scholarly journals Luspatercept for the treatment of β-thalassemia: from preclinical research to clinical practice and beyond

2021 ◽  
Author(s):  
Filomena Longo ◽  
Nicolò Tesio ◽  
Andrea Piolatto ◽  
Giovanni Battista Ferrero ◽  
Antonio Piga
Keyword(s):  
Clinical Practice ◽  
Standard Of Care ◽  
Blood Transfusions ◽  
Inherited Disease ◽  
Disease Phenotype ◽  
Ineffective Erythropoiesis ◽  
Preclinical Research ◽  
Chronic Anemia ◽  
Number Of Patients ◽  
Hemoglobin Production

β-thalassemia is an inherited disease causing an impaired hemoglobin production, eventually leading to a severe chronic anemia. Resolutive treatments are still limited to a small number of patients and blood transfusions still represent the standard of care. In this scenario, luspatercept is the first approved drug able to significantly modify the disease phenotype. Developed as a fusion protein, it binds TGF-β ligands, contributing to a reduction of ineffective erythropoiesis. As shown by clinical trials in thalassemia, this effect determines an increase in mean hemoglobin levels and/or a decrease in transfusion burden. While some potential indications are still being evaluated in trials, luspatercept has recently entered the clinical practice for transfusion-dependent thalassemia patients.

Percutaneous Mitral Annuloplasty for Treatment of Functional Mitral Regurgitation

2009 ◽  
Vol 5 (1) ◽  
pp. 67
Author(s):  
Lutz Buellesfeld ◽  
Lazar Mandinov ◽  
Eberhard Grube ◽  
◽  
◽  
...  
Keyword(s):  
Mitral Regurgitation ◽  
Coronary Sinus ◽  
Standard Of Care ◽  
Mitral Annulus ◽  
Functional Mitral Regurgitation ◽  
Invasive Treatment ◽  
Large Variability ◽  
Mitral Annuloplasty ◽  
Number Of Patients ◽  
Anatomical Relationship

Functional mitral regurgitation affects a substantial proportion of patients with congestive heart failure due to myocardial infarction or dilated cardiomyopathy. Functional mitral regurgitation greatly increases morbidity and mortality. Surgical annuloplasty is the standard of care for symptomatic patients with moderate or severe functional mitral regurgitation; however, a large number of patients are refused surgery. Several percutaneous approaches have been developed to address the need for less invasive treatment of mitral annulus dilatation. Devices using coronary sinus to cinch the mitral annulus are relatively easy to use; however, a number of factors may limit their clinical application, such as suboptimal anatomical relationship between the coronary sinus and mitral annulus, risk of coronary artery compression, large variability in the coronary venous anatomy and conflict with other therapies such as ablation or cardiac resynchronisation. Direct mitral annuloplasty is anticipated to be more effective than the coronary sinus approaches; however, it has yet to prove its safety and efficacy in carefully designed clinical trials. The best candidates and the best timing for each percutaneous mitral annuloplasty therapy, whether direct or indirect, have yet to be identified.

Features of the complex treatment of ulcerative colitis in clinical practice

2020 ◽  
pp. 6-11
Author(s):  
Svetlana Svetlana ◽  
Mikhail Klimentov ◽  
Olga Neganova ◽  
Alina Nazmieva ◽  
Anastasiya Kochurova
Keyword(s):  
Ulcerative Colitis ◽  
Clinical Practice ◽  
Statistical Study ◽  
Age Groups ◽  
Length Of Hospital Stay ◽  
Unknown Etiology ◽  
Number Of Patients ◽  
First Republic ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Nowadays there are certain difficulties in the early diagnosis of ulcerative colitis, proceeding with minimal intestinal symptoms. The etiology of the disease remains unclear to this day; there is no exact information about the prevalence of the disease due to the large number of latent forms and the low number of patients seeking medical help. This article presents the results of a retrospective analysis of the incidence of ulcerative colitis in the coloproctology department of the First Republic Clinical Hospital of Izhevsk. The study was conducted to assess the frequency of occurrence and determine the internal picture of ulcerative colitis. To achieve this goal, we selected 34 patients with ulcerative colitis. A statistical study was conducted on the following criteria: gender composition, age groups, forms of the disease, localization, complications, and main complaints. The length of hospital stay often was not more than 20 days. The literature on this pathology was also studied and presented in the form of a theoretical basis, which consisted of the determination and etiology of inflammatory bowel diseases. Due to the unknown etiology, insufficiently studied pathogenesis, difficult differential diagnosis with other intestinal diseases and insufficiently perfect treatment methods, there are a large number of unresolved problems in the field of ulcerative colitis. That is why, in this article we tried to reveal the problem of the features of the course and complex therapy of that disease in clinical practice.

Imaging of Bacteria: Is there Any Hope for the Future Based on Past Experience?

2018 ◽  
Vol 24 (7) ◽  
pp. 772-786 ◽  
Author(s):  
Thomas Ebenhan ◽  
Elena Lazzeri ◽  
Olivier Gheysens
Keyword(s):  
Clinical Practice ◽  
Sterile Inflammation ◽  
Ageing Population ◽  
Major Health Problem ◽  
Major Health ◽  
Number Of Patients ◽  
Implanted Medical Devices ◽  
Neutropenic Patients ◽  
Socio Economic Impact ◽  
Made In

Infectious diseases remain a major health problem and cause of death worldwide. It is expected that the socio-economic impact will further intensify due to escalating resistance to antibiotics, an ageing population and an increase in the number of patients under immunosuppressive therapy and implanted medical devices. Even though radiolabeled probes and leukocytes are routinely used in clinical practice, it might still be difficult to distinguish sterile inflammation from inflammation caused by bacteria. Moreover, the majority of these probes are based on the attraction of leukocytes which may be hampered in neutropenic patients. Novel approaches that can be implemented in clinical practice and allow for swift diagnosis of infection by targeting the microorganism directly, are posing an attractive strategy. Here we review the current strategies to directly image bacteria using radionuclides and we provide an overview of the preclinical efforts to develop and validate new approaches. Indeed, significant progress has been made in the past years, but very few radiopharmaceuticals (that were promising in preclinical studies) have made it into clinical practice. We will discuss the challenges that remain to select good candidates for imaging agents targeting bacteria.

scholarly journals Late Thrombectomy in Clinical Practice

2021 ◽  
Author(s):  
Moriz Herzberg ◽  
Korbinian Scherling ◽  
Robert Stahl ◽  
Steffen Tiedt ◽  
Frank A. Wollenweber ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Clinical Outcome ◽  
Perfusion Imaging ◽  
Time Window ◽  
Ct Perfusion ◽  
Large Trial ◽  
Real World Data ◽  
Baseline Trial ◽  
Good Outcome ◽  
Number Of Patients

Abstract Background and Purpose To provide real-world data on outcome and procedural factors of late thrombectomy patients. Methods We retrospectively analyzed patients from the multicenter German Stroke Registry. The primary endpoint was clinical outcome on the modified Rankin scale (mRS) at 3 months. Trial-eligible patients and the subgroups were compared to the ineligible group. Secondary analyses included multivariate logistic regression to identify predictors of good outcome (mRS ≤ 2). Results Of 1917 patients who underwent thrombectomy, 208 (11%) were treated within a time window ≥ 6–24 h and met the baseline trial criteria. Of these, 27 patients (13%) were eligible for DAWN and 39 (19%) for DEFUSE3 and 156 patients were not eligible for DAWN or DEFUSE3 (75%), mainly because there was no perfusion imaging (62%; n = 129). Good outcome was not significantly higher in trial-ineligible (27%) than in trial-eligible (20%) patients (p = 0.343). Patients with large trial-ineligible CT perfusion imaging (CTP) lesions had significantly more hemorrhagic complications (33%) as well as unfavorable outcomes. Conclusion In clinical practice, the high number of patients with a good clinical outcome after endovascular therapy ≥ 6–24 h as in DAWN/DEFUSE3 could not be achieved. Similar outcomes are seen in patients selected for EVT ≥ 6 h based on factors other than CTP. Patients triaged without CTP showed trends for shorter arrival to reperfusion times and higher rates of independence.

scholarly journals The Interplay between Drivers of Erythropoiesis and Iron Homeostasis in Rare Hereditary Anemias: Tipping the Balance

2021 ◽  
Vol 22 (4) ◽  
pp. 2204
Author(s):  
Simon Grootendorst ◽  
Jonathan de Wilde ◽  
Birgit van Dooijeweert ◽  
Annelies van Vuren ◽  
Wouter van Solinge ◽  
...  
Keyword(s):  
Iron Overload ◽  
Iron Metabolism ◽  
Iron Homeostasis ◽  
Significant Problem ◽  
Blood Transfusions ◽  
Intrinsic Defects ◽  
Chronic Anemia ◽  
Erythroid Development ◽  
Disease Specific

Rare hereditary anemias (RHA) represent a group of disorders characterized by either impaired production of erythrocytes or decreased survival (i.e., hemolysis). In RHA, the regulation of iron metabolism and erythropoiesis is often disturbed, leading to iron overload or worsening of chronic anemia due to unavailability of iron for erythropoiesis. Whereas iron overload generally is a well-recognized complication in patients requiring regular blood transfusions, it is also a significant problem in a large proportion of patients with RHA that are not transfusion dependent. This indicates that RHA share disease-specific defects in erythroid development that are linked to intrinsic defects in iron metabolism. In this review, we discuss the key regulators involved in the interplay between iron and erythropoiesis and their importance in the spectrum of RHA.

Concrescence of the cervical vertebrae and neurological complications

2021 ◽  
pp. 195-201
Author(s):  
Sabiyat Abdulaevna Yakhyaeva ◽  
Naida Isagadzhievna Garabova ◽  
Madina Garunovna Burzhunova
Keyword(s):  
Cervical Spine ◽  
Clinical Practice ◽  
Research Methods ◽  
Neurological Disorders ◽  
Cervical Vertebrae ◽  
Clinical Manifestations ◽  
Neurological Complications ◽  
Timely Diagnosis ◽  
Number Of Patients ◽  
Genetically Determined

In clinical practice, a sufficiently large number of patients complain of neurological disorders caused by osteochondrosis of the cervical spine. Despite this, in some cases, the development and progression of this symptomatology may be due to an anomaly in the structure of the cervical spine (Klippel-Feil syndrome), which is genetically determined. Timely diagnosis of this pathology with the implementation of complex research methods allows you to develop individual tactics for each individual patient, taking into account the severity of clinical manifestations to slow the progression of complications.

scholarly journals Blue rubber bleb nevus syndrome: case report

2003 ◽  
Vol 58 (2) ◽  
pp. 109-112 ◽  
Author(s):  
Magaly Gemio Teixeira ◽  
Marcos Vinicius Perini ◽  
Carlos Frederico S. Marques ◽  
Angelita Habr-Gama ◽  
Desidério Kiss ◽  
...  
Keyword(s):  
Reliable Method ◽  
Intestinal Resection ◽  
Blood Transfusions ◽  
Effective Management ◽  
Effective Technique ◽  
Chronic Anemia ◽  
Systemic Disorder ◽  
Multiple Blood ◽  
Acquired Immunodeficiency ◽  
Immunodeficiency Syndrome

The case of a patient with blue rubber bleb nevus syndrome who is infected by acquired immunodeficiency syndrome virus due to multiple blood transfusions is presented. This case shows that although it is a rare systemic disorder, blue rubber bleb nevus syndrome has to be considered in the differential diagnosis of chronic anemia or gastrointestinal bleeding. Patients should be investigated by endoscopy, which is the most reliable method for detecting these lesions. The patient underwent gastroscopy and enteroscopy via enterotomy with identification of all lesions. Minimal resection of the larger lesions and string-purse suture of the smaller ones involving all the layers of the intestine were performed. The string-purse suture of the lesions detected by enteroscopy proved to be an effective technique for handling these lesions, avoiding extensive intestinal resection and stopping the bleeding. Effective management of these patients demands aggressive treatment and should be initiated as soon as possible to avoid risks involved in blood transfusions, as occurred in this case.

scholarly journals AIMAR survey on COPD phenotypes

2014 ◽  
Vol 9 ◽  
Author(s):  
Maria Sandra Magnoni ◽  
Andrea Rizzi ◽  
Alberto Visconti ◽  
Claudio F. Donner
Keyword(s):  
Clinical Practice ◽  
Clinical Outcomes ◽  
Significant Proportion ◽  
Clinical Signs ◽  
Inhaled Corticosteroid ◽  
Clinical Risk ◽  
Adherence To Medication ◽  
Number Of Patients ◽  
First Choice ◽  
Long Acting

Background: COPD is characterized by considerable diversity in terms of clinical signs and symptoms, physiopathological mechanisms, response to treatment and disease progression. For this reason, the identification of different patient subgroups (or possible phenotypes) is important both for prognosis and for therapeutic objectives. Based on the foregoing, AIMAR has decided to conduct a survey on the perception of the prevalence of the different clinical COPD phenotypes/subtypes in the clinical practice of physicians who treat patients with chronic obstructive pulmonary disease, and on their therapeutic objectives. Methods: The survey consisted of 19 multiple-choice questions, compiled through a form published online. All the data and answers entered into the system were checked for consistency and completeness directly online at the time they were entered, and each respondent could only complete the questionnaire once. Results: The survey took place from May through October 2012. A total of 1,434 questionnaires (60% of the sample approached) were eligible for analysis, broken down as follows: 537 pulmonologists, 666 general practitioners (GPs), 72 internal medicine specialists, 36 allergists, 30 geriatricians, 93 other specialists. The results show that a significant proportion of GPs (33%) identified more than 50 patients in their practices with a diagnosis of COPD. Although most patients are or have been in treatment with a long-acting bronchodilator, the most common reasons for seeing a GP or a specialist were exacerbations and worsening of the symptoms, suggesting the importance of an appropriate background therapy in order to reduce the risk of disease instability. The frequent exacerbator phenotype was the most commonly found phenotype in clinical practice (by 75% of specialists and 66% of GPs); patients with a prevalent phenotype of chronic bronchitis were reported more often by GPs, while specialists reported a higher number of patients with a prevalent phenotype of emphysema. A medical history of exacerbations and the extent of deterioration of the spirometry parameters were considered to be the major indicators for COPD severity and clinical risk. In managing the frequent exacerbator phenotype, the therapeutic objectives – both for GPs and for specialists – included reducing airway inflammation, improving bronchial dilation, and reducing pulmonary hyperinflation. For this type of patients at high clinical risk, specialists selected a first-line therapeutic option based on a predetermined combination of an inhaled corticosteroid (ICS) and a long-acting β2-agonist bronchodilator (LABA) and a second-line three-drug therapy (combination of ICS and two long-acting bronchodilators), while GPs’ choices are more diversified, without a clear-cut prevalence of one type of treatment. In patients with COPD and concomitant cardiovascular diseases, frequently observed in clinical practice by all physicians, the combination of ICS and LABA was considered the first-choice option by the highest proportion of GPs (43%) and specialists (37%), while a smaller number of specialists (35%) opted for the long acting muscarinic antagonists (LAMA). Both GPs and specialists believe that therapeutic continuity is of primary importance for the achievement of clinical outcomes with all classes of drugs. Conclusions: A good knowledge of COPD has been observed in a high percentage of GPs, indicating an increased awareness of this disease in Primary Health Care. The frequent exacerbator phenotype is viewed by all physicians as the most prevalent in clinical practice, bearing a high risk of hospitalization. For specialists, therapeutic measures aimed at reducing the number and severity of exacerbations are primarily based on the combination of inhaled corticosteroid and bronchodilator, presumably because of the complementary pharmacological action of its components, whereas while GPs’ choices tend to be more diversified. Adherence to medication regimens is of the essence for the achievement of clinical outcomes.

scholarly journals Discrepancy of Blast Percentage between the Bone Marrow Aspirate and Flow Cytometry and Its Impact on Survival Outcomes in Patients with Myelodysplastic Syndromes Excess Blast (MDS-EB)

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5441-5441
Author(s):  
Meera Yogarajah ◽  
Phuong L. Nguyen ◽  
Rong He ◽  
Hassan B. Alkhateeb ◽  
Mithun Vinod Shah ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
Small Sample Size ◽  
Scoring Systems ◽  
Standard Of Care ◽  
Risk Groups ◽  
Small Sample ◽  
International Prognostic Scoring System ◽  
P Value ◽  
Number Of Patients

Background MDS is a heterogeneous disease and the revised International Prognostic Scoring System (IPSS-R) is utilized in prognostication. The percentage (%) of blasts in the bone marrow is determined in the aspirate morphologically. Though the former is the standard of care the blast percentage is also reported by flow cytometry and biopsy which can many times be inconsistent. We previously presented the utilization of biopsy based blast percentage which showed meaningful prognostic groups compared to aspirate. In this study we compare the blasts as reported by the aspirate and flow cytometry in MDS-EB in calculating IPSS-R. Methods The MDS database was reviewed for cases of MDS-EB after due IRB approval at the Mayo clinic. We calculated IPSS-R scores based on the aspirate blast % (IPSS-RAsp) and flow blast% (IPSS-Rfl). The aspirate blast percentage was reported morphologically. Suboptimal aspirates were excluded from the study. The flow blast percentage was determined by immunophenotyping. The overall survival (OS) was determined by IPSS-RAsp and IPSS-RFl. OS estimates were calculated by Kaplan-Meier curves and log-rank testing using JMP v.13. Uno's concordance statistic was used to compare the 2 risk scoring systems. Results Of 1322 patients, 431 (33%) cases were identified with MDS-EB out of which 120 (29%) cases had blasts reported in the aspirate and flow. Based on aspirate MDS EB1: 54% (n=65), MDS EB2 46% (n=55). The hematological, cytogenetic and R-IPSS categories were compared between MDS-EB1 and MDS- EB 2. The blast percentage and hemoglobin levels was significantly different between MDS-EB1 and EB2 as seen in table 1, however the IPSS-R risk groups were not significantly different. The flow cytometry was concordant with aspirate in 66/120 (55%) cases. Out of the dis-concordant cases only 20% (11/54) was upstaged by flow cytometry with most of the patients being down staged as expected by the techniques used in processing the blood and hence not reliable when reported low (Figure 1). The OS outcomes based on the IPSS- R asp, IPSS-Rfl areshown in figure 2A,2B .The p value with aspirate based R-IPSS was more significant than flow cytometry based R-IPSS (p= 0.0007 vs 0.0174). We compared the two models for observed OS differences using the Uno model which was not statistically significant. (p= 0.6) Conclusions Both models did not show a difference which is likely due to the very small sample size. However flow cytometry did down stage more patients when disconcordant and may have less value in that setting. It would be ideal to compare all 3 models aspirate, biopsy and flow cytometry however we did not have enough number of patients to do the comparison. Disclosures Patnaik: Stem Line Pharmaceuticals.: Membership on an entity's Board of Directors or advisory committees. Al-Kali:Astex Pharmaceuticals, Inc.: Research Funding.

scholarly journals Association between early mobilization or rehabilitation and intensive care unit acquired weakness: A systematic review and meta-analysis of randomized controlled trials.

2020 ◽  
Author(s):  
Minghang Li ◽  
Mingyue Ding ◽  
Huanzhang Shao ◽  
Bingyu Qin ◽  
Xingwei Wang ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Meta Analysis ◽  
Early Mobilization ◽  
Standard Of Care ◽  
Cochrane Library ◽  
Care Group ◽  
China National Knowledge Infrastructure ◽  
Number Of Patients ◽  
Icu Discharge

Abstract Background The prognosis of intensive care unit acquired weakness (ICUAW) is poor and the treatment effect is not ideal. At present, some effective and safe early prevention means are urgently needed to reduce its incidence.This study evaluated the effectiveness and safety of early activities or rehabilitation in the prevention of ICUAW. Methods We searched for articles in five electronic databases, including PubMed, EMBASE, the Cochrane Library, the China National Knowledge Infrastructure (CNKI) and Wanfang Med Online. All publications until June, 2020 were searched. We have selected trials investigating early mobilization or rehabilitation as compared to standard of care in critically ill adults.The extracted data included adverse events, the number of patients with ICUAW, the length of stay in the ICU (ICU-LOS) the length of mechanical ventilation (MV) etc. Results The final results showed that compared with the usual care group, early mobilization or rehabilitation reduced the prevalence of ICUAW (RR, 0.73; [0.61, 0.87]; I2 = 44%; P = 0.0006), ICU-LOS (MD, − 1.47;[2.83, 0.10]; I2 = 56%; P = 0.04), length of MV (MD, − 1.96; [2.41, 1.51]; I2 = 0%; P = 0.00001), but the mortality (RR, 0.90; [0.62, 1.32]; I2 = 3%; P = 0.60) at ICU discharge was not associated. The subgroup analysis of ICUAW prevalence and ICU-LOS based on the intervention methods showed that early combined rehabilitation could reduce the prevalence of ICUAW (RR, 0.56; [0.43, 0.74]; I2 = 34%; P = 0.0001) and shorten the ICU-LOS (MD, − 2.21; [3.28, 0.97]; I2 = 23%; P = 0.0003). EGDM was not associated with a decrease in ICUAW prevalence (RR, 0.85; [0.65, 1.09]; I2 = 26%; P = 0.20), but it reduced the ICU-LOS (MD, − 2.27; [3.86, 0.68]; I2 = 0%; P = 0.005).Early in-bed cycling was not associated with reduced ICUAW prevalence(RR, 1.25; [0.73, 2.13]; I2 = 0%; P = 0.41) and ICU-LOS(MD, 2.27; [0.27, 4.80]; I2 = 0%; P = 0.08) . Conclusions Early mobilization or rehabilitation was associated with a shorter length of MV and ICU-LOS, but not mortality. Of course, not all early activities or forms of rehabilitation are effective. The early combined rehabilitation model is effective for the prevention of ICUAW. However, EGDM and early in-bed cycling were not effective in preventing ICUAW.

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