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Signal Transduction and Targeted Therapy Apr 2024Patients with refractory immune thrombocytopenia (ITP) frequently encounter substantial bleeding risks and demonstrate limited responsiveness to existing therapies....
Efficacy and safety of human umbilical cord-derived mesenchymal stem cells in the treatment of refractory immune thrombocytopenia: a prospective, single arm, phase I trial.
Patients with refractory immune thrombocytopenia (ITP) frequently encounter substantial bleeding risks and demonstrate limited responsiveness to existing therapies. Umbilical cord-derived mesenchymal stem cells (UC-MSCs) present a promising alternative, capitalizing on their low immunogenicity and potent immunomodulatory effects for treating diverse autoimmune disorders. This prospective phase I trial enrolled eighteen eligible patients to explore the safety and efficacy of UC-MSCs in treating refractory ITP. The research design included administering UC-MSCs at escalating doses of 0.5 × 10 cells/kg, 1.0 × 10 cells/kg, and 2.0 × 10 cells/kg weekly for four consecutive weeks across three cohorts during the dose-escalation phase, followed by a dose of 2.0 × 10 cells/kg weekly for the dose-expansion phase. Adverse events, platelet counts, and changes in peripheral blood immunity were monitored and recorded throughout the administration and follow-up period. Ultimately, 12 (with an addition of three patients in the 2.0 × 10 cells/kg group due to dose-limiting toxicity) and six patients were enrolled in the dose-escalation and dose-expansion phase, respectively. Thirteen patients (13/18, 72.2%) experienced one or more treatment emergent adverse events. Serious adverse events occurred in four patients (4/18, 22.2%), including gastrointestinal hemorrhage (2/4), profuse menstruation (1/4), and acute myocardial infarction (1/4). The response rates were 41.7% in the dose-escalation phase (5/12, two received 1.0 × 10 cells/kg per week, and three received 2.0 × 10 cells/kg per week) and 50.0% (3/6) in the dose-expansion phase. The overall response rate was 44.4% (8/18) among all enrolled patients. To sum up, UC-MSCs are effective and well tolerated in treating refractory ITP (ClinicalTrials.gov ID: NCT04014166).
Topics: Humans; Female; Male; Purpura, Thrombocytopenic, Idiopathic; Middle Aged; Adult; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Umbilical Cord; Prospective Studies; Aged
PubMed: 38653983
DOI: 10.1038/s41392-024-01793-5 -
Frontiers in Immunology 2024systemic inflammation disorders were observed in chronic kidney disease (CKD). Whether the systemic inflammatory indicators could be optimal predictors for the survival...
BACKGROUND
systemic inflammation disorders were observed in chronic kidney disease (CKD). Whether the systemic inflammatory indicators could be optimal predictors for the survival of CKD remains less studied.
METHODS
In this study, participants were selected from the datasets of the National Health and Nutrition Examination Survey (NHANES) between 1999 to 2018 years. Four systemic inflammatory indicators were evaluated by the peripheral blood tests including systemic immune-inflammation index (SII, platelet*neutrophil/lymphocyte), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR). Kaplan-Meier curves, restricted cubic spline (RCS), and Cox regression analysis were used to evaluate the association between the inflammatory index with the all-cause mortality of CKD. Receiver operating characteristic (ROC) and concordance index (C-index) were used to determine the predictive accuracy of varied systemic inflammatory indicators. Sensitive analyses were conducted to validate the robustness of the main findings.
RESULTS
A total of 6,880 participants were included in this study. The mean age was 67.03 years old. Among the study population, the mean levels of systemic inflammatory indicators were 588.35 in SII, 2.45 in NLR, 133.85 in PLR, and 3.76 in LMR, respectively. The systemic inflammatory indicators of SII, NLR, and PLR were all significantly positively associated with the all-cause mortality of CKD patients, whereas the high value of LMR played a protectable role in CKD patients. NLR and LMR were the leading predictors in the survival of CKD patients [Hazard ratio (HR) =1.21, 95% confidence interval (CI): 1.07-1.36, p = 0.003 (3 quartile), HR = 1.52, 95%CI: 1.35-1.72, p<0.001 (4 quartile) in NLR, and HR = 0.83, 95%CI: 0.75-0.92, p<0.001 (2 quartile), HR = 0.73, 95%CI: 0.65-0.82, p<0.001 (3 quartile), and = 0.74, 95%CI: 0.65-0.83, p<0.001 (4 quartile) in LMR], with a C-index of 0.612 and 0.624, respectively. The RCS curves showed non-linearity between systemic inflammatory indicators and all-cause mortality risk of the CKD population.
CONCLUSION
Our study highlights that systemic inflammatory indicators are important for predicting the survival of the U.S. population with CKD. The systemic inflammatory indicators would add additional clinical value to the health care of the CKD population.
Topics: Humans; Renal Insufficiency, Chronic; Male; Female; Nutrition Surveys; Aged; Middle Aged; Prospective Studies; Inflammation; Neutrophils; Biomarkers; Lymphocytes; Prognosis; Monocytes
PubMed: 38650947
DOI: 10.3389/fimmu.2024.1365591 -
BMC Gastroenterology Apr 2024Endoscopic features of intestinal transplant-associated microangiopathy (iTAM) have not been comprehensively investigated. This study aimed to examine the endoscopic...
BACKGROUND
Endoscopic features of intestinal transplant-associated microangiopathy (iTAM) have not been comprehensively investigated. This study aimed to examine the endoscopic characteristics of patients diagnosed with iTAM.
METHODS
This retrospective analysis included 14 patients pathologically diagnosed with iTAM after stem cell transplantation for hematolymphoid neoplasms (n = 13) or thalassemia (n = 1). The sex, age at diagnosis, endoscopic features, and prognosis of each patient were assessed. Serological markers for diagnosing transplant-associated thrombotic microangiopathy were also evaluated.
RESULTS
The mean age at the time of iTAM diagnosis was 40.2 years. Patients diagnosed based on the pathognomonic pathological changes of iTAM presented with diverse symptoms at the times of endoscopic examinations, including diarrhea (n = 10), abdominal pain (n = 5), nausea (n = 4), appetite loss (n = 2), bloody stools (n = 2), abdominal discomfort (n = 1), and vomiting (n = 1). At the final follow-up, six patients survived, while eight patients succumbed, with a median time of 100.5 days (range: 52-247) post-diagnosis. Endoscopic manifestations included erythematous mucosa (n = 14), erosions (n = 13), ulcers (n = 9), mucosal edema (n = 9), granular mucosa (n = 9), and villous atrophy (n = 4). Erosions and/or ulcers were primarily observed in the colon (10/14, 71%), followed by the ileum (9/13, 69%), stomach (4/10, 40%), cecum (5/14, 36%), duodenum (3/10, 30%), rectum (4/14, 29%), and esophagus (1/10, 10%). Cytomegalovirus infection (n = 4) and graft-versus-host disease (n = 2) coexisted within the gastrointestinal tract. Patients had de novo prolonged or progressive thrombocytopenia (6/14, 43%), decreased hemoglobin concentration (4/14, 29%), reduced serum haptoglobin level (3/14, 21%), and a sudden and persistent increase in lactate dehydrogenase level (2/14, 14%). Peripheral blood samples from 12 patients were evaluated for schistocytes, with none exceeding 4%.
CONCLUSIONS
This study provides a comprehensive exploration of the endoscopic characteristics of iTAM. Notably, all patients exhibited erythematous mucosa throughout the gastrointestinal tract, accompanied by prevalent manifestations, such as erosions (93%), ulcers (64%), mucosal edema (64%), granular mucosa (64%), and villous atrophy (29%). Because of the low positivity for serological markers of transplant-associated thrombotic microangiopathy in patients with iTAM, endoscopic evaluation and biopsy of these lesions are crucial, even in the absence of these serological features.
Topics: Humans; Male; Female; Adult; Retrospective Studies; Middle Aged; Thrombotic Microangiopathies; Young Adult; Intestinal Mucosa; Endoscopy, Gastrointestinal; Adolescent; Hematologic Neoplasms; Stem Cell Transplantation; Intestinal Diseases; Diarrhea; Hematopoietic Stem Cell Transplantation; Aged
PubMed: 38649868
DOI: 10.1186/s12876-024-03221-y -
The Kobe Journal of Medical Sciences Apr 2024Hemolysis, elevated liver enzyme levels, and low platelet count (HELLP) syndrome is one of the most severe complications of hypertensive disorders of pregnancy. HELLP...
Hemolysis, elevated liver enzyme levels, and low platelet count (HELLP) syndrome is one of the most severe complications of hypertensive disorders of pregnancy. HELLP syndrome occurring before 22 gestational weeks (GWs) is extremely rare, and patients prevalently exhibit underlying maternal diseases or fetal abnormalities. Here, we report the case of a pregnant woman who had HELLP syndrome at 20 GWs without any obvious underlying maternal diseases or fetal abnormalities. A 38-year-old pregnant woman was referred to Kobe University Hospital from another hospital at 19 + 5/7 GWs for hypertension, proteinuria, generalized edema, and fetal growth restriction. She was diagnosed with partial HELLP syndrome according to the Mississippi classification at 20 + 2/7 GWs. The patient was managed following the Mississippi protocol, including intravenous dexamethasone, magnesium sulfate, and antihypertensive drugs. She received intensive blood pressure and laboratory data monitoring using an arterial line and additional treatments, including platelet transfusion, intravenous haptoglobin infusion, and human atrial natriuretic peptide. The pregnancy ended in an induced delivery at 20 + 3/7 GWs, and she was discharged without complications 10 days postnatal. We performed laboratory tests for diagnosing underlying diseases but identified no obvious underlying diseases. This report indicates that early and intensive treatment of patients with HELLP syndrome occurring before 22 GWs according to the Mississippi protocol may enable clinicians to complete pregnancy termination without maternal complications and provide useful information to clinical practitioners in perinatal medicine.
Topics: Adult; Female; Humans; Pregnancy; Antihypertensive Agents; Dexamethasone; HELLP Syndrome; Magnesium Sulfate; Pregnancy Trimester, Second
PubMed: 38644297
DOI: 10.24546/0100488386 -
Transfusion and Apheresis Science :... Apr 2024While there are various aspects of platelet biology that can be studied in the lab (i.e. adhesion, degranulation, integrin activation), the master test for platelet... (Review)
Review
While there are various aspects of platelet biology that can be studied in the lab (i.e. adhesion, degranulation, integrin activation), the master test for platelet function is that which gives a measure of the platelet aggregation capacity upon stimulation with an agonist. Platelet function testing is necessary for the diagnosis of platelet disorders and the monitoring of patients receiving anti-platelet treatments. Furthermore, it becomes relevant in the quality control of platelet concentrates for transfusion purposes, especially considering the global concern about long term storage, other forms of storage (i.e. cryopreservation, lyophilization), and the impact of Pathogen Reduction Treatments (PRTs) on platelet performance upon transfusion. However, it has been acknowledged as technically difficult and demanding, since a fine platelet function test must be carried out under specific conditions. Still, there might be occasions that preclude the platelet function testing abiding to the gold standard requirements, thus, leaving us with the necessity to redefine which variables may condition or limit the analysis of platelet function testing. In the present manuscript, we test different variables (such as the anticoagulant used or the time elapsed since extraction) and the possibility to reconstitute blood prior to platelet function analysis. This study aims to provide windows of action at the diagnostics lab, especially when not all of the recommended procedures and conditions can be followed: for example, when a sample is sent from a long distance, when there is a limitation on blood extraction volume or when certain parameters (platelet count) preclude reliable test results.
PubMed: 38644062
DOI: 10.1016/j.transci.2024.103930 -
Scientific Reports Apr 2024Serious hematological adverse drug reactions (HADRs) may lead to or prolong hospitalization and even cause death. The aim of this study was to determine the regulatory...
Serious hematological adverse drug reactions (HADRs) may lead to or prolong hospitalization and even cause death. The aim of this study was to determine the regulatory factors associated with HADRs caused by drugs that were authorized up to July 2023 by the European Medicines Agency (EMA) and to evaluate the frequency of HADRs. Using a cross-sectional approach, the type and frequency of HADRs were collected from the Summaries of Product Characteristics of Drugs Authorized by the EMA and analyzed within proprietary, nonproprietary, and biosimilar/biological frameworks. Multivariate statistical analysis was used to investigate the associations of generic status, biosimilar status, conditional approval, exceptional circumstances, accelerated assessment, orphan drug status, years on the market, administration route, and inclusion on the Essential Medicines List (EML) with HADRs. In total, 54.78% of proprietary drugs were associated with HADRs at any frequency, while anemia, leucopenia, and thrombocytopenia were observed in approximately 36% of the patients. The predictors of any HADR, anemia, and thrombocytopenia of any frequency are generic status, biosimilar status, and inclusion on the EML, while the only protective factor is the administration route. Biosimilars and their originator biologicals have similar frequencies of HADRs; the only exception is somatropin. Knowledge of the regulatory factors associated with HADRs could help clinicians address monitoring issues when new drugs are introduced for the treatment of patients.
Topics: Humans; Pharmaceutical Preparations; Biosimilar Pharmaceuticals; Drug-Related Side Effects and Adverse Reactions; Drugs, Generic; Thrombocytopenia; Leukopenia; Drugs, Essential; Anemia; Drug Approval
PubMed: 38643204
DOI: 10.1038/s41598-024-59710-3 -
Scientific Reports Apr 2024Immune thrombocytopenia (ITP), an acquired autoimmune disease, is characterized by immune-mediated platelet destruction. A biomarker is a biological entity that...
Immune thrombocytopenia (ITP), an acquired autoimmune disease, is characterized by immune-mediated platelet destruction. A biomarker is a biological entity that contributes to disease pathogenesis and reflects disease activity. Metabolic alterations are reported to be associated with the occurrence of various diseases. As metabolic biomarkers for ITP have not been identified. This study aimed to identify metabolism-related differentially expressed genes as potential biomarkers for pathogenesis of ITP using bioinformatic analyses.The microarray expression data of the peripheral blood mononuclear cells were downloaded from the Gene Expression Omnibus database (GSE112278 download link: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE112278 ). Key module genes were intersected with metabolism-related genes to obtain the metabolism-related key candidate genes. The hub genes were screened based on the degree function in the coytoscape sofware. The key ITP-related genes were subjected to functional enrichment analysis. Immune infiltration analysis was performed using a single-sample gene set enrichment analysis algorithm to evaluate the differential infiltration levels of immune cell types between ITP patient and control. Molecular subtypes were identified based on the expression of hub genes. The expression of hub genes in the ITP patients was validated using quantitative real-time polymerase chain reaction analysis. This study identified five hub genes (ADH4, CYP7A1, CYP1A2, CYP8B1, and NR1H4), which were be associated with the pathogenesis of ITP, and two molecular subtypes of ITP. Among these hub genes, CYP7A1 and CYP8B1 involved in cholesterol metabolism,were further verified in clinical samples.
Topics: Humans; Purpura, Thrombocytopenic, Idiopathic; Leukocytes, Mononuclear; Steroid 12-alpha-Hydroxylase; Thrombocytopenia; Biomarkers; Computational Biology
PubMed: 38641637
DOI: 10.1038/s41598-024-59493-7 -
Acta Medica Portuguesa Apr 2024
Topics: Child; Humans; Purpura, Thrombocytopenic, Idiopathic; Portugal; Benzoates; Hydrazines; Chronic Disease; Pyrazoles
PubMed: 38631059
DOI: 10.20344/amp.20532 -
Hellenic Journal of Nuclear Medicine 2024In patients with normal liver function, patients with acute or chronic thyroid disease are more likely to develop liver dysfunction. Although the mechanisms underlying...
OBJECTIVE
In patients with normal liver function, patients with acute or chronic thyroid disease are more likely to develop liver dysfunction. Although the mechanisms underlying this process are not yet fully understood, it has been shown that hypothyroidism can lead to hepatic injury. We evaluated haematological function trends in patients with differentiated thyroid cancer (DTC) at baseline and approximately 4 weeks after l-thyroxine withdrawal before radioactive iodine ablation.
SUBJECTS AND METHODS
This is a retrospective study, and 157 patients were enrolled. Logistic regression analysis was used to find significant predictors. Four weeks after LT4 withdrawal, 64 patients belonged to the group of liver injury, and 93 patients belonged to the group of normal liver function.
RESULTS
Univariate analysis determined that platelet count (PC) (P=0.005), mean platelet volume (MPV) (P=0.013), platelet distribution width (PDW) (P=0.039) and absolute lymphocyte count (ALC) (P=0.008) were responsible risk factors for liver injury in DTC patients after withdrawal of levothyroxine (l-thyroxine). Multivariate analysis showed that slight increases in PC (OR: 2.243, P: 0.024) and ALC (OR: 0.398, P: 0.017) were closely associated with liver injury in DTC patients after 4 weeks LT4 withdrawal before radioactive iodine ablation.
CONCLUSION
Our results suggest that PC and ALC are independent predictors of hypo-related liver injury. Our study is the first to suggest that haematological indices can be used for predicting the development and progression of hypo-related liver disorders.
Topics: Humans; Female; Male; Middle Aged; Retrospective Studies; Thyroid Neoplasms; Adult; Thyroxine; Reproducibility of Results; Liver Function Tests; Sensitivity and Specificity; Prognosis
PubMed: 38629813
DOI: 10.1967/s002449912700 -
Journal of Cardiothoracic Surgery Apr 2024Thrombocytopenia following Perceval aortic valve replacement has been described previously with variable outcome. Studies have lacked a robust analysis of platelet...
OBJECTIVES
Thrombocytopenia following Perceval aortic valve replacement has been described previously with variable outcome. Studies have lacked a robust analysis of platelet fluctuation and factors affecting it. We aimed to statistically describe the trend in thrombocyte variability as compared with conventional aortic valve replacement, and to assess predictors as well as impact on associated outcomes.
METHODS
One hundred consecutive patients with first-time Perceval were retrospectively compared to 219 patients after Perimount Magna Ease valve replacement. The primary outcome was the serial thrombocyte count on day 0-6. Generalized estimating equations were used to analyse the data using fixed-effect models: for the effect of the post-operative day on platelet count, and random-effect models estimating both time-variant (platelets) and time in-variant variables (valve type, age, LV function, pre-op platelet level).
RESULTS
Perceval patients were older (72 ± 1 vs 68 ± 1 years, p < 0.01) with higher NYHA status (3(2-3) vs 2(1-2), p < 0.001). Mean platelet count in the sutureless group was lowest on day 2 (91.9 ± 31.6 vs 121.7 ± 53.8 × 10 µl), and lower on day 4 (97.9 ± 44) and 6 (110.6 ± 61) compared to the conventional group (157.2 ± 60 and 181.7 ± 79) but did not result in a higher number of transfusions, bleeding or longer hospital stay (p > 0.05). Reduced platelet count was a strong predictor of red cell transfusion in the conventional (p = 0.016), but not in the sutureless group (p = 0.457). Age (Coef -1.025, 95%CI-1.649--0.401, p < 0.001) and CPB-time (Coef 0.186, 95%CI-0.371--0.001, p = 0.048) were predictors for lower platelet levels.
CONCLUSION
Considering the older patient profile treated with Perceval, postoperative thrombocytopenia does not impact on outcome in terms of transfusions, complications or hospital stay.
Topics: Humans; Aortic Valve; Retrospective Studies; Heart Valve Prosthesis Implantation; Aortic Valve Stenosis; Treatment Outcome; Bioprosthesis; Prosthesis Design; Heart Valve Prosthesis; Thrombocytopenia; Risk Factors; Disease Progression
PubMed: 38627820
DOI: 10.1186/s13019-024-02755-2