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BMC Nephrology May 2024Fruquintinib is a highly selective inhibitor of vascular endothelial growth factor receptor (VEGFR). Currently, there are no reported cases of fruquintinib causing...
BACKGROUND
Fruquintinib is a highly selective inhibitor of vascular endothelial growth factor receptor (VEGFR). Currently, there are no reported cases of fruquintinib causing kidney-restrictive thrombotic microangiopathy (TMA) in the available Chinese and foreign literature.
CASE PRESENTATION
In this case report, we presented a 73-year-old patient receiving fruquintinib for metastatic colon cancer, manifesting abundant proteinuria, in which kidney-restrictive TMA was also diagnosed through renal biopsy. As far as we were concerned, this was the frst reported in terms of fruquintinib-induced kidney-restrictive TMA confrmed by renal biopsy.
CONCLUSION
This case indicates that fruquintinib may result in kidney-restrictive TMA, which is a rare but life-threatening complication of cancer treatment drug. Therefore, regular monitoring of proteinuria and blood pressure is imperative for all patients undergoing anti-VEGF drug therapy. And renal biopsy should be promptly conducted to facilitate early detection of thrombotic microangiopathy.
Topics: Humans; Thrombotic Microangiopathies; Aged; Male; Colonic Neoplasms; Quinazolines
PubMed: 38762494
DOI: 10.1186/s12882-024-03598-8 -
Advances in Protein Chemistry and... 2024Platelets, derived from bone marrow megakaryocytes, are essential for vascular integrity and play multifaceted roles in both physiological and pathological processes... (Review)
Review
Platelets, derived from bone marrow megakaryocytes, are essential for vascular integrity and play multifaceted roles in both physiological and pathological processes within the vasculature. Despite their small size and absence of a nucleus, platelets are increasingly recognized for their diverse immune functions. Recent research highlights their pivotal role in interactions with various immune cells, including professional cells like macrophages, dendritic cells, natural killer cells, T cells, and B cells, influencing host immune responses. Platelets also engage with non-professional immune cells, contributing to immune responses and structural maintenance, particularly in conditions like inflammation and atherosclerosis. This review underscores the emerging significance of platelets as potent immune cells, elucidating their interactions with the immune system. We explore the mechanisms of platelet activation, leading to diverse functions, such as aggregation, immunity, activation of other immune cells, and pathogen clearance. Platelets have become the predominant immune cells in circulation, involved in chronic inflammation, responses to infections, and autoimmune disorders. Their immunological attributes, including bioactive granule molecules and immune receptors, contribute to their role in immune responses. Unlike professional antigen-presenting cells, platelets process and present antigens through an MHC-I-dependent pathway, initiating T-cell immune responses. This review illuminates the unique features of platelets and their central role in modulating host immune responses in health and disease.
Topics: Humans; Blood Platelets; Cell Communication; Animals; T-Lymphocytes; Dendritic Cells
PubMed: 38762274
DOI: 10.1016/bs.apcsb.2023.12.010 -
Journal of Clinical Immunology May 2024Chronic Granulomatous Disease (CGD) is a rare immunodeficiency disorder characterized by impaired phagocytic function, leading to recurrent infections and granuloma...
BACKGROUND
Chronic Granulomatous Disease (CGD) is a rare immunodeficiency disorder characterized by impaired phagocytic function, leading to recurrent infections and granuloma formation. Genetic mutations in NADPH oxidase complex components, such as CYBB, NCF1, NCF2, and CYBA genes, contribute to the pathogenesis. This case report explores the possible ocular and hematologic complications associated with CGD.
CASE PRESENTATION
A 6-year-old girl with a history of vitrectomy, membranotomy, and laser therapy due to congenital blindness (diagnosed with chorioretinopathy) was referred to the hospital with generalized ecchymosis and thrombocytopenia. Diagnostic workup initially suggested chronic immune thrombocytopenic purpura (ITP). Subsequent admissions revealed necrotic wounds, urinary tract infections, and recurrent thrombocytopenia. Suspecting immunodeficiency, tests for CGD, Nitroblue tetrazolium (NBT) and dihydrorhodamine (DHR) were performed. She had a low DHR (6.7), and her NBT test was negative (0.0%). Her whole exome sequencing results confirmed autosomal recessive CGD with a homozygous NCF1 mutation.
CONCLUSION
This case underscores the diverse clinical manifestations of CGD, including recurrent thrombocytopenia and possible early-onset ocular involvement. The diagnostic challenges highlight the importance of a multidisciplinary approach involving hematologists, immunologists, and ophthalmologists for accurate diagnosis and management. The rare coexistence of ITP in CGD emphasizes the intricate link between immunodeficiency and autoimmunity, requiring tailored therapeutic strategies.
Topics: Humans; Female; Granulomatous Disease, Chronic; Child; Purpura, Thrombocytopenic, Idiopathic; NADPH Oxidases; Mutation; Exome Sequencing
PubMed: 38760640
DOI: 10.1007/s10875-024-01731-8 -
Scientific Reports May 2024With its increasing use in the treatment of thrombocytopenia, avatrombopag's associated adverse events (AEs) pose a major challenge to its clinical application. This...
With its increasing use in the treatment of thrombocytopenia, avatrombopag's associated adverse events (AEs) pose a major challenge to its clinical application. This study aims to comprehensively study AEs associated with avatrombopag by using real-world evidence. We curated AE reports for avatrombopag from the first quarter of 2018 to the fourth quarter of 2023 in the US Food and Drug Administration's Adverse Event Reporting System (FAERS) database. AEs were coded using the Medical Dictionary for Regulatory Activities of Preferred Terms and System Organ Classes. The reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and multi-item Gamma-Poisson Shrinker were used to investigate the relationship between avatrombopag and AE reports. Among 9,060,312 reported cases in the FAERS database, 1211 reports listed avatrombopag as "primary suspected" drug. Disproportionality analysis identified 44 preferred terms across 17 organ systems met the criteria for at least one of the four algorithms. The most commonly reported AEs were platelet count decreased (20.2%), headache (16.7%), platelet count increased (11.9%), platelet count abnormal (6.3%), contusion (2.7%), pulmonary embolism (2.3%), and deep vein thrombosis (2.1%). Unexpected AEs such as seasonal allergy, rhinorrhea, antiphospholipid syndrome, ear discomfort, and photopsia were also observed. Excluding the other serious outcomes, hospitalization (34.6%) was the most frequently reported serious outcome, followed by death (15.4%). Most reported AEs occurred within the first 2 days of initiating avatrombopag therapy, and the median onset time was 60 days. We identified new and unexpected AEs with clinical use of avatrombopag, and our results may provide valuable information for clinical monitoring and identifying risks associated with avatrombopag.
Topics: Humans; Pharmacovigilance; United States Food and Drug Administration; United States; Adverse Drug Reaction Reporting Systems; Retrospective Studies; Data Mining; Male; Female; Middle Aged; Aged; Adult; Thrombocytopenia; Databases, Factual; Thiazoles; Young Adult; Adolescent; Child; Thiophenes
PubMed: 38760419
DOI: 10.1038/s41598-024-62129-5 -
The National Medical Journal of India 2023Background Thrombotic thrombocytopenic purpura (TTP) is a multisystem disorder characterized by widespread microthrombosis that can predispose to multiple organ failure....
Background Thrombotic thrombocytopenic purpura (TTP) is a multisystem disorder characterized by widespread microthrombosis that can predispose to multiple organ failure. The literature is sparse on the outcomes of critically ill patients with TTP managed in intensive care units (ICUs). We aimed to determine the mortality of ICU patients admitted with TTP and evaluate the predictors of survival. We also compared the incidence of nosocomial infection among those who did or did not receive plasma exchange (PE). Methods We conducted a retrospective study in a tertiary ICU. Two authors screened patients for eligibility from the hospital information system based on peripheral smear reports. Adult critically ill TTP patients managed in ICU were included. Patients with a diagnosis of haemolytic uraemic syndrome, autoimmune causes of haemolysis and pregnancy-related conditions, etc. were excluded. Two authors extracted data from medical charts. No imputation of missing variables was done. Non-parametric statistics were used to report data. Statistical analyses were performed using Stata version 16. Results Of the 535 records that were screened, 33 patients were deemed eligible. Mortality among TTP patients was 14 (42%). The women to men ratio was 7:3. At admission, greater degree of anaemia, thrombocytopenia, and higher lactate dehydrogenase levels were observed in non-survivors compared to survivors (5.4 g/dl [4.8-7.1] v. 7.6 g/dl [6.1-8.9], p=0.05; 17x103 μl v. 21x103 μl, p=0.63; and 2987 (1904-3614) U/L v. 2126 U/L (1941-3319), p=0.71; respectively]. Nineteen (57%) patients had acute kidney injury (AKI), of which 11 survived: 6 recovered completely from renal failure and 5 progressed to end-stage renal disease. Nosocomial infection rates were not different among those receiving and not receiving PE therapy (7 [33%] v. 3 [25%], respectively). Conclusion TTP is more common in women and has a high mortality. Older age, low haemoglobin and higher platelet transfusions are predictors of poor survival. Nosocomial infection rates were similar irrespective of receiving PE therapy.
Topics: Humans; Purpura, Thrombotic Thrombocytopenic; Female; Male; Retrospective Studies; Adult; Intensive Care Units; Plasma Exchange; Middle Aged; Cross Infection; India; Critical Illness; Treatment Outcome; Hospital Mortality
PubMed: 38759978
DOI: 10.25259/NMJI_205_21 -
Medicine May 2024Thrombotic thrombocytopenic purpura (TTP) is a syndrome characterized by widespread blood vessel clotting and bleeding. It can affect individuals of any age but is more... (Review)
Review
RATIONALE
Thrombotic thrombocytopenic purpura (TTP) is a syndrome characterized by widespread blood vessel clotting and bleeding. It can affect individuals of any age but is more commonly observed in females, particularly during pregnancy. Pregnancy combined with TTP is a critical and rapidly progressing condition that is often misdiagnosed as an obstetric disorder like severe preeclampsia or HELLP syndrome. To deepen the understanding of TTP during pregnancy with the help of a clinical case.
PATIENT CONCERNS
A 20-year-old patient, is pregnancy 1 birth 0, 32 weeks dated by her last menstrual period, presented chest tightness, and shortness of breath after physical activity for 3 days.
DIAGNOSES
TTP.
INTERVENTIONS
At present, there are no preventive measures. Timely diagnosis and treatment are useful. Plasma exchange and treat to the patient hinder autoantibodies, such as gamma globulin, methylprednisolone, rituximab, and cyclosporine were effective.
OUTCOMES
The patient exhibited stable vital signs, normal examination results, and experienced no complications. We continued to monitor her progress after she was discharged.
LESSONS SUBSECTIONS
The acute onset of TTP is often associated with pregnancy, as it is a triggering factor. Timely identification, accurate diagnosis, and a comprehensive treatment approach involving plasma exchange, immunosuppressants, and the termination of pregnancy can lead to remission and a favorable outlook for the majority of patients.
Topics: Humans; Female; Pregnancy; Purpura, Thrombotic Thrombocytopenic; Plasma Exchange; Young Adult; Pregnancy Complications, Hematologic
PubMed: 38758904
DOI: 10.1097/MD.0000000000038112 -
Scientific Reports May 2024Immune thrombocytopenia (ITP) is an autoimmune disease caused by T-cell dysfunction. Recently, several studies have shown that a disturbed Th17/Treg balance contributes...
Immune thrombocytopenia (ITP) is an autoimmune disease caused by T-cell dysfunction. Recently, several studies have shown that a disturbed Th17/Treg balance contributes to the development of ITP. MicroRNAs (miRNAs) are small noncoding RNA moleculesthat posttranscriptionally regulate gene expression. Emerging evidences have demonstrated that miRNAs play an important role in regulating the Th17/Treg balance. In the present study, we found that miR-641 was upregulated in ITP patients. In primary T cells, overexpression of miR-641 could cause downregulation of its target genes STIM1 and SATB1, thus inducing a Th17 (upregulated)/Treg (downregulated) imbalance. Inhibition of miR-641 by a miR-641 sponge in primary T cells of ITP patients or by antagomiR-641 in an ITP murine model could cause upregulation of STIM1 and SATB1, thus restoring Th17/Treg homeostasis. These results suggested that the miR-641-STIM/SATB1 axis plays an important role in regulating the Th17/Treg balance in ITP.
Topics: MicroRNAs; Matrix Attachment Region Binding Proteins; Th17 Cells; T-Lymphocytes, Regulatory; Stromal Interaction Molecule 1; Humans; Animals; Mice; Purpura, Thrombocytopenic, Idiopathic; Female; Male; Neoplasm Proteins; Adult; Middle Aged; Gene Expression Regulation; Disease Models, Animal
PubMed: 38755179
DOI: 10.1038/s41598-024-61660-9 -
Blood May 2024
Topics: ADAMTS13 Protein; Humans; Purpura, Thrombotic Thrombocytopenic; Mutation
PubMed: 38753355
DOI: 10.1182/blood.2024024065 -
Frontiers in Cardiovascular Medicine 2024Hypertensive disorders of pregnancy (HDP) is a significant cause of maternal and neonatal mortality. This study aims to identify risk factors for new-onset HDP and to...
BACKGROUND AND AIMS
Hypertensive disorders of pregnancy (HDP) is a significant cause of maternal and neonatal mortality. This study aims to identify risk factors for new-onset HDP and to develop a prediction model for assessing the risk of new-onset hypertension during pregnancy.
METHODS
We included 446 pregnant women without baseline hypertension from Liyang People's Hospital at the first inspection, and they were followed up until delivery. We collected maternal clinical parameters and biomarkers between 16th and 20th weeks of gestation. Logistic regression was used to determine the effect of the risk factors on HDP. For model development, a backward selection algorithm was applied to choose pertinent biomarkers, and predictive models were created based on multiple machine learning methods (generalised linear model, multivariate adaptive regression splines, random forest, and k-nearest neighbours). Model performance was evaluated using the area under the curve.
RESULTS
Out of the 446 participants, 153 developed new-onset HDP. The HDP group exhibited significantly higher baseline body mass index (BMI), weight change, baseline systolic/diastolic blood pressure, and platelet counts than the control group. The increase in baseline BMI, weight change, and baseline systolic and diastolic blood pressure significantly elevated the risk of HDP, with odds ratios and 95% confidence intervals of 1.10 (1.03-1.17), 1.10 (1.05-1.16), 1.04 (1.01-1.08), and 1.10 (1.05-1.14) respectively. Restricted cubic spline showed a linear dose-dependent association of baseline BMI and weight change with the risk of HDP. The random forest-based prediction model showed robust performance with the area under the curve of 0.85 in the training set.
CONCLUSION
This study establishes a prediction model to evaluate the risk of new-onset HDP, which might facilitate the early diagnosis and management of HDP.
PubMed: 38751664
DOI: 10.3389/fcvm.2024.1272779 -
Scientific Reports May 2024Sudden infant death syndrome (SIDS) is the leading cause of post-neonatal infant mortality, but the underlying cause(s) are unclear. A subset of SIDS infants has...
Sudden infant death syndrome (SIDS) is the leading cause of post-neonatal infant mortality, but the underlying cause(s) are unclear. A subset of SIDS infants has abnormalities in the neurotransmitter, serotonin (5-hydroxytryptamine [5-HT]) and the adaptor molecule, 14-3-3 pathways in regions of the brain involved in gasping, response to hypoxia, and arousal. To evaluate our hypothesis that SIDS is, at least in part, a multi-organ dysregulation of 5-HT, we examined whether blood platelets, which have 5-HT and 14-3-3 signaling pathways similar to brain neurons, are abnormal in SIDS. We also studied platelet surface glycoprotein IX (GPIX), a cell adhesion receptor which is physically linked to 14-3-3. In infants dying of SIDS compared to infants dying of known causes, we found significantly higher intra-platelet 5-HT and 14-3-3 and lower platelet surface GPIX. Serum and plasma 5-HT were also elevated in SIDS compared to controls. The presence in SIDS of both platelet and brainstem 5-HT and 14-3-3 abnormalities suggests a global dysregulation of these pathways and the potential for platelets to be used as a model system to study 5-HT and 14-3-3 interactions in SIDS. Platelet and serum biomarkers may aid in the forensic determination of SIDS and have the potential to be predictive of SIDS risk in living infants.
Topics: Humans; Serotonin; Sudden Infant Death; Blood Platelets; 14-3-3 Proteins; Female; Male; Infant; Infant, Newborn
PubMed: 38750089
DOI: 10.1038/s41598-024-61949-9