Management of Orthostatic Hypotension, Postprandial Hypotension, and Supine Hypertension

AbstractThis review provides recommendations for the treatment of neurogenic orthostatic hypotension (nOH), postprandial hypotension, and supine hypertension. It focuses on novel treatment strategies and new insights into the mechanism underlying these conditions. Our goal is to provide practical advice for clinicians on how to screen, diagnose, and treat these conditions with nonpharmacological and pharmacological approaches. For each disorder, we offered a stepwise recommendation on how to apply these new concepts to successfully ameliorate the symptoms associated with OH to prevent syncope and falls. The management of OH in patients who also have supine hypertension requires special considerations and pharmacotherapy. It is noteworthy that there are few therapeutic options for OH and only two Food and Drug Administration–approved drugs for the treatment of OH and nOH based on randomized clinical trials. We will use these studies to develop evidence-based guidelines for OH. The research is limited for postprandial hypotension and supine hypertension, and therefore the recommendations will be based on small studies, clinical expertise, and, above all, an understanding of the underlying pathophysiology.

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Paroxysmal Orthostatic Ventricular Tachycardia in a Patient With Supine Hypertension and Orthostatic Hypotension

Journal of Investigative Medicine High Impact Case Reports ◽

10.1177/2324709620958303 ◽

2020 ◽

Vol 8 ◽

pp. 232470962095830

Author(s):

Khalil Kanjwal ◽

Shakeel M. Jamal ◽

David W. McComb ◽

Majid Mughal ◽

Asim Kichloo

Keyword(s):

Blood Pressure ◽

Ventricular Tachycardia ◽

Orthostatic Hypotension ◽

Autonomic Dysfunction ◽

Treatment Strategies ◽

Upright Posture ◽

Supine Hypertension ◽

Nonsustained Ventricular Tachycardia ◽

Premature Ventricular Beats ◽

Orthostatic Hypertension

Supine orthostatic hypertension with orthostatic hypotension is an autonomic dysfunction where the patients present with hypertension when supine and with decrease in blood pressure while bearing an upright posture. We report on a 74-year-old male who was admitted with dizziness and was found to have profound orthostatic hypotension with supine hypertension. The patient also developed orthostatic paroxysmal premature ventricular beats as well as nonsustained ventricular tachycardia. In this report, we attempt to present the possible mechanism of orthostatic ventricular tachycardia in our patient and the overview of the treatment strategies used in management of patients with supine hypertension and orthostatic hypotension.

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Conventional and Novel Treatment Strategies to Combat COVID-19 along with Review of most Affected Countries

Global Drug Design & Development Review ◽

10.31703/gdddr.2020(v-i).03 ◽

2020 ◽

Vol V (I) ◽

pp. 25-32

Author(s):

Umair-Ul-Hassan ◽

Rana Muhammad Awais Khan ◽

Shafiq-Ur-Rehman ◽

Amjad Khan

Keyword(s):

Viral Genome ◽

Plasma Proteins ◽

Treatment Strategies ◽

Advance Technology ◽

Novel Technique ◽

Novel Treatment ◽

Novel Treatment Strategies ◽

Approved Drugs ◽

Fda Approved Drugs

This review illustrates a comparison of currently implemented strategies and the need of a novel technique to cure the COVID-19. Current strategies served a lot to cope up with the situation by decreasing the rate of fatalities i.e. some FDA approved drugs and giving immunity by the plasma proteins of cured patients, however these approaches could not eliminate the pandemic from the society emphasizing that some advance technology need to be considered in order to fight with SARS-COV-2 virus. CRISPR-Cas based approach to inactivate the virus before its fusion with host DNA has been successful in in-vitro studies performed at Stanford University along with SHERLOCK & MAMMOTH biosciences who were able to degrade 80 % viral genome. Here we have also done a literature review of major affected countries China, Italy, United states, and India.

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Myocardial infarction in a neonate

Hämostaseologie ◽

10.5482/hamo-16-09-0038 ◽

2017 ◽

Vol 37 (03) ◽

pp. 219-222

Author(s):

Werner Streif

Keyword(s):

Myocardial Infarction ◽

Myocardial Function ◽

Management Strategies ◽

Treatment Strategies ◽

Evidence Based ◽

Cardiac Cell ◽

Novel Treatment ◽

Vascular Patency ◽

Novel Treatment Strategies ◽

Evidence Based Guidelines

SummaryDue to the lack of evidence-based guidelines, management strategies for neonatal MI should be individualized and administered largely at the discretion of responsible treating teams. Supportive care with a focus on preserving adequate circulation and antithrombotic therapy with a view to restoring vascular patency are the mainstays of treatment. Thrombolytic therapy of neonatal MI includes a chance to completely restore myocardial function. Understanding the resilience of the neonatal heart and mechanism of cardiac cell repair in neonates may spark novel treatment strategies for severe MI in the large number of affected individuals in an aging population.

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Novel Treatments and Technologies Applied to the Cure of Neuroblastoma

Children ◽

10.3390/children8060482 ◽

2021 ◽

Vol 8 (6) ◽

pp. 482

Author(s):

Irene Paraboschi ◽

Laura Privitera ◽

Gabriela Kramer-Marek ◽

John Anderson ◽

Stefano Giuliani

Keyword(s):

Research Effort ◽

Treatment Strategies ◽

Adverse Outcomes ◽

Treatment Protocols ◽

Ongoing Research ◽

Hematopoietic Stem ◽

Novel Treatments ◽

Therapeutic Modalities ◽

High Risk Disease ◽

Novel Treatment Strategies

Neuroblastoma (NB) is the most common extracranial solid tumour in childhood, accounting for approximately 15% of all cancer-related deaths in the paediatric population1. It is characterised by heterogeneous clinical behaviour in neonates and often adverse outcomes in toddlers. The overall survival of children with high-risk disease is around 40–50% despite the aggressive treatment protocols consisting of intensive chemotherapy, surgery, radiation therapy and hematopoietic stem cell transplantation2,3. There is an ongoing research effort to increase NB’s cellular and molecular biology knowledge to translate essential findings into novel treatment strategies. This review aims to address new therapeutic modalities emerging from preclinical studies offering a unique translational opportunity for NB treatment.

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Immune Cell Modulation of the Extracellular Matrix Contributes to the Pathogenesis of Pancreatic Cancer

Biomolecules ◽

10.3390/biom11060901 ◽

2021 ◽

Vol 11 (6) ◽

pp. 901

Author(s):

Ramiz S. Ahmad ◽

Timothy D. Eubank ◽

Slawomir Lukomski ◽

Brian A. Boone

Keyword(s):

Pancreatic Cancer ◽

Extracellular Matrix ◽

Immune Cells ◽

Immune Cell ◽

Treatment Strategies ◽

Stellate Cells ◽

Pancreatic Stellate Cells ◽

Ductal Adenocarcinoma ◽

Cellular Mechanisms ◽

Novel Treatment Strategies

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with a five-year survival rate of only 9%. PDAC is characterized by a dense, fibrotic stroma composed of extracellular matrix (ECM) proteins. This desmoplastic stroma is a hallmark of PDAC, representing a significant physical barrier that is immunosuppressive and obstructs penetration of cytotoxic chemotherapy agents into the tumor microenvironment (TME). Additionally, dense ECM promotes hypoxia, making tumor cells refractive to radiation therapy and alters their metabolism, thereby supporting proliferation and survival. In this review, we outline the significant contribution of fibrosis to the pathogenesis of pancreatic cancer, with a focus on the cross talk between immune cells and pancreatic stellate cells that contribute to ECM deposition. We emphasize the cellular mechanisms by which neutrophils and macrophages, specifically, modulate the ECM in favor of PDAC-progression. Furthermore, we investigate how activated stellate cells and ECM influence immune cells and promote immunosuppression in PDAC. Finally, we summarize therapeutic strategies that target the stroma and hinder immune cell promotion of fibrogenesis, which have unfortunately led to mixed results. An enhanced understanding of the complex interactions between the pancreatic tumor ECM and immune cells may uncover novel treatment strategies that are desperately needed for this devastating disease.

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Current Insights into Immunology and Novel Therapeutics of Atopic Dermatitis

Cells ◽

10.3390/cells10061392 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1392

Author(s):

Hidaya A. Kader ◽

Muhammad Azeem ◽

Suhib A. Jwayed ◽

Aaesha Al-Shehhi ◽

Attia Tabassum ◽

...

Keyword(s):

Atopic Dermatitis ◽

Skin Diseases ◽

Current Knowledge ◽

Treatment Strategies ◽

Developed Countries ◽

Food Allergies ◽

Th2 Response ◽

Therapeutic Outcomes ◽

Environmental Agents ◽

Novel Treatment Strategies

Atopic dermatitis (AD) is one of the most prevalent inflammatory disease among non-fatal skin diseases, affecting up to one fifth of the population in developed countries. AD is characterized by recurrent pruritic and localized eczema with seasonal fluctuations. AD initializes the phenomenon of atopic march, during which infant AD patients are predisposed to progressive secondary allergies such as allergic rhinitis, asthma, and food allergies. The pathophysiology of AD is complex; onset of the disease is caused by several factors, including strong genetic predisposition, disrupted epidermal barrier, and immune dysregulation. AD was initially characterized by defects in the innate immune system and a vigorous skewed adaptive Th2 response to environmental agents; there are compelling evidences that the disorder involves multiple immune pathways. Symptomatic palliative treatment is the only strategy to manage the disease and restore skin integrity. Researchers are trying to more precisely define the contribution of different AD genotypes and elucidate the role of various immune axes. In this review, we have summarized the current knowledge about the roles of innate and adaptive immune responsive cells in AD. In addition, current and novel treatment strategies for the management of AD are comprehensively described, including some ongoing clinical trials and promising therapeutic agents. This information will provide an asset towards identifying personalized targets for better therapeutic outcomes.

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Molecular mechanisms underpinning sarcomas and implications for current and future therapy

Signal Transduction and Targeted Therapy ◽

10.1038/s41392-021-00647-8 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Victoria Damerell ◽

Michael S. Pepper ◽

Sharon Prince

Keyword(s):

Molecular Mechanisms ◽

Epithelial To Mesenchymal Transition ◽

Treatment Strategies ◽

Mesenchymal Transition ◽

Mesenchymal To Epithelial Transition ◽

Cells Of Origin ◽

Novel Treatment Strategies ◽

Future Therapy

AbstractSarcomas are complex mesenchymal neoplasms with a poor prognosis. Their clinical management is highly challenging due to their heterogeneity and insensitivity to current treatments. Although there have been advances in understanding specific genomic alterations and genetic mutations driving sarcomagenesis, the underlying molecular mechanisms, which are likely to be unique for each sarcoma subtype, are not fully understood. This is in part due to a lack of consensus on the cells of origin, but there is now mounting evidence that they originate from mesenchymal stromal/stem cells (MSCs). To identify novel treatment strategies for sarcomas, research in recent years has adopted a mechanism-based search for molecular markers for targeted therapy which has included recapitulating sarcomagenesis using in vitro and in vivo MSC models. This review provides a comprehensive up to date overview of the molecular mechanisms that underpin sarcomagenesis, the contribution of MSCs to modelling sarcomagenesis in vivo, as well as novel topics such as the role of epithelial-to-mesenchymal-transition (EMT)/mesenchymal-to-epithelial-transition (MET) plasticity, exosomes, and microRNAs in sarcomagenesis. It also reviews current therapeutic options including ongoing pre-clinical and clinical studies for targeted sarcoma therapy and discusses new therapeutic avenues such as targeting recently identified molecular pathways and key transcription factors.

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Unique Genomic Landscape of High-Grade Neuroendocrine Cervical Carcinoma: Implications for Rethinking Current Treatment Paradigms

JCO Precision Oncology ◽

10.1200/po.19.00248 ◽

2020 ◽

pp. 972-987

Author(s):

Ramez N. Eskander ◽

Julia Elvin ◽

Laurie Gay ◽

Jeffrey S. Ross ◽

Vincent A. Miller ◽

...

Keyword(s):

Treatment Strategies ◽

Current Treatment ◽

High Grade ◽

Novel Treatment ◽

Sample Average ◽

Genomic Landscape ◽

Comprehensive Genomic Profiling ◽

Tumor Mutational Burden ◽

Sample Range ◽

Novel Treatment Strategies

PURPOSE High-grade neuroendocrine cervical cancer (HGNECC) is an uncommon malignancy with limited therapeutic options; treatment is patterned after the histologically similar small-cell lung cancer (SCLC). To better understand HGNECC biology, we report its genomic landscape. PATIENTS AND METHODS Ninety-seven patients with HGNECC underwent comprehensive genomic profiling (182-315 genes). These results were subsequently compared with a cohort of 1,800 SCLCs. RESULTS The median age of patients with HGNECC was 40.5 years; 83 patients (85.6%) harbored high-risk human papillomavirus (HPV). Overall, 294 genomic alterations (GAs) were identified (median, 2 GAs/sample; average, 3.0 GAs/sample, range, 0-25 GAs/sample) in 109 distinct genes. The most frequently altered genes were PIK3CA (19.6% of cohort), MYC (15.5%), TP53 (15.5%), and PTEN (14.4%). RB1 GAs occurred in 4% versus 32% of HPV-positive versus HPV-negative tumors ( P < .0001). GAs in HGNECC involved the following pathways: PI3K/AKT/mTOR (41.2%); RAS/MEK (11.3%); homologous recombination (9.3%); and ERBB (7.2%). Two tumors (2.1%) had high tumor mutational burden (TMB; both with MSH2 alterations); 16 (16.5%) had intermediate TMB. Seventy-one patients (73%) had ≥ 1 alteration that was theoretically druggable. Comparing HGNECC with SCLC, significant differences in TMB, microsatellite instability, HPV-positive status, and in PIK3CA, MYC, PTEN, TP53, ARID1A, and RB1 alteration rates were found. CONCLUSION This large cohort of patients with HGNECC demonstrated a genomic landscape distinct from SCLC, calling into question the biologic and therapeutic relevance of the histologic similarities between the entities. Furthermore, 73% of HGNECC tumors had potentially actionable alterations, suggesting novel treatment strategies for this aggressive malignancy.

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