Associations of three differential white blood cell counts, platelet counts, and their derived inflammatory indices with cancer-related fatigue in patients with breast cancer undergoing chemotherapy.

PURPOSE: Inflammation is thought to be a vital element in the etiology of cancer-related fatigue (CRF), and circulating blood cell parameters could be important markers of inflammatory response. However, the associations of several major blood cell counts and their derived inflammatory indices with CRF are not well described. The present study aimed to establish whether a relationship exists between the counts of three white blood cell (WBC) types, platelets, and CRF and investigate whether several systemic inflammatory indices were associated with CRF in patients with breast cancer (BC). METHODS: A cross-sectional survey was conducted with a sample of 824 patients with BC undergoing chemotherapy. The cancer fatigue scale was administered to assess CRF. Hematological indicators, including neutrophils, lymphocytes, monocytes, and platelets, were retrieved from routine blood test. Network analyses were used to examine the associations among them. RESULTS: Among 824 participants, the mean score of CRF was (27 ± 10), ranging from 0 to 57. The results of network models indicated that physical fatigue was negatively linked to lymphocyte counts (weight = - 0.161), and affective fatigue was positively associated with neutrophil counts (weight = 0.070). Additionally, physical fatigue was positively linked to the platelet-to-lymphocyte ratio (PLR) (weight = 0.049). CONCLUSION: There were preliminary associations of counts of three WBC types, platelet counts, and systemic inflammatory indices, with distinct dimensions of CRF in patients with BC. Findings provide empirical support for the cellular basis of fatigue-associated inflammatory states.

Momelotinib versus Continued Ruxolitinib or Best Available Therapy in JAK Inhibitor-Experienced Patients with Myelofibrosis and Anemia: Subgroup Analysis of SIMPLIFY-2.

INTRODUCTION: Some Janus kinase (JAK) inhibitors such as ruxolitinib and fedratinib do not address and may worsen anemia in patients with myelofibrosis. In these cases, the JAK inhibitor may be continued at a reduced dose in an effort to maintain splenic and symptom control, with supportive therapy and/or red blood cell (RBC) transfusions added to manage anemia. This post hoc descriptive analysis of the phase 3 SIMPLIFY-2 trial evaluated the relative benefits of this approach versus switching to the JAK1/JAK2/activin A receptor type 1 inhibitor momelotinib in patients for whom anemia management is a key consideration. METHODS: SIMPLIFY-2 was a randomized (2:1), open-label, phase 3 trial of momelotinib versus best available therapy (BAT; 88.5% continued ruxolitinib) in JAK inhibitor-experienced patients with myelofibrosis (n = 156). Patient subgroups (n = 105 each) were defined by either baseline (1) hemoglobin (Hb) of < 100 g/L or (2) non-transfusion independence (not meeting the criteria of no transfusions and no Hb of < 80 g/L for the previous 12 weeks); outcomes have been summarized descriptively. RESULTS: In both subgroups of interest, week 24 transfusion independence rates were higher with momelotinib versus BAT/ruxolitinib: baseline Hb of < 100 g/L, 22 (33.3%) versus 5 (12.8%); baseline non-transfusion independent, 25 (34.7%) versus 1 (3.0%). Mean Hb levels over time were also generally higher in both subgroups with momelotinib, despite median transfusion rates through week 24 with momelotinib being comparable to or lower than with BAT/ruxolitinib. Spleen and symptom response rates with momelotinib in these subgroups were comparable to the intent-to-treat population, while rates with BAT/ruxolitinib were lower. CONCLUSION: In patients with moderate-to-severe anemia and/or in need of RBC transfusions, outcomes were improved by switching to momelotinib rather than continuing ruxolitinib and using anemia supportive therapies. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02101268.

Patients with the rare blood cancer myelofibrosis often experience symptoms such as tiredness, an increase in the size of their spleens (an organ involved in filtering the blood), and anemia (too few red blood cells). One type of treatment for myelofibrosis, called a Janus kinase (JAK) inhibitor, can help patients to feel better and reduce the size of their spleens, but some JAK inhibitors do not help with anemia and may make it worse. In those situations, patients may continue to take their JAK inhibitor but also receive another type of treatment, called an anemia supportive therapy, and may also receive red blood cell transfusions. This study compared 2 treatment approaches, continuing the JAK inhibitor ruxolitinib and adding an anemia supportive therapy and/or transfusions versus switching to another treatment called momelotinib, in 2 groups of patients from a clinical trial: (1) patients with levels of hemoglobin (a red blood cell protein) at the start of the trial that indicated that they had anemia, and (2) patients who were already receiving red blood cell transfusions at the start of the trial. In both groups, more patients did not need red blood cell transfusions anymore at week 24 with momelotinib, and their hemoglobin levels on average became higher over time. More patients also had improvements in spleen size and symptoms with momelotinib. Overall, outcomes were improved by switching to momelotinib rather than continuing ruxolitinib and using supportive therapies and/or red blood cell transfusions to treat anemia.

Human red blood cells express the RNA sensor TLR7.

Red blood cells (RBCs) express the nucleic acid-binding toll-like receptor 9 (TLR9) and bind CpG-containing DNA. However, whether human RBCs express other nucleic acid-binding TLRs is unknown. Here we show that human RBCs express the RNA sensor TLR7. TLR7 is present on the red cell membrane and is associated with the RBC membrane protein Band 3. In patients with SARS-CoV2-associated sepsis, TLR7-Band 3 interactions in the RBC membrane are increased when compared with healthy controls. In vitro, RBCs bind synthetic ssRNA and RNA from ssRNA viruses. Thus, RBCs may serve as a previously unrecognized sink for exogenous RNA, expanding the repertoire of non-gas exchanging functions performed by RBCs.

Application of neutrophil-lymphocyte ratio and red blood cell distribution width in diabetes mellitus complicated with heart failure.

BACKGROUND: Accumulating clinical evidence has shown that diabetes mellitus (DM) is a serious risk factor for cardiovascular disorders and an important factor for adverse cardiovascular events. AIM: To explore the value of the combined determination of the neutrophil-lymphocyte ratio (NLR) and red blood cell distribution width (RDW) in the early diagnosis and prognosis evaluation of DM complicated with heart failure (HF). METHODS: We retrospectively analyzed clinical data on 65 patients with type 2 DM (T2DM) complicated with HF (research group, Res) and 60 concurrent patients with uncomplicated T2DM (control group, Con) diagnosed at Zhejiang Provincial People's Hospital between January 2019 and December 2021. The NLR and RDW values were determined and comparatively analyzed, and their levels in T2DM + HF patients with different cardiac function grades were recorded. The receiver operating characteristic (ROC) curves were plotted to determine the NLR and RDW values (alone and in combination) for the early diagnosis of HF. The correlation between NLR and RDW with the presence or absence of cardiac events was also investigated. RESULTS: Higher NLR and RDW levels were identified in the Res vs the Con groups (P < 0.05). The NLR and RDW increased gradually and synchronously with the deterioration of cardiac function in the Res group, with marked differences in their levels among patients with grade II, III, and IV HF (P < 0.05). ROC curve analysis revealed that NLR combined with RDW detection had an area under the curve of 0.915, a sensitivity of 76.9%, and a specificity of 100% for the early diagnosis of HF. Furthermore, HF patients with cardiac events showed higher NLR and RDW values compared with HF patients without cardiac events. CONCLUSION: NLR and RDW were useful laboratory indicators for the early diagnosis of DM complicated with HF, and their joint detection was beneficial for improving diagnostic efficiency. Additionally, NLR and RDW values were directly proportional to patient outcomes.

Mitochondrial oxygen tension in critically ill patients receiving red blood cell transfusions: a multicenter observational cohort study.

PURPOSE: Currently, there is no marker of efficacy of red blood cell (RBC) transfusion. This study describes the impact of RBC transfusion on mitochondrial oxygen tension (mitoPO2) and mitochondrial oxygen consumption (mitoVO2) in critically ill patients with anemia. METHODS: Critically ill patients with a hemoglobin concentration < 10 g/dL, for whom a single RBC unit had been ordered, were included. MitoPO2 was measured with the COMET device immediately before RBC transfusion, 0.5 h, 1 h, 3 h, and 24 h after RBC transfusion. MitoVO2 was calculated from dynamic mitoPO2 measurements during cessation of local oxygen supply. RESULTS: Sixty-three patients participated, median age 64.0 (interquartile range (IQR) 52.3-72.8) years, median hemoglobin concentration before transfusion 7.4 (IQR 7.1-7.7) g/dL. Median mitoPO2 values were 55.0 (IQR 49.6-63.0) mmHg before RBC transfusion, 51.0 (IQR 41.5-61.2) directly after and 67.3 (IQR 41.6-83.7) at 24 h after RBC transfusion. Median mitoVO2 values were 3.3 (IQR 2.1-5.9) mmHg/s before RBC transfusion, 3.7 (IQR 2.0-5.1) mmHg/s directly after, and 3.1 (IQR 2.5-4.8) mmHg/s 24 h after RBC transfusion. In the higher Hb concentration group (> 7 g/dL), we saw a dissociation of the effect of RBC transfusion on mitoPO2 versus on mitoVO2 values. MitoPO2 and mitoVO2 values were not associated with commonly used parameters of tissue perfusion and oxygenation. CONCLUSION: RBC transfusion did not alter mitoPO2 and mitoVO2 in critically ill patients with anemia. MitoPO2 and mitoVO2 values were not notably associated with Hb concentrations, parameters of severity of illness and markers of tissue perfusion or oxygenation. Given the high baseline value, it cannot be excluded nor confirmed whether RBC can improve low mitoPO2. Trial registration number NCT03092297 (registered 27 March 2017).

[TCL1-family negative T-cell prolymphocytic leukemia with rapid progression of extranodal disease despite a normal white blood cell count].

Here we describe the case of a 69-year-old man who was found to have moderate thrombocytopenia and severe splenomegaly during a medical checkup at the age of 67. At the first visit, his white blood cell (WBC) count was 7,400/µl with 80% lymphocytes, and bone marrow aspiration showed 24% atypical lymphocytes. Flow cytometry of atypical lymphocytes was positive for mature T-cell markers, and T-cell clonality was revealed by T-cell receptor gene rearrangement. TCL1 was negative on immunohistochemistry. We diagnosed TCL1-family negative T-cell prolymphocytic leukemia (T-PLL) and employed watchful waiting. Thirty months after diagnosis, the patient developed urinary retention and right lower-limb paresis despite a normal WBC count, and an extradural tumor around the thoracic vertebrae and spinal cord compression were detected. The tumor was diagnosed as extranodal involvement of TCL1-family negative T-PLL, but the patient's general condition deteriorated rapidly, and no treatment was possible. T-PLL is a rare disease characterized by leukocytosis, and the WBC count generally increases with disease progression. Although blood counts are recommended for observation, it is important to keep in mind that the disease may worsen even if blood counts do not change.

Association of Red Blood Cell Transfusion Thresholds and Outcomes in Medical Patients with Acute Respiratory Failure Supported with Extra Corporeal Membrane Oxygenation: A Single-Center Retrospective Cohort Study.

BACKGROUND: The hemoglobin value to trigger red blood cell (RBC) transfusion for patients receiving venovenous extracorporeal membrane oxygenation (VV-ECMO) is controversial. Previous guidelines recommended transfusing to a normal hemoglobin, but recent studies suggest more RBC transfusions are associated with increased adverse outcomes. RESEARCH QUESTION: Is implementation of different institutional RBC transfusion thresholds for patients receiving VV-ECMO associated with changes in RBC utilization and patient outcomes? STUDY DESIGN AND METHODS: Single-center retrospective study of patients receiving VV-ECMO using segmented regression to test associations between implementation of institutional transfusion thresholds and trends in RBC utilization. Associations with secondary outcomes, including in-hospital survival, were also assessed. RESULTS: The study included 229 patients: 91 in the "no threshold (NT)" cohort, 48 in the "hemoglobin <8 g/dL (<8 g/dL)" cohort and 90 in the "hemoglobin <7 g/dL (<7 g/dL)" cohort. Despite a decrease in RBC/ECMO day following implementation of different thresholds, (mean +/- SD; 0.6 +/- 1.0 in the NT cohort, 0.3 +/- 0.8 in the <8 g/dL cohort, and 0.3 +/- 1.1 in the <7 g/dL cohort, p < 0.001), segmented regression showed no association between implementation of transfusion thresholds and changes in trends in RBC/ECMO day. We observed an increased hazard of death in the NT cohort compared to the <8 g/dL cohort (aHR: 2.08, 95% CI: 1.12-3.88), and in the <7 g/dL cohort compared to the <8g/dL cohort (aHR: 1.93, 95% CI: 1.02-3.62). There was no difference in the hazard of death between the NT and <7 g/dL cohorts (aHR: 1.08, 95% CI: 0.69-1.69). INTERPRETATION: We observed a decrease in RBC/ECMO day over time, but changes were not associated temporally with implementation of transfusion thresholds. A transfusion threshold of hemoglobin <8 g/dL was associated with a lower hazard of death, but these findings are limited by study methodology. Further research is needed investigating optimal RBC transfusion practices for patients supported with VV-ECMO.

The effect of exercise and disease status on mobilization of anti-tumorigenic and pro-tumorigenic immune cells in women with breast cancer.

Background: Mobilization of certain immune cells may improve the ability of the immune system to combat tumor cells, but the effect of acute exercise on mobilizing immune cells has been sparsely investigated in cancer patients. Therefore, we examined how acute exercise influences circulating immune cells in breast cancer patients. Methods: Nineteen newly diagnosed breast cancer patients aged 36-68 performed 30 minutes of moderate-intensity exercise with a cycle ergometer. Blood samples were collected at various time points: at rest, at 15 (E15) and 30 minutes (E30) after onset of the exercise, and at 30 and 60 minutes post-exercise. We analyzed several immune cell subsets using flow cytometry. Results: Acute exercise increased the number of total leukocytes, neutrophils, lymphocytes, monocytes, basophils, total T-cells, CD4+ T-cells, T helper (Th) 2-cells, Th 17-cells, CD8+ T-cells, CD4-CD8- T-cells, CD56+ natural killer (NK) cells, and CD14-CD16+ monocytes. Many of the changes were transient. Proportions of NK-cells and CD8+ T-cells increased, while the proportion of myeloid derived suppressor cells (MDSCs) reduced, and proportion of regulatory T-cells remained unchanged by exercise. Several associations were detected between cell mobilizations and disease state. For instance, tumor size correlated negatively with NK cell mobilization at E15, and progesterone receptor positivity correlated negatively with CD8+ T-cell mobilization. Conclusion: The findings show that the proportions of CD8+ T-cells and NK cells increased and the proportion of MDSCs proportion decreased in breast cancer patients after 30-minute exercise, suggesting a change in the profile of circulating immune cells towards more cytotoxic/anti-tumorigenic. The mobilization of some immune cells also appears to be related to the disease state.

Evaluating Reduced Blood Monitoring Frequency and the Detection of Hematological Abnormalities in Clozapine-Treated Patients With Schizophrenia: A Chart Review Study From the COVID-19 Pandemic.

BACKGROUND AND HYPOTHESIS: In response to Health Canada's March 2020 directive, patients on clozapine for over 12 months were allowed to extend hematological testing intervals from 4 to 8 weeks during the COVID-19 pandemic. We hypothesized that this change would not affect the timely detection of hematological abnormalities in patients with severe mental illness. STUDY DESIGN: A chart review was conducted of patients at the Royal Ottawa who were prescribed clozapine from March 2019 to March 2021. We analyzed clinical and hematological data from electronic health records and Clozaril Support and Assistance Network database to compare occurrences of hematological abnormalities [leukopenia (white blood cell count <3.5 × 109/L) and agranulocytosis (absolute neutrophil count <0.5 × 109/L)] from March 17, 2020 to March 16, 2021, between standard and extended monitoring protocols using binomial logistic and zero-inflated negative binomial regressions. STUDY RESULTS: Of 621 patients, 196 were on extended blood monitoring, and 425 followed standard blood monitoring. Clozapine dose did not differ between groups (standard: 370 ±â€…201 mg; extended: 352 ±â€…172 mg; P = .14, ds = 0.10). Clozapine treatment duration up to March 2021 was 12.6 ±â€…8.3 years, with the extended group (10 ±â€…7.9 years) having a significantly (P < .01, ds = 0.50) shorter duration than the standard (14 ±â€…8.2 years). Extended monitoring did not significantly impact likelihood of detecting hematological abnormalities (OR = 0.83, 95% CI [0.58,1.41], P = .55) after controlling for age, sex, total bloodwork, and other psychotropics associated with neutrophil counts (ie, valproate, olanzapine). No patient on the extended regimen developed agranulocytosis. CONCLUSIONS: Reducing blood monitoring frequency in patients on clozapine for more than 12 months did not compromise detection of hematological abnormalities.

An outer membrane vesicle specific lipoprotein promotes Porphyromonas gingivalis aggregation on red blood cells.

Porphyromonas gingivalis uses a variety of mechanisms to actively interact with and promote the hydrolysis of red blood cells (RBCs) to obtain iron in the form of heme. In this study, we investigated the function of lipoprotein PG1881 which was previously shown to be up-regulated during subsurface growth and selectively enriched on outer membrane vesicles (OMVs). Our results show that wildtype strain W83 formed large aggregates encompassing RBCs whereas the PG1881 deletion mutant remained predominately as individual cells. Using a PG1881 antibody, immunofluorescence revealed that the wildtype strain's aggregation to RBCs involves an extracellular matrix enriched with PG1881. Our findings discover that RBCs elicit cell aggregation and matrix formation by P. gingivalis and that this process is promoted by an OMV-specific lipoprotein. We propose this strategy is advantageous for nutrient acquisition as well as dissemination from the oral cavity and survival of this periodontal pathogen.

Decoding Endothelial MPL and JAK2V617F Mutation: Insight Into Cardiovascular Dysfunction in Myeloproliferative Neoplasms.

BACKGROUND: Patients with JAK2V617F-positive myeloproliferative neoplasms (MPNs) and clonal hematopoiesis of indeterminate potential face a significantly elevated risk of cardiovascular diseases. Endothelial cells carrying the JAK2V617F mutation have been detected in many patients with MPN. In this study, we investigated the molecular basis for the high incidence of cardiovascular complications in patients with MPN. METHODS: We investigated the impact of endothelial JAK2V617F mutation on cardiovascular disease development using both transgenic murine models and MPN patient-derived induced pluripotent stem cell lines. RESULTS: Our investigations revealed that JAK2V617F mutant endothelial cells promote cardiovascular diseases under stress, which is associated with endothelial-to-mesenchymal transition and endothelial dysfunction. Importantly, we discovered that inhibiting the endothelial TPO (thrombopoietin) receptor MPL suppressed JAK2V617F-induced endothelial-to-mesenchymal transition and prevented cardiovascular dysfunction caused by mutant endothelial cells. Notably, the endothelial MPL receptor is not essential for the normal physiological regulation of blood cell counts and cardiac function. CONCLUSIONS: JAK2V617F mutant endothelial cells play a critical role in the development of cardiovascular diseases in JAK2V617F-positive MPNs, and endothelial MPL could be a promising therapeutic target for preventing or ameliorating cardiovascular complications in these patients.

Erythrocytes of the common carp are immune sentinels that sense pathogen molecular patterns, engulf particles and secrete pro-inflammatory cytokines against bacterial infection.

Introduction: Red blood cells (RBCs), also known as erythrocytes, are underestimated in their role in the immune system. In mammals, erythrocytes undergo maturation that involves the loss of nuclei, resulting in limited transcription and protein synthesis capabilities. However, the nucleated nature of non-mammalian RBCs is challenging this conventional understanding of RBCs. Notably, in bony fishes, research indicates that RBCs are not only susceptible to pathogen attacks but express immune receptors and effector molecules. However, given the abundance of RBCs and their interaction with every physiological system, we postulate that they act in surveillance as sentinels, rapid responders, and messengers. Methods: We performed a series of in vitro experiments with Cyprinus carpio RBCs exposed to Aeromonas hydrophila, as well as in vivo laboratory infections using different concentrations of bacteria. Results: qPCR revealed that RBCs express genes of several inflammatory cytokines. Using cyprinid-specific antibodies, we confirmed that RBCs secreted tumor necrosis factor alpha (TNFα) and interferon gamma (IFNγ). In contrast to these indirect immune mechanisms, we observed that RBCs produce reactive oxygen species and, through transmission electron and confocal microscopy, that RBCs can engulf particles. Finally, RBCs expressed and upregulated several putative toll-like receptors, including tlr4 and tlr9, in response to A. hydrophila infection in vivo. Discussion: Overall, the RBC repertoire of pattern recognition receptors, their secretion of effector molecules, and their swift response make them immune sentinels capable of rapidly detecting and signaling the presence of foreign pathogens. By studying the interaction between a bacterium and erythrocytes, we provide novel insights into how the latter may contribute to overall innate and adaptive immune responses of teleost fishes.

Successful treatment of severe hepatic impairment in erythropoietic protoporphyria: A case report and review of literature.

BACKGROUND: Erythropoietic protoporphyria (EPP) is a rare genetic disorder stemming from ferrochelatase gene mutations, which leads to abnormal accumulation of protoporphyrin IX primarily in erythrocytes, skin, bone marrow and liver. Although porphyria-related severe liver damage is rare, its consequences can be severe with limited treatment options. CASE SUMMARY: This case study highlights a successful intervention for a 35-year-old male with EPP-related liver impairment, employing a combination of red blood cell (RBC) exchange and therapeutic plasma exchange (TPE). The patient experienced significant symptom relief and a decrease in bilirubin levels following multiple PE sessions and an RBC exchange. CONCLUSION: The findings suggest that this combined approach holds promise for managing severe hepatic impairment in EPP.

Temporal Assessment of Protein Stability in Dried Blood Spots.

The use of protein biomarkers in blood for clinical settings is limited by the cost and accessibility of traditional venipuncture sampling. The dried blood spot (DBS) technique offers a less invasive and more accessible alternative. However, protein stability in DBS has not been well evaluated. Herein, we deployed a quantitative LC-MS/MS system to construct proteomic atlases of whole blood, DBSs, plasma, and blood cells. Approximately 4% of detected proteins' abundance was significantly altered during blood drying into blood spots, with overwhelming disturbances in cytoplasmic fraction. We also reported a novel finding suggesting a decrease in the level of membrane/cytoskeletal proteins (SLC4A1, RHAG, DSC1, DSP, and JUP) and an increase in the level of proteins (ATG3, SEC14L4, and NRBP1) related to intracellular trafficking. Furthermore, we identified 19 temporally dynamic proteins in DBS samples stored at room temperature for up to 6 months. There were three declined cytoskeleton-related proteins (RDX, SH3BGRL3, and MYH9) and four elevated proteins (XPO7, RAN, SLC2A1, and SLC29A1) involved in cytoplasmic transport as representatives. The instability was governed predominantly by hydrophilic proteins and enhanced significantly with an increasing storage time. Our analyses provide comprehensive knowledge of both short- and long-term storage stability of DBS proteins, forming the foundation for the widespread use of DBS in clinical proteomics and other analytical applications.

[Chinese expert consensus on the technical and clinical practice specifications of artificial intelligence assisted morphology examination of blood cells (2024)].

Blood cell morphological examination is a crucial method for the diagnosis of blood diseases, but traditional manual microscopy is characterized by low efficiency and susceptibility to subjective biases. The application of artificial intelligence (AI) technology has improved the efficiency and quality of blood cell examinations and facilitated the standardization of test results. Currently, a variety of AI devices are either in clinical use or under research, with diverse technical requirements and configurations. The Experimental Diagnostic Study Group of the Hematology Branch of the Chinese Medical Association has organized a panel of experts to formulate this consensus. The consensus covers term definitions, scope of application, technical requirements, clinical application, data management, and information security. It emphasizes the importance of specimen preparation, image acquisition, image segmentation algorithms, and cell feature extraction and classification, and sets forth basic requirements for the cell recognition spectrum. Moreover, it provides detailed explanations regarding the fine classification of pathological cells, requirements for cell training and testing, quality control standards, and assistance in issuing diagnostic reports by humans. Additionally, the consensus underscores the significance of data management and information security to ensure the safety of patient information and the accuracy of data.

The association of platelet to white blood cell ratio with diabetes: a nationwide survey in China.

Background: Inflammation is integral to diabetes pathogenesis. The novel hematological inflammatory biomarker, platelet to white blood cell ratio (PWR), is linked with various conditions such as chronic kidney disease and stroke. However, the association of this novel clinical indicator with diabetes still remains unclear, which is investigated in this study. Materials and Methods: A total of 10,973 Chinese participants were included and grouped according to the tertiles of PWR (T1, T2, and T3 groups). Diagnosis of prediabetes and diabetes adhered to American Diabetes Association criteria. Binary logistic regression was adopted to assess the relationship between PWR and both diabetes and prediabetes. The dose-response relationship of PWR and diabetes was examined using restricted cubic spline regression. Subgroup and interaction analyses were conducted to investigate potential covariate interactions. Results: Individuals with higher PWR had better lifestyles and lipid profiles (all P < 0.05). After adjusting for all the covariates, the T2 group had a 0.83-fold (95% CI: 0.73-0.93, P < 0.01) risk of diabetes and that for the T3 group was 0.68-fold (95% CI: 0.60-0.78. P < 0.001). Dose-response analysis identified non-linear PWR-diabetes associations in the general population and females (both P < 0.05), but absent in males. Participants with prediabetes in the T2 and T3 groups had lower risks of diabetes (OR = 0.80 for the T2 group, P < 0.001 and 0.68 for the T3 group, P < 0.001) in the full models. All the sensitivity analysis support consistent conclusions. Conclusions: An increase in PWR significantly correlates with reduced diabetes risks. A non-linear PWR-diabetes relationship exists in the general population and females, but not in males. The correlation between PWR and diabetes indicates that PWR holds potentials in early identification and prevention of diabetes.

Sex-specific association of peripheral blood cell indices and inflammatory markers with depressive symptoms in early adolescence.

BACKGROUND: Previous studies have reported the correlation of dysregulated blood cell indices and peripheral inflammatory markers with depression in adults but limited studies have examined this correlation in early adolescents. METHODS: This study used data from the Chinese Early Adolescents Cohort Study, which was conducted in Anhui, China. Students' depression symptoms were repeatedly measured using the Chinese version of the Center for Epidemiological Studies Depression Scale for Children. Students' blood samples were collected in September 2019 and September 2021. The peripheral blood cell counts and inflammatory marker levels were determined using routine blood tests. Multivariate regression models were used to explore the associations between blood cell indices and adolescent depressive symptoms in both the whole sample and the sex-stratified samples. RESULTS: The white blood cell (WBC) count, neutrophil count (NC), platelet (PLT) count, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio, and systemic immune inflammation index (SII) were positively correlated with the severity of depressive symptoms during follow-up. The mean corpuscular volume (MCV), mean hemoglobin (HGB) volume (MCH), and mean corpuscular HGB concentration (MCHC) exhibited a negative temporal correlation with depressive symptoms. Additionally, several sex-specific blood cell markers were correlated with depression. Male adolescents with increased red blood cell (RBC) and female adolescents with decreased HGB levels and upregulated WBC, NC, NLR, and SII levels exhibited severe depressive symptoms at follow-up. CONCLUSIONS: These findings suggested the potential usefulness of peripheral blood cell indices in the assessment of depression in early adolescents.

Detection and clinical application of red blood cell survival. / çº¢ç»†èƒžå¯¿å‘½çš„æ£€æµ‹åŠå ¶ä¸´åºŠåº”ç”¨.

There are 2 techniques for detecting red blood cell survival (RBCS) detection techniques: red blood cell labeling test and carbon monoxide (CO) breath test. The former has disadvantages such as long measurement times and complicated procedures, while the latter is simple, convenient, moderately priced, and capable of dynamically monitoring changes in RBCS before and after treatment. Currently, the CO breath test is gradually being implemented in clinical practice. RBCS is not only applied to hematologic diseases such as multiple myeloma, myelodysplastic syndromes, lymphoma, and thalassemia, but also to non-hematologic diseases like type 2 diabetes and chronic kidney disease. It can assist in diagnosis, guide treatment, evaluate drug treatment efficacy, and predict disease progression.

Immune Response to Molecular Radiotherapy with 177Lu-DOTATOC: Predictive Value of Blood Cell Counts for Therapy Outcome.

Purpose: In a prior, retrospective study, 76% of patients with advanced neuroendocrine tumors undergoing 177Lu-DOTATOC molecular radiotherapy (MRT) showed their best response within 8 months from the first MRT cycle. In 24% of patients, latency was much greater up to >22 months after the first cycle, and long after near-complete decay of 177Lu from the last cycle. An immune response induced by MRT seems a likely explanation. As a crude measure of immunocompetence, the authors investigated whether blood cell counts (BCCs) may have predictive value for MRT outcome with 177Lu-DOTATOC. Methods: 56 Patients with neuroendocrine tumors (NET) were administered 177Lu-DOTATOC (mean 2.1 cycles; range 1-4) with median radioactivity of 7.0 GBq/cycle at 3-month intervals. Patients' BCCs were evaluated for four responder categories: CR, PR, SD, and PD (RECIST 1.1). Furthermore, baseline BCCs were correlated with progression-free survival (PFS). Finally, BCCs of patients with (PMT+) and without prior medical therapy (PMT-) were compared. Results: Significant differences between responder categories were found for baseline hemoglobin (Hb), erythrocytes, neutrophils, lymphocytes, neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and LEHN-score, integrating lymphocyte, erythrocyte, and neutrophil counts, and Hb level, but not for leukocytes and platelets. LEHN-score yielded an almost complete separation between CR and PD groups. In analogy, PFS times showed significant correlations with baseline Hb, erythrocytes, neutrophils, lymphocytes, NLR, PLR, and LEHN-score, the LEHN-score showing the strongest correlation, but not with leukocytes and platelets. For PMT- patients, median PFS was 34.5 months, compared with 20.8 months in PMT+ patients, with corresponding baseline lymphocyte (32.1 ± 9.6% vs. 24.5 ± 11.6%, p = 0.028) and neutrophil (54.9 ± 11.6% vs. 63.5 ± 13.7%, p = 0.039) counts. Conclusion: These findings emphasize the significance of an immune response to MRT for obtaining optimal therapy efficacy and support concepts to enhance the immune response of less immunocompetent patients before MRT. It seems advisable to avoid prior or concomitant immunosuppressant medical therapy.