Anemia and Its Connections to Inflammation in Older Adults: A Review.

Anemia is a common hematological disorder that affects 12% of the community-dwelling population, 40% of hospitalized patients, and 47% of nursing home residents. Our understanding of the impact of inflammation on iron metabolism and erythropoiesis is still lacking. In older adults, anemia can be divided into nutritional deficiency anemia, bleeding anemia, and unexplained anemia. The last type of anemia might be caused by reduced erythropoietin (EPO) activity, progressive EPO resistance of bone marrow erythroid progenitors, and the chronic subclinical pro-inflammatory state. Overall, one-third of older patients with anemia demonstrate a nutritional deficiency, one-third have a chronic subclinical pro-inflammatory state and chronic kidney disease, and one-third suffer from anemia of unknown etiology. Understanding anemia's pathophysiology in people aged 65 and over is crucial because it contributes to frailty, falls, cognitive decline, decreased functional ability, and higher mortality risk. Inflammation produces adverse effects on the cells of the hematological system. These effects include iron deficiency (hypoferremia), reduced EPO production, and the elevated phagocytosis of erythrocytes by hepatic and splenic macrophages. Additionally, inflammation causes enhanced eryptosis due to oxidative stress in the circulation. Identifying mechanisms behind age-related inflammation is essential for a better understanding and preventing anemia in older adults.

Diagnostic and Prognostic Value of Circulating DNA Fragments in Glioblastoma Multiforme Patients.

Novel blood-circulating molecules, as potential biomarkers for glioblastoma multiforme (GBM) diagnosis and monitoring, are attracting particular attention due to limitations of imaging modalities and invasive tissue biopsy procedures. This study aims to assess the diagnostic and prognostic values of circulating cell-free DNA (cfDNA) in relation to inflammatory status in GBM patients and to determine the concentration and average size of DNA fragments typical of tumour-derived DNA fractions. Preoperative plasma samples from 40 patients (GBM 65.0 ± 11.3 years) and 40 healthy controls (HC 70.4 ± 5.4 years) were compared. The cfDNA concentrations and lengths were measured using the electrophoresis platform, and inflammatory indices (NLR, PLR, LMR, and SII) were calculated from complete blood cell analysis. More fragmented cfDNA and 4-fold higher 50-700 bp cfDNA concentrations were detected in GBM patients than in healthy controls. The average cfDNA size in the GBM group was significantly longer (median 336 bp) than in the HC group (median 271 bp). Optimal threshold values were 1265 pg/µL for 50-700 bp cfDNA (AUC = 0.857) and 290 bp for average cfDNA size (AUC = 0.814). A Kaplan-Meier survival curves analysis also demonstrated a higher mortality risk in the GBM group with a cut-off >303 bp cfDNA. This study is the first to have revealed glioblastoma association with high levels of cfDNA > 1000 pg/µL of 50-700 bp in length, which can be aggravated by immunoinflammatory reactivity.

Cytokine Profile in Development of Glioblastoma in Relation to Healthy Individuals.

Cytokines play an essential role in the control of tumor cell development and multiplication. However, the available literature provides ambiguous data on the involvement of these proteins in the formation and progression of glioblastoma (GBM). This study was designed to evaluate the inflammatory profile and to investigate its potential for the identification of molecular signatures specific to GBM. Fifty patients aged 66.0 ± 10.56 years with newly diagnosed high-grade gliomas and 40 healthy individuals aged 71.7 ± 4.9 years were included in the study. White blood cells were found to fall within the referential ranges and were significantly higher in GBM than in healthy controls. Among immune cells, neutrophils showed the greatest changes, resulting in elevated neutrophil-to-lymphocyte ratio (NLR). The neutrophil count inversely correlated with survival time expressed by Spearman's coefficient rs = -0.359 (p = 0.010). The optimal threshold values corresponded to 2.630 × 103/µL for NLR (the area under the ROC curve AUC = 0.831, specificity 90%, sensitivity 76%, the relative risk RR = 7.875, the confidence intervals 95%CI 3.333-20.148). The most considerable changes were recorded in pro-inflammatory cytokines interleukin IL-1ß, IL-6, and IL-8, which were approx. 1.5-2-fold higher, whereas tumor necrosis factor α (TNFα) and high mobility group B1 (HMGB1) were lower in GBM than healthy control (p < 0.001). The results of the ROC, AUC, and RR analysis of IL-1ß, IL-6, IL-8, and IL-10 indicate their high diagnostics potential for clinical prognosis. The highest average RR was observed for IL-6 (RR = 2.923) and IL-8 (RR = 3.151), which means there is an approx. three-fold higher probability of GBM development after exceeding the cut-off values of 19.83 pg/mL for IL-6 and 10.86 pg/mL for IL-8. The high values of AUC obtained for the models NLR + IL-1ß (AUC = 0.907), NLR + IL-6 (AUC = 0.908), NLR + IL-8 (AUC = 0.896), and NLR + IL-10 (AUC = 0.887) prove excellent discrimination of GBM patients from healthy individuals and may represent GBM-specific molecular signatures.

Prognostic Values of Systemic Inflammatory Immunological Markers in Glioblastoma: A Systematic Review and Meta-Analysis.

BACKGROUND: Neutrophils are an important part of the tumor microenvironment, which stimulates inflammatory processes through phagocytosis, degranulation, release of small DNA fragments (cell-free DNA), and presentation of antigens. Since neutrophils accumulate in peripheral blood in patients with advanced-stage cancer, a high neutrophil-to-lymphocyte ratio can be a biomarker of a poor prognosis in patients with glioblastoma. The present study aimed to explore the prognostic value of the preoperative levels of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune inflammation index (SII), systemic inflammation response index (SIRI), and cell-free DNA (cfDNA) to better predict prognostic implications in the survival rate of glioblastoma patients. METHODS: The meta-analysis was carried out according to the recommendations and standards established by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Databases of PubMed, EBSCO, and Medline were systematically searched to select all the relevant studies published up to December 2022. RESULTS: Poorer prognoses were recorded in patients with a high NLR or PLR when compared with the patients with a low NLR or PLR (HR 1.51, 95% CI 1.24-1.83, p < 0.0001 and HR 1.34, 95% CI 1.10-1.63, p < 0.01, respectively). Similarly, a worse prognosis was reported for patients with a higher cfDNA (HR 2.35, 95% CI 1.27-4.36, p < 0.01). The SII and SIRI values were not related to glioblastoma survival (p = 0.0533 and p = 0.482, respectively). CONCLUSIONS: Thus, NLR, PLR, and cfDNA, unlike SII and SIRI, appeared to be useful and convenient peripheral inflammatory markers to assess the prognosis in glioblastoma.

Prognostic Values of Combined Ratios of White Blood Cells in Glioblastoma: A Retrospective Study.

In some malignant tumours, the changes in neutrophil counts in relation to other blood cells are connected with unfavourable prognosis. Nevertheless, the prognostic value of the combinations of the haematological components in glioblastoma (GBM) remains under dispute. The clinical significance of the neutrophil-to-lymphocyte ratio (NLR), systemic immune inflammation index (SII), and systemic inflammation response index (SIRI) was investigated in our study. We retrospectively studied 358 patients (males n = 195; females n = 163) aged 59.9 ± 13.5 yrs with newly diagnosed glioma and admitted to the Neurosurgery Centre. Routine blood tests and clinical characteristics were recorded within the first hour of hospital admission. The inflammatory variables: NLR, SII and SIRI exceeded the reference values and were significantly elevated in Grade 3 and Grade 4 tumour. The Cox model analysis showed that the age ≥ 63 years, NLR ≥ 4.56 × 103/µL, SII ≥ 2003 × 103/µL and SIRI ≥ 3.03 × 103/µL significantly increased the risk of death in Grade 4 tumour patients. In the inflammatory variables, NLR demonstrated the highest impact on the survival time (HR 1.56; 95% CI 1.145-2.127; p = 0.005). In the first Polish study including GBM patients, the age in relation to simple parameters derived from complete blood cell count were found to have prognostic implications in the survival rate.

Inflammatory Predictors of Prognosis in Patients with Traumatic Cerebral Haemorrhage: Retrospective Study.

We aimed to evaluate the relationship between neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR), systemic inflammation index (SII), and Glasgow Coma Scale (GCS) score in patients with traumatic intracerebral haemorrhage (TICH). We retrospectively investigated 95 patients with TICH hospitalised at the Neurosurgery Department in Zielona Gora from January 2017 to March 2021. Routine blood tests were performed 5 h after injury. NRL and SII were significantly higher in patients with GCS ≤ 8 than patients with GCS > 8 and exceeded reference values in 95% of patients. GCS was inversely correlated with NLR and SII. Receiver operating characteristic (ROC) analysis confirmed the value of NLR and SII regarding GCS score; Area Under the Curve (AUC) 0.748, 95% Confidence Interval (CI) 0.615-0.880. An optimised NLR cut-off value of 0.154 was identified with a sensitivity of 0.90 and specificity of 0.56. The value of SII regarding GCS was confirmed with ROC curves; AUC 0.816, 95% CI 0.696-0.935. An optimised NLR cut-off value of 0.118 was identified with a sensitivity of 0.95 and specificity of 0.57. NLR and SII are significantly related to GCS scores and are promising predictors of clinical prognosis in TICH patients.

Multiple Cryotherapy Attenuates Oxi-Inflammatory Response Following Skeletal Muscle Injury.

The oxi-inflammatory response is part of the natural process mobilizing leukocytes and satellite cells that contribute to clearance and regeneration of damaged muscle tissue. In sports medicine, a number of post-injury recovery strategies, such as whole-body cryotherapy (WBC), are used to improve skeletal muscle regeneration often without scientific evidence of their benefits. The study was designed to assess the impact of WBC on circulating mediators of skeletal muscle regeneration. Twenty elite athletes were randomized to WBC group (3-min exposure to -120 °C, twice a day for 7 days) and control group. Blood samples were collected before the first WBC session and 1 day after the last cryotherapy exposure. WBC did not affect the indirect markers of muscle damage but significantly reduced the generation of reactive oxygen and nitrogen species (H2O2 and NO) as well as the concentrations of serum interleukin 1ß (IL-1ß) and C-reactive protein (CRP). The changes in circulating growth factors, hepatocyte growth factor (HGF), insulin-like growth factor (IGF-1), platelet-derived growth factor (PDGFBB), vascular endothelial growth factor (VEGF), and brain-derived neurotrophic factor (BDNF), were also reduced by WBC exposure. The study demonstrated that WBC attenuates the cascade of injury-repair-regeneration of skeletal muscles whereby it may delay skeletal muscle regeneration.

Translation, validation, and cross-cultural adaptation of the Polish version of the pain sensitivity questionnaire.

INTRODUCTION: The purpose of this study was to provide a translation, cross-cultural adaptation, and validation of the Polish language version of the pain sensitivity questionnaire (PSQ). The process followed widely accepted guidelines. METHODS: The translated questionnaire underwent thorough psychometric testing. In total, the data of 144 subjects (mean age 52.53±13 years), who underwent evaluation for lower back pain, were included. RESULTS: The exploratory factor analysis revealed a two-factor structure, PSQ-moderate and PSQ-minor. The internal consistency was good (Cronbach's α was 0.96). There was a fair and significant correlation between the results of the PSQ and the coping strategy questionnaire (CSQ; Spearman's rho was 0.27). The test-retest reliability was favorable, and the intraclass correlation coefficient (ICC) for the CSQ total was 0.93 with a mean interval of 9.04 days between administrations. CONCLUSION: Our results show that the Polish version of the PSQ is valid and can be recommended for Polish-speaking patients.

Steroids in Acute Spinal Cord Injury: All But Gone Within 5 Years.

BACKGROUND: Spinal cord injury (SCI) is a devastating event often leading to poor neurologic outcomes. One of the most widely practiced treatments has been the administration of methylprednisolone. However, today its use has been called into question over concerns of efficacy and safety. The present study evaluated the changes in the practice of steroid administration in acute SCI among members of the National Spinal Society in Poland in comparison with the results of the survey conducted in 2013. METHODS: The questionnaire, comprising 5 questions, was distributed among 240 spinal surgeons, members of the Polish Society of Spinal Surgery; of these, 97 (40%) responded. The results were compared with data from the previous survey conducted in 2013. RESULTS: Over a period of 5 years, the prevalence of steroid administration in acute SCI has completely reversed; the proportion of steroid users declined from 73% to 27%. The main rationale for using it was belief in efficacy, rather than fear of litigation. The differences between specialization and age groups were not statistically significant in both administrations. CONCLUSIONS: A significant decrease was observed in the number of surgeons using steroids in the acute SCI, similar to that reported in the literature. The critical appraisal of the existing clinical evidence, as well as the formulation of guidelines by professional organizations, exerted a profound impact on the practice pattern.

Treatment of lumbar disc herniation with radiculopathy. Clinical practice guidelines endorsed by The Polish Society of Spinal Surgery.

INTRODUCTION: Herniated lumbar disc (HLD) is arguably the most common spinal disorder requiring surgical intervention. Although the term is fairly straightforward, the exact pathology and thus the clinical picture and natural history may vary. Therefore, it is immensely difficult to formulate universal guidelines for surgical treatment. AIM: The aim of this paper is to organize the terminology and clear the inconsistencies in phraseology, review treatment options and gather available published evidence to address the clinical questions to create a set of clinical guidelines in relevant to the topic. METHODS AND RESULTS: Twelve queries, addressing optimal surgical treatment of the HLD have been formulated. The results, based on the literature review are described in the present work. The final product of the analysis was a set of guidelines for the surgical treatment of symptomatic HLD. Categorized into four tiers based on the level of evidence (I-III and X), they have been designed to assist in the selection of optimal, effective treatment leading to the successful outcome. CONCLUSIONS: The evidence based medicine (EBM) is becoming ever more popular among spinal surgeons. Unfortunately this is not always feasible. Lack of uniform guidelines and numerous conflicts of interest introduce flaws in the decision making process. The key role of experts and professional societies is to provide high value recommendation based on the most current literature. Present work contains a set of guidelines for the surgical treatment of HLD officially endorsed by the Polish Spine Surgery Society.

Treatment of degenerative cervical spondylosis with radiculopathy. Clinical practice guidelines endorsed by The Polish Society of Spinal Surgery.

INTRODUCTION: Degenerative cervical spondylosis (DCS) with radiculopathy is the most common indication for cervical spine surgery despite favorable natural history. Advances in spinal surgery in conjunction with difficulties in measuring the outcomes caused the paucity of uniform guidelines for the surgical management of DCS. AIMS: The aim of this paper is to develop guidelines for surgical treatment of DCS. For this purpose the available up-to-date literature relevant on the topic was critically reviewed. METHODS AND RESULTS: Six questions regarding most important clinical questions encountered in the daily practice were formulated. They were answered based upon the systematic literature review, thus creating a set of guidelines. The guidelines were categorized into four tiers based on the level of evidence (I-III and X). They were designed to assist in the selection of optimal and effective treatment leading to the most successful outcome. CONCLUSIONS: The evidence based medicine (EBM) is increasingly popular among spinal surgeons. It allows making unbiased, optimal clinical decisions, eliminating the detrimental effect of numerous conflicts of interest. The key role of opinion leaders as well as professional societies is to provide guidelines for practice based on available clinical evidence. The present work contains a set of guidelines for surgical treatment of DCS officially endorsed by the Polish Spine Surgery Society.