Evaluating Treatment Options for Common Bovine Diseases Using Published Data and Clinical Experience

Treatment options for effective treatment of cancer with minimum off-target effects and maximum clinical outcomes have remained overarching goals in the clinical oncology. Vitamin C has remained in the shadows of controversy since the past few decades; burgeoning evidence has started to shed light on wide-ranging anticancer effects exerted by Vitamin C to induce apoptosis in drug-resistant cancer cells, inhibit uncontrolled proliferation of the cancer cells and metastatic spread. Landmark achievements in molecular oncology have ushered in a new era, and researchers have focused on the identification of oncogenic pathways regulated by Vitamin C in different cancers. However, there are visible knowledge gaps in our understanding related to the ability of Vitamin C to modulate a myriad of transduction cascades. There are scattered pieces of scientific evidence about promising potential of Vitamin C to regulate JAK-STAT, TGF/SMAD, TRAIL and microRNAs in different cancers. However, published data is insufficient and needs to be investigated comprehensively to enable basic and clinical researchers to reap full benefits and promote result-oriented transition of Vitamin C into various phases of clinical trials. In this review, we will emphasize on available evidence related to the regulation of oncogenic cell signaling pathways by Vitamin C in different cancers. We will also highlight the conceptual gaps, which need detailed and cutting-edge research.

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Patterns of care for prostate cancer radiotherapy—results from a survey among German-speaking radiation oncologists

Strahlentherapie und Onkologie ◽

10.1007/s00066-020-01738-1 ◽

2021 ◽

Author(s):

Marco M. E. Vogel ◽

Sabrina Dewes ◽

Eva K. Sage ◽

Michal Devecka ◽

Jürgen E. Gschwend ◽

...

Keyword(s):

Prostate Cancer ◽

Online Survey ◽

Treatment Options ◽

Equivalent Dose ◽

Patterns Of Care ◽

Treatment Recommendation ◽

Published Data ◽

Prostate Bed ◽

Radiation Oncologists ◽

German Speaking

Abstract Background Emerging moderately hypofractionated and ultra-hypofractionated schemes for radiotherapy (RT) of prostate cancer (PC) have resulted in various treatment options. The aim of this survey was to evaluate recent patterns of care of German-speaking radiation oncologists for RT of PC. Methods We developed an online survey which we distributed via e‑mail to all registered members of the German Society of Radiation Oncology (DEGRO). The survey was completed by 109 participants between March 3 and April 3, 2020. For evaluation of radiation dose, we used the equivalent dose at fractionation of 2 Gy with α/β = 1.5 Gy, equivalent dose (EQD2 [1.5 Gy]). Results Median EQD2(1.5 Gy) for definitive RT of the prostate is 77.60 Gy (range: 64.49–84.00) with median single doses (SD) of 2.00 Gy (range: 1.80–3.00), while for postoperative RT of the prostate bed, median EQD2(1.5 Gy) is 66.00 Gy (range: 60.00–74.00) with median SD of 2.00 Gy (range: 1.80–2.00). For definitive RT, the pelvic lymph nodes (LNs) are treated in case of suspect findings in imaging (82.6%) and/or according to risk formulas/tables (78.0%). In the postoperative setting, 78.9% use imaging and 78.0% use the postoperative tumor stage for LN irradiation. In the definitive and postoperative situation, LNs are irradiated with a median EQD2(1.5 Gy) of 47.52 Gy with a range of 42.43–66.00 and 41.76–62.79, respectively. Conclusion German-speaking radiation oncologists’ patterns of care for patients with PC are mainly in line with the published data and treatment recommendation guidelines. However, dose prescription is highly heterogenous for RT of the prostate/prostate bed, while the dose to the pelvic LNs is mainly consistent.

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Pulmonary Hypertension in Acute and Chronic High Altitude Maladaptation Disorders

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18041692 ◽

2021 ◽

Vol 18 (4) ◽

pp. 1692

Author(s):

Akylbek Sydykov ◽

Argen Mamazhakypov ◽

Abdirashit Maripov ◽

Djuro Kosanovic ◽

Norbert Weissmann ◽

...

Keyword(s):

Pulmonary Hypertension ◽

High Altitude ◽

Clinical Experience ◽

Current Knowledge ◽

Hypoxic Pulmonary Vasoconstriction ◽

Treatment Options ◽

Right Heart Failure ◽

Channel Blockers ◽

The Right ◽

Extensive Clinical Experience

Alveolar hypoxia is the most prominent feature of high altitude environment with well-known consequences for the cardio-pulmonary system, including development of pulmonary hypertension. Pulmonary hypertension due to an exaggerated hypoxic pulmonary vasoconstriction contributes to high altitude pulmonary edema (HAPE), a life-threatening disorder, occurring at high altitudes in non-acclimatized healthy individuals. Despite a strong physiologic rationale for using vasodilators for prevention and treatment of HAPE, no systematic studies of their efficacy have been conducted to date. Calcium-channel blockers are currently recommended for drug prophylaxis in high-risk individuals with a clear history of recurrent HAPE based on the extensive clinical experience with nifedipine in HAPE prevention in susceptible individuals. Chronic exposure to hypoxia induces pulmonary vascular remodeling and development of pulmonary hypertension, which places an increased pressure load on the right ventricle leading to right heart failure. Further, pulmonary hypertension along with excessive erythrocytosis may complicate chronic mountain sickness, another high altitude maladaptation disorder. Importantly, other causes than hypoxia may potentially underlie and/or contribute to pulmonary hypertension at high altitude, such as chronic heart and lung diseases, thrombotic or embolic diseases. Extensive clinical experience with drugs in patients with pulmonary arterial hypertension suggests their potential for treatment of high altitude pulmonary hypertension. Small studies have demonstrated their efficacy in reducing pulmonary artery pressure in high altitude residents. However, no drugs have been approved to date for the therapy of chronic high altitude pulmonary hypertension. This work provides a literature review on the role of pulmonary hypertension in the pathogenesis of acute and chronic high altitude maladaptation disorders and summarizes current knowledge regarding potential treatment options.

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Molecular Pathology of Breast Cancer: The Journey From Traditional Practice Toward Embracing the Complexity of a Molecular Classification

Archives of Pathology & Laboratory Medicine ◽

10.5858/2010-0734-rair.1 ◽

2011 ◽

Vol 135 (5) ◽

pp. 544-557 ◽

Cited By ~ 2

Author(s):

Aaron M. Gruver ◽

Bryce P. Portier ◽

Raymond R. Tubbs

Keyword(s):

Molecular Diagnostics ◽

Treatment Options ◽

Molecular Classification ◽

Published Data ◽

Breast Carcinomas ◽

Developing Regions ◽

Traditional Practice ◽

The Moment

Abstract Context.—Adenocarcinoma of the breast is the most frequent cancer affecting women in both developed and developing regions of the world. From the moment of clinical presentation until the time of pathologic diagnosis, patients affected by this disease will face daunting questions related to prognosis and treatment options. While improvements in targeted therapies have led to increased patient survival, these same advances have created the imperative to accurately stratify patients to achieve maximum therapeutic efficacy while minimizing side effects. In this evolving era of personalized medicine, there is an ever-increasing need to overcome the limitations of traditional diagnostic practice. Objective.—To summarize the molecular diagnostics traditionally used to guide prognostication and treatment of breast carcinomas, to highlight published data on the molecular classification of these tumors, and to showcase molecular assays that will supplement traditional methods of categorizing the disease. Data Sources.—A review of the literature covering the molecular diagnostics of breast carcinomas with a focus on the gene expression and array studies used to characterize the molecular signatures of the disease. Special emphasis is placed on summarizing evolving technologies useful in the diagnosis and characterization of breast carcinoma. Conclusions.—Available and emerging molecular resources will allow pathologists to provide superior diagnostic, prognostic, and predictive information about individual breast carcinomas. These advances should translate into earlier identification and tailored therapy and should ultimately improve outcome for patients affected by this disease.

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Are Community Acquired Respiratory Viral Infections an Underestimated Burden in Hematology Patients?

Microorganisms ◽

10.3390/microorganisms7110521 ◽

2019 ◽

Vol 7 (11) ◽

pp. 521 ◽

Cited By ~ 3

Author(s):

Popescu ◽

Ursache ◽

Feketea ◽

Bocsan ◽

Jimbu ◽

...

Keyword(s):

Hematological Malignancies ◽

Viral Infections ◽

Treatment Options ◽

Published Data ◽

Evidence Based ◽

Respiratory Viral Infection ◽

Improve Outcome ◽

Diagnosis And Management ◽

Respiratory Viral Infections ◽

Evidence Based Guidelines

Despite a plethora of studies demonstrating significant morbidity and mortality due to community-acquired respiratory viral (CRV) infections in intensively treated hematology patients, and despite the availability of evidence-based guidelines for the diagnosis and management of respiratory viral infections in this setting, there is no uniform inclusion of respiratory viral infection management in the clinical hematology routine. Nevertheless, timely diagnosis and systematic management of CRV infections in intensively treated hematology patients has a demonstrated potential to significantly improve outcome. We have briefly summarized the recently published data on CRV infection epidemiology, as well as guidelines on the diagnosis and management of CRV infections in patients intensively treated for hematological malignancies. We have also assessed available treatment options, as well as mentioned novel agents currently in development.

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Surgical treatment of hemorrhoids: a critical appraisal of the current options

ABCD Arquivos Brasileiros de Cirurgia Digestiva (São Paulo) ◽

10.1590/s0102-67202014000100016 ◽

2014 ◽

Vol 27 (1) ◽

pp. 66-70 ◽

Cited By ~ 12

Author(s):

Marlise Mello CERATO ◽

Nilo Luiz CERATO ◽

Patrícia PASSOS ◽

Alberto TREIGUE ◽

Daniel C. DAMIN

Keyword(s):

Surgical Treatment ◽

Postoperative Pain ◽

Treatment Options ◽

Surgical Techniques ◽

Postoperative Recurrence ◽

Long Term Results ◽

Published Data ◽

Complication Rates ◽

Recurrence Rates

Introduction : Surgical treatment of hemorrhoids is still a dilemma. New techniques have been developed leading to a lower rate of postoperative pain; however, they are associated with a greater likelihood of recurrence. Aim : To review current indications as well as the results and complications of the main techniques currently used in the surgical treatment of hemorrhoidal disease. Methods : A systematic search of the published data on the options for treatment of hemorrhoids up to December 2012 was conducted using Medline/PubMed, Cochrane, and UpToDate. Results : Currently available surgical treatment options include procedure for prolapse and hemorrhoids (PPH), transanal hemorrhoidal dearterialization (THD), and conventional hemorrhoidectomy techniques. Excisional techniques showed similar results regarding pain, time to return to normal activities, and complication rates. PPH and THD were associated with less postoperative pain and lower complication rates; however, both had higher postoperative recurrence rates. Conclusion : Conventional surgical techniques yield better long-term results. Despite good results in the immediate postoperative period, PPH and THD have not shown consistent long-term favorable results.

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Novel Tyrosine Kinase Inhibitors Trigger Drug Sensitivity of Primary CLL Cells by Controlling Glucosylation of Ceramides

Blood ◽

10.1182/blood.v120.21.3905.3905 ◽

2012 ◽

Vol 120 (21) ◽

pp. 3905-3905

Author(s):

Janine Schwamb ◽

Valeska Feldhaus ◽

Michael Baumann ◽

Michaela Patz ◽

Susanne Brodesser ◽

...

Keyword(s):

Tyrosine Kinase ◽

Kinase Inhibitors ◽

Kinase Inhibitor ◽

Conflicts Of Interest ◽

Treatment Options ◽

Cell Receptor ◽

Lymphocytic Leukemia ◽

Published Data ◽

The Novel ◽

Apoptosis Resistance

Abstract Abstract 3905 Background: Apoptosis resistance of chronic lymphocytic leukemia (CLL) cells is mediated by several pro-survival stimuli. In particular, engagement of the B-cell receptor (BCR), CD40-CD40 ligand (CD40L) interaction or stimulation by interleukin-(IL)-4 were identified as major factors to regulate chemoresistance. Sphingolipids are known to be involved in several metabolic pathways involved in chemoresitance. Therefore, we focused on ceramide as pro-apoptotic molecule and its counterpart glucosylceramide, which rather contributes to proliferation and survival. Methods and Results: Applying liquid chromatography electrospray ionization tandem mass spectrometry, we revealed a significant decrease of pro-apoptotic ceramide in BCR/IL-4/CD40L-stimulated primary CLL cells compared to untreated controls (p=0.0258, p=0.0478, p=0.0114). Anti-apoptotic glucosylceramide levels were significantly increased after BCR cross-linking (p=0.0435) while other stimuli caused no relevant change in glucosylceramide expression. We identified BCR engagement to catalyze the crucial modification of ceramide to glucosylceramide via the enzyme UDP-glucose ceramide glucosyltransferase (UGCG) (p=0.0001). Besides specific UGCG inhibitors, we could show for the first time that IgM-mediated UGCG expression was significantly inhibited by the novel and highly effective PI3Kδ and BTK inhibitors CAL-101 and PCI-32765, which were able to revert IgM-induced apoptosis resistance of CLL cells. Recently published data revealed sphingolipids to be essential for mediation of apoptosis via mitochondria. Therefore, we chose ABT-737 – a well-known and also mitochondria-targeting drug – as candidate partner for PI3Kδ and BTK inhibition. When combining each tyrosine kinase inhibitor with ABT-737, a synergistic apoptotic effect could be documented, even under protection by BCR stimulation. Conclusion: In summary, we could demonstrate that sphingolipids are critically involved in CLL pathogenesis. UGCG could be identified as drugable target by the novel kinase inhibitors CAL-101 and PCI-32765 resulting in even synergistic apoptosis following additional application of ABT-737. Sphingolipids seem to offer further targets providing novel treatment options in CLL. C.M.W. and L.P.F. contributed equally to this work. Disclosures: No relevant conflicts of interest to declare.

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Epidemiology Projection Trends for Hodgkin Lymphoma Patients in the U.S. and Europe

Blood ◽

10.1182/blood.v120.21.4782.4782 ◽

2012 ◽

Vol 120 (21) ◽

pp. 4782-4782

Author(s):

Jyotsna Mehta ◽

Adeline Abbe ◽

Peter C Trask ◽

Frank Neumann ◽

Alaa Hamed

Keyword(s):

Hodgkin Lymphoma ◽

Population Distribution ◽

Treatment Options ◽

Unmet Need ◽

Relative Survival ◽

Published Data ◽

Cancer Society ◽

Eu Countries ◽

Third Line ◽

Line Of Therapy

Abstract Abstract 4782 Background: Hodgkin lymphoma represents 11.7% of all types of lymphoma diagnosed in 2011. (Leukemia and Lymphoma Society) In 2012, an estimated 9,060 of new HL cases and 1,190 deaths will occur in North America and mostly in either young adults between 15 and 30 years of age, or after the age of 45. (American Cancer Society) The five-year relative survival rate for all patients with HL is 86.3% from 2001 to 2007 and 92.8% for patients less than 45 years at diagnosis. (SEER Review) Initial treatment of HL depends on the stage of the disease at diagnosis. Chemotherapy with or without radiation therapy is the most common treatment approach for HL patients. Stem cell transplantation and chemotherapy are the treatment options for patients with relapse disease. There is lack of published data on the distribution of patients across lines of therapy as well as percentage of relapsed and refractory patients. Understanding the distribution of patients across lines of therapy is critical to identify the unmet need and to help tailor future therapies. Methods: Epidemiological data was obtained for US and EU using the 'epic oncology' 2012 database (Epiphany Partners Inc.). The database includes line of therapy estimations using an advanced patient flow model combining survival by subset and course of treatment, response rates and outcomes, and treatment data from US and EU cancer registries coupled with primary research with a representative sample of physicians and secondary therapeutic reviews. We analyzed projection estimates up to 2020 across US and EU5 countries by line of therapy with specific attention to relapsed/refractory patients. These projection estimates are based on the current treatment options and does not account for introduction of future therapies. Refractory patients are defined as those who do not respond (do not go into remission) following therapy. Relapsed Patients are defined as those who have responded to therapy (enter remission) but re-enter the treatment population at a later stage due to progression of their cancer, recurrence of diagnostic markers, or symptomatology. Results: Projection estimates from 2010 to 2020 by line of therapy varied by country. Among EU countries, the highest number of treated HL patients was in France, followed by Italy and Spain. By 2020, the percentage of patients that are either relapsed or refractory to first, second and third line of therapy will increase by about 25% in US and by about 15% in EU. Regional variation observed across Europe are as follows: an increase by 38% in Spain, 25% in France, 12% in UK and 6% in Italy, while Germany will show a decline of 2%, this is due to a continuous decline in incidence rates since the early 1990s. Drug treated Hodgkin lymphoma population by line of therapy*: Conclusions: Due to the highly chemosensitive nature of the malignancy, only about 25% of Hodgkin lymphoma patients progress to a second line therapy and 30% of those move into third line. Smaller sample sizes, variation in growth rate among US and EU countries, and a bimodal incidence curve could cause differences in projection trends. The creation of a Hodgkin's disease based registry can help in validating emerging trends in therapy through providing up to date global projection estimates across line of therapy. Our results provide a global understanding of the HL patient population distribution across lines of therapy and are critical to identify the unmet need and guide future therapies in HL patients. Disclosures: Mehta: Sanofi: Employment. Abbe:Sanofi: Employment, Equity Ownership. Trask:Sanofi: Employment. Neumann:Sanofi-aventis: Employment. Hamed:Sanofi: Employment.

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The use of standardized order sets to optimize treatment for Guillain-Barre Syndrome: a literature review

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/cjn.2015.163 ◽

2015 ◽

Vol 42 (S1) ◽

pp. S35-S35

Author(s):

V Karnik ◽

T Roberts ◽

W Johnston

Keyword(s):

Treatment Options ◽

Specific Treatment ◽

Guillain Barre Syndrome ◽

Published Data ◽

Disease States ◽

Order Sets ◽

Guillain Barré Syndrome ◽

Guillain Barré ◽

Disease Specific ◽

Order Set

Background: Standardized order sets are thought to improve patient outcomes in multiple ways. They reduce costs without reducing quality of care, and improve efficiency. In both surgical and medical conditions patients benefit from order sets in various disease states. In Guillain-Barre syndrome (GBS), the use of standardized order sets may be beneficial as there are a defined set of disease-specific diagnostic tests and treatments to be implemented. Here, the primary aim was to search for, and evaluate standardized order sets for GBS, and to provide a basis for development of future pathways. Methods: We used the Cochrane, TRIP, and MEDLINE/PUBMED databases, searching between January 1966 and April 2014. Search terms included: “Guillain-Barre Syndrome” and its synonyms, “(standardized) order set”, “clinical pathway”, “neurology” and “admission bundle.” Results: Despite anecdotal evidence of order sets, no formal data has been published showing benefit after implementation of these sets in GBS or any neurological condition. Conclusions: Although evidence exists for use of standardized order sets in surgical and medical settings, no published data exist in neurology. Given GBS has a defined set of disease-specific and state-specific treatment options, a standardized order set used on admission for GBS patients may prove to be beneficial.

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Protocol for the economic evaluation of COVID-19 pandemic response policies

BMJ Open ◽

10.1136/bmjopen-2021-051503 ◽

2021 ◽

Vol 11 (9) ◽

pp. e051503

Author(s):

Brandon Wen Bing Chua ◽

Vinh Anh Huynh ◽

Jing Lou ◽

Fang Ting Goh ◽

Hannah Clapham ◽

...

Keyword(s):

Incremental Cost ◽

Treatment Options ◽

Indirect Costs ◽

Face Mask ◽

Primary Outcome Measure ◽

Cost Utility ◽

Resource Utilisation ◽

Published Data ◽

System Perspective ◽

Life Years

IntroductionSeveral treatment options are available for COVID-19 to date. However, the use of a combination of non-pharmaceutical interventions (NPIs) is necessary for jurisdictions to contain its spread. Although the implementation cost of NPIs may be low from the healthcare system perspective, it can be costly when considering the indirect costs from the societal perspective. COVID-19 vaccination campaigns have begun in several countries worldwide. Nonetheless, the quantity of vaccines available remain limited over the next 1 to 2 years. A tool for informing vaccine prioritisation that considers both cost and effectiveness will be highly useful. This study aims to identify the most cost-effective combination of COVID-19 response policies, using Singapore as an example.Methods and analysisAn age-stratified Susceptible-Exposed-Infectious-Recovered model will be used to generate the number of infections stratified by disease severity under different intervention scenarios. Polices of interest include test-trace-isolate, travel restriction, compulsory face mask and hygiene practices, social distancing, dexamethasone/remdesivir therapy and vaccination. The latest phase 3 trial results and the WHO Target Product Profiles for COVID-19 vaccines will be used to model vaccine characteristics. A cost (expected resource utilisation and productivity losses) and quality-adjusted life years (QALYs) will be attached to these outputs for a cost-utility analysis. The primary outcome measure will be the incremental cost-effectiveness ratio generated from the incremental cost of policy alternatives expressed as a ratio of the incremental benefits (QALYs gained). Efficacy of policy options will be gathered from literature review and from its observed impacts in Singapore. Cost data will be gathered from healthcare institutions, Ministry of Health and published data. Sensitivity analysis such as threshold analysis and scenario analysis will be conducted.Ethics and disseminationEthics approval was not required for this study. The study findings will be disseminated through peer-reviewed journals.

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