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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 -
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 -
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 -
BMC Nephrology May 2024Atypical haemolytic uremic syndrome (aHUS) is an uncommon form of thrombotic microangiopathy (TMA). However, it remains difficult to diagnose the disease early, given...
BACKGROUND
Atypical haemolytic uremic syndrome (aHUS) is an uncommon form of thrombotic microangiopathy (TMA). However, it remains difficult to diagnose the disease early, given its non-specific and overlapping presentation to other conditions such as thrombotic thrombocytopenic purpura and typical HUS. It is also important to identify the underlying causes and to distinguish between primary (due to a genetic abnormality leading to a dysregulated alternative complement pathway) and secondary (often attributed by severe infection or inflammation) forms of the disease, as there is now effective treatment such as monoclonal antibodies against C5 for primary aHUS. However, primary aHUS with severe inflammation are often mistaken as a secondary HUS. We presented an unusual case of adult-onset Still's disease (AOSD) with macrophage activation syndrome (MAS), which is in fact associated with anti-complement factor H (anti-CFH) antibodies related aHUS. Although the aHUS may be triggered by the severe inflammation from the AOSD, the presence of anti-CFH antibodies suggests an underlying genetic defect in the alternative complement pathway, predisposing to primary aHUS. One should note that anti-CFH antibodies associated aHUS may not always associate with genetic predisposition to complement dysregulation and can be an autoimmune form of aHUS, highlighting the importance of genetic testing.
CASE PRESENTATION
A 42 years old man was admitted with suspected adult-onset Still's disease. Intravenous methylprednisolone was started but patient was complicated with acute encephalopathy and low platelet. ADAMTS13 test returned to be normal and concurrent aHUS was eventually suspected, 26 days after the initial thrombocytopenia was presented. Plasma exchange was started and patient eventually had 2 doses of eculizumab after funding was approved. Concurrent tocilizumab was also used to treat the adult-onset Still's disease with MAS. The patient was eventually stabilised and long-term tocilizumab maintenance treatment was planned instead of eculizumab following haematology review. Although the aHUS may be a secondary event to MAS according to haematology opinion and the genetic test came back negative for the five major aHUS gene, high titre of anti-CFH antibodies was detected (1242 AU/ml).
CONCLUSION
Our case highlighted the importance of prompt anti-CFH antibodies test and genetic testing for aHUS in patients with severe AOSD and features of TMA. Our case also emphasized testing for structural variants within the CFH and CFH-related proteins gene region, as part of the routine genetic analysis in patients with anti-CFH antibodies associated aHUS to improve diagnostic approaches.
Topics: Humans; Still's Disease, Adult-Onset; Atypical Hemolytic Uremic Syndrome; Complement Factor H; Adult; Male; Autoantibodies; Macrophage Activation Syndrome
PubMed: 38745129
DOI: 10.1186/s12882-024-03548-4 -
Platelets Dec 2024Immune thrombocytopenia (ITP) is a common autoimmune hematological disorder. Despite this, diagnosis is still challenging due to clinical heterogeneity and the lack of a...
Immune thrombocytopenia (ITP) is a common autoimmune hematological disorder. Despite this, diagnosis is still challenging due to clinical heterogeneity and the lack of a specific diagnostic test. New findings in the pathology and the availability of new drugs have led to the development of different guidelines worldwide. In the present study, the Delphi methodology has been used to get a consensus on the management of adult patients with ITP in Spain and to help in decision-making. The Delphi questionnaire has been designed by a scientific ad hoc committee and has been divided into 13 topics, with a total of 127 items, covering the maximum possible scenarios for the management of ITP. As a result of the study, a total consensus of 81% has been reached. It is concluded that this Delphi consensus provides practical recommendations on topics related to diagnosis and management of ITP patients to help doctors to improve outcomes. Some aspects remain unclear, without consensus among the experts. Thus, more advances are needed to optimize ITP management.
Topics: Humans; Purpura, Thrombocytopenic, Idiopathic; Spain; Delphi Technique; Consensus; Surveys and Questionnaires
PubMed: 38742687
DOI: 10.1080/09537104.2024.2336104 -
Access Microbiology 2024is one of the predominant bacterial contaminants in platelet concentrates (PCs), a blood component used to treat bleeding disorders. PCs are a unique niche that...
is one of the predominant bacterial contaminants in platelet concentrates (PCs), a blood component used to treat bleeding disorders. PCs are a unique niche that triggers biofilm formation, the main pathomechanism of infections. We performed whole genome sequencing of four strains isolated from skin of healthy human volunteers (AZ22 and AZ39) and contaminated PCs (ST10002 and ST11003) to unravel phylogenetic relationships and decipher virulence mechanisms compared to 24 complete genomes in GenBank. AZ39 and ST11003 formed a separate unique lineage with strains 14.1 .R1 and SE95, while AZ22 formed a cluster with 1457 and ST10002 closely grouped with FDAAGOS_161. The four isolates were assigned to sequence types ST1175, ST1174, ST73 and ST16, respectively. All four genomes exhibited biofilm-associated genes , , , and . Additionally, AZ22 had and , whereas ST10002 had and . Notably, AZ39 possesses truncated and and harbours a toxin-encoding gene. All isolates carry multiple antibiotic resistance genes conferring resistance to fosfomycin (), β-lactams () and fluoroquinolones (). This study reveales a unique lineage for and provides insight into the genetic basis of virulence and antibiotic resistance in transfusion-associated strains.
PubMed: 38737800
DOI: 10.1099/acmi.0.000780.v3 -
Saudi Medical Journal May 2024To investigate the prevalence of hematologic findings and the relationship between hemogram parameters and brucellosis stages in patients.
OBJECTIVES
To investigate the prevalence of hematologic findings and the relationship between hemogram parameters and brucellosis stages in patients.
METHODS
This multi-center study included patients older than 16 years of age who were followed up with a diagnosis of brucellosis. Patients' results, including white blood cell, hemoglobin, neutrophil, lymphocyte, monocyte, mean platelet volume, platelet and eosinophil counts were analyzed at the initial diagnosis.
RESULTS
In this study 51.3% of the patients diagnosed with brucellosis were male. The age median was 45 years for female and 41 years for male. A total of 55.1% of the patients had acute brucellosis, 28.2% had subacute, 7.4% had chronic and 9% had relapse. The most common hematologic findings in brucellosis patients were anemia (25.9%), monocytosis (15.9%), eosinopenia (10.3%), and leukocytosis (7.1%). Pancytopenia occurred in 0.8% of patients and was more prominent in the acute phase. The acute brucellosis group had lower white blood cell, hemoglobin, neutrophil, eosinophil, and platelet counts and mean platelet volume, and higher monocyte counts compared to subacute and chronic subgroups.
CONCLUSION
It was noteworthy that in addition to anemia and monocytosis, eosinopenia was third most prominent laboratory findings in the study. Pancytopenia and thrombocytopenia rates were low.
Topics: Humans; Brucellosis; Male; Female; Adult; Middle Aged; Turkey; Young Adult; Thrombocytopenia; Adolescent; Aged; Anemia; Blood Cell Count
PubMed: 38734423
DOI: 10.15537/smj.2024.45.5.20230847 -
Nutrients Apr 2024Cardiovascular diseases are a broadly understood concept focusing on vascular and heart dysfunction. Lack of physical exercise, type 2 diabetes, obesity, hypertension,... (Review)
Review
Characterizations of White Mulberry, Sea-Buckthorn, Garlic, Lily of the Valley, Motherwort, and Hawthorn as Potential Candidates for Managing Cardiovascular Disease-In Vitro and Ex Vivo Animal Studies.
Cardiovascular diseases are a broadly understood concept focusing on vascular and heart dysfunction. Lack of physical exercise, type 2 diabetes, obesity, hypertension, dyslipidemia, thromboembolism, and kidney and lung diseases all contribute to the development of heart and blood vessel dysfunction. Although effective and important, traditional treatment with diuretics, statins, beta blockers, calcium inhibitors, ACE inhibitors, and anti-platelet drugs remains a second-line treatment after dietary interventions and lifestyle changes. Scientists worldwide are still looking for an herbal product that would be effective and free from side effects, either taken together with or before the standard pharmacological intervention. Such herbal-originated medication therapy may include L. (white mulberry), (L.) A. Nelson (sea-buckthorn), L. (garlic), L. (lily of the valley), L. (motherwort), and spp. (hawthorn). Valuable herbal raw materials include leaves, fruits, seeds, and even thorns. This short review focuses on six herbs that can constitute an interesting and potential therapeutic option in the management of cardiovascular disorders.
Topics: Crataegus; Cardiovascular Diseases; Morus; Animals; Garlic; Hippophae; Plant Extracts; Leonurus; Elaeagnaceae; Humans; Phytotherapy
PubMed: 38732560
DOI: 10.3390/nu16091313