Clinical Management of Hypertension, Inflammation and Thrombosis in Hospitalized COVID-19 Patients: Impact on Survival and Concerns

The most severe clinical manifestations of the Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are due to an unbalanced immune response and a pro-thrombotic hemostatic disturbance, with arterial hypertension or diabetes as acknowledged risk factors. While waiting for a specific treatment, the clinical management of hospitalized patients is still a matter of debate, and the effectiveness of treatments to manage clinical manifestations and comorbidities has been questioned. In this study, we aim to assess the impact of the clinical management of arterial hypertension, inflammation and thrombosis on the survival of COVID-19 patients. The Spanish cohorts included in this observational retrospective study are from HM Hospitales (2035 patients) and from Hospital Universitario Central de Asturias (72 patients). Kaplan Meier survival curves, Cox regression and propensity score matching analyses were employed, considering demographic variables, comorbidities and treatment arms (when opportune) as covariates. The management of arterial hypertension with angiotensin-converting enzyme 2 (ACE2) inhibitors or angiotensin receptor blockers is not detrimental, as was initially reported, and neither was the use of non-steroidal anti-inflammatory drugs (NSAIDs). On the contrary, our analysis shows that the use on itself of corticosteroids is not beneficial. Importantly, the management of COVID-19 patients with low molecular weight heparin (LMWH) as an anticoagulant significantly improves the survival of hospitalized patients. These results delineate the current treatment options under debate, supporting the effectiveness of thrombosis prophylaxis on COVID-19 patients as a first-line treatment without the need for compromising the treatment of comorbidities, while suggesting cautiousness when administering corticosteroids.

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Management of Plantar Keratodermas

Journal of the American Podiatric Medical Association ◽

10.7547/16-043 ◽

2017 ◽

Vol 107 (5) ◽

pp. 428-435 ◽

Cited By ~ 2

Author(s):

Rebecca M. Porter ◽

Albert A. Bravo ◽

Frances J.D. Smith

Keyword(s):

Gene Therapy ◽

Salicylic Acid ◽

Alternative Treatment ◽

Autosomal Dominant ◽

Treatment Options ◽

Clinical Manifestations ◽

Specific Treatment ◽

Inherited Mutations ◽

Pachyonychia Congenita

Plantar keratodermas can arise due to a variety of genetically inherited mutations. The need to distinguish between different plantar keratoderma disorders is becoming increasingly apparent because there is evidence that they do not respond identically to treatment. Diagnosis can be aided by observation of other clinical manifestations, such as palmar keratoderma, more widespread hyperkeratosis of the epidermis, hair and nail dystrophies, or erythroderma. However, there are frequent cases of plantar keratoderma that occur in isolation. This review focuses on the rare autosomal dominant keratin disorder pachyonychia congenita, which presents with particularly painful plantar keratoderma for which there is no specific treatment. Typically, patients regularly trim/pare/file/grind their calluses and file/grind/clip their nails. Topical agents, including keratolytics (eg, salicylic acid, urea) and moisturizers, can provide limited benefit by softening the skin. For some patients, retinoids help to thin calluses but may lead to increased pain. This finding has stimulated a drive for alternative treatment options, from gene therapy to alternative nongenetic methods that focus on novel findings regarding the pathogenesis of pachyonychia congenita and the function of the underlying genes.

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The predictive value of MAP2K1/2 mutations for efficiency of immunotherapy in melanoma.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e21587 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e21587-e21587

Author(s):

Ting Ye ◽

Jieying Zhang ◽

Xinyi Liu ◽

Mengmei Yang ◽

Yuhan Zhou ◽

...

Keyword(s):

Overall Survival ◽

Predictive Value ◽

Cox Regression ◽

Treatment Options ◽

Objective Response ◽

Progression Free Survival ◽

Driver Mutations ◽

Cox Regression Analysis ◽

Melanoma Patients ◽

The Impact

e21587 Background: Immunotherapies targeting immune checkpoint receptors have become the cornerstone of systemic treatment options for malignant melanoma. The response to these immunotherapies may correlate with driver mutations. MAP2K1/2 genes are mutated in approximately 10% of melanomas, however, the impact of MAP2K1/2 gene alterations on the efficiency of immunotherapy has not been clarified. Methods: Six metastatic melanoma clinical cohorts treated with ICIs were included to investigate the association between clinical efficacy of immunotherapy and MAP2K1/2 mutations. Survival analyses were conducted in cohorts receiving two kinds of ICB agents, namely anti-CTLA-4 or anti-PD-1. RNA expression profiling from these cohorts and from the TCGA melanoma cohort were used to explore the potential mechanism related to immune activation. Results: In an independent anti-CTLA-4-treated cohort (n = 110), we found that MAP2K1/2 mutations are predictive of high objective response rate (17.6% vs 1.3%, p = 0.0185) and long progression-free survival [median OS, 49.2 months vs 8.3 months; hazard ratio (HR) = 0.37; 95% CI, 0.15–0.91; p = 0.0307] and overall survival (median PFS, 19.4 months vs 2.8 months; HR = 0.2; 95% CI, 0.05–0.83; p = 0.0262). This predictive value was further validated in a pooled anti-CTLA-4-treated cohort (n = 235) in terms of overall survival (median OS, 49.3 months vs 22.0 months; HR = 0.44; 95% CI, 0.22–0.91; p = 0.0255). However, no correlation between MAP2K1/2 mutations and overall survival was observed in the anti-PD-1-treated cohort (n = 285). Subgroup Cox regression analysis indicated that MAP2K-mutated patients receive less benefit from the anti-PD-1 monotherapy than from the anti-CTLA-4 treatment (median OS, 27.0 months vs 49.3 months; HR = 3.26; 95% CI, 1.18–9.02; p = 0.0225), which was contrary to the result obtained for the total population. Furthermore, transcriptome profiling analysis revealed that MAP2K-mutated tumors are enriched in CD8+ T cells, B cells, and neutrophil cells and also express high levels of CD33 and IL10, which might be the underlying mechanism for melanoma patients with MAP2K1/2-mutated benefit more from anti-CTLA-4 treatment. Conclusions: We identified mutations in MAP2K1/2 genes as the independent predictive factors for anti-CTLA-4 therapy in melanoma patients and found that anti-CTLA-4 treatment in patient harbouring MAP2K1/2 mutations might be more effective than the anti-PD-1 therapy.

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Abstract 15514: Ace Inhibitors, Angiotensin Receptor Blockers, and Outcomes in Hospitalized Patients With Severe Covid-19 Pneumonia

Circulation ◽

10.1161/circ.142.suppl_3.15514 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Prabhjot Grewal ◽

Jeanwoo Yoo ◽

Aikaterini Papamanoli ◽

Azad Mojahedi ◽

Simrat Dhaliwal ◽

...

Keyword(s):

Ace Inhibitors ◽

Cox Regression ◽

Angiotensin Receptor Blockers ◽

Patient Characteristics ◽

University Hospital ◽

Target Cells ◽

Angiotensin Receptor ◽

Receptor Blockers ◽

Artery Disease ◽

The Impact

Introduction: Angiotensin converting enzyme (ACE) 2, is a co-receptor for the entry of SARS-CoV-2 into target cells. The impact of ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) on outcomes in patients with coronavirus disease 19 (COVID-19) is under investigation. Hypothesis: ACEIs/ARBs are associated with worse outcomes in patients hospitalized with COVID-19. Methods: We evaluated the in-hospital course of 469 adults admitted to Stony Brook University Hospital, NY, from March 1 to April 15, 2020 with severe COVID-19 pneumonia (need for high-flow O2). We excluded patients who required mechanical ventilation (MV) or died within 24h of admission. We used Cox regression models to examine the association of previous (home) use of ACEIs or ARBs with mortality and the composite of death or MV. Results: Table 1 summarizes the patient characteristics according to ACEI/ARB use (ACEI: 73; ARB: 73; 146/469 patients, 31.1%). After a median of 13 days (8-22), 123 patients (26.2%) died and 105 patients (22.4%) required MV and survived. In models adjusting for age, sex, race, body mass index, hypertension, diabetes, coronary artery disease, heart failure, atrial fibrillation, chronic lung disease, chronic kidney disease, and baseline 0 2 saturation, ACEIs/ARBs were not associated with mortality (HR 1.00; 95%CI 0.62-1.61; P=0.99). There was no difference between classes in mortality (ACEI vs. ARB: HR 1.14; 95%CI 0.61-2.15; P=0.68). However, there was a trend towards lower rates of death or MV with ACEI/ARB (HR 0.75; 95%CI 0.54-1.05; P=0.095), mainly because of lower MV rates. The protective effect of ARBs on the composite was significant (HR 0.66; 95%CI 0.44-0.99; P=0.046) whereas that of ACEIs was not (HR 0.87; 95%CI 0.57-1.31; P=0.50), albeit difference was not significant (P=0.28). Conclusions: In patients with severe COVID-19 pneumonia, ACEI/ARB use was not associated with mortality. Especially ARBs may reduce need for MV in this high-risk COVID-19 population.

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Delayed viral clearance and exacerbated airway hyperinflammation in hypertensive COVID-19 patients

10.1101/2020.09.22.20199471 ◽

2020 ◽

Author(s):

Saskia Trump ◽

Soeren Lukassen ◽

Markus S Anker ◽

Robert Lorenz Chua ◽

Johannes Liebig ◽

...

Keyword(s):

Cardiovascular Disease ◽

Immune Cell ◽

Angiotensin Receptor Blockers ◽

Treatment Options ◽

Angiotensin Converting Enzyme Inhibitors ◽

Sequencing Data ◽

Converting Enzyme Inhibitors ◽

Altered Expression ◽

The Impact

In COVID-19, hypertension and cardiovascular diseases have emerged as major risk factors for critical disease progression. Concurrently, the impact of the main anti-hypertensive therapies, angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB), on COVID-19 severity is controversially discussed. By combining clinical data, single-cell sequencing data of airway samples and in vitro experiments, we assessed the cellular and pathophysiological changes in COVID-19 driven by cardiovascular disease and its treatment options. Anti-hypertensive ACEi or ARB therapy, was not associated with an altered expression of SARS-CoV-2 entry receptor ACE2 in nasopharyngeal epithelial cells and thus presumably does not change susceptibility for SARS-CoV-2 infection. However, we observed a more critical progress in COVID-19 patients with hypertension associated with a distinct inflammatory predisposition of immune cells. While ACEi treatment was associated with dampened COVID-19-related hyperinflammation and intrinsic anti-viral responses, under ARB treatment enhanced epithelial-immune cell interactions were observed. Macrophages and neutrophils of COVID-19 patients with hypertension and cardiovascular comorbidities, in particular under ARB treatment, exhibited higher expression of CCL3, CCL4, and its receptor CCR1, which associated with critical COVID-19 progression. Overall, these results provide a potential explanation for the adverse COVID-19 course in patients with cardiovascular disease, i.e. an augmented immune response in critical cells for the disease course, and might suggest a beneficial effect of clinical ACEi treatment in hypertensive COVID-patients.

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La terapia enzimatica sostitutiva nella malattia di Fabry

Giornale di Clinica Nefrologica e Dialisi ◽

10.33393/gcnd.2019.528 ◽

2019 ◽

Vol 31 (3) ◽

pp. 197-200

Author(s):

Letizia Roggero ◽

Sara Auricchio ◽

Federico Pieruzzi

Keyword(s):

Treatment Options ◽

Clinical Manifestations ◽

Specific Treatment ◽

Left Ventricular ◽

Lysosomal Storage ◽

Igg Antibody ◽

Enzyme Replacement ◽

Gi Symptoms ◽

History Of ◽

Treat All

Anderson-Fabry disease (FD) is a X-linked lysosomal storage disorder, which involves glycosphingolipids metabolism. Specific treatment for FD has been available in the last two decades, after the development and commercialization of recombinant human alfa-galactosidase A. Since then enzyme replacement therapy (ERT) has changed the natural history of the disease. Two different enzymatic formulations are available: agalsidase alfa and agalsidase beta at different dosages. The safety and efficacy profiles are similar. ERT induces Gb3 deposits reduction in renal and cardiac biopsies, improves quality of life, reduces pain and GI symptoms, decreases left ventricular mass and slows down renal function decline. In case of organ involvement, clinical evidence confirms the need to treat all patients with enzyme therapy, both male and female. In all other clinical settings, the decision to start ERT is controversial, because of the extremely variable clinical manifestations of FD. However, data suggest a greater response to ERT if started as early as possible in any patients. Timely treatment appears to be effective in stabilizing and possibly delaying FD progression. ERT infusion reactions due to allergic hypersensitivity or IgG antibody development could occur but can be easily managed. In-hospital and at home infusions are possible. The wide genetic and phenotypic heterogeneity observed in all FD patients requires a tailored approach to treatment options. Patients should be referred to an expert multidisciplinary team for the long term management of this challenging disease.

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The Impact of SARS-CoV-2 Multiple Spike Protein Mutations on COVID-19 Outcomes

10.21203/rs.3.rs-700897/v1 ◽

2021 ◽

Author(s):

Gunadi ◽

Mohamad Saifudin Hakim ◽

Hendra Wibawa ◽

Marcellus ◽

Ika Trisnawati ◽

...

Keyword(s):

Phylogenetic Analysis ◽

Strong Association ◽

Clinical Manifestations ◽

Illumina Miseq ◽

Hospitalized Patients ◽

S Protein ◽

Factors Affecting ◽

Central Java ◽

The Impact ◽

Protein Variants

Abstract Background: Recent studies focusing on the association of SARS-CoV-2 variants of concern (VOC) on COVID-19 outcomes have been reported. However, studies of the impact of multiple mutations within the spike (S) protein of SARS-CoV-2 on COVID-19 illness are limited. This study determined the association between multiple mutations within the S protein, prognosis factors, and the disease outcomes of SARS-CoV-2 infection. Methods: We included 51 COVID-19 patients from Yogyakarta and Central Java, Indonesia. Whole genome sequences of SARS-CoV-2 were determined by the Illumina MiSeq next-generation sequencer, followed by the phylogenetic analysis of 170 full-genomes of SARS-CoV-2 from different regions. We analyzed characteristics of COVID-19 patients and multiple mutations in association with different outcomes.Results: Among 51 patients, the clinical manifestations of COVID-19 were as follows: without any symptoms (13.7%), mild (47%), moderate (19.6%), severe (4%), critical (2%), and died (13.7%). The age of hospitalized patients (53.4 ± 18 years) was higher than non-hospitalized patients (34.6 ± 19) (p=0.001). A significant association between diabetes, hypertension, and anticoagulant and the hospitalization of patients was noted with p-value of 0.039 (OR=4.47 [95% CI=1.07-18.58]), 0.001 (OR=17 [95% CI=2-144]), and 0.02 (OR=27.97 [95% CI=1.54-507.13]), respectively; whereas a strong association between patients’ age, diabetes, anticoagulant, and steroid with the mortality of patients was revealed with p-value of 0.016 (OR=8.44 [95% CI=1.5-47.49]), 0.019 (OR=8.5 [95% CI=1.43-50.66]), 0.001 (46.8 [95% CI=4.63-472.77]), and 0.009 (OR=15.75 [95% CI=2-123.86]), respectively. All viruses contained the D614G variant, except one case. Accordingly, the samples were classified as the following clade: L (2%), GH (84.3%), GR (11.7%), and O (2%). Besides the D614G, the most common variants in the S protein were L5F (18.8%), V213A (18.8%), and S689R (8.3%). There was no significant association between multiple S protein variants with either hospitalization or mortality of COVID-19 (p=0.11 and 0.69, respectively). Multivariate analysis showed that hypertension and anticoagulant were the strong factors affecting the hospitalization and mortality of patients with COVID-19 with a p-value of 0.009 (OR=17.06 [95% CI=2.02-144.36]) and 0.001 (OR=46.8 (95% CI=4.63-472.77), respectively. Interestingly, the multiple S protein variants almost reached a significant level affecting the hospitalization of patients (p=0.07). Phylogenetic analysis showed that although most of the viruses from this study belonged to clade GH, none were detected as the variant of concern (VOC) and the variant of interest (VOI) of SARS-CoV-2.Conclusions: Here, we show for the first time the association between SARS-CoV-2 mutations within the S protein besides the VOC with the COVID-19 outcomes. Our findings suggest that multiple mutations in the S protein might affect the severity of COVID-19. Our study further suggests the importance of genomic surveillance to monitor SARS-CoV-2 variants, particularly those that might influence the outcomes of COVID-19 patients.

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Current Progress on Assessing the Prognosis for Anti-N-Methyl-D-Aspartate Receptor (NMDAR) Encephalitis

BioMed Research International ◽

10.1155/2020/7506590 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8

Author(s):

Hao Wang ◽

Zheng Xiao

Keyword(s):

Positive Impact ◽

Treatment Options ◽

Clinical Manifestations ◽

Autoimmune Encephalitis ◽

Antibody Testing ◽

Aspartate Receptor ◽

Nmdar Encephalitis ◽

Behavioral Abnormalities ◽

Positron Emission ◽

The Impact

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is the most common antineuronal antibody encephalitis in autoimmune encephalitis found at present. It has complex clinical manifestations such as psychiatric and behavioral abnormalities, seizures, movement disorders, consciousness, and autonomic dysfunction. The relationship between those manifestations and prognosis is unclear. Electroencephalography (EEG) is gradually becoming useful in the evaluation of the prognosis of anti-NMDAR encephalitis patients, while imaging and antibody testing have a limited prognostic value. Starting the patients on adequate treatments (such as immunotherapy) in a timely fashion has a positive impact on their prognosis. Nevertheless, research on the prognosis of anti-NMDAR encephalitis remains scarce. Here, we review the current advances of prognosis-related research from the clinical manifestations of the disease and auxiliary examinations such as EEG, magnetic resonance imaging (MRI), 18F fluorodeoxyglucose positron emission tomography (FDG-PET), and antibody measurement. In addition, we also discuss the impact of different treatment options on prognosis. In-depth research on the prognosis of patients with anti-NMDAR encephalitis will contribute to a better understanding of this disease, leading to better treatments options and, ultimately, a better prognosis.

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Chronic Renal Failure: The Impact of Improved Medical Treatment Options on Rehabilitation

Journal of Applied Rehabilitation Counseling ◽

10.1891/0047-2220.27.1.7 ◽

1996 ◽

Vol 27 (1) ◽

pp. 7-12

Author(s):

Ruth Torkelson Lynch ◽

Susan Gallagher-Lepak

Keyword(s):

Renal Failure ◽

Chronic Renal Failure ◽

Medical Treatment ◽

Rehabilitation Counseling ◽

Treatment Options ◽

Life Quality ◽

Specific Treatment ◽

Rehabilitation Counselors ◽

Functional Implications ◽

The Impact

The life quality potential and functional outcome status of individuals with chronic renal failure has been and will continue to be influenced by improved medical treatment options. Rehabilitation counselors are strongly urged to keep their knowledge up-to-date regarding developments in healthcare and technology in order to readjust their perspectives regarding rehabilitation possibilities. The progression of chronic renal failure is described followed by an update on current medical treatment options. Functional implications are presented with an emphasis on how specific treatment methods impact functional outcomes. Rehabilitation counseling practice guidelines are provided for assessment, counseling, and job placement.

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Takayasu’s Arteritis: An Uncommon Cause of Renal Artery Stenosis and Therapeutic Considerations

The Open Urology & Nephrology Journal ◽

10.2174/1874303x01306010014 ◽

2013 ◽

Vol 6 (1) ◽

pp. 14-19

Author(s):

Mary Virmani1 ◽

Luis Ortega ◽

Loay Salman ◽

Tushar Vachharajani ◽

Arif Asif ◽

...

Keyword(s):

Takayasu’S Arteritis ◽

Treatment Options ◽

Clinical Manifestations ◽

Treatment Strategies ◽

Specific Treatment ◽

Transluminal Angioplasty ◽

Cytotoxic Agents ◽

Takayasu's Arteritis ◽

Revascularization Procedures ◽

Therapeutic Considerations

Takayasu’s arteritis is a rare disorder characterized by granulomatous and necro-inflammatory disease of the aorta and its major branches. Its etiology remains unknown. We report a young woman with Takayasu’s arteritis affecting the aortic arch, carotid, mesenteric, celiac and bilateral renal arteries resulting in severe hypertension, unilateral renal atrophy and renal insufficiency. The immunosuppressive therapy did not halt the progression of her vascular disease, which required revascularization procedures on numerous occasions. Here, the clinical manifestations and histopathological features of Takayasu’s arteritis are reviewed. In addition, the available medical treatment options including glucocorticoids, cytotoxic agents and TNF-alpha inhibitors are discussed. Furthermore, current revascularization procedures such as percutaneous transluminal angioplasty and reconstructive vascular surgery in the treatment of occlusive vasculopathy due to Takayasu’s arteritis are discussed. Although the prognosis of this debilitating disease has improved over the past two decades, a better understanding of its etiology and pathogenesis will facilitate the discovery of effective target-specific treatment strategies with a narrow adverse effects profile.

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Rocio Virus: An Updated View on an Elusive Flavivirus

Viruses ◽

10.3390/v13112293 ◽

2021 ◽

Vol 13 (11) ◽

pp. 2293

Author(s):

Marielena Vogel Saivish ◽

Vivaldo Gomes da Costa ◽

Gabriela de Lima Menezes ◽

Roosevelt Alves da Silva ◽

Gislaine Celestino Dutra da Silva ◽

...

Keyword(s):

Public Education ◽

Treatment Options ◽

Clinical Manifestations ◽

Specific Treatment ◽

Coastal Communities ◽

Control Measures ◽

Human Pathogen ◽

Transmission Cycle ◽

Natural Reservoir ◽

Paulo State

Rocio virus (ROCV) is a mosquito-borne flavivirus and human pathogen. The virus is indigenous to Brazil and was first detected in 1975 in the Sao Paulo State, and over a period of two years was responsible for several epidemics of meningoencephalitis in coastal communities leading to over 100 deaths. The vast majority of ROCV infections are believed to be subclinical and clinical manifestations can range from uncomplicated fever to fatal meningoencephalitis. Birds are the natural reservoir and amplification hosts and ROCV is maintained in nature in a mosquito-bird-mosquito transmission cycle, primarily involving Psorophora ferox mosquitoes. While ROCV has remained mostly undetected since 1976, in 2011 it re-emerged in Goiás State causing a limited outbreak. Control of ROCV outbreaks depends on sustainable vector control measures and public education. To date there is no specific treatment or licensed vaccine available. Here we provide an overview of the ecology, transmission cycles, epidemiology, pathogenesis, and treatment options, aiming to improve our ability to understand, predict, and ideally avert further ROCV emergence.

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