RESUMEN
Cellular circadian rhythms confer temporal organisation upon physiology that is fundamental to human health. Rhythms are present in red blood cells (RBCs), the most abundant cell type in the body, but their physiological function is poorly understood. Here, we present a novel biochemical assay for haemoglobin (Hb) oxidation status which relies on a redox-sensitive covalent haem-Hb linkage that forms during SDS-mediated cell lysis. Formation of this linkage is lowest when ferrous Hb is oxidised, in the form of ferric metHb. Daily haemoglobin oxidation rhythms are observed in mouse and human RBCs cultured in vitro, or taken from humans in vivo, and are unaffected by mutations that affect circadian rhythms in nucleated cells. These rhythms correlate with daily rhythms in core body temperature, with temperature lowest when metHb levels are highest. Raising metHb levels with dietary sodium nitrite can further decrease daytime core body temperature in mice via nitric oxide (NO) signalling. These results extend our molecular understanding of RBC circadian rhythms and suggest they contribute to the regulation of body temperature.
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Eritrocitos , Hemoglobinas , Humanos , Ratones , Animales , Eritrocitos/metabolismo , Hemoglobinas/metabolismo , Oxidación-Reducción , Hemo/metabolismo , Ritmo CircadianoRESUMEN
The clinical severity of sickle cell disease (SCD) is strongly influenced by the level of fetal haemoglobin (HbF) persistent in each patient. Three major HbF loci (BCL11A, HBS1L-MYB, and Xmn1-HBG2) have been reported, but a considerable hidden heritability remains. We conducted a genome-wide association study for HbF levels in 1006 Nigerian patients with SCD (HbSS/HbSß0), followed by a replication and meta-analysis exercise in four independent SCD cohorts (3,582 patients). To dissect association signals at the major loci, we performed stepwise conditional and haplotype association analyses and included public functional annotation datasets. Association signals were detected for BCL11A (lead SNP rs6706648, ß = -0.39, P = 4.96 × 10-34) and HBS1L-MYB (lead SNP rs61028892, ß = 0.73, P = 1.18 × 10-9), whereas the variant allele for Xmn1-HBG2 was found to be very rare. In addition, we detected three putative new trait-associated regions. Genetically, dissecting the two major loci BCL11A and HBS1L-MYB, we defined trait-increasing haplotypes (P < 0.0001) containing so far unidentified causal variants. At BCL11A, in addition to a haplotype harbouring the putative functional variant rs1427407-'T', we identified a second haplotype, tagged by the rs7565301-'A' allele, where a yet-to-be-discovered causal DNA variant may reside. Similarly, at HBS1L-MYB, one HbF-increasing haplotype contains the likely functional small indel rs66650371, and a second tagged by rs61028892-'C' is likely to harbour a presently unknown functional allele. Together, variants at BCL11A and HBS1L-MYB SNPs explained 24.1% of the trait variance. Our findings provide a path for further investigation of the causes of variable fetal haemoglobin persistence in sickle cell disease.
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Anemia de Células Falciformes , Proteínas de Unión al GTP , Estudio de Asociación del Genoma Completo , Haplotipos , Femenino , Humanos , Masculino , Alelos , Anemia de Células Falciformes/genética , Anemia de Células Falciformes/sangre , Predisposición Genética a la Enfermedad , Nigeria , Proteínas Nucleares/genética , Polimorfismo de Nucleótido Simple/genética , Proteínas Represoras/genéticaRESUMEN
AIMS/HYPOTHESIS: This study aimed to investigate acculturation's direct and mediated effects on HbA1c levels in individuals with type 2 diabetes from Arabic-speaking countries that are members of the Arab League who have emigrated to Australia. METHODS: In this multicentre cross-sectional study, we recruited 382 Arabic-speaking immigrants who were born in any of the 22 countries of the Arab League and who had type 2 diabetes from different healthcare settings in Australia. HbA1c levels were retrieved from medical records. A validated self-report questionnaire was used to assess behavioural and psychosocial outcomes. Acculturation was measured using the General Acculturation Index and the Adherence to Traditional Values tool. We used structural equation modelling to test mediation hypotheses. RESULTS: Participants had a mean HbA1c value of 63.9 mmol/mol (8.0%), a low acculturation level (mean±SD: 1.9±0.6; range: 1-5) and highly adhered to traditional values (mean General Acculturation Index value: 3.7±0.7; range: 1-5). Higher HbA1c was associated with lower acculturation levels (Pearson correlation coefficient [r] = -0.32, p<0.01) and higher adherence to traditional values (r=0.35, p<0.01). Self-efficacy, health literacy and self-care activities partially mediated the relationship between acculturation and HbA1c. CONCLUSIONS/INTERPRETATION: Among Arab immigrants in Australia with type 2 diabetes, the degree of acculturation is related to glycaemic control, suggesting possible avenues for new interventions.
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Diabetes Mellitus Tipo 2 , Emigrantes e Inmigrantes , Humanos , Árabes/psicología , Estudios Transversales , Aculturación , Control Glucémico , AustraliaRESUMEN
The thrombotic risk with haemoglobin C trait (HbAC) or haemoglobin C disease (HbCC) is unclear. However, individuals with HbCC have demonstrated chronic haemolysis, higher blood viscosity and altered rheology when compared to individuals with wild-type haemoglobin (HbAA). These physiological alterations may theoretically translate to increased risk of thrombosis; therefore, a systematic literature review was performed to investigate the possible association between HbAC and/or HbCC and thrombosis. Twenty-two studies met inclusion criteria representing 782 individuals with HbAC (n = 694) or HbCC (n = 88). Fifteen studies described the presence/absence of venous thromboembolism (VTE) in patients with HbAC (n = 685) or HbCC (n = 79), while seven studies described patients with HbAC (n = 9) or HbCC (n = 9) and arterial thrombosis. Most (n = 20) studies were case reports or case series; however, two studies suggested a potential increased VTE risk with HbAC compared to HbAA in (i) all patients (OR 2.2, 95% CI: 0.9-5.5) and in (ii) pregnant individuals (RR 3.7, 95% CI 0.9-16). This review is the largest assessment of patients with HbC trait or disease and thrombosis to date; despite its limitations, the findings suggest HbC may be a predisposing risk factor to thrombosis. Prospective cohort studies are warranted to definitively elucidate the risk of thrombosis in this population.
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Enfermedad de la Hemoglobina C , Hemoglobinopatías , Trombosis , Tromboembolia Venosa , Embarazo , Femenino , Humanos , Hemoglobina C , Tromboembolia Venosa/epidemiología , Tromboembolia Venosa/etiología , Estudios Prospectivos , Trombosis/etiología , Factores de RiesgoRESUMEN
Biallelic pathogenic variants in CAD, that encode the multienzymatic protein required for de-novo pyrimidine biosynthesis, cause early infantile epileptic encephalopathy-50. This rare disease, characterized by developmental delay, intractable seizures and anaemia, is amenable to treatment with uridine. We present a patient with macrocytic anaemia, elevated haemoglobin-A2 levels, anisocytosis, poikilocytosis and target cells in the blood smear, and mild developmental delay. A next-generation sequencing panel revealed biallelic variants in CAD. Functional studies did not support complete abrogation of protein function; however, the patient responded to uridine supplement. We conclude that biallelic hypomorphic CAD variants may cause a primarily haematological phenotype.
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Anemia Macrocítica , Anemia , Espasmos Infantiles , Humanos , Espasmos Infantiles/genética , Uridina , HemoglobinasRESUMEN
The degree of anaemia in sickle cell disease (SCD) is a well-known contributor to morbidity and mortality. We aimed to explore the factors affecting haemoglobin (Hb) level in African SCD patients, considering haemolysis biomarkers (LDH and bilirubin level, and reticulocyte count), leucocyte and platelet counts and socio-demographic characteristics (gender, age group, country of residence and BMI). The research was part of the CADRE multinational cohort and involved 3699 SCD patients living in Mali, Senegal, Ivory Coast, Democratic Republic of Congo, Gabon and Cameroon: 2936 SS/Sß0, 587 SC and 176 Sß + patients with median Hb level of 8, 11.3 and 11.2 g/dL respectively (p < 0.001). In multivariate analysis conducted in 1394 SS/Sß0 patients, living in Cameroon, female gender, lower BMI, higher haemolysis markers (especially LDH) and higher leucocyte and platelet counts were independently associated with lower Hb level (all p < 0.05). In 497 SC and 156 Sß + patients, female gender (p < 0.001), lower BMI (p < 0.05) and higher platelet counts (p < 0.001) were independently associated with lower Hb level. Anaemia in African SCD patients is not only associated with haemolysis but also with the country of residence, lower BMI and leucocyte or platelet counts which might reflect inflammation related to infectious burden in the region.
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Anemia de Células Falciformes , Hemoglobinas , Hemólisis , Humanos , Anemia de Células Falciformes/sangre , Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/epidemiología , Masculino , Femenino , Adulto , Hemoglobinas/análisis , Adolescente , Recuento de Plaquetas , África del Sur del Sahara/epidemiología , Niño , Recuento de Leucocitos , Adulto Joven , Preescolar , Persona de Mediana Edad , Biomarcadores/sangreRESUMEN
Accurate laboratory screening for sickle cell disease and other haemoglobin disorders is expanding worldwide. Two new reports describe different methods and strategies for screening in Mali and Denmark, respectively, and their encouraging results suggest that countries should tailor their screening programmes according to local needs, resources and opportunities. Commentary on: Guindo et al. Potential for a large-scale newborn screening strategy for sickle cell disease in Mali: a comparative diagnostic performance study of two rapid diagnostic tests (SickleScan® and HemotypeSC®) on cord blood. Br J Haematol 2024;204:337-345 and Gravholt et al. The Danish national haemoglobinopathy screening programme: report from 16 years of screening in a low-prevalence, non-endemic region. Br J Haematol 2024;204:329-336.
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Anemia de Células Falciformes , Hemoglobinopatías , Recién Nacido , Humanos , Hemoglobinopatías/diagnóstico , Hemoglobinopatías/epidemiología , Anemia de Células Falciformes/diagnóstico , Anemia de Células Falciformes/epidemiología , Tamizaje Neonatal/métodos , Sangre Fetal , HemoglobinasRESUMEN
Sickle cell disease (SCD) includes a group of heterogenous disorders that result in significant morbidities. HbSS is the most common type of SCD and HbSC is the second most common type of SCD. The prevalence of HbSC disease in the United States and United Kingdom is ~1 in 7174 births and 1 in 6174 births respectively. Despite its frequency, however, HbSC disease has been insufficiently studied and was historically categorized as a more 'mild' form of SCD. We conducted this study of HbSC disease as part of the NHLBI funded Sickle Cell Disease Implementation Consortium (SCDIC). The SCDIC registry included 2282 individuals with SCD, ages 15-45 years of whom 502 (22%) had HbSC disease. Compared with people with sickle cell anaemia (SCA), the study found that people with HbSC disease had a higher frequency of splenomegaly (n (%) = 169 (33.7) vs. 392 (22.1)) and retinopathy (n (%) = 116 (23.1) vs. 189 (10.6)). A Many people with HbSC also had avascular necrosis (n (%) = 112 (22.3)), pulmonary embolism (n (%) = 43 (8.6)) and acute chest syndrome (n (%) = 228 (45.4)) demonstrating significant disease severity. HbSC disease is more clinically severe than was previously recognized and deserves additional evaluation and targeted treatments.
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Anemia de Células Falciformes , Humanos , Adolescente , Masculino , Femenino , Adulto , Persona de Mediana Edad , Adulto Joven , Anemia de Células Falciformes/epidemiología , Anemia de Células Falciformes/complicaciones , Enfermedad de la Hemoglobina SC/complicaciones , Sistema de Registros , Estados Unidos/epidemiología , Esplenomegalia/etiología , Esplenomegalia/epidemiologíaRESUMEN
We report a large series of 40 patients presenting EPAS1-mutated paraganglioma (PGL) in whom we investigated a cause underlying chronic hypoxia. Four patients suffered from hypoxaemic heart disease. In patients with available haemoglobin electrophoresis results, 59% presented with a haemoglobin disorder, including six with sickle cell disease, five with sickle cell trait and two with heterozygous haemoglobin C disease. Histological and transcriptomic characterization of EPAS1 tumours revealed increased angiogenesis and high similarities with pseudohypoxic PGLs caused by VHL gene mutations. Sickle haemoglobinopathy carriers could thus be at increased risk for developing EPAS1-PGLs, which should be taken into account in their management and surveillance.
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Neoplasias de las Glándulas Suprarrenales , Hemoglobinopatías , Paraganglioma , Humanos , Hemoglobinas/genética , Hipoxia/genética , Mutación , Paraganglioma/genética , Paraganglioma/patologíaRESUMEN
The available evidence on the impact of specific non-pharmacological interventions on glycaemic control is currently limited. Consequently, there is a need to determine which interventions could provide the most significant benefits for the metabolic health of young individuals with type 1 diabetes mellitus. The aim of this study was to identify optimal nonpharmacological interventions on glycaemic control, measured by glycated haemoglobin (HbA1c), in children and adolescents with type 1 diabetes. Systematic searches were conducted in PubMed, Web of Science, Scopus, and SPORTDiscus from inception to July 1, 2023. Randomised clinical trials (RCT) investigating nonpharmacological interventions (e.g., physical activity, nutrition, and behavioural therapies) were included. Primary outcome was change in HbA1c levels. Secondary outcome was change in daily insulin dose requirement. Seventy-four RCT with 6,815 participants (49.43% girls) involving 20 interventions were analysed using a network meta-analysis. Most interventions showed greater efficacy than standard care. However, multicomponent exercise, which includes aerobic and strength training (n = 214, standardised mean difference [SMD] =- 0.63, 95% credible interval [95% CrI] - 1.09 to - 0.16) and nutritional supplements (n = 146, SMD =- 0.49, - 0 .92 to - 0.07) demonstrated the greatest HbA1c reductions. These interventions also led to the larger decreases in daily insulin needs (n = 119, SMD =- 0.79, 95% CrI - 1.19 to - 0.34) and (n = 57, SMD =- 0.62, 95% CrI - 1.18 to - 0.12, respectively). The current study underscores non-pharmacological options such as multicomponent exercise and nutritional supplements, showcasing their potential to significantly improve HbA1c in youth with type 1 diabetes. Although additional research to confirm their efficacy is required, these approaches could be considered as potential adjuvant therapeutic options in the management of type 1 diabetes among children and adolescents.
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Teorema de Bayes , Biomarcadores , Glucemia , Diabetes Mellitus Tipo 1 , Hemoglobina Glucada , Hipoglucemiantes , Metaanálisis en Red , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/terapia , Diabetes Mellitus Tipo 1/diagnóstico , Hemoglobina Glucada/metabolismo , Adolescente , Niño , Femenino , Masculino , Resultado del Tratamiento , Glucemia/metabolismo , Biomarcadores/sangre , Hipoglucemiantes/uso terapéutico , Control Glucémico , Factores de Edad , Insulina/uso terapéutico , Insulina/sangre , Suplementos Dietéticos , Terapia por Ejercicio , Ejercicio Físico , PreescolarRESUMEN
This systematic review and meta-analysis pooled evidence from randomised controlled trials (RCTs) on the effectiveness of educational programs for people with or at risk of diabetes-related foot disease (DFD). A systematic search identified RCTs evaluating the effectiveness of educational programs in preventing or managing DFD. The primary outcome was risk of developing a foot ulcer. Secondary outcomes included any amputation, mortality, changes in cardiovascular risk factors, foot-care knowledge and self-care behaviours. Meta-analyses were performed using random effects models. Risk of bias was assessed using Cochrane's ROB-2 tool. Education programs were tested in 29 RCTs (n = 3891) and reduced risk of a foot ulcer by approximately half although the upper 95% confidence interval (CI) reached 1.00 (odds ratio [OR], OR 0.54; 95% CI 0.29, 1.00, I2 = 65%). Education programs reduced risk of any amputation (OR 0.34; 95% CI 0.13, 0.88, I2 = 38%) and HbA1c levels (standardized mean difference -0.73; 95% CI -1.26, -0.20, I2 = 93%) without affecting all-cause mortality (OR 1.09; 95% CI 0.57, 2.07, I2 = 0%). Education programs mostly significantly improved DFD knowledge (13 of 16 trials) and self-care behaviour scores (19 of 20 trials). Only one trial was deemed at low risk of bias. Previously tested education programs have mostly effectively improved participants' knowledge and self-care behaviours and reduced risk of foot ulceration and amputation. Larger high quality trials with longer follow-up are needed.
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Diabetes Mellitus , Pie Diabético , Enfermedades del Pie , Humanos , Pie Diabético/etiología , Pie Diabético/prevención & control , Amputación QuirúrgicaRESUMEN
Dysbiosis or imbalance of microbes in the gut has been associated with susceptibility and progression of type 1 diabetes mellitus (T1DM). The present systematic review and meta-analysis examined the effects of probiotics, prebiotics, and synbiotics on fasting blood glucose (FBG), haemoglobin A1c (HbA1c), C-peptide, and insulin requirements in T1DM patients. A systematic search for trials published up to October 2022 was conducted in PubMed, EMBASE, Scopus, Google Scholar, ScienceDirect, Web of Science, and the Central Cochrane Library. Random effect models were used to synthesise quantitative data by STATA14 . After the evaluation of 258 identified entries, five randomised controlled trials (n = 356; mean age = 11.7 years old) were included. The pooled effect size showed that FBG decreased following probiotic supplementation (weighted mean difference = -31.24 mg/dL; 95% confidence interval = -45.65, -16.83; p < 0.001), however, there was no significant improvement in serum HbA1c, C-peptide, and insulin requirements. Probiotic supplementation could be a complementary therapeutic strategy in T1DM. The evidence is limited; therefore, it is crucial to conduct more trials.
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Diabetes Mellitus Tipo 1 , Probióticos , Simbióticos , Humanos , Niño , Prebióticos , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Hemoglobina Glucada , Péptido C , Probióticos/uso terapéutico , Insulina , Insulina Regular HumanaRESUMEN
AIMS: The role of maternal genetic factors in the association between high glycated haemoglobin (HbA1c) levels and adverse birth outcomes remains unclear. MATERIALS AND METHODS: In this study, the maternal HbA1c levels of 5108 normoglycemic pregnant women in China were measured, and A1298C and C677T polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene were genotyped. RESULTS: Elevated HbA1c levels during the second trimester were associated with increased risks of macrosomia, large-for-gestational age (LGA), preterm birth (PTB), and reduced gestational age (p < 0.05). Pregnant women with MTHFR A1298C AA or C677T CT + TT genotypes were susceptible to adverse pregnancy outcomes related to HbA1c levels. Among pregnant women with the A1298C AA genotype, each standard deviation (SD) increase in HbA1c levels increased the risk of PTB by 1.32-times and reduced the gestational age by 0.11 weeks (p < 0.05). For MTHFR C677T CC + TT genotype carriers, higher HbA1c levels were associated with 1.49-, 1.24-, and 1.23-times increased risks of macrosomia, LGA, and PTB, respectively (p < 0.05). A U-shaped curve for PTB risk in relation to HbA1c levels was observed among the C677T CC + TT participants, with a cut-off value of 4.58%. Among subjects with the A1298C AA genotype combined with the C677T CT + TT genotype, each SD increase in HbA1c levels was associated with 1.40 and 1.37-times increased risks of LGA and PTB, respectively. CONCLUSIONS: Our findings highlight the importance of glycaemic control during pregnancy and the potential impact of genetic factors on birth outcomes. However, further large-scale studies are required to confirm these findings.
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Polimorfismo de Nucleótido Simple , Nacimiento Prematuro , Recién Nacido , Humanos , Femenino , Embarazo , Hemoglobina Glucada , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Macrosomía Fetal/genética , Nacimiento Prematuro/genética , Genotipo , Predisposición Genética a la EnfermedadRESUMEN
AIMS: Diabetes is known to increase morbidity and mortality after major surgery. However, literature is conflicting on whether elevated preoperative haemoglobin A1c (HbA1c) levels are associated with worse outcomes following major noncardiac surgery. We aimed to investigate the effect of incremental preoperative HbA1c levels on postoperative outcomes in adults who had undergone major noncardiac surgery. METHODS: We systematically searched PubMed, EMBASE and the Cochrane Library databases for eligible studies published between January 2012 and July 2023. Randomised controlled trials and observational studies (cohort and case-control studies) which measured HbA1c within 6 months before surgery and compared outcomes between at least three incremental subgroups or analysed HbA1c as a continuous variable were included. The systematic review protocol was registered with PROSPERO (CRD42023391946). RESULTS: Twenty observational studies investigating outcomes across multiple surgical types were included. Higher preoperative HbA1c levels were associated with increased odds of overall postoperative complications, postoperative acute kidney injury, anastomotic leak, surgical site infections and increased length of stay. Each 1% increase in preoperative HbA1c was associated with increased odds of these complications. No association with reoperations and 30-day mortality was identified. The literature was highly variable with respect to composite major complications, perioperative cardiovascular events, hospital readmissions, postoperative pneumonia and systemic thromboembolism. CONCLUSIONS: Current evidence suggested that higher preoperative HbA1c levels were associated with increased odds of postoperative complications and extended length of stay in adults undergoing major noncardiac surgery. Further high-quality studies would be needed to quantify the risks posed and determine whether early intervention improves outcomes.
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AIMS: The safety and efficacy of insulin analogue insulin aspart (IAsp) have been demonstrated in a randomised clinical trial in pregnant women with Type 1 diabetes (T1D), and IAsp is widely used during pregnancy. The aim of this study was to assess glycaemic control and safety of IAsp versus other bolus insulins in Type 1 diabetic pregnancy in a real-world setting. METHODS: This was a post hoc analysis of a prospective cohort study of 1840 pregnant women with T1D, treated with IAsp (n = 1434) or other bolus insulins (n = 406) in the Diabetes Pregnancy Registry. The primary (composite) outcome was the proportion of pregnancies resulting in major congenital malformations or perinatal or neonatal death. Secondary outcomes included all HbA1c values measured immediately before and during pregnancy and major hypoglycaemia, as well as abortion, pre-eclampsia, pre-term delivery, large for gestational age at birth, stillbirth and fetal malformations. RESULTS: There were no significant differences found in any of the pregnancy outcomes between treatment with IAsp and other bolus insulins in either the crude or propensity score-adjusted analyses. However, maternal HbA1c was lower in the IAsp group at the end of the third trimester (adjusted difference, -0.16% point [95% CI -0.28;-0.05]; -1.8 mmol/mol [95% CI -3.1;-0.6]; p = 0.0046). CONCLUSIONS: No significant differences in safety or pregnancy outcomes were demonstrated when comparing treatment with IAsp versus other bolus insulins in women with T1D during pregnancy. The observed improvement in HbA1c with IAsp in late pregnancy should be confirmed in other studies.
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Acute breath-holding (apnoea) induces a spleen contraction leading to a transient increase in haemoglobin concentration. Additionally, the apnoea-induced hypoxia has been shown to lead to an increase in erythropoietin concentration up to 5 h after acute breath-holding, suggesting long-term haemoglobin enhancement. Given its potential to improve haemoglobin content, an important determinant for oxygen transport, apnoea has been suggested as a novel training method to improve aerobic performance. This review aims to provide an update on the current state of the literature on this topic. Although the apnoea-induced spleen contraction appears to be effective in improving oxygen uptake kinetics, this does not seem to transfer into immediately improved aerobic performance when apnoea is integrated into a warm-up. Furthermore, only long and intense apnoea protocols in individuals who are experienced in breath-holding show increased erythropoietin and reticulocytes. So far, studies on inexperienced individuals have failed to induce acute changes in erythropoietin concentration following apnoea. As such, apnoea training protocols fail to demonstrate longitudinal changes in haemoglobin mass and aerobic performance. The low hypoxic dose, as evidenced by minor oxygen desaturation, is likely insufficient to elicit a strong erythropoietic response. Apnoea therefore does not seem to be useful for improving aerobic performance. However, variations in apnoea, such as hypoventilation training at low lung volume and repeated-sprint training in hypoxia through short end-expiratory breath-holds, have been shown to induce metabolic adaptations and improve several physical qualities. This shows promise for application of dynamic apnoea in order to improve exercise performance. HIGHLIGHTS: What is the topic of this review? Apnoea is considered as an innovative method to improve performance. This review discusses the effectiveness of apnoea (training) on performance. What advances does it highlight? Although the apnoea-induced spleen contraction and the increase in EPO observed in freedivers seem promising to improve haematological variables both acutely and on the long term, they do not improve exercise performance in an athletic population. However, performing repeated sprints on end-expiratory breath-holds seems promising to improve repeated-sprint capacity.
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Reduced pulmonary diffusing capacity for carbon monoxide (DLCO) can be observed in pulmonary arterial hypertension (PAH) and associates with increased mortality. However, the prognostic value of DLCO when corrected for haemoglobin (DLCOc), an independent modifier of DLCO, remains understudied. Additionally, the prognostic role of ventilation (V)-perfusion (Q) emission computed tomography (V/Q SPECT) findings in patients with PAH, which may concurrently be performed to rule out chronic thromboembolic pulmonary hypertension, is uncertain. A retrospective cohort study was conducted on 152 patients with PAH referred to a tertiary hospital for evaluation from January 2011 to January 2020. Lung function tests, clinical data and V/Q SPECT were ascertained. Cox regression analysis was performed to evaluate the association between DLCOc, DLCO and V/Q SPECT defects at referral with all-cause mortality. In equally adjusted Cox regression analysis, each percentage increase in DLCOc % predicted (%pred) (hazard ratio (HR) 0.97; 95% CI: 0.94-0.99) and DLCO%pred (HR 0.97; 95% CI: 0.94-0.99) was similarly associated with all-cause mortality. There was no detectable difference in area under the curve for prediction of all-cause mortality by DLCOc%pred and DLCO%pred (C-index 0.71 and 0.72, respectively, P = 0.85 for difference). None of the defects noted on V/Q SPECT were significantly associated with mortality, but mismatched defects were associated with lower values of DLCOc%pred and DLCO%pred. DLCOc%pred and DLCO%pred perform equally as prognostic markers in PAH, supporting the use of either metric when available for prognostic stratification.
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Monóxido de Carbono , Hipertensión Arterial Pulmonar , Capacidad de Difusión Pulmonar , Tomografía Computarizada de Emisión de Fotón Único , Humanos , Femenino , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Monóxido de Carbono/metabolismo , Hipertensión Arterial Pulmonar/fisiopatología , Hipertensión Arterial Pulmonar/mortalidad , Hipertensión Arterial Pulmonar/diagnóstico por imagen , Tomografía Computarizada de Emisión de Fotón Único/métodos , Anciano , Adulto , Pulmón/fisiopatología , Pulmón/diagnóstico por imagen , Gammagrafía de Ventilacion-Perfusión/métodos , Pruebas de Función Respiratoria/métodosRESUMEN
OBJECTIVES: Anaemia is a major cause of mortality and transfusion in children in low- and middle-income countries (LMICs); however, current diagnostics are slow, costly and frequently unavailable. Point-of-care haemoglobin tests (POC(Hb)Ts) could improve patient outcomes and use of resources by providing rapid and affordable results. We systematically reviewed the literature to investigate what, where and how POC(Hb)Ts are being used by health facilities in LMICs to diagnose childhood anaemia, and to explore challenges to their use. METHODS: We searched a total of nine databases and trial registries up to 10 June 2022 using the concepts: anaemia, POC(Hb)T, LMIC and clinical setting. Adults ≥21 years and literature published >15 years ago were excluded. A single reviewer conducted screening, data extraction and quality assessment (of diagnostic studies) using QUADAS-2. Outcomes including POC(Hb)T used, location, setting, challenges and diagnostic accuracy were synthesised. RESULTS: Of 626 records screened, 41 studies were included. Evidence is available on the use of 15 POC(Hb)Ts in hospitals (n = 28, 68%), health centres (n = 9, 22%) and clinics/units (n = 10, 24%) across 16 LMICs. HemoCue (HemoCue AB, Ängelholm, Sweden) was the most used test (n = 31, 76%). Key challenges reported were overestimation of haemoglobin concentration, clinically unacceptable limits of agreement, errors/difficulty in sampling, environmental factors, cost, inter-observer variability and supply of consumables. Five POC(Hb)Ts (33%) could not detect haemoglobin levels below 4.5 g/dL. Diagnostic accuracy varied, with sensitivity and specificity to detect anaemia ranging from 24.2% to 92.2% and 70% to 96.7%, respectively. CONCLUSIONS: POC(Hb)Ts have been successfully utilised in health facilities in LMICs to diagnose childhood anaemia. However, limited evidence is available, and challenges exist that must be addressed before wider implementation. Further research is required to confirm accuracy, clinical benefits and cost-effectiveness.
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Anemia , Países en Desarrollo , Adulto , Humanos , Niño , Sistemas de Atención de Punto , Anemia/diagnóstico , Hemoglobinas/análisis , Pruebas en el Punto de AtenciónRESUMEN
BACKGROUND: To explore the cut-off values of haemoglobin (Hb) on adverse clinical outcomes in incident peritoneal dialysis (PD) patients based on a national-level database. METHODS: The observational cohort study was from the Peritoneal Dialysis Telemedicine-assisted Platform (PDTAP) dataset. The primary outcomes were all-cause mortality, major adverse cardiovascular events (MACE) and modified MACE (MACE+). The secondary outcomes were the occurrences of hospitalization, first-episode peritonitis and permanent transfer to haemodialysis (HD). RESULTS: A total of 2591 PD patients were enrolled between June 2016 and April 2019 and followed up until December 2020. Baseline and time-averaged Hb <100 g/l were associated with all-cause mortality, MACE, MACE+ and hospitalizations. After multivariable adjustments, only time-averaged Hb <100 g/l significantly predicted a higher risk for all-cause mortality {hazard ratio [HR] 1.83 [95% confidence interval (CI) 1.19-281], P = .006}, MACE [HR 1.99 (95% CI 1.16-3.40), P = .012] and MACE+ [HR 1.77 (95% CI 1.15-2.73), P = .010] in the total cohort. No associations between Hb and hospitalizations, transfer to HD and first-episode peritonitis were observed. Among patients with Hb ≥100 g/l at baseline, younger age, female, use of iron supplementation, lower values of serum albumin and renal Kt/V independently predicted the incidence of Hb <100 g/l during the follow-up. CONCLUSION: This study provided real-world evidence on the cut-off value of Hb for predicting poorer outcomes through a nation-level prospective PD cohort.
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Fallo Renal Crónico , Diálisis Peritoneal , Peritonitis , Humanos , Femenino , Estudios Prospectivos , Diálisis Peritoneal/efectos adversos , Diálisis Renal/efectos adversos , Hemoglobinas , Fallo Renal Crónico/epidemiología , Peritonitis/etiología , Estudios RetrospectivosRESUMEN
BACKGROUND: The trajectories of haemoglobin in patients with chronic kidney disease (CKD) have been poorly described. In such patients, we aimed to identify typical haemoglobin trajectory profiles and estimate their risks of major adverse cardiovascular events (MACE). METHODS: We used 5-year longitudinal data from the CKD-REIN cohort patients with moderate to severe CKD enrolled from 40 nationally representative nephrology clinics in France. A joint latent class model was used to estimate, in different classes of haemoglobin trajectory, the competing risks of (i) MACE + defined as the first event among cardiovascular death, non-fatal myocardial infarction, stroke or hospitalization for acute heart failure, (ii) initiation of kidney replacement therapy (KRT) and (iii) non-cardiovascular death. RESULTS: During the follow-up, we gathered 33 874 haemoglobin measurements from 3011 subjects (median, 10 per patient). We identified five distinct haemoglobin trajectory profiles. The predominant profile (n = 1885, 62.6%) showed an overall stable trajectory and low risks of events. The four other profiles had nonlinear declining trajectories: early strong decline (n = 257, 8.5%), late strong decline (n = 75, 2.5%), early moderate decline (n = 356, 11.8%) and late moderate decline (n = 438, 14.6%). The four profiles had different risks of MACE, while the risks of KRT and non-cardiovascular death consistently increased from the haemoglobin decline. CONCLUSION: In this study, we observed that two-thirds of patients had a stable haemoglobin trajectory and low risks of adverse events. The other third had a nonlinear trajectory declining at different rates, with increased risks of events. Better attention should be paid to dynamic changes of haemoglobin in CKD.