Anemia Syndrome Research Articles

Состояние костномозгового кроветворения у больных хронической лучевой болезнью, облученных с различной мощностью дозы

Purpose: to study the features of the state of the bone marrow according to cytological and histological studies at different periods of the course of CRD, caused by exposure to different dose rates, which developed as a result of professional prolonged exposure in a cohort of former employees of a radiation hazardous enterprise who underwent inpatient examination at the clinic of the A.I. Burnazyan Federal Medical and Biomedical Center in the period up to 1995. Material and methods: the study of the results of cytological and histological studies of the bone marrow was carried out in former workers of the Mayak Production Association who were exposed to long-term industrial exposure with a dose rate of 0.008−0.07 Gy / day (15 people), 0.003−0.007 Gy / day (12 people) and less than 0.001 Gy/day (25 people), during periods of formation, outcomes, immediate and long-term consequences of CRS. At the stage of studying the results of histological examination of the bone marrow, 54 more patients with CRS were added to the third group, irradiated with a dose rate of less than 0.001 Gy / day. Statistical processing of the material was carried out using the IBM SPSS Statistics software package.23 using the Kruskal‒Wallis test and the Mann‒Whitney U-test for independent samples. The results obtained were considered statistically significant at p < 0.05. Results: At a dose rate of 0.008−0.07 Gy / day during the formation period, the myelogram revealed narrowing of the granulocyte and expansion of the red germs, acceleration of maturation of granulocytes with a normal erythrocyte maturation index and leuko-erythroblast ratio. In peripheral blood – agranulocytosis. In the period of outcomes and immediate consequences − narrowing of the granulocytic, expansion of erythrocyte germs, acceleration of maturation of neutrophils with other myelogram parameters within normal limits. In the blood − agranulocytosis, anemic syndrome. In the long term, in the case of restoration of hematopoietic function, narrowing of the granulocytic germ with other myelogram parameters within the reference values. However, with a similar course of CRS in 60 % of patients in periods of outcomes and long-term consequences, the development of myelodysplastic syndrome with transformation into acute leukemia or aplastic anemia is possible. At an irradiation dose rate of 0.003−0.007 Gy / day in the period of CRD formation, the myelogram revealed an expansion of the granulocytic germ, with other indicators within the normal range. In the period of outcomes and immediate consequences, an acceleration of maturation of granulocytes and an increase in the leuko-erythroblastic ratio were found. In the long term, a narrowing of the granulocytic and expansion of the erythrocyte sprouts, a slight acceleration of the maturation of granulocytes were found. Hystological examination: polymorphocellular bone marrow – in 11 out of 25 patients, hypoplasia – in 9 out of 25, signs of hyperplasia – in 5 out of 25. In the long term, 2 patients from this group developed oncohematological diseases. At an irradiation power of less than 0.001 Gy / day, during all periods of CRD, normal values of granulocytic and erythrocyte sprouts were noted in the myelograms of patients. In the period of CRD formation, the normal size of the granulocytic germ was achieved due to the accelerated maturation of neutrophils. The leuko-erythroblastic ratio in the period of long-term consequences was significantly higher than the norm (5.29 and 4.5, respectively). Hystological examination: 32 out of 64 patients had polymorphocellular bone marrow, 22 out of 64 had hypoplastic bone marrow, 7 out of 64 had bone marrow hyperplasia. Conclusion: regular changes in hematopoietic tissue and peripheral blood in CRD can serve as diagnostic criteria, based on which it is possible to assume the dose rate of radiation to which the patient was exposed, and also on their basis, it is possible to predict the outcome and long-term consequences of CRD that developed as a result of this exposure.

Assessment of Bone Marrow Failure Syndrome Management Outcome in Pediatrics – Saudi Perspective

Bone Marrow Failure Syndrome (BMFS) is a rare yet severe condition affecting pediatric populations, characterized by a reduced production of hematopoietic lineages leading to pancytopenia. This article explores the multifaceted nature of BMFS in children, its diverse etiologies, treatment modalities, and outcomes, with a particular focus on the Saudi Arabian context. BMFS encompasses both inherited and acquired forms, often presenting diagnostic challenges due to its heterogeneity. Inherited BMFS accounts for 30% of cases and includes rare conditions like Fanconi Anemia and Schwachman-Diamond Syndrome, where treatment approaches vary depending on severity. Acquired BMFS, constituting 70% of cases, may exhibit complete recovery or require prolonged treatment with immunosuppressants. Hematopoietic Stem Cell Transplantation (HSCT) remains a primary treatment option, with outcomes influenced by factors such as donor type and graft success. Saudi Arabia, despite its high-income status, has faced limited data availability on BMFS outcomes, but the number of HSCT procedures performed in the country is steadily increasing. Survival rates in HSCT patients vary based on factors such as donor match and the underlying cause of BMFS. Additionally, the risk of secondary malignancies is relatively high in BMFS patients, adding complexity to long-term management. While Saudi studies indicate survival rates comparable to international standards, challenges in the assessment of BMFS outcomes persist, given the condition's rarity and diversity. This article underscores the importance of continued research and data collection to enhance our understanding and management of BMFS in the pediatric population, both in Saudi Arabia and globally.

Problems of applying inflammatory markers to diagnostics of anemia of chronic disease in patients with type 1 and type 2 diabetes

The purpose of the study was to evaluate the severity of changes in the values of markers-candidates for the differential diagnosis of anemia of chronic diseases in patients with type 1 and type 2 diabetes mellitus. The total number of leukocytes, erythrocyte sedimentation rate, content of C-reactive protein, TNFa, ferritin and hepcidin were evaluated. 50 people with type 1 diabetes mellitus and 81 people with type 2 diabetes mellitus were examined. The diagnosis of anemia was established on the basis of data on the level of hemoglobin, the content of erythrocytes in the blood, ferritin and serum iron. Next, the type of anemic syndrome was determined. The patients were divided into groups: 14 patients with diabetes mellitus and anemia of chronic diseases, 15 people with diabetes mellitus and iron deficiency anemia, 38 patients with diabetes with latent iron deficiency and 64 patients with diabetes mellitus without anemia. The comparison group consisted of 17 healthy volunteers. It was shown that in the general sample of patients with diabetes mellitus anemia of chronic diseases was distinguished only by the erythrocyte sedimentation rate, which was higher than in iron deficiency anemia, latent iron deficiency and in patients without anemia. The severity of inflammation in diabetic patients was analyzed depending on its type. The concentration of hepcidin in the blood of diabetic patients, regardless of type, exceeded its content in the blood of healthy individuals. Elevated serum concentrations of TNFα were characteristic of inflammation in type 1 diabetes mellitus. Diabetes mellitus type 2 was characterized by an increase in: erythrocyte sedimentation rate - relatively healthy individuals; concentrations of C-reactive protein - in comparison with healthy volunteers and patients with type 1 diabetes mellitus; ferritin levels compared with patients with type 1 diabetes mellitus. Taking into account the type of diabetes and the type of iron metabolism disorder, it was found that in type 1 and type 2 diabetes mellitus, only the erythrocyte sedimentation rate in patients with anemia of chronic diseases was significantly higher than in patients with iron deficiency anemia and without anemia. The article discusses the reasons for the difficulties in using inflammatory markers (ferritin and hepcidin) as parameters for verifying anemia of chronic diseases in patients with diabetes mellitus. It is pointed out that it is necessary to take into account the differences in the mechanisms of inflammation development in type 1 or type 2 diabetes mellitus when trying to use cytokines and C-reactive protein as additional diagnostic markers in practice. The rationale is given for the prospects of determining the erythrocyte sedimentation rate, with the recommendation of a certain threshold value, for the detection of anemia of chronic diseases in patients with type 1 and type 2 diabetes mellitus.

The prevalence of cardiorenal anemia syndrome among patients with heart failure and its association with all-cause hospitalizations: a retrospective single-center study from the Middle East.

Little is known about the burden of cardiorenal syndrome (CRS) and cardiorenal anemia syndrome (CRAS) in the Middle East Region. Furthermore, whether the occurrence rates of CRAS differ across heart failure (HF) phenotypes is not widely investigated. We aimed to examine the prevalence of CRS and CRAS in patients with HF, compare characteristics of patients with CRAS-HFrEF vs. CRAS-HFpEF, and investigate anemia association with 1-year all-cause hospitalizations. HF patients who visited a multidisciplinary HF clinic at a single center between 10-2015 and 06-2022 (n = 968) were retrospectively included. Differences in rates of CRAS prevalence, and patients' characteristics of those with CRAS-HFrEF vs. CRAS-HFpEF were determined using appropriate testing methods. Generalized estimating equation (GEE) models were used to determine if anemia was associated with higher rates of hospitalization. CRS was prevalent in 34.4% of subjects, while 25.3% had CRAS. CRAS prevalence rates among patients with HFpEF vs. HFrEF were comparable (27.2% vs. 24.2%, p = 0.3). Compared to patients with HFrEF-CRAS, those with HFpEF-CRAS were more likely females (p < 0.001), had a higher burden of hypertension (p = 0.01), and lower hemoglobin (p = 0.02). In an adjusted GEE model, anemia was associated with an average increase of 1.8 admissions in CRS patients (p = 0.015). In patients with HF, 1 in 3 patients presented with CRS, and 1 in 4 patients had CRAS. The prevalence of CRAS was comparable among those HFpEF and HFrEF. Anemia was associated with an increased rate of 1-year all-cause hospitalization in CRS patients.

Use of steroids in the management of low-risk myelodysplastic syndromes with autoimmune features.

The boundaries between myelodysplastic syndromes (MDS) and immune-mediated cytopenias are often difficult to establish and both conditions may benefit from immunosuppressive therapy. The optimal timing and doses of immunosuppressants are largely unknown. We systematically evaluated a retrospective cohort of 79 patients with low-risk MDS tested for anti-erythrocyte or anti-platelet autoantibodies to assess their frequency and the efficacy of immunosuppression, particularly with steroids. We found autoantibody positivity in 43% of cases and overt autoimmune diseases in 18%, including autoimmune hemolytic anemia, immune thromboctyopenia, and Evans syndrome. Steroid treatment improved cytopenia in about half of patients, with 26% achieving a complete recovery lasting for a median of 12 months. Better responses were observed in anemic patients with anti-erythrocyte autoantibodies than in those with anti-platelet autoantibodies, and the combination with recombinant erythropoietin (7/10) had a possible synergistic effect. Steroid doses were heterogeneous depending on the clinical intent (i.e., anti-inflammatory, immunosuppressive, anabolizing). Patients treated with a dose of 1 mg/kg day of prednisone for overt autoimmune cytopenia showed high rates of complete responses (60%). This observation suggests a trial with a short course (2-3 weeks) of standard steroid doses to ascertain efficacy and properly silence the autoimmune pathogenic mechanism. Steroid-related adverse events (16% of cases) should be monitored carefully in this elderly, frail population. In conclusion, features of autoimmunity are present in more than two-thirds of low-risk MDS patients and a trial with prednisone 0.5-1 mg/kg day for 2-3 weeks, with proper monitoring of adverse events, may be useful to improve cytopenias in selected cases.

A longitudinal analysis of paroxysmal nocturnal haemoglobinuria-type cells in patients with bone marrow failure: Results of a prospective multi-centre study in Japan.

To determine the prevalence and clinical relevance of glycosylphosphatidylinositol-anchored protein-deficient (GPI[-]) cell populations (paroxysmal nocturnal haemoglobinuria [PNH]-type cells) in patients with acquired aplastic anaemia (AA) or myelodysplastic syndrome (MDS), we prospectively studied peripheral blood samples of 2402 patients (1075 with AA, 900 with MDS, 144 with PNH, and 283 with other anaemia) using a high-sensitivity flow cytometry assay in a nationwide multi-centre observational study. PNH-type cells were detected in 52.6% of AA and 13.7% of MDS patients. None of the 35 patients with refractory anaemia (RA) with ringed sideroblasts or the 86 patients with RA with excess of blasts carried PNH-type cells. Among the 317 patients possessing PNH-type granulocytes, the percentage of PNH-type granulocytes increased by ≥10% in 47 patients (14.8%), remained unchanged in 240 patients (75.7%), and decreased by ≥10% in 30 patients (9.5%) during 3 years of follow-up. PNH-type granulocyte expansion occurred more frequently (27.1%) in the 144 patients who originally carried PNH-type granulocytes ≥1% than in the 173 patients with PNH-type granulocytes <1% (4.6%). This study confirmed that PNH-type cells are undetectable in authentic clonal MDS patients, and the presence of ≥1% PNH-type granulocytes predicts a higher likelihood of PNH-type cell expansion than with <1% PNH-type granulocytes.

Атипичное течение макроглобулинемии «под маской» анемии (клиническое наблюдение)

Waldenström macroglobulinemia (WM) is a type of plasma cell disease that is a malignant B-cell lymphoplasmacytic lymphoma. In patients with WM, immunological blood tests may remain unchanged for a while without pathological changes, but then tumor infiltration of the bone marrow gradually leads to anemia and thrombocytopenia. This patient has anemic syndrome according to clinical and laboratory examination, in which a number of diseases were diagnosed. An early diagnostic method, electrophoresis allows the consideration of immunoproliferative disorders with monoclonal IgM. Immunotyping is widely used with the eye chart of gammopathies using antisera to light (G, A, M) and light (kappa, lambda) chains of immunoglobulins. An increase in blood vessels IgM &gt; 30 g/l, when identified with neurological symptoms of the source, associate these manifestations with hyperviscosity syndrome in WM.

Intestinal cavernous hemangioma as a cause of anemic syndrome and gastrointestinal bleeding

There are multiple causes of non-variceal gastrointestinal bleeding, some more commonly diagnosed than others. Therefore, the finding of a cavernous hemangioma in the jejunum should make us consider patients who present with anemic syndrome due to occult gastrointestinal bleeding, once the more common pathologies have been ruled out, this after extensive studies, including upper endoscopy, colonoscopy, imaging studies and some cases endoscopic capsule. It is described that cavernous hemangiomas account for 0.05% of gastrointestinal neoplasms and up to 7-10% of benign tumors of the small intestine. They can also be found in up to 7.7% of patients with gastrointestinal bleeding.

Thiamine-Responsive Megaloblastic Anemia Syndrome Combined with Thalassemia Trait: A Rare Association

Abstract Introduction Thiamine-responsive megaloblastic anemia syndrome (TRMA, OMIM reference 249270), also known as Rogers' syndrome, is a rare type of anemia characterized by the triad megaloblastic anemia, sensorineural hearing loss, and diabetes mellitus (DM). Disturbance of thiamine transport into cells results from homozygous or compound heterozygous mutations in the SLC19A2 gene. Case Report We report the case of an 8-year-old girl who presented at age 4 years with anemia. She had a combined hematological profile of microcytic and macrocytic anemia. The parents refused bone marrow aspiration and genetic diagnosis. Hemoglobin electrophoresis established the thalassemia trait. She was later confirmed to have sensorineural deafness and monogenic DM. A tentative TRMA diagnosis was based on megaloblastic anemia, sensorineural deafness, and monogenic DM triad. The patient was treated empirically with a daily dose of thiamine 200 mg; her hemoglobin level normalized, but the deafness and DM did not improve. Conclusion In routine practice, patients with TRMA must be evaluated thoroughly for other causes of megaloblastic anemia, including therapeutic thiamine trials in the presence of sensorineural deafness or DM. These patients should be followed throughout their life span both for DM and to control their response to thiamine therapy for megaloblastic anemia.

Small Bowel Lymphoma Associated with Celiac Disease: 2 Cases Report

Small bowel lymphoma associated with celiac disease is rare. The annual incidence varies from 0.5 to 1 per million inhabitants. We report two cases of small bowel lymphoma associated with celiac disease. The first case is a 50-year-old patient, treated for celiac disease since 2010 and whose tumor was revealed on abdominal CT as part of the etiological assessment of abdominal pain with an anemic syndrome. In the other case, it was a 52-year-old patient presenting the same symptomatology, in whom endoscopy revealed total villous atrophy, indicating the diagnosis of celiac disease, and CT showed a small bowel tumor. Both patients underwent segmental resection with single-stage anastomosis. The anatomopathological study concluded to a small lymphoma. Adjuvant chemotherapy was administered in both cases, and their evolution was favorable.

Mannich Base PIP-199 Is a Chemically Unstable Pan-Assay Interference Compound.

Mannich base PIP-199 is the only reported small-molecule inhibitor of the Fanconi anemia complementation group M-RecQ-mediated genome instability protein (FANCM-RMI), a protein-protein interaction that governs genome instability in the genetic disorders Fanconi anemia and Bloom's syndrome. PIP-199 and analogues with the same indole-derived Mannich base scaffold have been used as tool compounds in diverse biological studies. We report the first published synthesis of PIP-199 and its analogues, demonstrating that PIP-199 immediately decomposes in common aqueous buffers and some organic solvents. Neither PIP-199 nor its more hydrolytically stable analogues show any observable activity in binding and competitive biophysical assays for FANCM-RMI. We conclude that PIP-199 is not an effective tool compound for biological studies and that apparent cellular activity likely arises from the nonspecific toxicity of breakdown products. More generally, apparent inhibitors that share this Mannich scaffold potentially represent a new family of pan-assay interference compounds (PAINS) that should be thoroughly assessed for aqueous stability prior to use in biological studies.

ДИНАМИКА ПОКАЗАТЕЛЕЙ ПЕРИФЕРИЧЕСКОЙ КРОВИ В РАЗЛИЧНЫЕ ПЕРИОДЫ ТЕЧЕНИЯ ХРОНИЧЕСКОЙ ЛУЧЕВОЙ БОЛЕЗНИ, ВЫЗВАННОЙ РАДИАЦИОННЫМ ВОЗДЕЙСТВИЕМ С РАЗЛИЧНОЙ МОЩНОСТЬЮ ДОЗЫ

Purpose: To study the effect of the radiation dose rate on the dynamics of peripheral blood indicators in various periods of chronic radiation syndrome (CRS), which developed as a result of professional prolonged radiation exposure in a cohort of former employees of the Mayak plant who underwent inpatient examination at the clinic of the A.I. Burnazyan Federal Medical Biophysical Center of the FMBA of Russia in the period up to 1995. Material and methods: The study of the dynamics of absolute peripheral blood indices in former employees of Mayak plant who were exposed to prolonged industrial radiation with a dose rate of less than 0.001 Gy/day (25 people), 0.003‒0.007 Gy/day (12 people) and 0.008‒0.07 G/day (15 people) during the periods of formation, outcomes and immediate, as well as long-term consequences of CRS. Statistical processing of the material was performed using the IBM SPSS Statistics software package 23.0 using the Kruskal–Wallis criteria and the Mann–Whitney U-test for independent samples. The results obtained were considered statistically reliable at p &lt; 0.05. Results: In a group of patients irradiated with a dose rate of 0.008‒0.07 Gy/day during the periods of formation, as well as the outcomes and immediate consequences of CRS, platelet-, leuco- and deep neutropenia were noted. A decrease in the number of erythrocytes and hemoglobin was detected only in the period of outcomes and immediate consequences. The development of agranulocytosis and anemic syndrome are signs that distinguish the course of CRS in this group of patients from the clinical picture of typical CRS. In the period of long-term consequences, 60 % of patients (9 out of 15) developed oncohematological diseases. At an irradiation power of 0.003‒0.007 Gy/day anemic syndrome was found in 4 out of 12 patients. Leukopenia was observed in the periods of outcomes and immediate consequences. Granulocytopenia was detected in all three periods of the course of CRS. In the long term, 2 patients from this group developed oncohematological diseases At an irradiation power of less than 0.001 Gy/day shallow thrombocytopenia and neutropenia are noted in the periods of outcomes and immediate consequences of CRS. In the period of long-term consequences, all the average values of peripheral blood indicators correspond to normal levels. Conclusions: With prolonged irradiation of a person with a dose rate of 0.008‒0.07 Gy/ day or more, with the accumulation of a total dose of 1.7‒9.6 Gy and a contact duration of 6‒96 months, one can expect the development of CRS with a peculiar subacute clinical course of bone marrow syndrome (BMS), manifested by the defeat of all three hematopoietic sprouts, the development of agranulocytosis, anemia and, probably, in 60 % of cases of leukemia development with an unfavorable prognosis for the patient’s life. The main factor determining this feature of the course of BMC CRS is the dose rate, which exceeds 0.008 Gy / day (2 Gr/year). At a dose rate of 0.003‒0.007 Gy / day (0.7‒1.7 Gy / year), the course of CRS with the development of agranulocytosis is possible in 25 %, anemia – in 33 % of observations. This course of the disease is most likely with a dose rate approaching the upper limit of the named range and high total doses. In other cases, the course of the disease is favorable. In the long-term period, moderate, transient leuko-, neutro- and thrombocytopenia are possible. With prolonged irradiation with a dose rate of less than 0.001 Gy / day (0.25 Gy / year), the course of the disease is relatively favorable with almost complete restoration of hematopoiesis in the long term.

Fanconi anemia and Aldehyde Degradation Deficiency Syndrome: Metabolism and DNA repair protect the genome and hematopoiesis from endogenous DNA damage

We have identified a set of Japanese children with hypoplastic anemia caused by combined defects in aldehyde degrading enzymes ADH5 and ALDH2. Their clinical characteristics overlap with a hereditary DNA repair disorder, Fanconi anemia. Our discovery of this disorder, termed Aldehyde Degradation Deficiency Syndrome (ADDS), reinforces the notion that endogenously generated aldehydes exert genotoxic effects; thus, the coupled actions of metabolism and DNA repair are required to maintain proper hematopoiesis and health.

Fluctuation of Heart Failure with Preserved Ejection Fraction During the Course of Cardiorenal Anemia Syndrome: A Case Report

Heart failure (HF) with preserved ejection function (HFpEF) has a high prevalence in older adults. HF in the elderly tends to be complicated by renal failure and anemia, known as cardio-renal anemia syndrome (CRAS), with each pathology adversely affecting the other, leading to a negative spiral. The temporal evolution from the onset of HFpEF in CRAS is not well understood. We experienced an elderly case in which the initial onset of CRAS was followed by repeated exacerbations with HFpEF. Multiple medications, including a sodium-glucose cotransporter-2 inhibitor and an angiotensin receptor neprilysin inhibitor, were effective in conjunction with extensive cardiac rehabilitation. Our case highlights the difficulty of treating HFpEF with CRAS.

Identification of Plasma Thrombopoietin Level and Its Significance in Patients with Aplastic Anemia and Myelodysplastic Syndrome.

Objective Our objective was to investigate the concentration of plasma thrombopoietin (TPO) in patients with aplastic anemia (AA) and myelodysplastic syndrome (MDS), as well as its relationship with patients' responses to recombined human TPO (rhTPO) therapy. Methods We detected the concentration of plasma TPO in 31 patients with AA, 27 patients with MDS, and 11 normal controls using enzyme-linked immunosorbent assay. Results The median concentration of plasma TPO in patients with AA, MDS, and controls was (841.08 ± 768.64), (212.41 ± 338.93), and (35.09 ± 18.21) pg/mL, respectively. The TPO concentration in patients with AA and MDS was significantly higher than that in controls ( p < 0.05). The median platelet (PLT) counts were (184 ± 34) ×10 9 /L in the control group and (24 ± 19) ×10 9 /L and (80 ± 71) ×10 9 /L in AA and MDS patients, respectively. Negative correlations were found between plasma TPO concentration and PLT counts as well as megakaryocytes in bone marrow ( p < 0.05). In AA patients treated with rhTPO, a negative correlation was observed between increased PLT counts and pretreatment TPO levels ( p < 0.05). Conclusion Plasma TPO concentration in AA and MDS was significantly higher than that in normal controls. Plasma TPO was negatively correlated with peripheral blood PLT counts and bone marrow megakaryocyte counts. The pretreatment TPO level may serve as a prognostic indicator for the therapeutic effect of rhTPO in AA patients.

Treatment of anemic syndrome in patients receiving surgical and chemotherapeutic treatment for breast and colorectal cancer

Introduction. Anemia syndrome is a common disease that reduces the quality and life expectancy of cancer patients. Prevention, timely diagnosis and effective treatment of anemia are statistically significantly associated with a favorable clinical outcome of the treatment of patients, and also contributes to better tolerability of anticancer therapy.Aim. Evaluation of the effectiveness of oral iron preparations and parenteral use of erythropoietin-alpha in patients with breast cancer and colorectal cancer, iron deficiency anemia or severe iron deficiency, immediate and long-term results of treatment, as well as the quality of life of patients with breast cancer and colorectal cancer.Materials and methods. A retrospective analysis of the material from the Blokhin National Medical Research Center of Oncology, involved 133 patients (validation group 68 people, control group – 65 people), patients with breast cancer or colorectal cancer, suffering from anemia. Depending on the form of anemia, patients were prescribed therapy – oral iron preparations with epoetin alfa in combination or in monotherapy. The effectiveness of therapy was assessed by the rate of blood hemoglobin. Analysis and statistical processing of results using IBM SPSS Statistics 26.0. Survival analysis was carried out using the KaplanMeier method. Descriptive statistics methods are used to analyze socio-demographic and traditional patients.Results. With a median follow-up of 61.2 months, the exclusion groups did not have significant differences in overall survival (p &gt; 0.05). However, the group of patients with IDA who received therapy to correct the anemic syndrome and the group with FDA without adequate therapy had a greater significance in terms of 5-year OS (93.5 and 69.6%, respectively; p = 0.02). There were also no significant values for the 5-year DFS indicator (p &gt; 0.05). However, the groups of patients with IDA who received and did not receive therapy to correct anemia probably made a big difference in terms of 5-year DFS (90.3 and 63.9%, respectively; p = 0.025). The group of patients with IDA treated with anemia to correct anemic syndrome clearly differed from the group of patients with FAD without therapy to correct anemia in terms of 5-year OS (90.3 and 43.6%, respectively; p &lt; 0.001).Conclusions. Carrying out antianemic therapy can significantly increase the 5-year relapse-free survival in patients with iron deficiency anemia (90.3 and 63.9%, with and without therapy, respectively; p = 0.025).

Sintilimab plus bevacizumab, oxaliplatin and capecitabine as first-line therapy in RAS-mutant, microsatellite stable, unresectable metastatic colorectal cancer: an open-label, single-arm, phase II trial

Microsatellite stable (MSS) and RAS-mutant metastatic colorectal cancer (mCRC) patients are characterized by an immunosuppressive microenvironment and a low response rate to immunotherapy. Chemotherapy and anti-angiogenesis therapy have been reported to potentially promote immunotherapy response. This study aims to assess the preliminary anti-tumor activity and safety of sintilimab plus bevacizumab, oxaliplatin and capecitabine as a treatment option for patients with RAS-mutant MSS mCRC. This study was an open-label, single-arm, phase II trial in China. Patients with unresectable, RAS-mutant and MSS metastatic colorectal adenocarcinoma received treatment by intravenous sintilimab (200mg, day 1) plus bevacizumab (7.5mg/kg, day 1), oxaliplatin (135mg/m2, day 1) and oral capecitabine (1g/m2, day 1-14) in each 21-day cycle. The primary endpoints included objective response rate (ORR) and adverse events. Biomarker analysis was performed to identify potential predictors of good response to treatment. This study is registered with ClinicalTrials.gov, number NCT04194359. Between April 2021 and December 2021, 25 patients were enrolled. Two (8%) patients showed complete response (CR), 19 (76%) had partial response (PR) and 4 (16%) presented with stable disease. ORR reached 84% (95% CI, 63.9-95.5) and the disease control rate was 100% (95% CI, 86.3-100). The median progression-free survival (PFS) was 18.2 months for the full analysis set. The most common treatment-related adverse events (TRAEs) in all grades were anemia (21/25, 84%), neutropenia (20/25, 80%), and hand-foot syndrome (14/25, 56%). The most frequent grade 3 or 4 TRAEs were neutropenia (3/25, 12%) and increased alanine transaminase (2/25, 8%). No grade 5 adverse events occurred. In the exploration of biomarkers, 5 patients could be characterized as TTN/OBSCN "double-hit" after treatment, and the copy number variants burden was significantly decreased in tumor tissues after treatment compared with the baseline. Nanostring panel RNA sequencing analysis indicated a better tumor immune microenvironment cell infiltration in CR/PR patients compared with non-CR/PR patients as well as the PFS-long (≥12.5 months) group compared with the PFS-short group. Combination treatment with sintilimab plus bevacizumab, oxaliplatin and capecitabine as first-line treatment demonstrated a promising antitumor activity and a manageable safety profile in RAS-mutant, MSS and unresectable mCRC. Exploratory biomarker assessment analysis showed that some RAS-mutant and MSS patients changed into "immune-hot" subtype after the treatment. This study was supported by the Key R&D Program of Zhejiang Province (2021C03125 to Ying Yuan), the National Natural Science Foundation of China (81872481 to Ying Yuan, 82072624 to Kefeng Ding), the Fundamental Research Funds for the Central Universities (No. 226-2022-00009 to Kefeng Ding), and the Zhejiang Provincial Natural Science Foundation of China (No. LY22H160024 to Hanguang Hu).

Non-alcoholic fatty liver disease as a risk factor for anemia of chronic inflammation (experimental research)

The aim of the study. In recent years, non-alcoholic fatty liver disease (NAFLD) has been considered a hepatic manifestation of the metabolic syndrome. The main consequence of NAFLD is chronic hepatic inflammation, which leads to dyslipidemia, inflammation, increased oxidative stress, and endothelial dysfunction. Immune activation in response to interaction with agents of a metabolic nature induces the release of pro-inflammatory cytokines in the liver, which subsequently cause iron сhomeostasis disorder. This leads to a frequent association of NAFLD with anemia of various etiology. In this regard, we considered it important to assess the severity of the systemic inflammatory response in NAFLD in the experiment in order to -diagnose anemia of chronic inflammation.Materials and methods. The study was carried out on 26 male Wistar rats, which were divided into control and experimental groups. In animals of the experimental group, NAFLD was modeled according to the generally accepted method. In order to assess metabolic disorders, we determined the main biochemical parameters, a complete blood count with the calculation of erythrocyte indices, the concentration of the main pro-inflammatory cytokines – interleukin (IL) 1, IL-6. Results. In laboratory rats with NAFLD, a statistically significant increase of intrahepatic enzymes in blood serum was found. The state of the erythrocyte lineage of hematopoiesis in the experimental group progressively worsened and caused the development of anemic syndrome. Synchronously, a statistically significant increase in serum levels of IL-1, IL-6 was recorded, which confirms the correlation of NAFLD with anemia of chronic inflammation.Conclusions. A high concentration of IL-1, IL-6 cytokines in NAFLD inhibits iron absorption in the duodenum, leads to the activation of macrophages, blocking the release of iron processed from aging erythrocytes into plasma. Further study of the mechanisms of anemia in NAFLD provides important therapeutic targets in the treatment of both NAFLD and its comorbidities.

Trastuzumab-Induced Cardiac Dysfunction. A Case Report

Oncological pathology and the management of patient with cancer are real challenges in cardiology practice. Unpredictable situations triggered by this pathology, as well as adverse reactions of oncological therapy on the cardiovascular system, are increasing. A 71-year-old female patient who was known with HER2-positive breast cancer, with sectorial mastectomy and treated with chemo-radio-immunotherapy in 2018, then diagnosed with liver metastases and ulcerated gastric adenocarcinoma in May 2022, was referred to the Cardiology Clinic for chest pain and dyspnea. On the ECG, ST-segment depression was seen in the infero-lateral territory. Positive myocardial necrosis enzymes were documented, and also moderate microcytic hypochromic anemia. The current clinical, electrical, and biological picture was suggestive for acute coronary syndrome. It should be mentioned that the patient has been on monoclonal antibody therapy with Trastuzumab, recently discontinued after echocardiographic evaluation where decreased systolic performance was noted. Considering all the particular aspects of this case, as cardiotoxicity of oncological therapy, acute coronary event and anemic syndrome, multidisciplinary management is required, with adjustment of cardiovascular therapy and cancer treatment.

Essential thrombocythemia masked by vitamin B 12 deficiency megaloblastic anemia: A case report

The association of megaloblastic vitamin B12 deficiency anemia and essential thrombocythemia is very rarely described in the literature. We reported a case of a 65-year-old patient with an isolated chronic anemic syndrome secondary to megaloblastic vitamin B12 deficiency anemia treated with vitamin B12 therapy by injection. The evolution was marked three months after treatment by the an ischemic cerebrovascular accident and thrombocytosis. Additional investigations confirmed essential thrombocythemia. The patient was put under hydroxyuria and an anticoagulant treatment with a good evolution.