compared to warfarin, and offer the advantages of absolution of monitoring therefore avoid the risk of hemorrhages in the context of narrow therapeutic window and under-treatment characteristic of warfarin, particularly in high-risk patients. One major concern and disadvantage for DOACs was lack of reversal agents, which have largely been ameliorated by the approval of Idarucizumab for dabigatran and Andexanet alfa for both apixaban and rivaroxaban, with Ciraparantag as a universal reversal agent for all DOACs undergoing Fast-Track Review from FDA. In this article, we will be providing a broad review of anticoagulation for atrial fibrillation with a focus on risk stratification schemes and anticoagulation agents (warfarin, aspirin, DOACs) including special clinical considerations.

Corneal permeability changes in dry eye disease: an observational study.

BACKGROUND: Diagnostic tests for dry eye disease (DED), including ocular surface disease index (OSDI), tear breakup time (TBUT), corneal fluorescein staining, and lissamine staining, have great deal of variability. We investigated whether fluorophotometry correlated with previously established DED diagnostic tests and whether it could serve as a novel objective metric to evaluate DED. METHODS: Dry eye patients who have had established signs or symptoms for at least 6 months were included in this observational study. Normal subjects with no symptoms of dry eyes served as controls. Each eye had a baseline fluorescein scan prior to any fluorescein dye. Fluorescein dye was then placed into both eyes, rinsed with saline solution, and scanned at 5, 10, 15, and 30 min. Patients were administered the following diagnostic tests to correlate with fluorophotometry: OSDI, TBUT, fluorescein, and lissamine. Standard protocols were used. P < 0.05 was considered significant. RESULTS: Fifty eyes from 25 patients (DED = 22 eyes, 11 patients; Normal = 28 eyes, 14 patients) were included. Baseline scans of the dry eye and control groups did not show any statistical difference (p = 0.84). Fluorescein concentration of DED and normal patients showed statistical significance at all time intervals (p < 10(-5), 0.001, 0.002, 0.049 for 5, 10, 15, & 30 min respectively). Fluorophotometry values converged towards baseline as time elapsed, but both groups were still statistically different at 30 min (p < 0.01). We used four fluorophotometry scoring methods and correlated them with OSDI, TBUT, fluorescein, and lissamine along with adjusted and aggregate scores. The four scoring schemes did not show any significant correlations with the other tests, except for correlations seen with lissamine and 10 (p = 0.045, 0.034) and 15 min (p = 0.013, 0.012), and with aggregate scores and 15 min (p = 0.042, 0.017). CONCLUSIONS: Fluorophotometry generally did not correlate with any other DED tests, even though it showed capability of differentiating between DED and normal eyes up to 30 min after fluorescein dye instillation. There may be an aspect of DED that is missed in the current regimen of DED tests and only captured with fluorophotometry. Adding fluorophotometry may be useful in screening, diagnosing, and monitoring patients with DED.

Screening assay for small-molecule inhibitors of synaptojanin 1, a synaptic phosphoinositide phosphatase.

Elevation of amyloid ß-peptide (Aß) is critically associated with Alzheimer disease (AD) pathogenesis. Aß-induced synaptic abnormalities, including altered receptor trafficking and synapse loss, have been linked to cognitive deficits in AD. Recent work implicates a lipid critical for neuronal function, phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2], in Aß-induced synaptic and behavioral impairments. Synaptojanin 1 (Synj1), a lipid phosphatase mediating the breakdown of PI(4,5)P2, has been shown to play a role in synaptic vesicle recycling and receptor trafficking in neurons. Heterozygous deletion of Synj1 protected neurons from Aß-induced synaptic loss and restored learning and memory in a mouse model of AD. Thus, inhibition of Synj1 may ameliorate Aß-associated impairments, suggesting Synj1 as a potential therapeutic target. To this end, we developed a screening assay for Synj1 based on detection of inorganic phosphate liberation from a water-soluble, short-chain PI(4,5)P2. The assay displayed saturable kinetics and detected Synj1's substrate preference for PI(4,5)P2 over PI(3,4,5)P3. The assay will enable identification of novel Synj1 inhibitors that have potential utility as chemical probes to dissect the cellular role of Synj1 as well as potential to prevent or reverse AD-associated synaptic abnormalities.

Emerging drugs for the treatment of dry eye disease.

INTRODUCTION: Dry eye disease (DED) is a common, age-related ocular condition that in its mildest forms causes bothersome symptoms of ocular discomfort, fatigue, and visual disturbance that interfere with quality of life and in its more severe forms causes chronic pain and fluctuating vision. Though it is highly prevalent and costs billions of dollars to manage, current treatments have largely been inadequate, making it a frustrating condition, both for physicians and patients alike. AREAS COVERED: This article will cover the recently discovered pathophysiology of DED that has prompted investigators to explore new molecules that target the core mechanisms that drive DED. These include anti-inflammatory/immune-modulatory drugs, secretagogues, lubricant, hormones, and autologous serum. Their potential mechanism of action and data from recent trials on efficacy/safety will be reviewed. EXPERT OPINION: The emerging drugs have a vast range of putative mechanisms of action that may not only provide symptomatic relief but may potentially break the vicious cycle of DED and provide long-lasting cure. Current and future research may change our perspective on DED and redefine its treatment algorithms.