Haemochromatosis in children: A national retrospective cohort promoted by the A.I.E.O.P. (Associazione Italiana Emato-Oncologia Pediatrica) study group.

Haemochromatosis (HC) encompasses a range of genetic disorders. HFE-HC is by far the most common in adults, while non-HFE types are rare due to mutations of HJV, HAMP, TFR2 and gain-of-function mutations of SLC40A1. HC is often unknown to paediatricians as it is usually asymptomatic in childhood. We report clinical and biochemical data from 24 paediatric cases of HC (10 cases of HFE-, 5 TFR2-, 9 HJV-HC), with a median follow-up of 9.6 years. Unlike in the adult population, non-HFE-HC constitutes 58% (14/24) of the population in our series. Transferrin saturation was significantly higher in TFR2- and HJV-HC compared to HFE-HC, and serum ferritin and LIC were higher in HJV-HC compared to TFR2- and HFE-HC. Most HFE-HC subjects had relatively low ferritin and LIC at the time of diagnosis, so therapy could be postponed for most of them after the age of 18. Our results confirm that HJV-HC is a severe form already in childhood, emphasizing the importance of early diagnosis and treatment to avoid the development of organ damage and reduce morbidity and mortality. Although phlebotomies were tolerated by most patients, oral iron chelators could be a valid option in early-onset HC.

Adverse effects of therapeutic phlebotomies: Prospective study of 587 procedures.

BACKGROUND: Therapeutic phlebotomy (TP), a widely used medical procedure, can be performed on diverse patients with iron overload or polyglobulia. However, its adverse events are not well known as most of the information on phlebotomy is derived from healthy blood donors (0.1%-5.3%). In contrast, TP is applicable to a broader, more complex population with comorbidities and old age. To ascertain the incidence of adverse events in phlebotomies, we conducted a prospective study on patients who attended our Unit. STUDY DESIGN AND METHODS: We prospectively gathered data from patients referred to our Unit for TP. Data regarding demographics, health status, and adverse events within at least 24 h of phlebotomy were gathered via a structured questionnaire during each visit. RESULTS: Between August 2021 and September 2022, 189 patients underwent 587 procedures. Most patients were men, over 60 (57.3%) had comorbidities, and 93% underwent at least two procedures during the study period. Twenty patients (10.8%) presented 25 adverse events (4.3% of phlebotomies), usually vasovagal reactions, none of which were clinically relevant, and all were managed by nursing staff on site, with full patient recovery. DISCUSSION: The rate of adverse events (<5%) in patients undergoing TP was low and comparable to that seen in healthy blood donors. Consequently, even old patients and those with some comorbidities can safely undergo TP when the process is carefully managed.

Ropeginterferon phase 2 randomized study in low-risk polycythemia vera: 5-year drug survival and efficacy outcomes.

In patients with low-risk polycythemia vera, exposure to low-dose Ropeginterferon alfa-2b (Ropeg) 100 µg every 2 weeks for 2 years was more effective than the standard treatment of therapeutic phlebotomy in maintaining target hematocrit (HCT) (< 45%) with a reduction in the need for phlebotomy without disease progression. In the present paper, we analyzed drug survival, defined as a surrogate measure of the efficacy, safety, adherence, and tolerability of Ropeg in patients followed up to 5 years. During the first 2 years, Ropeg and phlebotomy-only (Phl-O) were discontinued in 33% and 70% of patients, respectively, for lack of response (12 in the Ropeg arm vs. 34 in the Phl-O arm) or adverse events (6 vs. 0) and withdrawal of consent in (3 vs. 10). Thirty-six Ropeg responders continued the drug for up to 3 years, and the probability of drug survival after a median of 3.15 years was 59%. Notably, the primary composite endpoint was maintained in 97%, 94%, and 94% of patients still on drug at 3, 4, and 5 years, respectively, and 60% of cases were phlebotomy-free. Twenty-three of 63 Phl-O patients (37%) failed the primary endpoint and were crossed over to Ropeg; among the risk factors for this failure, the need for more than three bloodletting procedures in the first 6 months emerged as the most important determinant. In conclusion, to improve the effectiveness of Ropeg, we suggest increasing the dose and using it earlier driven by high phlebotomy need in the first 6 months post-diagnosis.

Diagnosing aceruloplasminemia: navigating through red herrings.

A 58-year-old female was found to have hyperferritinemia (Serum ferritin:1683 ng/mL) during work-up for mild normocytic anemia. Transferrin saturation(TSAT) was low-normal. Magnetic resonance imaging (MRI) abdomen showed evidence of hepatic iron deposition. Liver biopsy showed 4 + hepatic iron deposition without any evidence of steatosis or fibrosis. Quantitative liver iron was elevated at 348.3 µmol/g dry liver weight [Reference range(RR): 3-33 µmol/g dry liver weight]. She was presumptively diagnosed with tissue iron overload, cause uncertain. A diagnosis of ferroportin disease (FD) was considered, but the pattern of iron distribution in the liver, mainly within the hepatic parenchyma (rather than in the hepatic Kupffer cells seen in FD), and the presence of anemia (uncommon in FD) made this less likely. She was treated with intermittent phlebotomy for over a decade with poor tolerance due to worsening normocytic to microcytic anemia. A trial of deferasirox was done but it was discontinued after a month due to significant side effects. During the course of treatment, her ferritin level decreased. Over the past 1.5 years, she developed progressively worsening neurocognitive decline. MRI brain showed areas of susceptibility involving basal ganglia, midbrain and cerebellum raising suspicion for metabolic deposition disease. Neuroimaging findings led to testing for serum copper and ceruloplasmin levels which were both found to be severely low. Low serum copper, ceruloplasmin levels and neuroimaging findings led us to consider Wilson disease however prior liver biopsy showing elevated hepatic iron rather than hepatic copper excluded the diagnosis of Wilson disease. After shared decision making, ceruloplasmin gene analysis was not pursued due to patient's preference and prohibitive cost of testing. The diagnosis of aceruloplasminemia was ultimately made. The biochemical triad of hyperferritinemia, low-normal TSAT and microcytic anemia should raise the possibility of aceruloplasminemia. Since neurological manifestations are rare in most inherited iron overload syndromes, neurological symptoms in a patient with tissue iron overload should prompt consideration of aceruloplasminemia as a differential diagnosis.

Ruxolitinib in patients with polycythemia vera resistant and/or intolerant to hydroxyurea: European observational study.

BACKGROUND: Hydroxyurea (HU) is a commonly used first-line treatment in patients with polycythemia vera (PV). However, approximately 15%-24% of PV patients report intolerance and resistance to HU. METHODS: This phase IV, European, real-world, observational study assessed the efficacy and safety of ruxolitinib in PV patients who were resistant and/or intolerant to HU, with a 24-month follow-up. The primary objective was to describe the profile and disease burden of PV patients. RESULTS: In the 350 enrolled patients, 70% were >60 years old. Most patients (59.4%) had received ≥1 phlebotomy in the 12 months prior to the first dose of ruxolitinib. Overall, 68.2% of patients achieved hematocrit control with 92.3% patients having hematocrit <45% and 35.4% achieved hematologic remission at month 24. 85.1% of patients had no phlebotomies during the study. Treatment-related adverse events were reported in 54.3% of patients and the most common event was anemia (22.6%). Of the 10 reported deaths, two were suspected to be study drug-related. CONCLUSION: This study demonstrates that ruxolitinib treatment in PV maintains durable hematocrit control with a decrease in the number of phlebotomies in the majority of patients and was generally well tolerated.

Small-volume blood sample collection tubes in adult intensive care units: A rapid practice guideline.

BACKGROUND: This Intensive Care Medicine Rapid Practice Guideline (ICM-RPG) provides an evidence-based recommendation to address the question: in adult patients in intensive care units (ICUs), should we use small-volume or conventional blood collection tubes? METHODS: We included 23 panelists in 8 countries and assessed and managed financial and intellectual conflicts of interest. Methodological support was provided by the Guidelines in Intensive Care, Development, and Evaluation (GUIDE) group. We conducted a systematic review, including evidence from observational and randomized studies. Using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach, we evaluated the certainty of evidence and developed recommendations using the Evidence-to-Decision framework. RESULTS: We identified 8 studies (1 cluster and 2 patient-level randomized trials; 5 observational studies) comparing small-volume to conventional tubes. We had high certainty evidence that small-volume tubes reduce daily and cumulative blood sampling volume; and moderate certainty evidence that they reduce the risk of transfusion and mean number of red blood cell units transfused, but these estimates were limited by imprecision. We had high certainty that small-volume tubes have a similar rate of specimens with insufficient quantity. The panel considered that the desirable effects of small-volume tubes outweigh the undesirable effects, are less wasteful of resources, and are feasible, as demonstrated by successful implementation across multiple countries, although there are upfront implementation costs to validate small-volume tubes on laboratory instrumentation. CONCLUSION: This ICM-RPG panel made a strong recommendation for the use of small-volume sample collection tubes in adult ICUs based on overall moderate certainty evidence.

Use of Esmarch bandage does not increase peripheral vein size in healthy volunteers: A randomized clinical trial.

INTRODUCTION: Ultrasound is used for peripheral intravenous (PIV) cannulation in patients with difficult landmark-guided IV access in the Emergency Department. Distal-to-proximal application of an Esmarch bandage on the target limb has been suggested as a method for increasing vein size and ease of cannulation. METHODS: This study was a single-blinded crossover randomized controlled trial comparing basilic vein size under ultrasound with use of an Esmarch bandage in addition to standard IV tourniquet ("tourniquet + Esmarch") compared to use of a standard IV tourniquet alone. Participant discomfort with the tourniquet + Esmarch was also compared to that with standard IV tourniquet alone. RESULTS: Twenty-two healthy volunteers were used to measure basilic vein size with and without the Esmarch bandage. There was no difference in basilic vein size between the two groups, with a mean diameter of 6.0 ± 1.5 mm in the tourniquet + Esmarch group and 6.0 ± 1.4 mm in the control group, p = 0.89. Discomfort score (from 0 to 10) was different between the groups, with a mean discomfort score of 2.1 in the tourniquet + Esmarch group and 1.1 in the standard IV tourniquet alone group (p < 0.001). CONCLUSIONS: This study showed that the use of an Esmarch bandage does not increase basilic vein size in healthy volunteers but is associated with a mild increase in discomfort.

Evaluation of a scoring system for vein suitability in platelet apheresis donors.

INTRODUCTION: Donor vein assessment for the selection of good quality veins is crucial for a successful apheresis procedure. This study intends to find out the effectiveness of a vein assessment scoring tool (VST) used and found to be effective in selecting whole blood donors to reduce the difficulty in identifying good quality veins for the plateletpheresis procedure. MATERIALS AND METHODS: This was a prospective observational study on platelet apheresis donors with the application of a VST consisting of three vein descriptor parameters (vein visibility, vein palpability, and vein size) with 5 Likert-type responses constituting a score of 0-12 for each arm. Two vein assessors independently evaluated the vein in both arms and marked their responses blinded from each other as well from the principal investigator. The scores were then calculated and analyzed at the end of the study for their association with phlebotomy and procedural outcomes. RESULTS: A total of 190 donors were recruited. The mean scores for the arms with successful and failed phlebotomy were 9.1 and 9.4 (SD 2.3), respectively. The intra-class correlation Alpha Cronbach value was 0.834 and 0.837 for total scoring in the left arm and right arm, respectively, between the two assessors. Scores neither showed a correlation with other outcomes like low flow alarms, hematoma formation, number of phlebotomy attempts, and procedure completion. CONCLUSION: The study showed that the vein score tool did not truly predict the phlebotomy outcome in apheresis donors, though there was a good degree of inter-assessor reliability.

Effect of using smaller blood volume tubes and closed blood collection devices on total blood loss in patients undergoing major cardiac and vascular surgery.

BACKGROUND: Diagnostic laboratory tests are an integral part of managing hospitalized patients. In particular, patients in the intensive care units (ICUs) can experience a concerning amount of blood loss due to diagnostic testing, which can increase the risk developing iatrogenic anemia. Several interventions exist to curtail avoidable blood loss, for example computerized decision support, smaller phlebotomy tubes, and other blood conservation devices. Nevertheless, use of these interventions is not standardized. Therefore, the objective of our study was to quantify the daily phlebotomy volume taken from patients who had undergone major cardiac or vascular surgery. METHODS: We estimated the number of blood analyses and volumes of drawn blood of 400 consecutive patients (≥ 18 yr) undergoing major cardiac or vascular surgery. The amount of blood saved using small-volume tubes and in combination with blood conservation device rather than standard-volume tubes was estimated for serum chemistry (serum), ethylenediaminetetraacetic acid (EDTA) tubes, sodium citrate coagulation (SCC) tubes, and arterial blood gas (ABG) analysis. RESULTS: The mean total blood loss due to phlebotomy drawing using standard-volume tubes during hospitalization was 167.9 mL (95% confidence interval [CI], 158.0 to 177.8), 255.6 mL (95% CI, 226.5 to 284.6), and 695.3 mL (95% CI, 544.1 to 846.4) for patients undergoing cardiac surgery with a hospital length of stay (LOS) of 0-10, 11-20, and ≥ 21 days, respectively. The mean total blood loss due to phlebotomy during hospitalization was 80.5 mL (95% CI, 70.5 to 90.6), 225.0 mL (95% CI, 135.1 to 314.8 mL) and 470.3 mL (95% CI, 333.5 to 607.1) for vascular surgery patients with LOS 0-10, 11-20, and ≥ 21 days, respectively. Patients with at least a two-day stay at the ICU had a mean blood loss of 146.6 mL (95% CI, 134.6 to 158.6 mL) and those with ≥ 11 days incurred a loss of 1,428 mL (95% CI, 1,117.8 to 1,739.2). The use of closed blood collection device and small-volume tubes (serum, EDTA, SCC, and ABG) reduced blood loss by 82.8 mL for patients with an ICU stay of 2 days and up to 824.0 mL for patients with a ICU stay of ≥ 11 days. CONCLUSION: Diagnostic laboratory tests are associated with significant patient blood loss, but are a modifiable risk factor. The use of small-volume tubes and closed blood collection devices decreases the volume of patient blood drawn for analysis and prevents blood waste.

RéSUMé: CONTEXTE: Les tests diagnostiques de laboratoire font partie intégrante de la prise en charge des personnes hospitalisées. Plus spécifiquement, la patientèle des unités de soins intensifs (USI) peut perdre une quantité inquiétante de sang en raison des tests de diagnostic, ce qui peut augmenter le risque d'anémie iatrogène. Plusieurs interventions existent pour réduire les pertes de sang évitables, par exemple une aide à la décision informatisée, des tubes de phlébotomie plus petits et d'autres dispositifs de conservation du sang. Néanmoins, le recours à ces interventions n'est pas normalisé. Par conséquent, l'objectif de notre étude était de quantifier le volume quotidien de phlébotomie prélevée chez des patient·es ayant bénéficié d'une chirurgie cardiaque ou vasculaire majeure. MéTHODE: Nous avons estimé le nombre d'analyses sanguines et les volumes de sang prélevés de 400 personnes consécutives (≥ 18 ans) bénéficiant d'une chirurgie cardiaque ou vasculaire majeure. La quantité de sang économisée à l'aide de tubes de petit volume et en combinaison avec un dispositif de conservation du sang plutôt que des tubes de volume standard a été estimée pour la chimie sérique (sérum), les tubes d'acide éthylène-diamine-tétra-acétique (EDTA), les tubes de coagulation au citrate de sodium (CCS) et l'analyse des gaz du sang artériel (GSA). RéSULTATS: La perte sanguine totale moyenne due au prélèvement de phlébotomie à l'aide de tubes de volume standard pendant l'hospitalisation était de 167,9 mL (intervalle de confiance [IC] à 95 %, 158,0 à 177,8), 255,6 mL (IC 95 %, 226,5 à 284,6) et 695,3 mL (IC 95 %, 544,1 à 846,4) chez les patient·es bénéficiant d'une chirurgie cardiaque avec une durée de séjour à l'hôpital de 0 à 10, 11 à 20, et ≥ 21 jours, respectivement. La perte sanguine totale moyenne due à la phlébotomie pendant l'hospitalisation était de 80,5 mL (IC 95 %, 70,5 à 90,6), 225,0 mL (IC 95 %, 135,1 à 314,8 mL) et 470,3 mL (IC 95 %, 333,5 à 607,1) chez les patient·es ayant bénéficié d'une chirurgie vasculaire avec des durées de séjour de 0-10, 11-20 et ≥ 21 jours, respectivement. Les patient·es ayant séjourné au moins deux jours à l'USI ont eu une perte de sang moyenne de 146,6 mL (IC 95 %, 134,6 à 158,6 mL) et celles et ceux ayant séjourné ≥ 11 jours ont subi une perte de 1428 mL (IC 95 %, 1117,8 à 1739,2). L'utilisation d'un dispositif de prélèvement sanguin fermé et de tubes de petit volume (sérum, EDTA, SCC et gsa) a réduit la perte de sang de 82,8 mL pour les patient·es ayant séjourné à l'USI 2 jours et jusqu'à 824,0 mL pour les patient·es ayant séjourné en USI ≥ 11 jours. CONCLUSION: Les tests de laboratoire diagnostiques sont associés à une perte de sang importante chez les patient·es, mais constituent un facteur de risque modifiable. L'utilisation de tubes de petit volume et de dispositifs fermés de prélèvement sanguin diminue le volume de sang prélevé pour analyse et prévient le gaspillage de sang.

Blood volume contributes to the mechanical synchrony of the myocardium during moderate and high intensity exercise in women.

PURPOSE: Whether blood volume (BV) primarily determines the synchronous nature of the myocardium remains unknown. This study determined the impact of standard blood withdrawal on left ventricular mechanical dyssynchrony (LVMD) in women. METHODS: Transthoracic speckle-tracking echocardiography and central hemodynamic measurements were performed at rest and during moderate- to high-intensity exercise in healthy women (n = 24, age = 53.6 ± 16.3 year). LVMD was determined via the time to peak standard deviation (TPSD) of longitudinal and transverse strain and strain rates (LSR, TSR). Measurements were repeated within a week period immediately after a 10% reduction of BV. RESULTS: With intact BV, all individuals presented cardiac structure and function variables within normative values of the study population. Blood withdrawal decreased BV (5.3 ± 0.7 L) by 0.5 ± 0.1 L. Resting left ventricular (LV) end-diastolic volume (- 8%, P = 0.040) and passive filling (- 16%, P = 0.001) were reduced after blood withdrawal. No effect of blood withdrawal was observed for any measure of LVMD at rest (P ≥ 0.225). During exercise at a fixed submaximal workload (100 W), LVMD of myocardial longitudinal strain (LS TPSD) was increased after blood withdrawal (36%, P = 0.047). At peak effort, blood withdrawal led to increased LVMD of myocardial transverse strain rate (TSR TPSD) (31%, P = 0.002). The effect of blood withdrawal on TSR TPSD at peak effort was associated with LV concentric remodeling (r = 0.59, P = 0.003). CONCLUSION: Marked impairments in the mechanical synchrony of the myocardium are elicited by moderate blood withdrawal in healthy women during moderate and high intensity exercise.

The effect of vibrating cold application and puppet use on pain and fear during phlebotomy in children: A randomized controlled study.

BACKGROUND: Non-pharmacological methods are often used as a creative strategy to reduce pain and fear in children during a painful procedure such as phlebotomy. OBJECTIVES: This study was conducted to evaluate the effects of Bee Buzzy and puppet use on pain and fear during phlebotomy in children. METHODS: This randomized controlled study was conducted in the pediatric phlebotomy unit of a university hospital. The CONSORT checklist was used in this study. The sample of 3-6 years children (n = 105) was divided into groups by block randomization. Children's pain and fear scores were evaluated with the Wong-Baker Faces Pain Rating Scale and Children's Fear Scale by the parents and the nurse who attempted phlebotomy during phlebotomy. RESULTS: A statistically significant difference was found between the Bee Buzzy and puppet and Bee Buzzy and control groups in pain scores (p < .05). Pain scores were lower in the Bee Buzzy group than in the puppet and control groups. A statistical difference was found between Bee Buzzy and the control group or puppet and control group according to all fear scores (p < .05). Fear scores were lower in the Bee Buzzy and puppet group (p < .05). CONCLUSIONS: The results show that the use of Bee Buzzy during phlebotomy has a pain-relieving effect, and the use of Bee Buzzy and puppet has an anti-fear effect in 3-6-year-old children. IMPLICATIONS FOR PRACTICES: The use of Bee-Buzzy and puppets is effective in reducing pain and fear in children as they increase effective communication and distract attention. CLINICAL TRIAL REGISTRATION: National Institutes of Health (NIH), ClinicalTrials.gov, NCT05827783.

The effects of virtual reality and stress ball distraction on procedure-related emotional appearance, pain, fear, and anxiety during phlebotomy in children: A randomized controlled study.

BACKGROUND: Virtual reality (VR) and stress balls can be used during phlebotomy in school-age children. OBJECTIVES: This randomized controlled study was conducted to evaluate the effect of distraction methods using VR and stress balls on the emotional behavior, pain, fear, and anxiety associated with phlebotomy in children aged 7-12. METHODS: A parallel trial with a three-arm design approach was adopted for this randomized controlled trial, guided by the CONSORT checklist. The study sample (n = 150) was divided into VR, stress ball, and control group using stratified randomization. The mean scores obtained from the Children's Emotional Manifestation Scale, Wong-Baker FACES Pain Rating Scale, Child Anxiety Scale-State, and Child Fear Scale were compared between the groups. Linear regression analysis and correlation analysis were performed. RESULTS: Significant differences were found in phlebotomy-related pain, fear, and anxiety. While there was no difference in emotional behavior before the phlebotomy, a significant difference was found after the phlebotomy. Being in the virtual reality group explained 30.8 % of the difference between the before and after phlebotomy-related-emotional behavior scores. A strong, positive, and significant relationship was found between emotional behavior scores after phlebotomy and phlebotomy-related fear, pain, and anxiety scores (p < .01). CONCLUSION: Virtual reality and stress ball distraction were found to be effective in reducing pain, fear, and anxiety during phlebotomy. Virtual reality distraction is effective in reducing negative emotional behaviors. APPLICATION TO PRACTICE: The VR distraction can be used in the pediatric population in pain, fear, anxiety, and emotional behavior management during phlebotomy. CLINICALTRIALS: gov Identifier: NCT05818761.

Hemochromatosis: Ferroptosis, ROS, Gut Microbiome, and Clinical Challenges with Alcohol as Confounding Variable.

Hemochromatosis represents clinically one of the most important genetic storage diseases of the liver caused by iron overload, which is to be differentiated from hepatic iron overload due to excessive iron release from erythrocytes in patients with genetic hemolytic disorders. This disorder is under recent mechanistic discussion regarding ferroptosis, reactive oxygen species (ROS), the gut microbiome, and alcohol abuse as a risk factor, which are all topics of this review article. Triggered by released intracellular free iron from ferritin via the autophagic process of ferritinophagy, ferroptosis is involved in hemochromatosis as a specific form of iron-dependent regulated cell death. This develops in the course of mitochondrial injury associated with additional iron accumulation, followed by excessive production of ROS and lipid peroxidation. A low fecal iron content during therapeutic iron depletion reduces colonic inflammation and oxidative stress. In clinical terms, iron is an essential trace element required for human health. Humans cannot synthesize iron and must take it up from iron-containing foods and beverages. Under physiological conditions, healthy individuals allow for iron homeostasis by restricting the extent of intestinal iron depending on realistic demand, avoiding uptake of iron in excess. For this condition, the human body has no chance to adequately compensate through removal. In patients with hemochromatosis, the molecular finetuning of intestinal iron uptake is set off due to mutations in the high-FE2+ (HFE) genes that lead to a lack of hepcidin or resistance on the part of ferroportin to hepcidin binding. This is the major mechanism for the increased iron stores in the body. Hepcidin is a liver-derived peptide, which impairs the release of iron from enterocytes and macrophages by interacting with ferroportin. As a result, iron accumulates in various organs including the liver, which is severely injured and causes the clinically important hemochromatosis. This diagnosis is difficult to establish due to uncharacteristic features. Among these are asthenia, joint pain, arthritis, chondrocalcinosis, diabetes mellitus, hypopituitarism, hypogonadotropic hypogonadism, and cardiopathy. Diagnosis is initially suspected by increased serum levels of ferritin, a non-specific parameter also elevated in inflammatory diseases that must be excluded to be on the safer diagnostic side. Diagnosis is facilitated if ferritin is combined with elevated fasting transferrin saturation, genetic testing, and family screening. Various diagnostic attempts were published as algorithms. However, none of these were based on evidence or quantitative results derived from scored key features as opposed to other known complex diseases. Among these are autoimmune hepatitis (AIH) or drug-induced liver injury (DILI). For both diseases, the scored diagnostic algorithms are used in line with artificial intelligence (AI) principles to ascertain the diagnosis. The first-line therapy of hemochromatosis involves regular and life-long phlebotomy to remove iron from the blood, which improves the prognosis and may prevent the development of end-stage liver disease such as cirrhosis and hepatocellular carcinoma. Liver transplantation is rarely performed, confined to acute liver failure. In conclusion, ferroptosis, ROS, the gut microbiome, and concomitant alcohol abuse play a major contributing role in the development and clinical course of genetic hemochromatosis, which requires early diagnosis and therapy initiation through phlebotomy as a first-line treatment.

Increased maximal oxygen uptake after sprint-interval training is mediated by central haemodynamic factors as determined by right heart catheterization.

There is a lack of knowledge regarding the contribution of central and peripheral factors to the increases in VO2max following sprint-interval training (SIT). This study investigated the importance of maximal cardiac output (Qmax ) in relation to VO2max improvements following SIT and the relative importance of the hypervolemic response on Qmax and VO2max . We also investigated whether systemic O2 extraction increased with SIT as has been previously suggested. Healthy men and women (n = 9) performed 6 weeks of SIT. State-of-the-art measurements: right heart catheterization, carbon monoxide rebreathing and respiratory gas exchange analysis were used to assess Qmax , arterial O2 content (ca O2 ), mixed venous O2 content (cv O2 ), blood volume (BV) and VO2max before and after the intervention. In order to assess the relative contribution of the hypervolemic response to the increases in VO2max , BV was re-established to pre-training levels by phlebotomy. Following the intervention, VO2max , BV and Qmax increased by 11% (P < 0.001), 5.4% (P = 0.013) and 8.8% (P = 0.004), respectively. cv O2 decreased by 12.4% (P = 0.011) and systemic O2 extraction increased by 4.0% (P = 0.009) during the same period, both variables were unaffected by phlebotomy (P = 0.589 and P = 0.548, respectively). After phlebotomy, VO2max and Qmax reverted back to pre-intervention values (P = 0.064 and P = 0.838, respectively) and were significantly lower compared with post-intervention (P = 0.016 and P = 0.018, respectively). The decline in VO2max after phlebotomy was linear to the amount of blood removed (P = 0.007, R = -0.82). The causal relationship between BV, Qmax and VO2max shows that the hypervolemic response is a key mediator of the increases in VO2max following SIT. KEY POINTS: Sprint-interval training (SIT) is an exercise model involving supramaximal bouts of exercise interspersed with periods of rest known for its efficiency in improving maximal oxygen uptake (VO2max ). In contrast to the commonly accepted view where central haemodynamic adaptations are considered to be the key mediators of increases in VO2max there have been propositions highlighting peripheral adaptations as the main mediators in the context of SIT-induced changes in VO2max . By combining right heart catheterization, carbon monoxide rebreathing and phlebotomy, this study shows that increases in maximal cardiac output due to the expansion of the total blood volume is a major explanatory factor for the improvement in VO2max following SIT, with a smaller contribution from improved systemic oxygen extraction. The present work not only clarifies a controversy in the field by using state-of-the-art methods, but also encourages future research to investigate regulatory mechanisms that could explain how SIT can lead to improvements in VO2max and maximal cardiac output similar to those that have previously been reported for traditional endurance exercise.

A prospective assessment of the time required to obtain one unit of fresh whole blood by civilian phlebotomists and Army laboratory technicians (68 K).

BACKGROUND: Resuscitation with blood products improves survival after major hemorrhage. Blood product administration at or near the point-of-injury (POI) amplifies this benefit. Size, weight, and cold-chain management challenges all limit the amount of blood medics can carry. Warm fresh whole blood (WFWB) transfusions from a pre-screened donor within the unit represent an alternative source of blood at the POI. We measured the time required for civilian and Army technicians performing phlebotomy frequently to obtain one unit of blood to serve as a goal metric for combat medics being trained in this skill. METHODS: We gathered demographic and experience data along with proportion of first intravenous cannulation attempt success, time to blood flow initiated, and time to unit draw complete. RESULTS: We prospectively enrolled 12 civilian phlebotomy technicians and 10 Army laboratory technicians performing whole blood collections on 50 and 68 donors respectively. The mean time from setup to needle insertion was 3.7 min for civilians versus 4.2 min for Army technicians. The mean time from blood flowing to the bag being full was 10.7 min versus 8.4 min for civilians versus Army technicians respectively. The mean bag weights were 514 g versus 522 g. First-pass intravenous cannulation success was 96% versus 98% respectively. CONCLUSIONS: We found a high first intravenous cannulation attempt success among both the civilian and Army technicians. Medians times were <5 min to obtain venipuncture and <11 min to obtain one unit. These findings provide time-based benchmarks for potential use during transfusion training among military medics.

Real-world treatments and thrombotic events in polycythemia vera patients in the USA.

Polycythemia vera (PV) is a myeloproliferative neoplasm associated with increased risk of thrombotic events (TE) and death. Therapeutic interventions, phlebotomy and cytoreductive medications, are targeted to maintain hematocrit levels < 45% to prevent adverse outcomes. This retrospective observational study examined medical and pharmacy claims of 28,306 PV patients initiating treatment for PV in a data period inclusive of 2011 to 2019. Study inclusion required ≥ 2 PV diagnosis codes in the full data period, at least 1 year of PV treatment history, and ≥ 1 prescription claim and medical claim in both 2018 and 2019. Patients having ≥ 2 hematocrit (HCT) test results in linked outpatient laboratory data (2018-2019) were designated as the HCT subgroup (N = 4246). Patients were characterized as high- or low-risk at treatment initiation based on age and prior thrombotic history. The majority of patients in both risk groups (60% of high-risk and 83% of low-risk) initiated treatment with phlebotomy monotherapy, and during a median follow-up period of 808 days, the vast majority (81% low-risk, 74% high-risk) maintained their original therapy during the follow-up period. Hematocrit control was suboptimal in both risk groups; 54% of high-risk patients initiating with phlebotomy monotherapy sometimes/always had HCT levels > 50%; among low-risk patients, 64% sometimes/always had HCT levels above 50%. Overall, 16% of individuals experienced at least 1 TE subsequent to treatment initiation, 20% (n = 3920) among high-risk and 8% (n = 629) among low-risk patients. This real-world study suggests that currently available PV treatments may not be used to full advantage.

Survey on the usage of therapeutic erythrocytapheresis in transfusion services in Italy for the treatment of polycythemia vera, secondary erythrocytosis and hemochromatosis.

INTRODUCTION: Erythrocytapheresis, an apheresis treatment which selectively removes red blood cells, is an alternative to therapeutic phlebotomy, over which it has several advantages. Actually there is a high degree of variability in the use of this treatment. This prompted SIdEM (Italian Society of Hemapheresis and Cell Manipulation) to conduct a survey on the use of erythrocytapheresis in the Italian Transfusion Services. The purpose is to monitor this activity in the treatment of Polycythemia Vera (pv), secondary erythrocytosis and hemochromatosis. MATERIALS AND METHODS: A data collection file was sent to the SIdEM regional delegates who, in turn, involved the Transfusion Centers in the areas they cover. The data collected were processed on a Microsoft Excel spreadsheet. RESULTS: 75 centers from 14 Italian regions responded to the Survey: 36 centers (48 %) use erythrocytapheresis (35 centers perform therapeutic apheresis and 1 center only donor apheresis), 39 centers (52 %) do not (15 centers perform therapeutic apheresis, 18 centers only donor apheresis and 6 centers do not perform either therapeutic apheresis or donor apheresis). Although most centers have a substantially uniform attitude concerning the indications for which erythrocytapheresis is used, the survey shows that there are still differences more evident in the treatment of secondary erythrocytosis than in the treatment of pv or hemochromatosis. CONCLUSIONS: This survey has been useful to document the current Italian reality and to raise awareness about the need for improvement in optimizing and standardizing the use of a therapy with a great potential to exploit properly.

Effectiveness of non-immersive virtual reality in the management of procedure-related pain in preschool children: a randomized clinical trial.

The objective of this study is to assess the effectiveness of non-immersive virtual reality as a pain-distraction measure in children between the ages of 3 and 5 years undergoing painful injection procedures in an outpatient setting. We carried out a randomized, unmasked clinical trial in children undergoing venipuncture or intramuscular injection procedures. Patients were randomized to a distraction virtual reality video or standard care. After the procedure, three independent observers (parents, researchers, nursing staff) rated pain on the LLANTO pain scale. We recruited 122 subjects, half of which were randomized to virtual reality. The median age was of approximately 60 months (IQR: 15 months), and the sample was balanced with regard to sex. There were significant differences in LLANTO scales scores between the VR subjects and controls of - 3.34 (95% CI - 4.15; - 2.54), - 3.02 (95% CI - 3.90; - 2.14), and - 2.98 (95% CI - 3.87; - 2.09), as rated by parents, researchers, and nursing staff, respectively. Agreement between raters was high for all three types of observers, with Cohen Kappas over 0.79 in all cases. Bivariate analysis showed reductions in the risk of obtaining higher scores in the LLANTO scale. Linear regression models showed a reduction of approximately 3 points in the scale, regardless of the type of observer. These models were adjusted for sex, age, kind of procedure, use of prior analgesia, and recruitment center. CONCLUSIONS: Non-immersive virtual reality is an effective adjunctive therapy for the reduction of pain in children undergoing painful injection procedures in an outpatient setting. This strategy may be used to improve the quality of care in pediatric outpatient services. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03985930 (Registered June 14, 2019). WHAT IS KNOWN: •The use of immersive virtual reality (VR) has been described as an effective adjunctive distraction method during painful procedures in children over 5 years. WHAT IS NEW: •The utility of non-immersive VR in children below that age is not yet clear. This randomized clinical trial comparing non-immersive VR vs. standard care showed an average reduction of three points in the LLANTO pain scale favoring non-immersive VR. Non-immersive VR is an effective and inexpensive non-pharmacological technique that reduces fear and pain in pediatric patients.

Ultrasound-guided phlebotomy in primary care for people who inject drugs.

OBJECTIVES: Persons who inject drugs (PWID) commonly experience venous degradation as a complication of prolonged injection, which makes routine phlebotomy difficult. Clients may decline care due to the perceived lack of skilled phlebotomy services, and this contributes to significant delays in infectious disease screening and treatment. In this study, we investigated ultrasound-guided phlebotomy in clients with difficult venous access receiving care at two low-threshold buprenorphine clinics. Our objectives were to increase the accuracy of vascular access, expedite infectious disease treatment for hepatitis C virus (HCV) and human immunodeficiency virus (HIV), and increase client satisfaction with phlebotomy services. METHODS: PWID who declined routine phlebotomy at two clinic sites were offered ultrasound-guided vascular access by a trained clinician. Participants completed a survey to collect data regarding acceptability of the intervention. RESULTS: Throughout a 14-month period, 17 participants were enrolled. Of the total 30 procedures, 41.2% of clients returned for more than one phlebotomy visit, and 88.2% of clients achieved vascular access within 1 attempt. Of participating clients, 52.9% described themselves as having difficult venous access and at conclusion of the study, 58.8% expressed more willingness to have phlebotomy performed with an ultrasound device. CONCLUSIONS: Offering ultrasound-guided phlebotomy for PWID with difficult venous access resulted in decreased access attempts, increased patient satisfaction, and expedited screening and treatment for HIV and HCV point-of-care ultrasound technology is an effective approach to improving care for persons who inject drugs.

A semi-automated device rapidly determine circulating blood volume in healthy males and carbon monoxide uptake kinetics of arterial and venous blood.

We examined whether a semi-automated carbon monoxide (CO) rebreathing method accurately detect changes in blood volume (BV) and total hemoglobin mass (tHb). Furthermore, we investigated whether a supine position with legs raised reduced systemic CO dilution time, potentially allowing a shorter rebreathing period. Nineteen young healthy males participated. BV and tHb was quantified by a 10-min CO-rebreathing period in a supine position with legs raised before and immediately after a 900 ml phlebotomy and before and after a 900 ml autologous blood reinfusion on the same day in 16 subjects. During the first CO-rebreathing, arterial and venous blood samples were drawn every 2 min during the procedure to determine systemic CO equilibrium in all subjects. Phlebotomy decreased (P < 0.001) tHb and BV by 166 ± 24 g and 931 ± 247 ml, respectively, while reinfusion increased (P < 0.001) tHb and BV by 143 ± 21 g and 862 ± 250 ml compared to before reinfusion. After reinfusion BV did not differ from baseline levels while tHb was decreased (P < 0.001) by 36 ± 21 g. Complete CO mixing was achieved within 6 min in venous and arterial blood, respectively, when compared to the 10-min sample. On an individual level, the relative accuracy after donation for tHb and BV was 102-169% and 55-165%, respectively. The applied CO-rebreathing procedure precisely detect acute BV changes with a clinically insignificant margin of error. The 10-min CO-procedure may be reduced to 6 min with no clinical effects on BV and tHb calculation. Notwithstanding, individual differences may be of concern and should be investigated further.