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Japanese Clinical Medicine 2018The use of generic drugs has been increasing. However, studies of the safety of generic cisplatin (CDDP) for the treatment of head and neck cancer (HNC) have not been...
The use of generic drugs has been increasing. However, studies of the safety of generic cisplatin (CDDP) for the treatment of head and neck cancer (HNC) have not been reported. This study investigated the treatment completion rates and incidence of CDDP-related adverse events in patients with advanced HNC treated with concurrent chemoradiotherapy (CRT) using generic CDDP. This study included 72 patients who received concurrent CRT using generic CDDP. The number of courses of CDDP was 3 in 45 patients, 2 in 19 patients, and 1 in 8 patients. During 154 courses of 80 mg/m generic CDDP, grade 3/4 leukopenia in 21 (14%), neutropenia in 18 (12%), and hypochromia in 8 (5%) cases were reported. Grade 2 elevated serum creatinine occurred in 4 cases (3%), but no grade 3/4 elevated serum creatinine was reported. These results suggest that CRT using generic CDDP is well tolerated in patients with HNC.
PubMed: 29434483
DOI: 10.1177/1179670717749231 -
Polish Journal of Pathology : Official... 2022The nuclear features that are thought to be classic indicators of thyroid nodules are not fully observed in core needle biopsies (CNB). The aim of this study was to...
INTRODUCTION
The nuclear features that are thought to be classic indicators of thyroid nodules are not fully observed in core needle biopsies (CNB). The aim of this study was to evaluate the histopathological differences between CNB samples and resection sections.
MATERIAL AND METHODS
The haematoxylin and eosin-stained CNB and resection sections of thyroid nodules were retrospectively re-evaluated in terms of nuclear and architectural parameters. The evaluations were conducted by 2 pathologists. Statistical analysis was applied in 80 selected cases diagnosed as benign (n = 37) and papillary carcinoma/suspicious for papillary carcinoma (n = 43).
RESULTS
The nuclear findings in the CNB were more subtle than in the resection sections. The nuclei were smaller (measurements of the nuclear areas, major axes, and minor axes in CNB and resection sections were 52.62 µm2, 9.89 µm, 6.75 µm, 129.18 µm2, 14.53 µm, and 10.79 µm, respectively). Hypochromia was detected in 46.5% of the papillary carcinoma cases. Grooves and pseudoinclusions were the other nuclear features that could be detected. However, nuclear contour irregularity was the most reliable finding that could predict papillary carcinoma diagnosis in the CNB sections (v: 0.82, p < 0.001).
CONCLUSIONS
We believe that the histopathological differences we found have an important place in diagnostics and should be emphasized, and new diagnostic algorithms should be developed.
Topics: Humans; Thyroid Nodule; Thyroid Neoplasms; Biopsy, Large-Core Needle; Carcinoma, Papillary; Retrospective Studies
PubMed: 36946267
DOI: 10.5114/pjp.2022.125778 -
Genetics and Molecular Biology 2017Alpha-thalassemias are among the most common genetic diseases in the world. They are characterized by hypochromic and microcytic anemia and great clinical variability,...
Alpha-thalassemias are among the most common genetic diseases in the world. They are characterized by hypochromic and microcytic anemia and great clinical variability, ranging from a practically asymptomatic phenotype to severe anemia, which can lead to intrauterine or early neonatal death. Deletions affecting the α-globin genes, located on chromosome 16p13.3, are the main causes of α-thalassemia. Multiplex ligation-dependent probe amplification (MLPA) can be used to detect rearrangements that cause α-thalassemia, particularly large deletions involving the whole α cluster and/or deletions in the HS-40 region. Here, MLPA was used to investigate the molecular basis of α-thalassemia in five unrelated patients, three of whom had Hb H disease. In addition to the -α3.7 deletion identified in the patients with Hb H disease, four different α0 deletions removing 15 to 225 kb DNA segments were found: two of them remove both the α genes, one affects only the regulatory element (HS-40) region, and another one extends over the entire α cluster and the HS-40 region. These results illustrate the diversity of α-thalassemia deletions in the Brazilian population and highlight the importance of molecular investigation in cases that present with microcytosis and hypochromia without iron deficiency and normal or reduced Hb A2 levels..
PubMed: 28981562
DOI: 10.1590/1678-4685-GMB-2016-0330 -
Journal of Clinical Laboratory Analysis Sep 2016Iron deficiency (ID) is the most common cause of anemia in fertile women and hemoglobin (Hb) within the reference interval does not exclude ID. The consequence of an...
BACKGROUND
Iron deficiency (ID) is the most common cause of anemia in fertile women and hemoglobin (Hb) within the reference interval does not exclude ID. The consequence of an imbalance between the iron requirements and supply is a reduction of red-cell Hb content, which causes hypochromic cells. The aim of this study was to assess the reliability of new parameters low Hb density (LHD%), reticulocyte Hb equivalent (RetHe), and percentage of hypochromic erythrocytes (%HypoHe) in the detection of latent ID (LID), defined as depletion of iron stores without anemia.
METHODS
Two hundred fifty consecutive nonanemic women in fertile age (18-40 years, mean 33.5 years), whose analyses had been requested by general practitioners, were included. Independent samples t-test, receiver operating characteristic (ROC) curve analysis (gold standard for detecting LID ferritin <30 μg/l), and Cohen's kappa index were applied.
RESULTS
One hundred fifty-three women had ferritin within the reference range and Hb >120 g/L; 97 (38.8%) had LID. The results were as follows: %HypoHe-AUC 0.934, cutoff 1.6%, sensitivity 85.7%, specificity 92.1%; RetHe-AUC 0.914, cutoff 29.9 pg, sensitivity 86.8%, specificity 85.7%; LHD%-AUC 0.898, cutoff 5.0%, sensitivity 85.9%, specificity 84.1%. Applying those cutoffs, agreement between ferritin and %HypoHe was κ 0.61 and 0.56 for RetHe and LHD%.
CONCLUSIONS
LHD%, %HypoHe, and RetHe emerge as reliable tests for the investigation of LID and could improve the ability to detect ID before anemia is present.
Topics: Adolescent; Adult; Anemia, Hypochromic; Biomarkers; Female; Humans; Iron Deficiencies; Premenopause; ROC Curve; Referral and Consultation; Young Adult
PubMed: 26899023
DOI: 10.1002/jcla.21912 -
Therapeutic Advances in Rare Disease 2021Erythropoietic protoporphyria (EPP) is an ultra-rare inherited disorder with overproduction of protoporphyrin in maturating erythroblasts. This excess protoporphyrin...
UNLABELLED
Erythropoietic protoporphyria (EPP) is an ultra-rare inherited disorder with overproduction of protoporphyrin in maturating erythroblasts. This excess protoporphyrin leads to incapacitating phototoxic burns in sunlight exposed skin. Its biliary elimination causes cholestatic liver injury in 20% and terminal liver failure in 4% of EPP patients. Thereby, the risk of liver injury increases with increasing erythrocyte protoporphyrin concentrations. Afamelanotide, an α-melanocyte-stimulating hormone (MSH) analog inducing skin pigmentation, was shown to improve sunlight tolerance in EPP. Beyond this well-known effect on pigmentation, the MSHs have liver-protective effects and improve survival of maturating erythroblasts, effects described in animal or models to date only. We investigated whether afamelanotide treatment in EPP has effects on erythropoiesis, protoporphyrin concentrations, and liver injury by analyzing retrospectively our long-term safety data.
METHODS
From the 47 Swiss EPP-patients treated at our center since 2006, we included those 38 patients in the current analysis who received at least one afamelanotide dose between 2016 and 2018 and underwent regular laboratory testing before and during the treatment. We compared the means of pretreatment measurements with those during the treatment.
RESULTS
Protoporphyrin concentrations dropped from 21.39 ± 11.12 (mean ± SD) before afamelanotide to 16.83 ± 8.24 µmol/L ( < .0001) during treatment. Aspartate aminotransferase decreased from 26.67 ± 13.16 to 22.9 ± 7.76 IU/L ( = .0146). For both entities, patients with higher values showed a more progressive decrease, indicating a risk reduction of EPP-related liver disease. The pre-existing hypochromia and broad mean red-cell distribution width were further augmented under afamelanotide. This was more likely due to an influence of afamelanotide on maturating erythroblasts than due to an exacerbated iron deficiency, as mean zinc-protoporphyrin decreased significantly and ferritin remained unchanged. No serious afamelanotide-related adverse events were observed for a total of 240 treatment years.
CONCLUSION
Our findings point to a protective effect of afamelanotide on erythroblast maturation and protoporphyrin-induced liver injury.
PLAIN LANGUAGE SUMMARY
Patients with erythropoietic protoporphyria (EPP), an inherited metabolic disease, suffer from light-induced skin burns and liver injury elicited by the accumulated light sensitizer protoporphyrin. The excess protoporphyrin is produced in red cell precursors in the bone marrow, and it is eliminated from the body the liver and bile. A high protoporphyrin excretion burden damages the liver cells, the risk for this increases with higher protoporphyrin concentrations. About 20% of EPP patients show some sign of liver injury and 4% develop life-threatening liver dysfunction.Afamelanotide, closely related to natural α-melanocyte stimulating hormone (MSH), induces skin tanning. This effect protects EPP patients from light-induced skin burns as shown in previous studies. We have treated Swiss EPP patients with afamelanotide since 2006, and we regularly perform safety tests of this treatment.Recent and animal studies demonstrated α-MSH effects other than skin tanning, including an improved synthesis of red blood cell precursors in the bone-marrow and protection of the liver from experimentally induced damage. Until now, it is unknown whether afamelanotide has similar effects in the human organism.To study this question, we analyzed retrospectively the safety laboratory data of 38 Swiss patients, who received at least one dose of afamelanotide from 2016 to 2019. We found that both, the average protoporphyrin concentrations and aspartate aminotransferase, a test for liver function, improved during afamelanotide treatment as compared to before.We concluded that afamelanotide applied to EPP patients to protect them from light-induced skin burns also may reduce their risk of liver injury.
PubMed: 37181106
DOI: 10.1177/26330040211065453 -
Congestive Heart Failure (Greenwich,... 2013Iron insufficiency has been associated with heart failure, but the impact of a reduction of hemoglobin content in the erythrocytes as estimated by mean corpuscular... (Comparative Study)
Comparative Study
Iron insufficiency has been associated with heart failure, but the impact of a reduction of hemoglobin content in the erythrocytes as estimated by mean corpuscular hemoglobin concentration (MCHC) to myocardial structure, performance, and long-term clinical outcomes has not been well-established. The authors examined hematologic data and long-term outcomes of 197 ambulatory patients with chronic systolic and symptomatic heart failure who underwent comprehensive echocardiographic evaluation. The authors observed that relative hypochromia (defined as low MCHC) was associated with higher natriuretic peptide levels (NT-proBNP, r =-0.40, P<.0001) and lower estimated glomerular filtration rate (eGFR; r = 0.45, P <. 0001) and correlated modestly with indices of left and right ventricular diastolic dysfunction (all P<.05), but were not related to left ventricular ejection fraction (LVEF, r=0.17, P=.079). After 5 years of follow-up, lower MCHC levels were associated with higher risk of death, transplant, or heart failure hospitalization after adjusting for age, LVEF, eGFR, and New York Heart Association class (hazard ratio, 1.34; 95% confidence interval, 1.04-1.72; P=.025), particularly in those with above-median hemoglobin (>13.8 g/dL; hazard ratio, 2.02; 95% confidence interval, 1.44-2.81, P<.0001). Taken together, the observations imply that physicians should take notice of the presence of relative hypochromia particularly in the absence of anemia in the setting of chronic systolic heart failure.
Topics: Anemia, Hypochromic; Echocardiography, Doppler; Female; Follow-Up Studies; Heart Failure, Systolic; Hemoglobins; Humans; Male; Middle Aged; Prognosis; Prospective Studies; Severity of Illness Index; Stroke Volume; Ventricular Function, Left
PubMed: 23279093
DOI: 10.1111/chf.12010 -
BMC Medical Genetics Aug 2018Thalassemias (TM) are the most common autosomal recessive disorders in Southeast Asian countries. Both α- and β-thalassemia lead to a decrease or absence of globin...
BACKGROUND
Thalassemias (TM) are the most common autosomal recessive disorders in Southeast Asian countries. Both α- and β-thalassemia lead to a decrease or absence of globin chains. The most serious of the thalassemia syndromes is thalassemia major which is characterized by a transfusion dependent anemia and subsequent iron overload caused by repeated blood transfusions. It is preventive by genotyping the parents. A better understanding of the laboratory data will help provide an accurate diagnosis of thalassemia major, and prevention and controlling programs in routine laboratories.
CASE PRESENTATION
The patient was a one-year-old boy born to non-consanguineous parents. He was referred to our outpatient clinic for hemolytic anemia after a cold. Hematological investigations revealed severe anemia (Hb57 g/dL). The red cells displayed microcytosis, hypochromia and misshapen erythrocytes (MCV48.8 fL, MCH15.7 pg). Capillary electrophoresis (CE) electropherogram revealed normal level of HbA2 (3.2%) and elevated HbF (35.1%). The patient was diagnosed with β-TM, based on severe microcytosis, hypochromia, normal Hb A2 and high Hb F level but no Hb H inclusion at the first visit. Later our molecular analysis revealed compound heterozygosity for codons 41-42 (-TTCT) (HBB: c.126_129delCTTT, β) and IVS-II-654 (C > T) (HBB: c.316-197C > T, β) mutation and deletional Hb H (--/-α). Thus, a combination of Hb H disease and a compound heterozygosity of β/β-thalassemia (β/β-thal) was finally diagnosed.
CONCLUSIONS
Genotype-phenotype analysis shows that heterozygous mutations in the β-globin gene could affect not only hematological parameters, but also elevate HbA2 levels. These effects could be ameliorated by the coinheritance of Hb H disease, which may be explained by the phenomena of the α-globin gene and of the β-globin gene balanced effect.
Topics: Humans; Infant; Male; Mutation; alpha-Globins; beta-Globins; beta-Thalassemia
PubMed: 30119651
DOI: 10.1186/s12881-018-0659-9 -
The Indian Journal of Medical Research Aug 2014In a routine community health survey conducted in adult Adivasis of the costal Maharashtra, microcytosis and hyprochromia were observed in more than 80 per cent of both...
BACKGROUND & OBJECTIVES
In a routine community health survey conducted in adult Adivasis of the costal Maharashtra, microcytosis and hyprochromia were observed in more than 80 per cent of both males and females having normal haemoglobin levels suggesting the possibility of α-thalassaemia in these communities. We conducted a study in Adivasi students in the same region to find out the magnitude of α-thalessaemia.
METHODS
The participants (28 girls and 23 boys) were 14-17 yr old studying in a tribal school. Fasting venous blood samples (5 ml) were subjected to complete blood count (CBC), Hb-HPLC and DNA analysis using gap-PCR for deletion of -α3.7 and -α4.2, the two most common molecular lesions observed in α-thalassaemia in India.
RESULTS
Microcytic hypochromic anaemia was observed 50 and 35 per cent girls and boys, respectively. Iron supplementation improved Hb levels but did not correct microcytois and hypochromia. m0 ore than 80 per cent non-anaemic students of both sexes showed microcytois and hypochromia. DNA analysis confirmed that the haematological alterations were due to α-thalassaemia trait characterized by deletion of -α3.7. Majority (>60%) of the affected students had two deletions (-α3.7/-α3.7 genotype α+ thalassaemia.
INTERPRETATION & CONCLUSIONS
This is perhaps the first report on the occurrence of α-thalassaemia in tribal communities of coastal Maharashtra. Very high (78.4%) haplotype frequency of -α3.7 suggests that the condition is almost genetically fixed. These preliminary observations should stimulate well planned large scale epidemiological studies on α-thalassaemia in the region.
Topics: Adolescent; Anemia, Hypochromic; Blood Cell Count; Chromatography, High Pressure Liquid; Ethnicity; Female; Haplotypes; Hemoglobins; Humans; India; Male; Polymerase Chain Reaction; alpha-Thalassemia
PubMed: 25297356
DOI: No ID Found -
Mediterranean Journal of Hematology and... 2022IVS-II-5 G>C () is a rare β-thalassemia mutation. However, there is no clear evidence regarding the effect of this defect or co-inheritance of other β-thalassemia...
BACKGROUND
IVS-II-5 G>C () is a rare β-thalassemia mutation. However, there is no clear evidence regarding the effect of this defect or co-inheritance of other β-thalassemia mutations on phenotypes.
METHODS
The clinical phenotypes associated with compound heterozygosity for the IVS-II-5 G>C mutation and other β-thalassemia mutations, together with the genetic modifiers' potential effect of the genetic modifiers α-thalassemia, were studied in 13 patients. In addition, analyses of red cell indices, hemoglobin component, iron status, and α-globin genes were carried out in 19 heterozygotes.
RESULTS
Next-generation sequencing of 24 undiagnosed patients with transfusion-dependent thalassemia (TDT) or non-transfusion-dependent thalassemia (NTDT) identified 13 carriers of the IVS-II-5 G>C mutation. There was a wide spectrum of phenotypic severity in compound heterozygotes and 6 (46.2%) of 13 were transfusion dependent. Analysis of 19 heterozygotes indicated that most were hematologically normal without appreciable microcytosis or hypochromia, and approximately half had normal hemoglobin A levels at the same time.
CONCLUSION
Compound heterozygotes for IVS-II-5 G>C and other severe β-thalassemia mutations are phenotypically severe enough to necessitate appropriate therapy and counselling. Co-inheritance of this nucleotide substitution with other β-thalassemia mutations may account for a considerable portion of the incidence of undiagnosed patients with NTDT and TDT in Guangxi. Therefore, the IVS-II-5 G>C mutation can pose serious difficulties in screening and counselling.
PubMed: 35615327
DOI: 10.4084/MJHID.2022.034 -
Journal of Clinical Laboratory Analysis Dec 2021Thalassemia is a group of inherited autosomal recessive hemolytic anemia disease caused by reduced or absent synthesis of globin chain/chains of hemoglobin. Only few... (Comparative Study)
Comparative Study
BACKGROUND
Thalassemia is a group of inherited autosomal recessive hemolytic anemia disease caused by reduced or absent synthesis of globin chain/chains of hemoglobin. Only few studies showed the molecular characterization of α- and β-thalassemia in Meizhou city of China.
METHODS
A total of 22,401 individuals were collected; hematological and hemoglobin electrophoresis analysis and thalassemia genetic testing were performed.
RESULTS
Eleven thousand and thirty (49.24%) cases with microcytosis (mean corpuscular volume (MCV) < 82 fl), 11,074 (49.44%) cases with hypochromia (mean corpuscular Hb (MCH) < 27 pg) in 22,401 subjects, 11,085 cases with abnormal hemoglobin results were identified in subjects aged ≥6 months. 7,322 (32.69%) subjects harbored thalassemia mutations, including 4,841 (21.61%) subjects with α-thalassemia, 2,237 (9.99%) with β-thalassemia, and 244 (1.09%) with α-thalassemia combined β-thalassemia. 18 genotypes of α-thalassemia mutations and 27 genotypes of β-thalassemia mutations were characterized. The most frequent α gene mutation was -- (64.69%), followed by -α (19.93%), -α (7.73%), α α (3.97%), and α α (2.83%). The six most common β-thalassemia mutations were IVS-II-654 (C>T) (39.79%), CD41-42 (-TCTT) (33.02%), -28 (A>G) (10.38%), CD17 (A>T) (9.08%), CD27-28 (+C) (2.14%), and CD26 (G>A) (2.02%). In addition, MCV and MCH were sensitive markers for α- and β-thalassemia except for -α /αα, -α /αα, α α/αα, α α/αα, and β /β .
CONCLUSIONS
The -- , -α , and -α deletions were the main mutations of α-thalassemia, while IVS-II-654 (C>T), CD41-42 (-TCTT), -28 (A>G), and CD17 (A>T) mutations of β-thalassemia in Meizhou. There were some differences in thalassemia mutation frequencies in Meizhou city from other populations in China.
Topics: Asian People; China; Cities; Erythrocyte Indices; Gene Frequency; Genotype; Hemoglobins; Humans; Mutation; Mutation Rate; alpha-Thalassemia; beta-Thalassemia
PubMed: 34752669
DOI: 10.1002/jcla.24105