Immunoinflammatory, Thrombohaemostatic, and Cardiovascular Mechanisms in COVID-19

AbstractThe global coronavirus disease 2019 (COVID-19) pandemic has deranged the recent history of humankind, afflicting more than 27 million individuals to date. While the majority of COVID-19 patients recuperate, a considerable number of patients develop severe complications. Bilateral pneumonia constitutes the hallmark of severe COVID-19 disease but an involvement of other organ systems, namely the cardiovascular system, kidneys, liver, and central nervous system, occurs in at least half of the fatal COVID-19 cases. Besides respiratory failure requiring ventilation, patients with severe COVID-19 often display manifestations of systemic inflammation and thrombosis as well as diffuse microvascular injury observed postmortem. In this review, we survey the mechanisms that may explain how viral entry and activation of endothelial cells by severe acute respiratory syndrome coronavirus 2 can give rise to a series of events including systemic inflammation, thrombosis, and microvascular dysfunction. This pathophysiological scenario may be particularly harmful in patients with overt cardiovascular disease and may drive the fatal aspects of COVID-19. We further shed light on the role of the renin–angiotensin aldosterone system and its inhibitors in the context of COVID-19 and discuss the potential impact of antiviral and anti-inflammatory treatment options. Acknowledging the comorbidities and potential organ injuries throughout the course of severe COVID-19 is crucial in the clinical management of patients affecting treatment approaches and recovery rate.

Download Full-text

Ambiguity avoidance as a factor in the rise of the English dative alternation

Cognitive Linguistics ◽

10.1515/cog-2021-0018 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Eva Zehentner

Keyword(s):

Quantitative Analysis ◽

Middle English ◽

Language Change ◽

Cognitive Factors ◽

Case Marking ◽

Dative Alternation ◽

Cue Reliability ◽

History Of ◽

Potential Impact

Abstract This paper discusses the role of cognitive factors in language change; specifically, it investigates the potential impact of argument ambiguity avoidance on the emergence of one of the most well-studied syntactic alternations in English, viz. the dative alternation (We gave them cake vs We gave cake to them). Linking this development to other major changes in the history of English like the loss of case marking, I propose that morphological as well as semantic-pragmatic ambiguity between prototypical agents (subjects) and prototypical recipients (indirect objects) in ditransitive clauses plausibly gave a processing advantage to patterns with higher cue reliability such as prepositional marking, but also fixed clause-level (SVO) order. The main hypotheses are tested through a quantitative analysis of ditransitives in a corpus of Middle English, which (i) confirms that the spread of the PP-construction is impacted by argument ambiguity and (ii) demonstrates that this change reflects a complex restructuring of disambiguation strategies.

Download Full-text

Abstract TMP8: The New Alteplase Package Insert: What is the Potential Impact?

Stroke ◽

10.1161/str.47.suppl_1.tmp8 ◽

2016 ◽

Vol 47 (suppl_1) ◽

Author(s):

Harn Shiue ◽

Karen Albright ◽

Kara Sands ◽

April Sisson ◽

Michael Lyerly ◽

...

Keyword(s):

Health Care ◽

Ischemic Stroke ◽

Health Care Costs ◽

Lifetime Cost ◽

Package Insert ◽

Cost Savings ◽

Number Of Patients ◽

History Of ◽

Potential Impact ◽

Care Costs

Background: Alteplase (tPA) contraindications for acute ischemic stroke (AIS) were originally derived from the 1995 NINDS trial. Recently, a history of intracranial hemorrhage (ICH) and recent stroke (within 3 months) were removed as contraindications from the drug package insert, which could increase the number of patients eligible for IV thrombolysis. We sought to define the potential impact on outcomes and health care costs in this newly eligible population. Methods: Consecutive patients (March 2014 - April 2015) who presented with AIS to our Comprehensive Stroke Center (CSC) were retrospectively analyzed. Demographics and tPA exclusions were recorded. The annual number of discharges with primary diagnosis of ischemic stroke in the U.S. was estimated from the National Inpatient Sample (2006 - 2011). A previously reported value of $25,000/patient was utilized to calculate lifetime cost savings in patients receiving tPA. Results: During the study period, 776 AIS were admitted to our CSC (median age 64; 55,74, 51% men, 62% white). Seventy-six percent of our patients (n=590) had ≥1 tPA exclusions according to the NINDS trial. Among these patients, 11 excluded had history of ICH, 15 with recent strokes, and 1 both. Following the new package insert, the proportion of patients with ≥1 tPA exclusion fell to 73% (n=563). Given the 432,000 ischemic stroke discharges annually, a 3% increase in patients eligible for tPA could translate to treatment of 12,960 more patients annually and a lifetime cost savings of $324,000,000. Furthermore, we estimate that 1,685 of these newly eligible patients will experience a favorable functional outcome based on the results of the NINDS trial (13% shift analysis for mRS 0-1). Conclusions: Our results suggest that the new tPA package insert has the potential to increase national tPA treatment rates, decrease U.S. health care costs, and improve functional outcomes in eligible AIS patients. National guidelines need to be updated to reflect these changes.

Download Full-text

Emerging Role of Immune Therapy in HCC

Digestive Disease Interventions ◽

10.1055/s-0041-1722932 ◽

2021 ◽

Author(s):

Stacey M. Stein

Keyword(s):

Kinase Inhibitors ◽

Immune Therapy ◽

Treatment Options ◽

Single Agent ◽

Small Subset ◽

Vascular Endothelial ◽

Number Of Patients ◽

Endothelial Growth Factor ◽

Expected Increase

AbstractHepatocellular carcinoma (HCC) remains a prevalent cancer diagnosis with an expected increase in incidence in the next decade. Treatment options for advanced disease have expanded significantly in the last decade since sorafenib was first approved in 2007. There have been approvals for multiple tyrosine kinase inhibitors (TKIs) with modest improvements in survival. Single-agent PD-1 inhibition has shown responses in ∼15% of patients, with a tail of the curve that is very beneficial to a small subset of patients. Most recently, studies of combination therapy with immune therapy drugs are showing more durable responses in a larger number of patients with unprecedented response rates over 30%. Different strategies have been pursued, including PD-1 and PD-L1 combinations with vascular endothelial growth factor inhibition, TKIs, and anti-CTLA-4 antibodies. This article provides a review of studies both completed and ongoing with immune therapy in advanced HCC.

Download Full-text

The Special Apparatus (al-Niẓām al-Khāṣṣ): The Rise of Nationalist Militancy in the Ranks of the Egyptian Muslim Brotherhood

Religions ◽

10.3390/rel13010077 ◽

2022 ◽

Vol 13 (1) ◽

pp. 77

Author(s):

Ahmed Abou El Zalaf

Keyword(s):

Political Violence ◽

Systematic Study ◽

Muslim Brotherhood ◽

British Colonization ◽

Special Apparatus ◽

Depth Study ◽

History Of ◽

Shed Light ◽

The Way

Existing scholarship has largely focused on the role of Sayyid Qutb’s ideas when analyzing the Muslim Brotherhood’s violent history. Perceiving Qutb’s ideas as paving the way for radical interpretations of jihad, many studies linked the Brotherhood’s violent history with this key ideologue. Yet, in so doing, many studies overlooked the importance of the Special Apparatus in shaping this violent history of the Brotherhood, long before Qutb joined the organization. Through an in-depth study of memoires and accounts penned by Brotherhood members and leaders, and a systematic study of British and American intelligence sources, I attempt to shed light on this understudied formation of the Brotherhood, the Special Apparatus. This paper looks at the development of anti-colonial militancy in Egypt, particularly the part played by the Brotherhood until 1954. It contends that political violence, in the context of British colonization, antedated the Brotherhood’s foundation, and was in some instances considered as a legitimate and even distinguished duty among anti-colonial factions. The application of violence was on no account a part of the Brotherhood’s core strategy, but the organization, nevertheless, established an armed and secret wing tasked with the fulfillment of what a segment of its members perceived as the duty of anti-colonial jihad.

Download Full-text

Abstract W P333: Seizure as the Presenting Symptom of ICH Patient Characteristics and EEG Utilization

Stroke ◽

10.1161/str.46.suppl_1.wp333 ◽

2015 ◽

Vol 46 (suppl_1) ◽

Author(s):

Kanika Arora ◽

Alyssa Gadpaille ◽

Karen C. Albright ◽

Muhammad Alvi ◽

Ayaz Khawaja ◽

...

Keyword(s):

Substance Abuse ◽

Clinical Evidence ◽

Patient Characteristics ◽

Rhythmic Pattern ◽

Epileptiform Discharges ◽

Number Of Patients ◽

Eeg Data ◽

History Of ◽

Ich Score

Background and Purpose: Seizures are the presenting symptom in a significant number of patients with spontaneous ICH. The role of EEG in the routine evaluation patients, with or without clinical evidence of seizures, is unclear. This study was undertaken to better understand seizures and the use of EEG in patients with ICH. Methods: Retrospective review of consecutive spontaneous ICH patients at our institution from 2008-2013. Patients were considered to have a seizure on presentation if a clinical evidence of a seizure was documented in the medical record; EEG data was not required to confirm seizure on presentation. Demographics, vascular risk factors, ICH score, and EEG findings were assessed. Results: Of 402 spontaneous ICH patients (mean age 63, 42% black, 43% female), 10% presented with seizure. Patients presenting with seizure were younger (mean age 65 vs. 54, p<.001). Compared to patients with ICH presenting without a seizure, blacks presented more frequently with seizure (62% vs. 40%, p=.009). A higher proportion of patients who presented with seizure had a history of alcohol use (50% vs. 27%, p=.008) and substance abuse (23% vs. 10%, p=.025). Patients who presented with seizure more frequently had cortical ICH (54% vs. 32%, p=.007). EEGs were performed more frequently in ICH patients that presented with seizure (66% vs. 19%, p<.001). Among patients with an EEG, epileptiform discharges or rhythmic pattern was more common in patients who presented with seizure (30% vs. 10%, p=.040) and with a cortical ICH (29% vs. 9%, p=.036). There were no significant differences in the proportion of patients that received EEG based on race, history of alcohol abuse, or history of substance abuse. Conclusions: Patients who presented with seizure were younger, black, and a higher proportion had a history of alcohol and substance abuse compared to patients with ICH who did not present with a seizure. Only 66% of those presenting with clinical seizure underwent EEG. Despite the prevalence of subclinical seizures in ICH patients, only 19% of patients who did not present with a seizure underwent EEG. Our study suggests that there may be room for improvement on the part of stroke neurologists in the diagnosis and management seizure of ICH patients.

Download Full-text

Diagnosis of Metastatic Breast Cancer—A Case Report Using Molecular Cancer Classification

Oncology & Hematology Review (US) ◽

10.17925/ohr.2011.07.2.116 ◽

2011 ◽

Vol 07 (02) ◽

pp. 116

Author(s):

Yogesh Gandhi ◽

Sunil Gandhi ◽

◽

Keyword(s):

Breast Cancer ◽

Case Report ◽

Effective Treatment ◽

Cancer Diagnosis ◽

Treatment Options ◽

Metastatic Breast ◽

Complete Response ◽

Molecular Profiling ◽

History Of

An accurate cancer diagnosis is critical as it can direct the use of site-directed, and potentially more effective, treatment options for specific types of cancer. A differential or uncertain diagnosis could prevent cancer patients from receiving optimal treatment, thus affecting their overall prognosis. Advances in molecular technology have led to the development of molecular cancer classifiers that can direct or confirm the diagnosis of metastatic cancers which would otherwise be considered uncertain or unknown. This case report describes the role of molecular diagnostics in the evaluation of a patient with a large pancreatic mass and a history of breast cancer. Results from a 92-gene molecular profiling assay (CancerTYPE ID®) predicted that this new mass was breast cancer. This diagnosis allowed for effective treatment and complete response in this patient.

Download Full-text

Impact of treatment line on outcomes with salvage ipilimumab + nivolumab in metastatic renal cell carcinoma (mRCC).

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e17092 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e17092-e17092

Author(s):

Ritesh Kotecha ◽

Chung-Han Lee ◽

Andrea Knezevic ◽

Neil J. Shah ◽

Maria Isabel Carlo ◽

...

Keyword(s):

Treatment Options ◽

Immune Checkpoint Blockade ◽

Clinical Progression ◽

Start Time ◽

Kaplan Meier ◽

Number Of Patients ◽

Time To Treatment Failure ◽

Treatment Sequencing ◽

Line Setting

e17092 Background: With the approval of ipilimumab plus nivolumab (I+N) and other immune checkpoint blockade (ICB) based combinations in the first-line setting, the role of I+N for salvage is of high interest for treatment sequencing, yet data is limited. Methods: We conducted a retrospective review of mRCC patients (pts) treated with I+N in the second-line (2L) and beyond settings at MSKCC between 2013-2019. Pt demographics, treatment history and toxicity were compiled. IMDC-risk status was calculated at I+N therapy start. Time to treatment failure (TTF) was defined as earliest date of clinical progression, therapy change or death, and overall survival (OS) was estimated by Kaplan-Meier method. Results: 36 pts received I+N in the 2+L setting, including 31/36 with clear-cell histology. Evaluable IMDC-risk at I+N start was favorable in 1/35 and intermediate-poor in 34/35 pts. The most common 1L therapies were anti-VEGF (22/36) and VEGF + ICB (6/36). 11/36 pts had ICB treatment exposure prior to I+N therapy. I+N therapy in the 2L, 3L and 4L was in 21/36, 8/36 and 7/36 pts, respectively, and 7/36 pts continue I+N at data cut-off. 8/36 pts discontinued I+N due to toxicity, 20/36 pts discontinued therapy due to disease progression, and 1 pt discontinued per pt preference. Cohort median OS was 14.8 months (95%CI: 4.2-44). Overall median TTF was 5.0 months (95%CI: 2.9-14.4), and TTF per 2L, 3L and 4+L was 8.3, 8.9 and 2.5 months, respectively. The number of patients who completed all 4 I+N induction cycles in the 2L, 3L, and 4+L was 11/21 (52%), 5/8 (63%), and 1/7 (14%). The number of patients who subsequently received nivolumab maintenance therapy after induction was 16/21 (76%) in the 2L, 1/8 (13%) in the 3L, and 0/7 (0%) in 4+L. Conclusions: With emerging treatment options for mRCC, this study reveals activity and safety for I+N in 2+L settings. In this limited cohort, completion of induction ipilimumab and use of maintenance nivolumab decline in later-line settings, suggesting limitations as salvage therapy. [Table: see text]

Download Full-text

Postoperative atrial fibrillation: Target for stroke prevention?

European Stroke Journal ◽

10.1177/2396987317719363 ◽

2017 ◽

Vol 2 (3) ◽

pp. 222-228 ◽

Cited By ~ 6

Author(s):

Vincent Thijs ◽

Robin Lemmens ◽

Omar Farouque ◽

Geoffrey Donnan ◽

Hein Heidbuchel

Keyword(s):

Atrial Fibrillation ◽

Lifestyle Changes ◽

Adverse Outcomes ◽

Postoperative Atrial Fibrillation ◽

Long Term Outcomes ◽

Number Of Patients ◽

History Of ◽

Long Term Mortality

Purpose A substantial number of patients without a history of atrial fibrillation who undergo surgery develop one or more episodes of atrial fibrillation in the first few days after the operation. We studied whether postoperative transient atrial fibrillation is a risk factor for future atrial fibrillation, stroke and death. Method We performed a narrative review of the literature on epidemiology, mechanisms, risk of atrial fibrillation, stroke and death after postoperative atrial fibrillation. We reviewed antithrombotic guidelines on this topic and identified gaps in current management. Findings Patients with postoperative atrial fibrillation are at high risk of developing atrial fibrillation in the long term. Mortality is also increased. Most, but not all observational studies report a higher risk of stroke. The optimal antithrombotic regimen for patients with postoperative atrial fibrillation has not been defined. The role of lifestyle changes and of surgical occlusion of the left atrial appendage in preventing adverse outcomes after postoperative atrial fibrillation is not established. Conclusion Further studies are warranted to establish the optimal strategy to prevent adverse long-term outcomes after transient, postoperative atrial fibrillation.

Download Full-text

Subglottic Hemangioma: Ten Years' Experience with the Carbon Dioxide Laser

Annals of Otology Rhinology & Laryngology ◽

10.1177/000348949410300301 ◽

1994 ◽

Vol 103 (3) ◽

pp. 167-172 ◽

Cited By ~ 86

Author(s):

Kathleen C. Y. Sie ◽

Trevor McGill ◽

Gerald B. Healy

Keyword(s):

Carbon Dioxide ◽

Carbon Dioxide Laser ◽

Treatment Options ◽

Fatal Outcome ◽

Benign Neoplasm ◽

Senior Author ◽

Airway Patency ◽

Proliferative Phase ◽

History Of

Patients with subglottic hemangioma present with biphasic stridor during infancy. The natural history of this lesion is characterized by progressive airway obstruction during the proliferative phase of the lesion, followed by resolution of symptoms during the subsequent involutive phase. Although this is a benign neoplasm, it can be associated with a fatal outcome. Treatment options have been directed at maintaining airway patency during the proliferative phase. The senior author (G.B.H.) originally described the role of the carbon dioxide laser in management of these patients in 1980. Thirty-one patients were treated for subglottic hemangioma at The Children's Hospital, Boston, between 1980 and 1990. The 10-year experience of management of subglottic hemangioma with endoscopic vaporization using the carbon dioxide laser is reviewed to assess the efficacy of this technique.

Download Full-text

Evaluation of Nail Findings in Patients with COVID-19 History and Wood’s Lamp Examination

Skin Appendage Disorders ◽

10.1159/000518983 ◽

2021 ◽

pp. 1-6

Author(s):

Irem Yanatma ◽

Hulya Cenk

Keyword(s):

Titanium Dioxide ◽

Ferric Oxide ◽

Case Reports ◽

Treatment Options ◽

History Of ◽

Day By Day ◽

Shed Light

Introduction: Various skin findings due to coronavirus have been identified. There are a few case reports on nail findings after coronavirus (COVID-19) infection. We aimed to document the nail findings of the COVID-19 survivors and shed light on the interesting luminescence seen under the Wood’s light. Methods: One hundred and seventy-four patients diagnosed with COVID-19 infection in the last 100 days were grouped in terms of the agents used in the treatment. Fifty-seven volunteers without a history of infection were included. Results: Patients treated with favipiravir had a significantly higher positivity of luminescence (p: 0.0001). The most common nail findings in patients were splinter hemorrhage (13%), followed by leukonychia (12%) and longitudinal ridges (7.9%). Discussion/Conclusions: The luminescence may be seen due to the accumulation of favipiravir or its excipients (titanium dioxide and yellow ferric oxide) on the nails. Wood’s lamp examination of the plasma taken from a patient after favipiravir’s first dose revealed the same luminescence as we saw on the nails. Accordingly, this accumulation may be seen in the vital organs. Although our knowledge about the virus increases day by day, the potentially hazardous effects of the virus and long-term complications of the treatment options are still being investigated.

Download Full-text