scholarly journals Management of Pulmonary Thromboembolism

2021 ◽  
Author(s):  
G. Ravi Kiran
Keyword(s):  
High Risk ◽  
Treatment Options ◽  
Supportive Therapy ◽  
Pulmonary Angiography ◽  
Risk Category ◽  
Pulmonary Vasodilators ◽  
Clinical Probability ◽  
Standard Management ◽  
Mortality Incidence ◽  
Associated Risk Factors

Pulmonary thrombo-embolism (PTE) is a major cause of cardiovascular morbidity and mortality. Incidence of PTE and its associated mortality is affected by the Prescence of associated risk factors, comorbid conditions and advancement in the treatment options. Clinical probability, D-Dimer, echocardiography and CT pulmonary angiography are used in the diagnosis. Management starts with stratification, with high-risk category being benefited from the thrombolytic therapy. Catheter directed therapy may be used in ineligible or failed cases with surgical embolectomy being used as final salvage therapy. Patients with persistent hemodynamic stability can be started on anticoagulation alone. Supportive therapy with fluid expansion and inhalational Nitric oxide may provide benefit in few. Patients with PTE should receive secondary preventive anticoagulation to prevent recurrences. High risk patients with sub-segmental PTE may benefit from anticoagulation. For early detection of long-term complications of PTE a patient cantered follow-up is needed. Chronic thrombo-embolic pulmonary hypertension (CTEPH) is a dreaded complication with pulmonary end-arterectomy being a gold standard management option in eligible patients with non-surgical therapy (balloon pulmonary angioplasty and pulmonary vasodilators) also being used in many cases.

scholarly journals Deciding on thrombolytic therapy in pulmonary embolism - is there room for lactate?

2018 ◽  
Vol 146 (7-8) ◽  
pp. 436-439
Author(s):  
Dusanka Obradovic ◽  
Biljana Joves ◽  
Svetislava Milic ◽  
Jovan Matijasevic ◽  
Stanislava Sovilj-Gmizic
Keyword(s):  
Pulmonary Embolism ◽  
High Risk ◽  
Thrombolytic Therapy ◽  
Hemodynamic Instability ◽  
Positive Outcome ◽  
Pulmonary Angiography ◽  
Clinical Probability ◽  
Tissue Hypoperfusion ◽  
Therapeutic Algorithms ◽  
Wells Score

Introduction. Diagnostic and therapeutic algorithms for pulmonary embolism (PE) have been frequently modified; however, determining clinical probability, which dictates further procedures, has remained the first step. The objective was to illustrate therapeutic dilemma in a patient with intermediate high risk for 30-day mortality. Case outline. The patient was a 56-years-old woman who was referred to our institution for suspected PE. According to the Wells score, the patient was deemed as low-probability for venous thromboembolism, and after further stratification she was placed in a group with intermediate high risk for 30-day mortality. PE was confirmed by computerised tomography pulmonary angiography and she initially received heparin. During the further clinical course, she developed hemodynamic instability, and she received thrombolytic therapy, with a positive outcome. The patient also had increased lactate at admission ? marker of tissue hypoperfusion which is not a part of the routine laboratory work-up in PE patients. Conclusion. Current guidelines state that patients with intermediate high risk for 30-day mortality should be treated with heparin, and then continuously monitored in order to timely recognize potential hemodynamic instability and consequently apply thrombolytics. In the outlined case, thrombolytic therapy was applied only after the patient developed hemodynamic instability, although previously she had early signs of tissue hypoperfusion.

scholarly journals The effects of a preoperative multidisciplinary conference on outcomes for high-risk patients with challenging surgical treatment options: a retrospective study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Masayoshi Koike ◽  
Mie Yoshimura ◽  
Yasushi Mio ◽  
Shoichi Uezono
Keyword(s):  
Patient Safety ◽  
Retrospective Study ◽  
High Risk ◽  
Treatment Plan ◽  
Treatment Options ◽  
High Risk Patients ◽  
Appropriate Treatment ◽  
Risk Patients ◽  
Treatment Plans ◽  
Multidisciplinary Conference

Abstract Background Surgical options for patients vary with age and comorbidities, advances in medical technology and patients’ wishes. This complexity can make it difficult for surgeons to determine appropriate treatment plans independently. At our institution, final decisions regarding treatment for patients are made at multidisciplinary meetings, termed High-Risk Conferences, led by the Patient Safety Committee. Methods In this retrospective study, we assessed the reasons for convening High-Risk Conferences, the final decisions made and treatment outcomes using conference records and patient medical records for conferences conducted at our institution from April 2010 to March 2018. Results A total of 410 High-Risk Conferences were conducted for 406 patients during the study period. The department with the most conferences was cardiovascular surgery (24%), and the reasons for convening conferences included the presence of severe comorbidities (51%), highly difficult surgeries (41%) and nonmedical/personal issues (8%). Treatment changes were made for 49 patients (12%), including surgical modifications for 20 patients and surgery cancellation for 29. The most common surgical modification was procedure reduction (16 patients); 4 deaths were reported. Follow-up was available for 21 patients for whom surgery was cancelled, with 11 deaths reported. Conclusions Given that some change to the treatment plan was made for 12% of the patients discussed at the High-Risk Conferences, we conclude that participants of these conferences did not always agree with the original surgical plan and that the multidisciplinary decision-making process of the conferences served to allow for modifications. Many of the modifications involved reductions in procedures to reflect a more conservative approach, which might have decreased perioperative mortality and the incidence of complications as well as unnecessary surgeries. High-risk patients have complex issues, and it is difficult to verify statistically whether outcomes are associated with changes in course of treatment. Nevertheless, these conferences might be useful from a patient safety perspective and minimize the potential for legal disputes.

scholarly journals Use of monoclonal antibody therapy for nosocomial SARS-CoV-2 infection in patients at high risk for severe COVID-19: experience from a tertiary-care hospital in Germany

Infection ◽  
2021 ◽  
Author(s):  
Johanna Koehler ◽  
Barbara Ritzer ◽  
Simon Weidlich ◽  
Friedemann Gebhardt ◽  
Chlodwig Kirchhoff ◽  
...  
Keyword(s):  
High Risk ◽  
Tertiary Care Hospital ◽  
Severe Disease ◽  
Treatment Options ◽  
Tertiary Care ◽  
Antibody Therapy ◽  
Additional Treatment ◽  
Care Hospital ◽  
Cross Sectional ◽  
Asymptomatic Patients

AbstractAdditional treatment options for coronavirus disease (COVID-19) are urgently needed, particularly for populations at high risk of severe disease. This cross-sectional, retrospective study characterized the outcomes of 43 patients with nosocomial severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection with and without treatment using monoclonal SARS-CoV-2 spike antibodies (bamlanivimab or casirivimab/imdevimab). Our results indicate that treatment with monoclonal antibodies results in a significant decrease in disease progression and mortality when used for asymptomatic patients with early SARS-CoV-2 infection.

scholarly journals Retargeting of NK-92 Cells against High-Risk Rhabdomyosarcomas by Means of an ERBB2 (HER2/Neu)-Specific Chimeric Antigen Receptor

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1443
Author(s):  
Leonie D. H. Gossel ◽  
Catrin Heim ◽  
Lisa-Marie Pfeffermann ◽  
Laura M. Moser ◽  
Halvard B. Bönig ◽  
...  
Keyword(s):  
High Risk ◽  
Tumor Cells ◽  
Chimeric Antigen Receptor ◽  
Treatment Options ◽  
Antigen Receptor ◽  
Proof Of Concept ◽  
Cell Monolayers ◽  
Novel Treatment ◽  
Dismal Prognosis

The dismal prognosis of pediatric and young adult patients with high-risk rhabdomyosarcoma (RMS) underscores the need for novel treatment options for this patient group. In previous studies, the tumor-associated surface antigen ERBB2 (HER2/neu) was identified as targetable in high-risk RMS. As a proof of concept, in this study, a novel treatment approach against RMS tumors using a genetically modified natural killer (NK)-92 cell line (NK-92/5.28.z) as an off-the-shelf ERBB2-chimeric antigen receptor (CAR)-engineered cell product was preclinically explored. In cytotoxicity assays, NK-92/5.28.z cells specifically recognized and efficiently eliminated RMS cell suspensions, tumor cell monolayers, and 3D tumor spheroids via the ERBB2-CAR even at effector-to-target ratios as low as 1:1. In contrast to unmodified parental NK-92 cells, which failed to lyse RMS cells, NK-92/5.28.z cells proliferated and became further activated through contact with ERBB2-positive tumor cells. Furthermore, high amounts of effector molecules, such as proinflammatory and antitumoral cytokines, were found in cocultures of NK-92/5.28.z cells with tumor cells. Taken together, our data suggest the enormous potential of this approach for improving the immunotherapy of treatment-resistant tumors, revealing the dual role of NK-92/5.28.z cells as CAR-targeted killers and modulators of endogenous adaptive immunity even in the inhibitory tumor microenvironment of high-risk RMS.

scholarly journals 789. Evaluation of Bezlotoxumab for Prevention of Recurrent Clostridioides difficile Infection in Patients at High Risk for Recurrence

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S438-S439
Author(s):  
Tanner M Johnson ◽  
Amanda Howard ◽  
Kerry Schwarz ◽  
Lorna Allen ◽  
Misha Huang ◽  
...  
Keyword(s):  
High Risk ◽  
Fecal Microbiota Transplantation ◽  
Therapeutic Option ◽  
Treatment Options ◽  
High Risk Patient ◽  
Recurrent Infection ◽  
Control Group ◽  
Clostridioides Difficile ◽  
All Cause Mortality ◽  
Clostridioides Difficile Infection

Abstract Background Recurrent Clostridioides difficile infection (rCDI) within 180 days of the index episode is associated with a 33% increase in mortality and, to-date, few treatment options exist to prevent recurrent infection. Bezlotoxumab (BEZ) is a novel therapeutic option for the prevention of rCDI, yet limited data exist regarding its effectiveness in patients at high-risk for recurrence outside of controlled trials. This study aimed to compare BEZ to a historical standard of care (SoC) cohort for the prevention of rCDI in patients at high risk for recurrence. Methods A multi-center retrospective cohort study of patients within an academic health-system with one or more risk factors for rCDI. Patients received SoC with oral vancomycin (VAN) or fidaxomicin (FDX) from January 2015 to December 2017 or BEZ, in addition to oral SoC, from September 2017 to September 2019. The primary outcome was rCDI within 90 days of completion of oral VAN or FDX. Secondary outcomes included all-cause readmission, all-cause mortality, and safety events at 90 days. Results One-hundred twenty patients received BEZ in addition to SoC (n=47) or SoC alone (n=73). Mean (SD) age was 55 (16) years, mean (SD) number of lifetime CDI was 3 (2) episodes, and 30.8% of patients had severe CDI. Six (12.8%) patients in the BEZ cohort and thirty-one (42.5%) in the SoC cohort experienced rCDI at 90 days [OR (95% CI) = 0.20 (0.07-0.53), p=< 0.01]. Incidence of all-cause mortality (2.1% vs 5.5%, p=0.67) and all-cause readmission (42.6% vs 56.2%, p=0.20) within 90 days were not statistically different between groups. Patient body weight, timing of BEZ administration, CDI severity, nor prior receipt of fecal microbiota transplantation significantly affected BEZ effectiveness. BEZ was well tolerated with one infusion-related reaction. There were no heart failure exacerbations among BEZ recipients and two exacerbations identified from control group. Conclusion In patients with at least one risk factor for rCDI, BEZ in addition to SoC was associated with lower rates of recurrent infection than SoC alone and may be a reasonable adjunct therapy in high risk patient populations. Disclosures matthew miller, PharmD, Allergan (Speaker’s Bureau)Tetraphase (Speaker’s Bureau)

scholarly journals Pulmonary embolism during the COVID-19 pandemic

2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
BV Silva ◽  
T Rodrigues ◽  
N Cunha ◽  
J Brito ◽  
P Alves Da Silva ◽  
...  
Keyword(s):  
Physical Activity ◽  
Pulmonary Embolism ◽  
Hospital Admissions ◽  
Reference Group ◽  
Group Versus ◽  
Pulmonary Angiography ◽  
Reference Period ◽  
Funding Sources ◽  
Clinical Probability

Abstract Funding Acknowledgements Type of funding sources: None. Background During the COVID-19 pandemic many countries have imposed lockdown restrictions to movement. Since the 18th of March in Portugal, thousands of people have been confined to their homes. While hospital admissions for COVID-19 patients increased exponentially, admissions for non-COVID-19 patients decreased dramatically. However, it remains unclear whether lockdown-related immobility can contribute to the increased incidence of pulmonary embolism. Purpose To compare the incidence of pulmonary embolism (PE) during the lockdown period (Abril 1 to May 31, 2020) compared to the reference period in 2019. Methods Retrospective study of consecutive outpatients who presented to the emergency department and underwent computed tomography pulmonary angiography (CTPA) due to suspicion of PE. Results Compared to the same period of 2019, the lockdown period was associated with a significant increase in PE diagnosis (29 versus 18 patients). PE patients during lockdown were older (median age 71 years; interquartile range [IQR][60-85] versus 59 years [44-76]; p = 0.046) and have lower prevalence of active cancer (14% versus 33% in the reference period). Women represent 55% (n = 16) of patients in lockdown group (versus 50% in 2019 group). Clinical probability (GENEVA score) was similar in both groups (median score 2.72 in lockdown group and 2.50 in reference group, p = 0.452). None of the patients with PE was diagnosed with COVID-19. Conclusion We have observed a marked increase (62%) in PE diagnosis during lockdown period compared to the reference period, which can be explained by the reduction in physical activity due to teleworking and closure of gyms and sports activities. These data reinforce the importance of promoting physical activity programs at home. The role of pharmacological or mechanical thromboprophylaxis in this scenario remains unclear.

scholarly journals 658 An Audit of Frequency of Cancer Genetics Referral in Patients with a Family History of Colorectal Cancer

2021 ◽  
Vol 108 (Supplement_2) ◽  
Author(s):  
M Abbakar ◽  
T James ◽  
P Boxall ◽  
M Lim
Keyword(s):  
Family History ◽  
High Risk ◽  
Hereditary Cancer ◽  
Risk Category ◽  
Average Risk ◽  
Insufficient Data ◽  
High Risk Patients ◽  
Amsterdam Criteria ◽  
Family History Questionnaire ◽  
Risk Patients

Abstract Introduction Guidelines on the management of hereditary colorectal cancers were updated in 2019. In this study, data from patients within the colonoscopy surveillance programme for hereditary cancer at York Teaching Hospitals Trust were analysed to assess category of risk and appropriateness of referrals to regional geneticists. Method After examination of electronic records and clinical notes, patients were assigned a risk category of average, moderate or high according to the Amsterdam criteria and latest BSG/ACPGBI/UKCGG guidelines. Patients were then assessed to see if a concurrent referral had been made to the regional cancer genetic services. Results There were 228 patients. 72(31.6%) patients were in the average, 81(35.5%) in the moderate and 41(18%) were in the high-risk category. 34 (14.9%) patients with insufficient data and/or assessments were in the indeterminate category. 18 of 72 (25%) patients with average risk were unnecessarily referred to the regional genetics team, while 5/41(12%) of high-risk patients were not. A large proportion of patients with insufficient data (19/34, 55.8%) were rightly or wrongly, referred to the regional genetics team. Conclusions Assessment of hereditary cancer risk is difficult in the absence of good quality information. Risk assessment may be improved with use of a dedicated family history questionnaire/template - this facilitates identification of high-risk patients that benefit most from referral to geneticists.

scholarly journals CRISPR-Cas and Restriction-Modification Act Additively against Conjugative Antibiotic Resistance Plasmid Transfer in Enterococcus faecalis

mSphere ◽  
2016 ◽  
Vol 1 (3) ◽  
Author(s):  
Valerie J. Price ◽  
Wenwen Huo ◽  
Ardalan Sharifi ◽  
Kelli L. Palmer
Keyword(s):  
Antibiotic Resistance ◽  
High Risk ◽  
Enterococcus Faecalis ◽  
Resistance Genes ◽  
Treatment Options ◽  
Antibiotic Resistance Genes ◽  
Multidrug Resistant ◽  
Content Type ◽  
New Genes ◽  
Restriction Modification

ABSTRACT Enterococcus faecalis is a bacterium that normally inhabits the gastrointestinal tracts of humans and other animals. Although these bacteria are members of our native gut flora, they can cause life-threatening infections in hospitalized patients. Antibiotic resistance genes appear to be readily shared among high-risk E. faecalis strains, and multidrug resistance in these bacteria limits treatment options for infections. Here, we find that CRISPR-Cas and restriction-modification systems, which function as adaptive and innate immune systems in bacteria, significantly impact the spread of antibiotic resistance genes in E. faecalis populations. The loss of these systems in high-risk E. faecalis suggests that they are immunocompromised, a tradeoff that allows them to readily acquire new genes and adapt to new antibiotics. Enterococcus faecalis is an opportunistic pathogen and a leading cause of nosocomial infections. Conjugative pheromone-responsive plasmids are narrow-host-range mobile genetic elements (MGEs) that are rapid disseminators of antibiotic resistance in the faecalis species. Clustered regularly interspaced short palindromic repeat (CRISPR)-Cas and restriction-modification confer acquired and innate immunity, respectively, against MGE acquisition in bacteria. Most multidrug-resistant E. faecalis isolates lack CRISPR-Cas and possess an orphan locus lacking cas genes, CRISPR2, that is of unknown function. Little is known about restriction-modification defense in E. faecalis. Here, we explore the hypothesis that multidrug-resistant E. faecalis strains are immunocompromised. We assessed MGE acquisition by E. faecalis T11, a strain closely related to the multidrug-resistant hospital isolate V583 but which lacks the ~620 kb of horizontally acquired genome content that characterizes V583. T11 possesses the E. faecalis CRISPR3-cas locus and a predicted restriction-modification system, neither of which occurs in V583. We demonstrate that CRISPR-Cas and restriction-modification together confer a 4-log reduction in acquisition of the pheromone-responsive plasmid pAM714 in biofilm matings. Additionally, we show that the orphan CRISPR2 locus is functional for genome defense against another pheromone-responsive plasmid, pCF10, only in the presence of cas9 derived from the E. faecalis CRISPR1-cas locus, which most multidrug-resistant E. faecalis isolates lack. Overall, our work demonstrated that the loss of only two loci led to a dramatic reduction in genome defense against a clinically relevant MGE, highlighting the critical importance of the E. faecalis accessory genome in modulating horizontal gene transfer. Our results rationalize the development of antimicrobial strategies that capitalize upon the immunocompromised status of multidrug-resistant E. faecalis. IMPORTANCE Enterococcus faecalis is a bacterium that normally inhabits the gastrointestinal tracts of humans and other animals. Although these bacteria are members of our native gut flora, they can cause life-threatening infections in hospitalized patients. Antibiotic resistance genes appear to be readily shared among high-risk E. faecalis strains, and multidrug resistance in these bacteria limits treatment options for infections. Here, we find that CRISPR-Cas and restriction-modification systems, which function as adaptive and innate immune systems in bacteria, significantly impact the spread of antibiotic resistance genes in E. faecalis populations. The loss of these systems in high-risk E. faecalis suggests that they are immunocompromised, a tradeoff that allows them to readily acquire new genes and adapt to new antibiotics.

Gene Therapy for Inherited Retinopathies: Update on Development Progress

2018 ◽  
Vol 2 (4) ◽  
pp. 219-226
Author(s):  
Susan Sun ◽  
Sandra R. Montezuma
Keyword(s):  
Gene Therapy ◽  
Genetic Disorders ◽  
Treatment Options ◽  
Genetic Material ◽  
Disease Process ◽  
Supportive Therapy ◽  
The Us ◽  
Retinal Disorders ◽  
The Status ◽  
Therapy Treatment

Inherited retinopathies are a group of genetic disorders that lead to blindness and/or vision impairment. Until now, treatment options for inherited retinopathies largely remained limited to supportive therapy. Gene therapy is an attractive therapeutic technique that allows repair of diseased genes, and it has shown success in vision improvement for patients affected by retinal disorders caused by genetic mutations. The US Food and Drug Administration approved the first gene therapy treatment for the eye, indicated for biallelic RPE65 mutation associated Leber congenital amaurosis (LCA), in December of 2017. Additionally, results from other ongoing clinical trials could further establish gene therapy as the milestone treatment that plays a role in disease process reversal for inherited retinopathies. This review article provides an update on the status of gene therapy for treatment of a variety of retinopathies, including LCA, choroideremia, achromatopsia, Stargardt disease, X-linked retinitis pigmentosa, and X-linked retinoschisis. Furthermore, this article explores transport methods of the genetic material, as well as therapy-delivery approaches used in the clinical setting.

scholarly journals Is there a role for adjuvant therapy after surgery in “high risk for recurrence” kidney cancer? An update on current concepts

2018 ◽  
Vol 25 (5) ◽  
Author(s):  
T. Sharma ◽  
C. Tajzler ◽  
A. Kapoor
Keyword(s):  
Clinical Trials ◽  
Targeted Therapy ◽  
High Risk ◽  
Adjuvant Therapy ◽  
Patient Population ◽  
Treatment Options ◽  
Significant Proportion ◽  
High Risk Patient ◽  
Disease Free Survival ◽  
Cochrane Reviews

BackgroundAlthough surgical resection remains the standard of care for localized kidney cancers, a significant proportion of patients experience systemic recurrence after surgery and hence might benefit from effective adjuvant therapy. So far, several treatment options have been evaluated in adjuvant clinical trials, but only a few have provided promising results. Nevertheless, with the recent development of targeted therapy and immunomodulatory therapy, a series of clinical trials are in progress to evaluate the potential of those novel agents in the adjuvant setting. In this paper, we provide a narrative review of the progress in this field, and we summarize the results from recent adjuvant trials that have been completed.MethodsA literature search was conducted. The primary search strategy at the medline, Cochrane reviews, and http://ClinicalTrials.gov/ databases included the keywords “adjuvant therapy,” “renal cell carcinoma,” and “targeted therapy or/and immunotherapy.”ConclusionsData from the s-trac study indicated that, in the “highest risk for recurrence” patient population, disease-free survival was increased with the use of adjuvant sunitinib compared with placebo. The assure trial showed no benefit for adjuvant sunitinib or sorafenib in the “intermediate- to high-risk” patient population. The ariser (adjuvant girentuximab) and protect (adjuvant pazopanib) trials indicated no survival benefit, but subgroup analyses in both trials recommended further investigation. The inconsistency in some of the current results can be attributed to a variety of factors pertaining to the lack of standardization across the trials. Nevertheless, patients in the “high risk of recurrence” category after surgery for their disease would benefit from a discussion about the potential benefits of adjuvant treatment and enrolment in ongoing adjuvant trials.

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