The Role of Fe, S, P, Ca, and Sr in Porous Skeletal Lesions: A Study on Non-adult Individuals Using pXRF.

Portable X-ray fluorescence is a new tool in the study of human bone. This research aims to investigate if variations in bone elemental concentrations are related with porous skeletal lesions (PSLs). One hundred well-preserved non-adult skeletons aged 0-11 years were selected from the archaeological site Convent of São Domingos, Lisbon (18th-19th century). Measuring a standard reference material and calculating the technical error of measurement assured elemental data reliability. Moreover, measuring soil samples excluded possible contamination of bones with elements from the soil, except for Pb. Additionally, the Ca/P ratio indicates maintenance of bone integrity. Cribra cranii, orbitalia, humeralis, and femoralis were recorded as present/absent, and the estimated intra-/inter-observer errors were low. The multivariate analysis found higher odds of having cribra orbitalia (OR = 1.76; CI = 0.97-3.20) and cribra femoralis (OR = 1.42; CI = 0.73-2.74) in individuals with lower Fe and higher S. Furthermore, higher levels of P, Ca, and Sr increased the odds of individuals developing cribra femoralis (OR = 2.30; CI = 1.23-4.29). Age also correlated with increased odds of exhibiting cribra orbitalia (OR = 1.86; CI = 0.94-3.68), cribra femoralis (OR = 6.97; CI = 2.78-17.45), and cribra humeralis (OR = 8.32; CI = 2.71-25.60). These findings suggest a shared etiology for these three cribras, contrasting with the higher Fe levels in individuals with cribra cranii. Lower Fe and higher S levels in individuals with cribra suggest a complex etiology, possibly involving conditions like megaloblastic or chronic disease anemia(s). Age-related elemental changes support the hypothesis that age influences cribra frequencies. This study highlights PSL complexity and opens new avenues for research.

Autoimmune Hemolytic Anemias: Classifications, Pathophysiology, Diagnoses and Management.

Autoimmune hemolytic anemias (AIHAs) are conditions involving the production of antibodies against one's own red blood cells (RBCs). These can be primary with unknown cause or secondary (by association with diseases or infections). There are several different categories of AIHAs recognized according to their features in the direct antiglobulin test (DAT). (1) Warm-antibody AIHA (wAIHA) exhibits a pan-reactive IgG autoantibody recognizing a portion of band 3 (wherein the DAT may be positive with IgG, C3d or both). Treatment involves glucocorticoids and steroid-sparing agents and may consider IVIG or monoclonal antibodies to CD20, CD38 or C1q. (2) Cold-antibody AIHA due to IgMs range from cold agglutinin syndrome (CAS) to cold agglutin disease (CAD). These are typically specific to the Ii blood group system, with the former (CAS) being polyclonal and the latter (CAD) being a more severe and monoclonal entity. The DAT in either case is positive only with C3d. Foundationally, the patient is kept warm, though treatment for significant complement-related outcomes may, therefore, capitalize on monoclonal options against C1q or C5. (3) Mixed AIHA, also called combined cold and warm AIHA, has a DAT positive for both IgG and C3d, with treatment approaches inclusive of those appropriate for wAIHA and cold AIHA. (4) Paroxysmal cold hemoglobinuria (PCH), also termed Donath-Landsteiner test-positive AIHA, has a DAT positive only for C3d, driven upstream by a biphasic cold-reactive IgG antibody recruiting complement. Although usually self-remitting, management may consider monoclonal antibodies to C1q or C5. (5) Direct antiglobulin test-negative AIHA (DAT-neg AIHA), due to IgG antibody below detection thresholds in the DAT, or by non-detected IgM or IgA antibodies, is managed as wAIHA. (6) Drug-induced immune hemolytic anemia (DIIHA) appears as wAIHA with DAT IgG and/or C3d. Some cases may resolve after ceasing the instigating drug. (7) Passenger lymphocyte syndrome, found after transplantation, is caused by B-cells transferred from an antigen-negative donor whose antibodies react with a recipient who produces antigen-positive RBCs. This comprehensive review will discuss in detail each of these AIHAs and provide information on diagnosis, pathophysiology and treatment modalities.

Etiology, Clinical Manifestations, Diagnosis, and Treatment of Cobalamin (Vitamin B12) Deficiency.

Cobalamin, also known as vitamin B12, is a water-soluble vitamin. Cobalamin deficiency can be frequently seen in people all around the world. It can have non-specific symptoms, and in patients who are in a very critical state, it can lead to neurological or hematological abnormalities. While pernicious anemia used to be the main cause, it now accounts for a smaller number of cases, with food-bound cobalamin malabsorption being more common. Early diagnosis and appropriate management are crucial to avoid severe complications like spinal cord degeneration and pancytopenia. The primary method of treatment has been injections of vitamin B12 which are given through the intramuscular route but now the oral replacement therapy has also been very effective in treating the patients. There is increasing evidence linking increased levels of vitamin B12 to hematological and hepatic disorders, particularly cancers. This review has primarily highlighted the metabolism, clinical manifestations, diagnosis, and treatment of cobalamin deficiency in the past decade.

Genomics of iron refractory iron deficiency anemia phenotype reveals a spectrum of novel pathogenic biallelic and monoallelic TMPRSS6 variants and rare overlapping disorders.

The study highlights genomic findings in a series of 13 IRIDA phenotype cases. All had microcytic hypochromic anemia with suboptimal oral iron response to two different oral iron preparations at 4-6 weeks and low-normal ferritin, low transferrin saturation, and inappropriately high hepcidin. Targeted NGS on a 26-gene iron panel revealed pathogenic TMPRSS6 variants in 5/13 (38 %) cases. In addition, 2 (15 %) cases revealed rare SMAD4 and TBXAS1 gene variants that can present with refractory anemia but were consistent with diagnosis of hereditary hemorrhagic telangiectasia and Ghosal hematodiaphyseal dysplasia respectively.

Incidence Trends of Inherited Anemias at the Global, Regional, and National Levels Over Three Decades.

Inherited anemia continues to pose a significant public health concern on a global scale, owing to its extensive geographical prevalence, substantial patient population, and profound ramifications. Here, we investigated detailed information on inherited anemias (including thalassemias, thalassemias trait, sickle cell disease, sickle cell trait, G6PD deficiency, and G6PD trait) for the period 1990-2019 from the Global Burden of Disease study. Over the course of three decades, there has been a persistent rise in the incidence of inherited anemias worldwide, culminating in a total of 44,896,026 incident cases in 2019. However, the prevalence of inherited anemias has exhibited a consistent downward trend over successive years. Significantly, these inherited anemias primarily impact females, exhibiting a male-to-female ratio of 1:1.88. Among males, the most prevalent inherited anemia is G6PD deficiency, whereas G6PD trait prevails among females. The incidence rates of inherited anemias and their temporal trend exhibited significant variations across different regions, with Central Sub-Saharan Africa displaying the highest incidence rates and Central Latin America experiencing the most substantial decline. The findings of this study suggest a significant correlation between the Socio-Demographic index (SDI) and incidence rates of inherited anemias, particularly in regions with lower SDI levels such as Africa and South Asia. These results contribute valuable insights for the analysis of global trends in the burden of inherited anemias.

Peroxiredoxins in erythrocytes: far beyond the antioxidant role.

The red blood cells (RBCs) are essential to transport oxygen (O2) and nutrients throughout the human body. Changes in the structure or functioning of the erythrocytes can lead to several deficiencies, such as hemolytic anemias, in which an increase in reactive oxidative species generation is involved in the pathophysiological process, playing a significant role in the severity of several clinical manifestations. There are important lines of defense against the damage caused by oxidizing molecules. Among the antioxidant molecules, the enzyme peroxiredoxin (Prx) has the higher decomposition power of hydrogen peroxide, especially in RBCs, standing out because of its abundance. This review aimed to present the recent findings that broke some paradigms regarding the three isoforms of Prxs found in RBC (Prx1, Prx2, and Prx6), showing that in addition to their antioxidant activity, these enzymes may have supplementary roles in transducing peroxide signals, as molecular chaperones, protecting from membrane damage, and maintenance of iron homeostasis, thus contributing to the overall survival of human RBCs, roles that seen to be disrupted in hemolytic anemia conditions.

Outcomes of therapeutic plasma exchange in severe autoimmune hemolytic anemia hospitalizations: An analysis of the National Inpatient Sample.

BACKGROUND: Autoimmune hemolytic anemia (AIHA) is characterized by humoral and/or cellular immune-mediated hemolysis of red blood cells. The role of therapeutic plasma exchange (TPE) in AIHA is unclear. STUDY DESIGN AND METHODS: We queried the National Inpatient Sample (NIS) for 2002-2019 to identify hospitalizations with the primary diagnosis of AIHA. We included hospitalizations with the highest severity subclass identified by All Patient Refined Disease Related Group (APR-DRG). We used multivariate regression analysis to compare in-hospital mortality and other relevant in-hospital outcomes between hospitalizations that received TPE and those that did not. RESULTS: We identified 255 weighted hospitalizations in the TPE group and 4973 in the control group. Those in the control group were older (median age 67 vs. 48 years, p < .001) and had a higher prevalence of most comorbidities. The TPE group had higher odds of all-cause in-hospital mortality (odds ratio [OR], 1.59; 95% confidence interval [CI], 1.19-2.11). They also had higher rates of many secondary outcomes, including requiring mechanical ventilation, developing circulatory shock, acute stroke, urinary tract infections, intracranial hemorrhage, acute kidney injury, and requiring new hemodialysis. No significant differences were noted in the rates of acute myocardial infarctions, bacterial pneumonia, sepsis/septicemia, thromboembolic events, and other bleeding events. Furthermore, the TPE group had a higher median length of hospital stay (19 vs. 9 days, p < .001). CONCLUSION: Hospitalizations with severe AIHA that received TPE had higher rates of adverse in-hospital outcomes.

New Cases and Mutations in SEC23B Gene Causing Congenital Dyserythropoietic Anemia Type II.

Congenital dyserythropoietic anemia type II (CDA II) is an inherited autosomal recessive blood disorder which belongs to the wide group of ineffective erythropoiesis conditions. It is characterized by mild to severe normocytic anemia, jaundice, and splenomegaly owing to the hemolytic component. This often leads to liver iron overload and gallstones. CDA II is caused by biallelic mutations in the SEC23B gene. In this study, we report 9 new CDA II cases and identify 16 pathogenic variants, 6 of which are novel. The newly reported variants in SEC23B include three missenses (p.Thr445Arg, p.Tyr579Cys, and p.Arg701His), one frameshift (p.Asp693GlyfsTer2), and two splicing variants (c.1512-2A>G, and the complex intronic variant c.1512-3delinsTT linked to c.1512-16_1512-7delACTCTGGAAT in the same allele). Computational analyses of the missense variants indicated a loss of key residue interactions within the beta sheet and the helical and gelsolin domains, respectively. Analysis of SEC23B protein levels done in patient-derived lymphoblastoid cell lines (LCLs) showed a significant decrease in SEC23B protein expression, in the absence of SEC23A compensation. Reduced SEC23B mRNA expression was only detected in two probands carrying nonsense and frameshift variants; the remaining patients showed either higher gene expression levels or no expression changes at all. The skipping of exons 13 and 14 in the newly reported complex variant c.1512-3delinsTT/c.1512-16_1512-7delACTCTGGAAT results in a shorter protein isoform, as assessed by RT-PCR followed by Sanger sequencing. In this work, we summarize a comprehensive spectrum of SEC23B variants, describe nine new CDA II cases accounting for six previously unreported variants, and discuss innovative therapeutic approaches for CDA II.

A case of TAFRO syndrome with DIC and neurologic and cardiac involvement.

We highlight a novel case of TAFRO syndrome with disseminated intravascular coagulation, neurologic changes, and non-ischemic cardiomyopathy. Through this clinical vignette, we hope to raise awareness of TAFRO syndrome and encourage providers to maintain a high level of suspicion for it when evaluating patients who meet the diagnostic criteria.

Association between sickle cell disease and periodontal disease: A systematic review.

Previous studies have evaluated the association between sickle cell disease (SCD) and periodontal disease; however, their effect on the periodontal parameters remains unclear. This systematic review aimed to investigate whether individuals with sickle cell disease (SCD) increase the risks of periodontal disease more than those without. For the selection of eligible studies, an electronic search was conducted in the MEDLINE/PubMed, Web of Science, Cochrane Library, and Scopus databases. The meta-analysis was based on the inversion of variance using the mean difference (MD) of the continuous outcomes. The quality assessment of included studies was performed using the JBI Critical Appraisal Tools. In total, 13 studies and 2381 participants were included in the qualitative analysis, while 9 studies were considered for the meta-analysis. The meta-analysis indicated that patients with SCD present similar Plaque Index, Clinical Attachment Level, Bleeding on Probing, and Probing Depth when compared to healthy patients (p > .05). However, the Gingival Index was higher for patients with SCD (p = .0002; MD: 0.20). Compared to healthy patients, patients with SCD did not have an increase in periodontal parameters, except for the gingival index. However, further well-designed studies are recommended to reassess the association between SCD and periodontal diseases.

Desire for biological parenthood and patient counseling on the risk of infertility among adolescents and adults with hemoglobinopathies.

BACKGROUND: Both diagnosis and treatment of hemoglobinopathies have been associated with an increased risk of fertility impairment. German guidelines recommend annual monitoring of fertility parameters to enable early detection of fertility impairment and/or to offer fertility preservation (FP) when indicated. We explored the general desire for parenthood, the frequency of recalling fertility counseling and testing, and the utilization of FP in adolescents and adults with hemoglobinopathies. PROCEDURE: In a cross-sectional study, patients aged 12-50 years, treated in Germany, Austria, or Switzerland, were surveyed on fertility-related aspects. Medical data, including fertility testing results, were collected from patient records. RESULTS: Overall, 116/121 eligible patients, diagnosed with sickle cell disease (70.7%), thalassemia (27.6%), or other hemoglobinopathy (1.7%), participated in our study (57.8% female, median age 17.0 years, range 12-50 years). All participants required treatment of the underlying hemoglobinopathy: 68.1% received hydroxyurea, 25.9% required regular blood transfusions, and 6.0% underwent hematopoietic stem cell transplantation (HSCT). Most patients (82/108, 75.9%) stated a considerable to strong desire for (future) parenthood, independent of sex, education, diagnosis, or subjective health status. Fertility counseling was only recalled by 32/111 patients (28.8%) and least frequently by younger patients (12-16 years) or those treated with regular blood transfusions or hydroxyurea. While fertility testing was documented for 59.5% (69/116) in medical records, only 11.6% (13/112) recalled previous assessments. FP was only used by 5.4% (6/111) of patients. CONCLUSION: Most patients with hemoglobinopathies wish to have biological children, yet only few recalled fertility counseling and testing. Adequate patient counseling should be offered to all patients at risk for infertility.

Computed tomography of hyper-attenuated liver: Pictorial essay.

Demonstration of a very dense or hyper-attenuated liver on the pre-contrast CT images of the abdomen can be an unexpected finding. It may present as a diagnostic challenge if the underlying cause of it is not apparent from the provided clinical history. There are about 12 different pathologic conditions that are associated with deposition of radiopaque elements within the hepatic parenchyma, resulting in diffuse or multi-lobar hyperdense appearance of the liver on abdominal radiographs and CT. Most of them are drug-induced or iatrogenic in nature, while others are the sequelae of genetic disorders like thalassemia, Wilson's disease, and primary hemochromatosis. This pictorial essay will present the CT appearance and etiology of hyper-attenuated liver in various clinical entities.

Microcytic hypochromic Anemia is a risk factor for postoperative HAEC: A retrospective study.

Background: Hirschsprung-associated enterocolitis (HAEC) is a common and life-threatening complication of Hirschsprung's disease (HSCR), which can occur before and after surgery. The aim of this study was to identify the risk factors associated with the development of HAEC. Methods: We retrospectively reviewed the medical records of HSCR patients admitted to the Children's Hospital of Shanxi Province, China, between January 2011 and August 2021. Diagnosis of HAEC was made using a scoring system with cutoff values ≥4 and included the patient's history, physical examination, and radiological and laboratory findings. The results are shown as frequency (%). The chi-square test was used to analyze a single factor with a significance level of P < 0.05. Logistic regression analysis was used to analyze multiple factors. Results: A total of 324 patients were included in this study, with 266 males and 58 females. In total, 34.3% (111/324) of patients had HAEC, including 85 males and 26 females; 18.9% (61/324) of patients had preoperative HAEC; and 15.4% (50/324) of patients had postoperative HAEC within one year after surgery. Gender, age at definitive therapy, and feeding methods were not found to be associated with preoperative HAEC in univariate analysis. Respiratory infection was associated with preoperative HAEC (P = 0.00003). No association was found between gender and age at definitive therapy and postoperative HAEC. Postoperative HAEC was associated with microcytic hypochromic anemia (P = 0.00058), preoperative history of HAEC (P = 0.00120), the creation of a preoperative stoma (P = 0.00097), long segment or total colon HSCR (P = 0.00057), and hypoalbuminemia (P = 0.03225). Regression analysis showed that microcytic hypochromic anemia (OR=2.716, 95% CI = 1.418-5.203, P = 0.003), preoperative history of HAEC (OR=2.814, 95% CI = 1.429-5.542, P = 0.003), the creation of a preoperative stoma (OR=2.332, 95% CI = 1.003-5.420, P = 0.049), and long segment or total colon HSCR (OR=2.167, 95% CI = 1.054-4.456, P = 0.035) were associated with postoperative HAEC. Conclusion: This study revealed that the incidence of preoperative HAEC at our hospital was associated with respiratory infections. In addition, microcytic hypochromic anemia, preoperative history of HAEC, the creation of a preoperative stoma, and long segment or total colon HSCR were risk factors of postoperative HAEC. The most important finding of this study was that microcytic hypochromic anemia was a risk factor for postoperative HAEC, which has been rarely reported. Further studies with larger sample sizes are necessary to confirm these findings.

The Continued Need for the Routine Assessment of Folate Status.

OBJECTIVE: The Choosing Wisely initiative recommended cessation of folate measurement, suggesting folate supplementation in macrocytic anemia. This study reviewed the need for continued blood folate testing at a large SafetyNet county teaching hospital. METHODS: Red blood cell (RBC) folate, vitamin B12, iron, ferritin, and hemoglobin results were obtained for utilization review. RESULTS: Of the 593 RBC folate results, 69 (11.7%) were deficient and 30 (5%) had high values. Collectively, 369 (73.9%) had normal vitamin B12 levels, 342 (70%) had low hemoglobin, 184 (62.5) had normal and 57 (19.4%) had low ferritin, 122 (38.2%) had normal and 188 (59%) had low iron levels. A total of 41 (12%) had normal folate, low ferritin, low hemoglobin, and low iron, suggestive of iron deficiency anemia. There were 11 patients who exhibited low folate, low or normal ferritin, low hemoglobin, and low iron levels, suggesting combined folate and iron deficiency anemias. CONCLUSION: This study highlights the need for institutions to assess the applicability of national recommendations to their local population.

[Autoimmune haemolytic anaemia]. / Anemia hemolítica autoinmune.

Autoimmune haemolytic anaemias (AIHA) are acquired haematological disorders caused by increased peripheral erythrocyte destruction mediated by autoantibodies against erythrocyte antigens. They classified according to aetiology into primary and secondary, and according to the type of antibody and reaction temperature into AIHA due to warm antibodies (w-AIHA) and AIHA due to cold antibodies (c-AIHA). The mainstay of management in w-AIHA remains glucocorticoid therapy, and the early addition of rituximab has shown good results in recent studies. Primary c-AIHA is mainly treated with rituximab, alone or in combination with chemotherapy. New drugs such as Syk inhibitors, anti-FcRn Ig and complement inhibitors are in advanced development and will expand the therapeutic arsenal, especially in refractory or relapsed cases.

Fortificación domiciliaria con polvos de micronutrientes. Lineamientos técnicos para el personal de salud

Introducción: La fortificación domiciliaria de los alimentos con polvos de micronutrientes se considera una intervención efectiva para reducir la anemia por deficiencia de hierro y otras carencias en la población infantil. Objetivo: Establecer los lineamientos técnicos para el personal de salud en el nivel primario de atención, en apoyo a la suplementación con polvos de micronutrientes a niños y niñas entre 6 y 23 meses de edad. Métodos: Se conformó el equipo técnico. Se revisaron las formulaciones utilizadas en la región y experiencia acumulada en intervenciones realizadas en provincias orientales, además, se elaboró el documento sustentado en evidencia científica con base en las recomendaciones nutricionales en esta población. Resultados: El suplemento permitió la prevención de las carencias nutricionales debido a que lograban cubrir la brecha de su requerimiento. Estuvieron disponibles los lineamientos técnicos dirigidos al personal de salud en los diferentes niveles de atención para asegurar el éxito de la consejería nutricional a la familia cubana, y el uso adecuado del suplemento. Conclusiones: Este trabajo brinda elementos y orientaciones técnicas para la capacitación del personal de salud con el fin de socializar, divulgar y brindar herramientas técnicas en el uso del suplemento como una medida costo efectiva para la prevención de las deficiencias de micronutrientes.

Introduction: Home fortification of food with micronutrient powders is considered an effective intervention to reduce iron deficiency anemia and other deficiencies in the child population. Objective: To provide technical guidelines for health personnel at the primary healthcare level to support the supplementation of children between 6 and 23 months of age with micronutrient powders. Methods: The technical team was established. The formulations used in the region and the experience gained in interventions conducted in eastern provinces were reviewed. Moreover, a document on scientific evidence was prepared based on the nutritional recommendations for this population. Results: The supplement allowed the prevention of nutritional deficiencies as it could cover the gaps in their requirement. Technical guidelines directed to health personnel at different healthcare levels were available to ensure the success of nutritional counselling to the Cuban family, and the adequate use of the supplement. Conclusions: This work provides elements and technical guidelines for the training of health personnel to socialize, disseminate and provide technical tools in the use of the supplement as a cost-effective measure for the prevention of micronutrient deficiencies.

Iron Metabolism in the Disorders of Heme Biosynthesis.

Given its remarkable property to easily switch between different oxidative states, iron is essential in countless cellular functions which involve redox reactions. At the same time, uncontrolled interactions between iron and its surrounding milieu may be damaging to cells and tissues. Heme-the iron-chelated form of protoporphyrin IX-is a macrocyclic tetrapyrrole and a coordination complex for diatomic gases, accurately engineered by evolution to exploit the catalytic, oxygen-binding, and oxidoreductive properties of iron while minimizing its damaging effects on tissues. The majority of the body production of heme is ultimately incorporated into hemoglobin within mature erythrocytes; thus, regulation of heme biosynthesis by iron is central in erythropoiesis. Additionally, heme is a cofactor in several metabolic pathways, which can be modulated by iron-dependent signals as well. Impairment in some steps of the pathway of heme biosynthesis is the main pathogenetic mechanism of two groups of diseases collectively known as porphyrias and congenital sideroblastic anemias. In porphyrias, according to the specific enzyme involved, heme precursors accumulate up to the enzyme stop in disease-specific patterns and organs. Therefore, different porphyrias manifest themselves under strikingly different clinical pictures. In congenital sideroblastic anemias, instead, an altered utilization of mitochondrial iron by erythroid precursors leads to mitochondrial iron overload and an accumulation of ring sideroblasts in the bone marrow. In line with the complexity of the processes involved, the role of iron in these conditions is then multifarious. This review aims to summarise the most important lines of evidence concerning the interplay between iron and heme metabolism, as well as the clinical and experimental aspects of the role of iron in inherited conditions of altered heme biosynthesis.

The management of peri-operative anaemia in patients undergoing major abdominal surgery in Australia and New Zealand: a prospective cohort study.

OBJECTIVES: To assess the prevalence and management of anaemia in patients undergoing major abdominal surgery, and the influence of guideline adherence on patient outcomes. DESIGN: Prospective observational cohort study. SETTING: 56 hospitals in Australia and New Zealand. PARTICIPANTS: People aged 18 years or more who underwent major abdominal surgery during two 2-week periods in July 2021. MAIN OUTCOME MEASURES: Proportions of patients managed according to Australian National Blood Authority patient blood management guidelines. SECONDARY OUTCOMES: anaemia prevalence, post-operative complications, length of hospital stay, re-admission within 30 days of discharge. RESULTS: Data were available for 2730 eligible patients (mean age, 56.7 years; SD, 17.3 years), including 1558 women (57.1%). Haemoglobin levels prior to surgery were documented for 2461 of 2727 patients (90.2%), 689 of whom had anaemia (28.0%). Pre-operative anaemia assessment and management were associated with lower likelihood of intra-operative (adjusted odds ratio [aOR], 0.33; 95% CI, 0.19-0.57) and post-operative blood transfusion (aOR, 0.36; 95% CI, 0.25-0.53), and of post-operative complications (aOR, 0.79; 95% CI, 0.63-0.99). Tranexamic acid was administered during 128 of 2728 procedures (4.7%); a restrictive transfusion strategy was followed for 96 of the 167 patients who received post-operative blood transfusions (58%). Post-operative anaemia was identified in 1227 of 2069 patients (59.3%) in whom haemoglobin was assessed prior to discharge. The proportion of people re-admitted to hospital within 30 days was larger for patients with anaemia at discharge (169 of 1207 patients followed up, 14.0% v 61 of 825, 7.4%). Haemoglobin assessments were recorded by 30 days after discharge for only 288 patients with post-operative anaemia (24.3%). CONCLUSIONS: The management of peri-operative anaemia differs between hospitals in Australia and New Zealand, with consequences for patient outcomes. Patients are often discharged after surgery with anaemia, which is therefore a potential therapeutic target. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12621001517864 (retrospective).

Effect of primary lesions in cytoskeleton proteins on red cell membrane stability in patients with hereditary spherocytosis.

We investigated by targeted next generation sequencing the genetic bases of hereditary spherocytosis in 25 patients and compared the molecular results with the biochemical lesion of RBC membrane obtained by SDS-PAGE analysis. The HS diagnosis was based on available guidelines for diagnosis of congenital hemolytic anemia, and patients were selected because of atypical clinical presentation or intra-family variability, or because presented discrepancies between laboratory investigation and biochemical findings. In all patients but 5 we identified pathogenic variants in SPTA1, SPTB, ANK1, SLC4A1, EPB42 genes able to justify the clinical phenotype. Interestingly, a correspondence between the biochemical lesion and the molecular defect was identified in only 11/25 cases, mostly with band 3 deficiency due to SLC4A1 mutations. Most of the mutations in SPTB and ANK1 gene didn't hesitate in abnormalities of RBC membrane protein; conversely, in two cases the molecular lesion didn't correspond to the biochemical defect, suggesting that a mutation in a specific cytoskeleton protein may result in a more complex RBC membrane damage or suffering. Finally, in two cases the HS diagnosis was maintained despite absence of both protein defect and molecular lesion, basing on clinical and family history, and on presence of clear laboratory markers of HS. The study revealed complex relationships between the primary molecular lesion and the final effect in the RBC membrane cytoskeleton, and further underlines the concept that there is not a unique approach to the diagnosis of HS.

Effect of Chinese Herbal Medicine Therapy on Risks of Overall, Diabetes-Related, and Cardiovascular Diseases-Related Mortalities in Taiwanese Patients With Hereditary Hemolytic Anemias.

Hereditary Hemolytic Anemias (HHAs) are a rare but heterogeneous group of erythrocytic diseases, characterized by intrinsic cellular defects due to inherited genetic mutations. We investigated the efficacy of Chinese herbal medicine (CHM) in reducing the overall, diabetes-related, and cardiovascular diseases (CVDs)-related mortalities among patients with HHAs using a nationwide population database. In total, we identified 33,278 patients with HHAs and included 9,222 non-CHM and 9,222 CHM matched pairs after matching. The Cox proportional hazards model was used to compare the risk of mortality between non-CHM and CHM users. The Kaplan-Meier method and log-rank test were used to compare the cumulative incidence mortality between non-CHM and CHM users. The CHM prescription patterns were presented by the association rules and network analyses, respectively. The CHM prescription patterns were presented by the association rules and network analyses, respectively. CHM users showed significant reduced risks for of overall (adjusted hazard ratio [aHR]: 0.67, 95% confidence interval [CI]: 0.61-0.73, p < 0.001), diabetes-related (aHR: 0.57, 95% CI: 0.40-0.82, p < 0.001), and CVDs-related (aHR: 0.59, 95% CI: 0.49-0.72, p < 0.001) mortalities compared with non-CHM users. Two CHM clusters are frequently used to treat Taiwanese patients with HHAs. Cluster 1 is composed of six CHMs: Bei-Mu (BM; Fritillaria cirrhosa D.Don), Gan-Cao (GC; Glycyrrhiza uralensis Fisch.), Hai-Piao-Xiao (HPX; Endoconcha Sepiae), Jie-Geng (JG; Platycodon grandiflorus (Jacq.) A.DC.), Yu-Xing-Cao (YXC; Houttuynia cordata Thunb.), and Xin-Yi-Qing-Fei-Tang (XYQFT). Cluster 2 is composed of two CHMs, Dang-Gui (DG; Angelica sinensis (Oliv.) Diels) and Huang-Qi (HQi; Astragalus membranaceus (Fisch.) Bunge). Further randomized clinical trials are essential to evaluate the safety and effectiveness of above CHM products and to eliminate potential biases in the current retrospective study.