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BMC Medical Genomics Jun 2024Haemochromatosis is a genetic disease characterized by the excessive deposition of iron in various tissues and organs, eventually results in organ damage including... (Review)
Review
BACKGROUND
Haemochromatosis is a genetic disease characterized by the excessive deposition of iron in various tissues and organs, eventually results in organ damage including cirrhosis, diabetes, cardiomyopathy, etc. SLC40A1-related haemochromatosis is associated with gain-of-function mutations in the SLC40A1 gene, which encodes ferroportin. While sporadic reports of this condition exist in mainland China, the understanding of the phenotype and genetic pattern associated with the SLC40A1 p.Y333H mutation remains incomplete.
CASE PRESENTATION
We report a pedigree with heterozygous p.Y333H mutation in Chinese Han population. The proband is a 64-year-old man complaining of persistent abnormality of liver enzyme levels for 1 year, with a history of knee joint pain, diabetes and skin pigmentation. He displayed markedly elevated serum ferritin level and transferrin saturation. Magnetic resonance imaging showed iron deposition in the liver, spleen, and pancreas, along with cirrhosis and splenomegaly. Whole exome sequencing identified a heterozygous allelic variant c.997T > C (p.Y333H). Genetic screening of family members identified four first-degree relatives and three second-degree relatives having the same mutation. Additional cases with this mutation from two published studies were included. Among the probands and screened relatives, all eight males aged over 30 y had ferritin level > 1000 µg/L, transferrin saturation > 90%. Four patients with organ damage in the present study received therapeutic phlebotomy, alleviating clinical symptoms and improving in transferrin saturation and serum ferritin.
CONCLUSIONS
This study reports the largest pedigree with heterozygous SLC40A1 p.Y333H mutation in the Chinese population to date. In Chinese families, males over 30 years old with hemochromatosis due to SLC40A1 p.Y333H mutation exhibit severe iron overload phenotypes.
Topics: Humans; Hemochromatosis; Male; Pedigree; Middle Aged; China; Cation Transport Proteins; Mutation; Female
PubMed: 38886778
DOI: 10.1186/s12920-024-01929-0 -
Journal of Evaluation in Clinical... Jun 2024The National Health Service (NHS) Long Term Plan was published in January 2019. One of its objectives was restructuring outpatient services, as part of an Outpatient...
RATIONALE
The National Health Service (NHS) Long Term Plan was published in January 2019. One of its objectives was restructuring outpatient services, as part of an Outpatient Transformation initiative. Monitoring of trusts' adherence to the objectives of the Long Term Plan is therefore required to benchmark progress against national objectives.
AIMS AND OBJECTIVES
We aimed to explore whether outpatient transformation initiatives and phlebotomy services that are managed by outpatients are appropriately staffed and to evaluate trusts' adherence to the objectives outlined in the Long Term Plan.
METHOD
A freedom of information (FOI) request was sent in January 2023 to 153 trusts across Great Britain (time span: 1 January 2022-31 December 2022). Parameters requested included number of outpatients seen/discharged, phlebotomy episodes, number of sites/wards covered by phlebotomy, target/actual did not attend (DNA) rates, time since inception of the outpatient transformation project (OTP), advice and refer (A&R) and patient-initiated follow-up (PIFU), phlebotomy and outpatient managerial establishment and use of electronic notes and patient portals.
RESULTS
A total of 117 trusts (76.5%) provided responses to the FOI request. The mean number of new outpatients seen face-to-face was 185,810. Of 73 trusts reporting both actual and target DNA rates, 62 (84.9%) did not meet their DNA targets. The actual DNA rate was significantly greater than the target DNA rate across trusts (p < 0.001, mean: 8.8% vs. 6.5%, respectively). A total of 58 different electronic systems and 29 patient portals were utilised across trusts. Thirty-six trusts (30.3%) did not have an outpatient transformation project manager and 16 trusts (13.7%) did not initiate an OTP. With phlebotomy provision, the mean number of outpatient phlebotomy episodes was lower than inpatient episodes (83,383 vs. 91,020, respectively).
CONCLUSION
There are deficiencies in current outpatient establishments that may hinder the achievement of objectives set in the NHS Long Term Plan. Changes at all levels of healthcare are required, with increased reliance on technologies and investment in support for transformation management.
PubMed: 38884163
DOI: 10.1111/jep.14057 -
Analytical Chemistry Jun 2024The high prevalence and economic burden of heart failure remain a challenge to global health. This lifelong disease leads to a buildup of permanent heart damage, making...
The high prevalence and economic burden of heart failure remain a challenge to global health. This lifelong disease leads to a buildup of permanent heart damage, making early detection and frequent monitoring crucial for effective treatment. N-terminal proBNP (NT-proBNP) is an important biomarker for monitoring the disease state, but current commercial and research NT-proBNP assays require phlebotomy and bulky equipment or do not satisfy clinical requirements such as sensitivity and detection thresholds. Here, we report a point-of-care (POC) compatible microfluidic digital immunoassay that can quantify the NT-proBNP concentration in a small volume of whole blood. Our automated microfluidic device takes whole blood samples mixed with biotinylated detection antibodies and passes through a plasma filter to react with a capture antibody-functionalized sensor surface. Streptavidin-coated gold nanoparticles (GNPs) are then released to mark the surface-bound single NT-proBNP immunocomplexes and recorded with bright-field microscopy. NT-proBNP concentrations in the sample are quantified via a hybrid digital/analog calibration curve. Digital counts of bound GNPs are used as readout signal at low concentrations for high sensitivity detection, and GNP pixel occupancies are used at high concentrations for extended dynamic range. With this approach, we detected NT-proBNP in the range of 8.24-10 000 pg/mL from 7 μL of whole blood in 10 min, with a limit of detection of 0.94 pg/mL. Finally, the method was validated with 15 clinical serum samples, showing excellent linear correlation ( = 0.998) with Roche's Elecsys proBNP II assay. This evidence indicates that this method holds promise for decentralized monitoring of heart failure.
PubMed: 38877973
DOI: 10.1021/acs.analchem.4c01046 -
PloS One 2024Peripheral Intravenous Cannulas (PIVCs) are frequently utilised in the Emergency Department (ED) for delivery of medication and phlebotomy. They are associated with... (Observational Study)
Observational Study
Prospective observational study of peripheral intravenous cannula utilisation and frequency of intravenous fluid delivery in the emergency department-Convenience or necessity?
BACKGROUND
Peripheral Intravenous Cannulas (PIVCs) are frequently utilised in the Emergency Department (ED) for delivery of medication and phlebotomy. They are associated with complications and have an associated cost to departmental resources. A growing body of international research suggests many of the PIVCs inserted in the ED are unnecessary.
METHODS
The objective of this study was to determine the rates of PIVC insertion and use. This was a prospective observational study conducted in one UK ED and one Italian ED. Adult ED patients with non-immediate triage categories were included over a period of three weeks in the UK ED in August 2016 and two weeks in the Italian ED in March and August 2017. Episodes of PIVC insertion and data on PIVC utilisation in adults were recorded. PIVC use was classified as necessary, unnecessary or unused. The proportion of unnecessary and unused PIVCs was calculated. PIVCs were defined as unnecessary if they were either used for phlebotomy only, or solely for IV fluids in patients that could have potentially been hydrated orally (determined against a priori defined criteria). PIVC classified as unused were not used for any purpose.
RESULTS
A total of 1,618 patients were included amongst which 977 PIVCs were inserted. Of the 977 PIVCs, 413 (42%) were necessary, 536 (55%) were unnecessary, and 28 (3%) were unused. Of the unnecessary PIVCs, 473 (48%) were used solely for phlebotomy and 63 (6%) were used for IV fluids in patients that could drink.
CONCLUSIONS
More than half of PIVCs placed in the ED were unnecessary in this study. This suggests that clinical decision making about the benefits and risks of PIVC insertion is not being performed on an individual basis.
Topics: Humans; Emergency Service, Hospital; Prospective Studies; Female; Male; Middle Aged; Aged; Catheterization, Peripheral; Adult; Fluid Therapy; Cannula; Phlebotomy; Aged, 80 and over; Administration, Intravenous; United Kingdom
PubMed: 38875242
DOI: 10.1371/journal.pone.0305276 -
Leukemia & Lymphoma Jun 2024There has been remarkable progress in the development of novel therapeutic approaches for patients with polycythemia vera (PV). Historically, therapy goals in PV were to... (Review)
Review
There has been remarkable progress in the development of novel therapeutic approaches for patients with polycythemia vera (PV). Historically, therapy goals in PV were to mitigate thrombotic risks and control blood counts and symptoms. There is now increased focus on disease modification through progressive attrition of -mutant stem/progenitor cells. The approval of ropeginterferon, a novel monoPEGylated interferon, coupled with findings from LOW-PV and longer-term data from CONTINUATION-PV that strongly support a disease-modifying effect for interferon therapy, have transformed the treatment paradigm for this disorder. Results from MAJIC-PV demonstrate that disease modification can also be induced with JAK inhibitors, suggesting an urgent need to incorporate prospective molecular monitoring into PV trials. Novel agents, such as hepcidin mimetics, aim to help patients with PV restore normal hematocrit levels and become phlebotomy-free. In this review, we will summarize past, current and future approaches to PV management and highlight findings from key clinical studies.
PubMed: 38871488
DOI: 10.1080/10428194.2024.2361836 -
Hepatology Research : the Official... Jun 2024Hereditary hemochromatosis (HH) is recognized as a progressive iron-storage disorder, and leading to severe organ impairments, including liver cirrhosis. Hereditary...
Hereditary hemochromatosis (HH) is recognized as a progressive iron-storage disorder, and leading to severe organ impairments, including liver cirrhosis. Hereditary hemochromatosis type 3 arises from mutations in the transferrin receptor 2 (TFR2) gene. However, HH type 3 is rare in Asia, and information regarding genetic mutations and associated phenotypes remains limited. Here, we reported the case of a Japanese patient with HH type 3, with a novel homozygous mutation of the TFR2 gene. A 69-year-old woman presented to our hospital with hand joint pain and was referred due to liver impairment. Viral hepatitis and autoimmune liver diseases were ruled out. However, the transferrin saturation was 92.2%, and the serum ferritin level was 1611.8 ng/mL. Additionally, abdominal computed tomography showed diffuse increased density of the liver parenchyma. Abdominal magnetic resonance imaging also suggested iron deposition. There is no history of prior treatments involving blood transfusions or iron agents. Her parents were involved in a consanguineous marriage, prompting genetic testing. She had a homozygous novel mutation, c.1337G>A (p.G446E), in the TFR2 gene. Serum hepcidin-25 level was decreased to 2.9 ng/mL. According to the American Society of Medical Genetics and Genomics guideline, the mutation was classified as likely pathogenic, leading to the diagnosis of HH type 3. Following phlebotomy, her arthritis resolved, and serum transaminase levels were normalized. This case marks the first demonstration of homozygous mutation, c.1337G>A (p.G446E), in the TFR2 gene in patients with HH type 3.
PubMed: 38850209
DOI: 10.1111/hepr.14079 -
Physiological Reports Jun 2024Large-volume therapeutic phlebotomy is the mainstay of hemochromatosis treatment and offers an opportunity to investigate the hemodynamic changes during acute...
Large-volume therapeutic phlebotomy is the mainstay of hemochromatosis treatment and offers an opportunity to investigate the hemodynamic changes during acute hypovolemia. An otherwise healthy 64-year-old male with hemochromatosis participated. On nine separate visits, 1000 mL therapeutic phlebotomy was performed. On one occasion, pre- and post-phlebotomy orthostatic challenge with 27° reverse Trendelenburg position was administered. Mean arterial pressure, heart rate, and stroke volume were measured continuously during the procedures. The patient's tolerance to the interventions was continuously evaluated. The procedures were well tolerated by the patient. Mean arterial pressure was maintained during hemorrhage and following phlebotomy in both supine and reverse Trendelenburg positions, primarily through an increase in heart rate and systemic vascular resistance. The present study found that 1000 mL therapeutic phlebotomy in a patient with hemochromatosis may be acceptably and safely used to model hemorrhage. The approach demonstrates high clinical applicability and ethically robustness in comparison with volunteer studies.
Topics: Humans; Male; Phlebotomy; Middle Aged; Polycythemia; Hemochromatosis; Heart Rate; Hemorrhage
PubMed: 38844733
DOI: 10.14814/phy2.16035 -
Clinical methemoglobinemia secondary to administration of hydroxyurea at therapeutic doses in a dog.Journal of Veterinary Internal Medicine Jun 2024Methemoglobinemia secondary to administration of hydroxyurea is only reported in veterinary medicine as a result of accidental ingestion of high doses, and once at...
Methemoglobinemia secondary to administration of hydroxyurea is only reported in veterinary medicine as a result of accidental ingestion of high doses, and once at therapeutic dose in human medicine. A 2.5-year-old female spayed mixed breed dog was presented for acute signs of neurologic disease and diagnosed with severe erythrocytosis without an identified underlying cause, leading to suspicion of polycythemia vera. The dog was managed with phlebotomies, supportive care, and administration of hydroxyurea. Within 2 h of administration of hydroxyurea (37 mg/kg) administration, respiratory distress with cyanosis, and methemoglobinemia developed. Signs resolved within 24 h but recurred after a second administration of lower dosage of hydroxyurea (17 mg/kg) 20 days later. The dog remained asymptomatic except for mild cyanosis but was humanely euthanized for lack of relevant improvement of signs of neurologic disease. This case report documents the repeated occurrence of methemoglobinemia in a dog after administration of hydroxyurea at therapeutic doses.
PubMed: 38822748
DOI: 10.1111/jvim.17127 -
Neurology India Mar 2024
Topics: Humans; Arteriovenous Fistula; Scalp; Phlebotomy; Iatrogenic Disease; Male; Female; Adult
PubMed: 38817181
DOI: 10.4103/neurol-india.Neurol-India-D-24-00063 -
The Journal of Pediatrics May 2024To evaluate the effectiveness of patient education, physician counseling, and point-of-care (POC) testing on improving adherence to lipid screening national guidelines...
OBJECTIVE
To evaluate the effectiveness of patient education, physician counseling, and point-of-care (POC) testing on improving adherence to lipid screening national guidelines in a general pediatric cardiology practice (2017-2023).
STUDY DESIGN
Regional primary care providers were surveyed regarding lipid screening practices. Key drivers were categorized (physician, patient, and system) with corresponding interventions. Pediatric cardiologists started offering lipid screening during regular visits by providing families with preventive cardiovascular education materials and lab phlebotomy testing. System redesign included educational posters, clinical intake protocol, physician counseling, electronic health record integration, and POC testing. Run charts and statistical process control charts measured screening rates and key processes.
RESULTS
The primary care survey response rate was 32% (95/294); 97% supported pediatric cardiologists conducting routine lipid screening. Pediatric cardiology mean baseline lipid screening rate was 0%, increased to 7% with patient education, and to 61% after system redesign including POC testing. Screening rates among 1467 patients were similar across age groups (P = .98). More patients received lipid screening by POC (91.7%) compared with phlebotomy (8.3%). Lipid abnormalities detected did not differ by screening methodology (P = .49).
CONCLUSION
Patient education, counseling, and POC testing improved adherence to national lipid screening guidelines, providing a possible model for primary care implementation.
PubMed: 38815743
DOI: 10.1016/j.jpeds.2024.114118