Clinical Characteristics of EGPA Patients in Comparison to GPA Subgroup with Increased Blood Eosinophilia from POLVAS Registry.

Objective: To characterize the eosinophilic granulomatosis with polyangiitis (EGPA) population from the POLVAS registry depending on ANCA status and diagnosis onset, including their comparison with the granulomatosis with polyangiitis (GPA) subset with elevated blood eosinophilia (min. 400/µl) (GPA HE) to develop a differentiating strategy. Methods: A retrospective analysis of the POLVAS registry. Results: The EGPA group comprised 111 patients. The ANCA-positive subset (n = 45 [40.54%]) did not differ from the ANCA-negative one in clinics. Nevertheless, cardiovascular manifestations were more common in ANCA-negative patients than in those with anti-myeloperoxidase (MPO) antibodies (46.97% vs. 26.92%, p = 0.045). Patients diagnosed before 2012 (n = 70 [63.06%]) were younger (median 41 vs. 49 years, p < 0.01), had higher blood eosinophilia at diagnosis (median 4,946 vs. 3,200/µl, p < 0.01), and more often ear/nose/throat (ENT) and cardiovascular involvement. GPA HE comprised 42 (13.00%) out of 323 GPA cases with reported blood eosinophil count. Both GPA subsets had a lower prevalence of respiratory, cardiovascular, and neurologic manifestations but more often renal and ocular involvement than EGPA. EGPA also had cutaneous and gastrointestinal signs more often than GPA with normal blood eosinophilia (GPA NE) but not GPA HE. The model differentiating EGPA from GPA HE, using ANCA status and clinical manifestations, had an AUC of 0.92, sensitivity of 96%, and specificity of 95%. Conclusion: Cardiovascular symptoms were more prevalent in the ANCA-negative subset than in the MPO-ANCA-positive one. Since EGPA and GPE HE share similarities in clinics, diagnostic misleading may result in an inappropriate therapeutic approach. Further studies are needed to optimize their differentiation and tailored therapy, including biologics.

Primary angiitis of the CNS and ANCA-associated vasculitis: from pathology to treatment.

Vasculitis of the central nervous system can be a localized process, such as primary angiitis of the central nervous system (PACNS), or systemic vasculitis, such as ANCA-associated vasculitis (AAV). Since both conditions share neurological manifestations, the following review will discuss the neurological aspects of both. This review aims to provide a comprehensive comparison of the pathogenesis, clinical manifestation and assessment, diagnostic workup, and treatment protocol for both PACNS and AAV with central nervous system involvement. To provide a comprehensive comparison and update, a literature review was conducted using PubMed and Ovid databases (Embase and Medline). Then, the references were retrieved, screened, and selected according to the inclusion and exclusion criteria. PACNS and AAV share similarities in clinical presentation and neurological symptoms, especially in terms of headache, focal deficits, and cognitive impairment. Additionally, both conditions may exhibit similarities in laboratory and radiological findings, making brain biopsy the gold standard for differentiation between the two conditions. Moreover, the treatment protocols for PACNS and AAV are nearly identical. Comparing PACNS and AAV with CNS involvement highlights the similarities in clinical presentation, radiological findings, and treatment protocols between the two conditions. Further research should focus on establishing a practical diagnostic protocol.

Effects of 12 weeks of neuromuscular electrical stimulation of the quadriceps muscles on the function and physio-biochemical traits in functionally fit female nursing-home residents aged 75 + years: a pilot study.

PURPOSE: Muscular changes induced by neuromuscular electrical stimulation (NMES) are well recognized, but knowledge of how NMES influences the physio-biochemical traits of the oldest old is still limited. This study investigated the effect of NMES applied for 12 weeks to the quadriceps muscles of female nursing-home residents aged 75 + on their functional capability and inflammatory, bone metabolism, and cardiovascular traits. METHODS: Nineteen women regularly taking part in two body conditioning sessions per week were randomized into an electrical stimulation group (ES; n = 10; 30 min sessions, 3 times per week) or a control group (CON; n = 9). At baseline and study week 12, all women performed the 30 s chair stand test (30sCST), the 6-minute walk test (6MWT), and the instrumented timed up and go test (iTUG). Resting heart rates, blood pressure, and the blood concentrations of inflammatory and bone metabolism markers were also measured twice. RESULTS: NMES increased the strength of participants' quadriceps muscles and their performance on the 30sCST and 6MWT while lowering resting arterial blood pressure and inflammatory marker levels; osteoclast activity showed a tendency to decrease. Changes in the iTUG results were not observed. A multiple regression analysis found that the results of functional tests in the ES group were best correlated with pulse pressure (the 30sCST and iTUG tests) and diastolic blood pressure (the 6MWT test). CONCLUSION: Twelve weeks of NMES treatment improved participants' functional capacity and inflammatory, bone metabolism, and cardiovascular traits. The ES group participants' performance on functional tests was best predicted by hemodynamic parameters.

SIRT1 and HSP90α feed-forward circuit safeguards chromosome segregation integrity in diffuse large B cell lymphomas.

Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive non-Hodgkin lymphoma in adults, exhibiting highly heterogenous clinical behavior and complex molecular background. In addition to the genetic complexity, different DLBCL subsets exhibit phenotypic features independent of the genetic background. For example, a subset of DLBCLs is distinguished by increased oxidative phosphorylation and unique transcriptional features, including overexpression of certain mitochondrial genes and a molecular chaperone, heat shock protein HSP90α (termed "OxPhos" DLBCLs). In this study, we identified a feed-forward pathogenetic circuit linking HSP90α and SIRT1 in OxPhos DLBCLs. The expression of the inducible HSP90α isoform remains under SIRT1-mediated regulation. SIRT1 knockdown or chemical inhibition reduced HSP90α expression in a mechanism involving HSF1 transcription factor, whereas HSP90 inhibition reduced SIRT1 protein stability, indicating that HSP90 chaperones SIRT1. SIRT1-HSP90α interaction in DLBCL cells was confirmed by co-immunoprecipitation and proximity ligation assay (PLA). The number of SIRT1-HSP90α complexes in PLA was significantly higher in OxPhos- dependent than -independent cells. Importantly, SIRT1-HSP90α interactions in OxPhos DLBCLs markedly increased in mitosis, suggesting a specific role of the complex during this cell cycle phase. RNAi-mediated and chemical inhibition of SIRT1 and/or HSP90 significantly increased the number of cells with chromosome segregation errors (multipolar spindle formation, anaphase bridges and lagging chromosomes). Finally, chemical SIRT1 inhibitors induced dose-dependent cytotoxicity in OxPhos-dependent DLBCL cell lines and synergized with the HSP90 inhibitor. Taken together, our findings define a new OxPhos-DLBCL-specific pathogenetic loop involving SIRT1 and HSP90α that regulates chromosome dynamics during mitosis and may be exploited therapeutically.

High-frequency ultrasound in anti-aging skin therapy monitoring.

Over the last few decades, high-frequency ultrasound has found multiple applications in various diagnostic fields. The fast development of this imaging technique opens up new diagnostic paths in dermatology, allergology, cosmetology, and aesthetic medicine. In this paper, being the first in this area, we discuss the usability of HFUS in anti-aging skin therapy assessment. The fully automated algorithm combining high-quality image selection and entry echo layer segmentation steps followed by the dermal parameters estimation enables qualitative and quantitative evaluation of the effectiveness of anti-aging products. Considering the parameters of subcutaneous layers, the proposed framework provides a reliable tool for TCA-peel therapy assessment; however, it can be successfully applied to other skin-condition-related problems. In this randomized controlled clinical trial, forty-six postmenopausal women were randomly assigned to the experimental and control groups. Women were treated four times at one-week intervals and applied skin cream daily between visits. The three month follow-up study enables measurement of the long-term effect of the therapy. According to the results, the TCA-based therapy increased epidermal (entry echo layer) thickness, indicating that the thinning process has slowed down and the skin's condition has improved. An interesting outcome is the obtained growth in the intensity of the upper dermis in the experimental group, which might suggest a reduced photo-aging effect of TCA-peel and increased water content. The same conclusions connected with the anti-aging effect of TCA-peel can be drawn by observing the parameters describing the contribution of low and medium-intensity pixels in the upper dermis. The decreased share of low-intensity pixels and increased share of medium-intensity pixels in the upper dermis suggest a significant increase in local protein synthesis.

Electrical Stimulation in the Treatment of Pressure Injuries: A Systematic Review of Clinical Trials.

GENERAL PURPOSE: To provide information on evidence-based practice regarding the use of electrical stimulation for pressure injury management. TARGET AUDIENCE: This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest in skin and wound care. LEARNING OBJECTIVES/OUTCOMES: After participating in this educational activity, the participant will:1. Apply clinical practice recommendations related to the use of electrical stimulation in the treatment of pressure injuries.2. Identify issues related to the use of electrical stimulation to treat pressure injuries.

To summarize evidence regarding the use of electrical stimulation for pressure injury (PI) management with a systematic review of randomized clinical trials. The authors searched scientific databases (PubMed, EBSCO, Medline, and Elsevier) and the online resources of gray publications for studies published between January 1, 1980, and June 20, 2021, using the keywords "electrostimulation," "electrical stimulation," "pressure ulcer," "pressure injury," "bedsore," and "decubitus ulcer." The search procedure generated 342 articles. Of these, 241 were disqualified after title screening, 52 after abstract screening, and 33 after full-text review; 16 articles were included in the review. Included articles were full-text reports of randomized clinical trials involving patients with PIs that had at least two patient groups, detailed how wounds healed, and were written in English. The authors extracted information about the purpose and design of each trial, patient inclusion and exclusion criteria, research methods, statistical analysis, findings, and conclusions. Researchers applied high-voltage monophasic pulsed current (HVMPC) in 10 trials, two trials used low-voltage monophasic pulsed current, three trials tested a low-voltage biphasic pulsed current, and one trial used low-intensity direct current. The effect of HVMPC in the treatment of PIs has been most thoroughly investigated in clinical trials. The results are consistent and indicate that HVMPC (twin-peak impulse, 50­154 µs, 100 pps, 45­60 min/d) is effective in PI treatment.

Effect of Physical Activity on Static and Dynamic Postural Balance in Women Treated for Breast Cancer: A Systematic Review.

BACKGROUND: Therapies against breast cancer (BC) frequently involve complications that impair patients' daily function and quality of life, the most common of which are motor coordination and balance disorders, increasing the risk of falls and injuries. In such cases, physical activity is recommended. Designed following the PRISMA guidelines, this study presents a systematic review of randomised and pilot clinical trials investigating the effect of physical exercises on postural balance in women treated for BC. METHODS: Scientific databases (PubMed, EBSCO) and the online resources of grey publications were searched for trial reports published between January 2002 and February 2022. The inclusion criteria necessitated full-text, English-language reports from randomised clinical trials (RCTs) or pilot clinical trials (pilot CTs), whose authors used physical exercises to treat women with BC and the experimental and control groups consisted of at least 10 women. The methodological quality of the RCTs and pilot CTs were measured using the Physiotherapy Evidence Database (PEDro) scale and the Methodological Index for Non-Randomized Studies (MINORS), respectively. Data were extracted on the effect of exercise on the women's static and dynamic balance. RESULTS: Seven reports, five RCTs and two pilot CTs involving a total of 575 women (aged 18-83 years) were included in the systematic review. Their training protocols utilised a variety of aerobic, strength, endurance, sensorimotor, Pilates exercises, and fitness exercises with elements of soccer. The experimental groups usually worked out in fitness or rehabilitation centres under the supervision of physiotherapists or trainers. Training sessions of 30-150 min were held 2 or 3 times a week for 1.5-24 months. Most trials reported that static and dynamic balance in the experimental groups improved significantly more compared with the control groups. CONCLUSIONS: Physical exercises are able to improve static and dynamic postural balance in women treated for BC. However, as all evidence in support of this conclusion comes from only two pilot CT and five RCTs whose methodologies varied widely, more high quality research is needed to validate their findings and determine which exercise protocols are the most effective in improving postural control in women with BC.

Effect of Whole-Body Vibration Training on Selected Intrinsic Risk Factors in Women Aged 60+ at Fall Risk: A Randomized Controlled Trial.

The aim of the study was to determine whether Whole Body Vibration Training (WBVT) affects intrinsic risk factors for falls in women aged 60+ at fall risk. DESIGN: Randomized controlled clinical trial. Blinding was applied to the persons in charge of evaluating the intervention's clinical results and statistical analysis. METHODS: Forty-two women over 60 years old were randomly assigned to an experimental group (EG-12-week WBVT; n = 22) and a control group (CG-no additional physical activities; n = 20). Fear of falling was measured by the FES-I questionnaire, gait and dynamic balance using the Time-Up and Go test (TUG), aerobic endurance with the 6-Minute Walk Test (6MWT), and the functional strength of the lower body muscles with the 30-s Chair Stand Test (30SCST) at baseline and post-intervention. Additionally assayed were participants' blood concentrations of interleukin-6 (IL-6). RESULTS: The 12-week WBVT improves gait and balance (TUG, p = 0.009), exercise tolerance (6MWT, p = 0.001), and functional strength (30SCST; p = 0.027) but does not reduce the intensity of fear of falling (FES-I, p = 0.655) and the IL-6 serum concentration (p = 0.377). CONCLUSIONS: WBVT affects selected fall risk factors in women aged 60+ at fall risk.

Associations Between Selected Biological Features and Absolute and Relative Swimming Performance of Prepubescent Boys Over a 3-Year Swimming Training Program: A Longitudinal Study.

The study aimed to investigate the effect of 3-year swimming training on selected biological variables in prepubescent male swimmers and to determine the best predictors of absolute (VSa) and relative (VSr) swimming velocity for 50 m and 400 m front crawl. Twenty-one 10-year old boys subjected to endurance swimming training (4 x 70 min per week) and 18 boys consisting a control group were assessed semi-annually for basic anthropometric and respiratory characteristics, breath-hold time (BHT), VO2max, leg explosiveness (HJ), and abdominal strength endurance (ASE). After three years of training, BHT (p < 0.001), VO2max (p < 0.01), HJ (p < 0.01) and ASE (p < 0.01) were greater in the swimmers than in the controls. VSa and VSr expressed as a percentage of baseline velocity increased more for the 50 m than for the 400 m distance (p < 0.001 and p < 0.01, respectively). The 50 m VSa and VSr positively correlated with those obtained for the distance of 400 m (in both cases p < 0.001). Baseline VSa was negatively correlated with the increase in absolute swimming velocity for both distances (50 m: r = -0.684, p < 0.001 and 400 m: r = -0.673, p < 0.001). The best predictors of VSa for 50 m and 400 m front crawl were HJ (r2 = 0.388; p < 0.001) and VO2max (r2 = 0.333; p < 0.001), respectively. The key predictors of VSr for both distances were age (50 m: r2 = 0.340, p < 0.001 and 400 m: r2 = 0.207, p < 0.001) and, after excluding it from analysis, HJ (50 m: r2 = 0.176, p < 0.001 and 400 m: r2 = 0.104, p < 0.001). These results suggest that regardless of prepubescent boys' initial abilities and exercise capacity, improvement in their swimming performance mainly depends on increases in power and neuromuscular coordination.

Efficacy and safety of tocilizumab in adult-onset Still's disease: Real-life experience from the international AIDA registry.

BACKGROUND/OBJECTIVES: Long-term efficacy and safety of tocilizumab (TCZ) in adult-onset Still's disease (AOSD) mostly derive from small case series. Herein we report a registry-based study investigating TCZ efficacy and safety in a cohort of patients with AOSD evaluated by clinical and serum inflammatory markers as well as drug retention rate analysis. METHODS: This is an international multicentre study analyzing data from patients with AOSD regularly enrolled in the AIDA registry. TCZ efficacy was evaluated between baseline and last follow-up assessment in terms of changes in the Pouchot score and laboratory findings. Drug-retention rate was estimated by the Kaplan-Meier method, while Cox-regression analysis was employed to detect potential predictive factors of treatment withdrawal. RESULTS: Data from 31 patients (15 men, 16 women) refractory to the conventional therapies and treated with TCZ were extracted from the AIDA registry. Mean ± SD time of treatment duration with TCZ was 24.32 ± 20.57 months. Median (IRQ) Pouchot score significantly decreased throughout the study period (p=0.001) with a significant difference between baseline [2.00 (4.00)] and 6 month-follow-up [0.00 (0.00)] (p=0.003) and between baseline and last follow-up assessment [0.00 (0.00)] (p=0.032), while no differences were observed between 6 month-evaluation and last follow-up assessment (p=0.823). Similarly, laboratory parameters significantly decreased from baseline to the last follow-up visit. With regard to drug survival, cumulative TCZ retention rate at 12-, 24-, and 36-month follow-up visit were 83.1%, 71.7% and 63.7%, respectively, without significant differences between biologic naïve patients and those previously treated with other biologics (p=0.329). Likewise, no significant differences were observed between chronic articular course of AOSD and other types of disease course (p=0.938) or between patients co-administered with conventional immunosuppressants and patients receiving TCZ as monotherapy (p=0.778). Cox-regression analysis identified no variable associated with a higher hazard of treatment withdrawal. Treatment was discontinued in 9 patients due to long-term remission (n=4), adverse events (n=2), loss of efficacy (n=1), non-medical reason (n=1) and unspecified cause (n=1). Mean glucocorticosteroids daily dose significantly decreased from baseline (18.36 ± 24.72 mg) to the last follow-up assessment (4.02 ± 4.99 mg, p=0.003). CONCLUSIONS: TCZ allows control of disease activity as well as normalization of serum inflammatory markers in both systemic and chronic articular form of AOSD. Additionally, TCZ displays an excellent drug retention rate while minimizing the risk of long-term exposure to corticosteroids.

A comparative study of the efficacy of radial and focused shock wave therapy for tennis elbow depending on symptom duration.

INTRODUCTION: In physical therapy, the duration and severity of pain complaints determine the choice of an appropriate physical agent and parameters needed. The aim of this study was to compare the therapeutic efficacy of focused and radial shock waves for tennis elbow with respect to the dysfunction period. MATERIAL AND METHODS: The patients with acute (n = 27) and chronic (n = 31) tennis elbow were randomly assigned to a treatment arm: focused shock wave therapy (3 sessions, 2000 shocks, 4 Hz, 0.2 mJ/mm²) or radial shock wave therapy (3 sessions, 2000 shocks, 8 Hz, 2.5 bar). In order to objectivize therapy effects, the severity of pain complaints (Visual Analog Scale), strength of wrist flexors and extensors and grip strength were assessed. We performed pre-intervention measurements and short-term follow-up at 1, 6 and 12 weeks of therapy completion. RESULTS: At 6 and 12 weeks of therapy completion, all groups exhibited significantly reduced pain complaints (p < 0.05). The most noticeable changes in grip strength, wrist extensors and flexors strength were observed in the affected extremities of all experimental groups while changes within the unaffected extremities were slight. Grip strength as well as the strength of flexor and extensor muscles of the affected limb were significantly greater at 12 weeks of therapy completion compared to pre-intervention values (p < 0.05). At the same time point, percent changes of all study parameters were comparable for all groups (p > 0.05). CONCLUSIONS: Focused and radial shock wave therapy tend to show a significant and comparable short-term therapeutic effect for acute and chronic tennis elbow.

Assessment of Quality of Life and Pain Severity in Older Men with Osteoporosis: Cross-Sectional Study.

BACKGROUND: The quality of life in osteoporosis is studied for men rather than for women. Aim of the study was to determine how bone mass density (BMD) relates to life quality components and the severity of pain felt by men affected by osteoporosis. METHODS: Presented research is a cross-sectional study. The cohort of 62 men aged 65 to 85 years was divided into a group with osteoporosis (N = 27) and a group without osteoporosis (N = 35). The participants' quality of life was measured with the Qualeffo41 Questionnaire, BMD was quantified by densitometry, and pain intensity was assessed on the Visual Analogue Scale. RESULTS: We found that lower BMD was strongly correlated to participants' quality of life (r = -0.72), especially the quality of leisure and social activities (r = -0.66), general health perception (r = -0.59), and mobility (r = -0.57). Pain significantly affected general health perception in older men with osteoporosis. General health assessment and pain were highly correlated with each other (r = 0.888). CONCLUSION: BMD and the overall quality of life of the study participants were related to each other. The strongest relationship occurred between reduced BMD and leisure and social activities component. The pain significantly affected participants' general health perception. The results may be employed to create new prophylactic strategies to improve life quality in men with osteoporosis.

Regulated on Activation, Normal T cell Expressed and Secreted (RANTES) drives the resolution of allergic asthma.

RANTES is implicated in allergic asthma and in T cell-dependent clearance of infection. RANTES receptor family comprises CCR1, CCR3, and CCR5, which are G-protein-coupled receptors consisting of seven transmembrane helices. Infections with respiratory viruses like Rhinovirus cause induction of RANTES production by epithelial cells. Here, we studied the role of RANTES in the peripheral blood mononuclear cells in cohorts of children with and without asthma and validated and extended this study to the airways of adults with and without asthma. We further translated these studies to a murine model of asthma induced by house dust mite allergen in wild-type RANTES and CCR5-deficient mice. Here we show an unpredicted therapeutic role of RANTES in the resolution of allergen-induced asthma by orchestrating the transition of effector GATA-3+CD4+ T cells into immune-regulatory-type T cells and inflammatory eosinophils into resident eosinophils as well as increased IL-10 production in the lung.

Inhibition of PIM Kinases in DLBCL Targets MYC Transcriptional Program and Augments the Efficacy of Anti-CD20 Antibodies.

The family of PIM serine/threonine kinases includes three highly conserved oncogenes, PIM1, PIM2, and PIM3, which regulate multiple prosurvival pathways and cooperate with other oncogenes such as MYC. Recent genomic CRISPR-Cas9 screens further highlighted oncogenic functions of PIMs in diffuse large B-cell lymphoma (DLBCL) cells, justifying the development of small-molecule PIM inhibitors and therapeutic targeting of PIM kinases in lymphomas. However, detailed consequences of PIM inhibition in DLBCL remain undefined. Using chemical and genetic PIM blockade, we comprehensively characterized PIM kinase-associated prosurvival functions in DLBCL and the mechanisms of PIM inhibition-induced toxicity. Treatment of DLBCL cells with SEL24/MEN1703, a pan-PIM inhibitor in clinical development, decreased BAD phosphorylation and cap-dependent protein translation, reduced MCL1 expression, and induced apoptosis. PIM kinases were tightly coexpressed with MYC in diagnostic DLBCL biopsies, and PIM inhibition in cell lines and patient-derived primary lymphoma cells decreased MYC levels as well as expression of multiple MYC-dependent genes, including PLK1. Chemical and genetic PIM inhibition upregulated surface CD20 levels in an MYC-dependent fashion. Consistently, MEN1703 and other clinically available pan-PIM inhibitors synergized with the anti-CD20 monoclonal antibody rituximab in vitro, increasing complement-dependent cytotoxicity and antibody-mediated phagocytosis. Combined treatment with PIM inhibitor and rituximab suppressed tumor growth in lymphoma xenografts more efficiently than either drug alone. Taken together, these results show that targeting PIM in DLBCL exhibits pleiotropic effects that combine direct cytotoxicity with potentiated susceptibility to anti-CD20 antibodies, justifying further clinical development of such combinatorial strategies. SIGNIFICANCE: These findings demonstrate that inhibition of PIM induces DLBCL cell death via MYC-dependent and -independent mechanisms and enhances the therapeutic response to anti-CD20 antibodies by increasing CD20 expression.

The Combined Effect of Neuromuscular Electrical Stimulation and Insulin Therapy on Glycated Hemoglobin Concentrations, Lipid Profiles and Hemodynamic Parameters in Patients with Type-2-Diabetes and Hemiplegia Related to Ischemic Stroke: A Pilot Study.

Type-2-diabetes mellitus (T2DM) is a global problem of medical, social and economic consequences. Physical activity is a vital therapy in patients with T2DM, but some of them cannot exercise for various reasons. The purpose of our pilot study was to determine whether a combination of neuromuscular electrostimulation (NMES) and insulin therapy could improve the management of T2DM patients with hemiplegia caused by an ischemic stroke. Fifteen immobile patients with T2DM on insulin therapy were enrolled in the study. NMES was applied to their lower limbs for 60 min, 5 days a week, over a period of 12 weeks. The intervention caused statistically significant reductions in the blood concentrations of glycated hemoglobin, total cholesterol and low-density cholesterol in the participants. Furthermore, systolic and diastolic blood pressure levels were significantly lower. More randomized clinical trials are needed to accurately measure the effect of NMES on T2DM treatment and to determine whether it can be an alternative for physical activity for immobile patients with T2DM.

Ground reaction force analysis for assessing the efficacy of focused and radial shockwaves in the treatment of symptomatic plantar heel spur.

BACKGROUND: Extracorporeal shock wave therapy is among the conservative treatments for symptomatic heel spur. OBJECTIVE: The purpose of this trial is to evaluate and compare the therapeutic effects of radial shock wave (RSWT) and focused shock wave (FSWT) applied in the treatment of symptomatic heel spur. METHODS: Fifty-five participants were randomly divided into two comparative groups that were administered FSWT and RSWT, respectively. The severity of dysfunction (Foot Function Index, FFI), ground reaction forces (GRF) and walking temporal parameters were measured in all patients at baseline and at weeks 1, 3, 6, 12 and 24 after treatment. RESULTS: In both groups, a gradual decrease in the FFI values occurred after treatment. The percentage reduction in the FFI was comparable for both groups. Statistically significant changes were only noted between some measurements of GRF and walking temporal parameters. The percentage changes in the values of the force and temporal parameters were similar between the groups. CONCLUSIONS: Both FSWT and RSWT are efficacious in the treatment of symptomatic heel spur and their therapeutic effects are comparable. Objective data registered by force platforms during walking are not useful for tracing the progress of treatment applied to patients with symptomatic heel spur between consecutive procedures.

SYK inhibition targets acute myeloid leukemia stem cells by blocking their oxidative metabolism.

Spleen tyrosine kinase (SYK) is an important oncogene and signaling mediator activated by cell surface receptors crucial for acute myeloid leukemia (AML) maintenance and progression. Genetic or pharmacologic inhibition of SYK in AML cells leads to increased differentiation, reduced proliferation, and cellular apoptosis. Herein, we addressed the consequences of SYK inhibition to leukemia stem-cell (LSC) function and assessed SYK-associated pathways in AML cell biology. Using gain-of-function MEK kinase mutant and constitutively active STAT5A, we demonstrate that R406, the active metabolite of a small-molecule SYK inhibitor fostamatinib, induces differentiation and blocks clonogenic potential of AML cells through the MEK/ERK1/2 pathway and STAT5A transcription factor, respectively. Pharmacological inhibition of SYK with R406 reduced LSC compartment defined as CD34+CD38-CD123+ and CD34+CD38-CD25+ in vitro, and decreased viability of LSCs identified by a low abundance of reactive oxygen species. Primary leukemic blasts treated ex vivo with R406 exhibited lower engraftment potential when xenotransplanted to immunodeficient NSG/J mice. Mechanistically, these effects are mediated by disturbed mitochondrial biogenesis and suppression of oxidative metabolism (OXPHOS) in LSCs. These mechanisms appear to be partially dependent on inhibition of STAT5 and its target gene MYC, a well-defined inducer of mitochondrial biogenesis. In addition, inhibition of SYK increases the sensitivity of LSCs to cytarabine (AraC), a standard of AML induction therapy. Taken together, our findings indicate that SYK fosters OXPHOS and participates in metabolic reprogramming of AML LSCs in a mechanism that at least partially involves STAT5, and that SYK inhibition targets LSCs in AML. Since active SYK is expressed in a majority of AML patients and confers inferior prognosis, the combination of SYK inhibitors with standard chemotherapeutics such as AraC constitutes a new therapeutic modality that should be evaluated in future clinical trials.

Remote Ischemic Preconditioning and Contrast-Induced Acute Kidney Injury in Patients Undergoing Elective Percutaneous Coronary Intervention: A Randomized Clinical Trial.

BACKGROUND: Contrast-induced acute kidney injury (CI-AKI) is a common cause of hospital-acquired AKI and a serious complication of percutaneous coronary intervention. OBJECTIVE: The aim of the present study was to assess whether remote ischemic preconditioning (RIPC) reduces the incidence of CI-AKI. METHODS: We conducted a prospective, randomized, sham-controlled clinical study. The study included 101 patients admitted to the Intensive Cardiac Therapy Clinic of Medical University of Lodz for elective percutaneous coronary intervention. The participants were randomly assigned in a 1:1 ratio to either a control group (n = 51) or an RIPC group (n = 50). In the latter, RIPC was achieved before percutaneous coronary intervention by 4 cycles of 5-minute inflation of a cuff on the left upper arm to 200 mm Hg followed by 5-minute deflation. In the control group, a deflated cuff was placed on the left arm for 40 minutes. Serum creatinine concentration was measured to check for the presence of CI-AKI within 48 to 72 hours of percutaneous coronary intervention. Serum neutrophil gelatinase-associated lipocalin level was also measured within 3 hours. RESULTS: CI-AKI occurred in 2 patients from the RIPC group (4%) and 3 patients from the control group (5.9%), but the difference was not significant (P = 0.98). The patients who developed CI-AKI also demonstrated increased serum neutrophil gelatinase-associated lipocalin concentrations (the area under the receiver operator characteristic curve = 0.97; 95% CI, 0.938-1.00; P < 0.00) and the optimal cutoff point value was 118.9 ng/mL. CONCLUSIONS: The use of RIPC before elective percutaneous coronary intervention was not found to prevent CI-AKI. ClinicalTrials.gov identifier: NCT03761368. (Curr Ther Res Clin Exp. 2020; 81:XXX-XXX).

Osteoporosis in Polish Older Women: Risk Factors and Osteoporotic Fractures: A Cross-Sectional Study.

Background: Osteoporosis is a skeletal disease. It is still not known which of the risk factors have the greatest impact on osteoporosis development. The study aimed to determine how the selected osteoporosis risk factors contribute to the development of the disease and to assess the risk of osteoporotic fractures in older women. Methods: A cohort of 99 older females was divided into two groups (with and without osteoporosis). The risk of osteoporosis was determined using assessment forms and bone densitometry data subjected to logistic regression. The risk of osteoporotic fractures was assessed by the FRAX tool (FRAX, Center for Metabolic Bone Diseases, University of Sheffield, UK). Results: The logistic regression analysis showed that the highest risk of developing osteoporosis associated with lifestyle, mainly cigarette smoking (odds ratio: OR = 2.12), past gynecological operations (OR = 1.46), corticosteroid therapies (OR = 1.38). More than half of participants were at a medium risk of femoral neck fractures (over 90% in the osteoporotic group). Conclusion: Most of the Polish women living in care facilities are at medium risk of low-energy fractures. Smoking appeared to have the strongest effect on osteoporosis among analyzed risk factors. The results may contribute to the creation of more appropriate prevention strategies.

Associations between the serum levels of selected bone turnover markers and biological traits in nursing home women aged 80+ without inflammation. A pilot study.

BACKGROUND: Bone turnover markers (BTM) reflect the status of bone remodeling processes responsible for bone mineral density. The existing body of evidence that osseous tissue can interact with many other body tissues and organs suggests that the cross-talks can lead to different relationships. The biological traits associated with BTMs have not been thoroughly studied in the elderly despite bone turnover being known to increase with age. OBJECTIVE: To determine whether the C-terminal crosslinking telopeptides of type I collagen (CTXI) and the serum levels of total (TAP) and bone-specific (BAP) alkaline phosphatase are associated with the biological traits in nursing home women aged 80-92 years without inflammation and, if so, to indicate the best predictors of these BTM's blood concentrations. METHODS: A group of 64 female volunteers aged 80 years and older, the residents of nursing homes, were screened for the study. Fifty two women were ineligible as they met the exclusion criteria. As a result, the study group consisted of 12 participants (85.1 ± 3.9 years; 58.1 ± 8.7 kg; 1.52 ± 0.06 m), all having blood C-reactive protein (CRP) levels below 3 mg/l. Also assessed were the participants' morphology, glucose and insulin levels, lipid profiles, CTXI, TAP, and BAP. Other measured parameters included body composition, resting heart rate and arterial blood pressure, isometric knee extension peak torque (IKEPT), and walking capacity (6-min walk test). The statistical analysis was performed using Pearson's correlation coefficients, the Benjamini-Hochberg procedure, and a stepwise multiple regression analysis with backward elimination. RESULTS: Inverse correlations were found between CTX-I and hemoglobin concentration (HGB) (r = -0.680; p = .015), red blood cells count (RBC) (r = -0.664; p = .019), fat-free mass (r = -0.633; p = .027), body weight (r = -0.589; p = .044), and total cholesterol (r = -0.581; p = .048). The multiple regression analysis of CTX-I showed that body weight was the only independent variable that was statistically significant (r2 = 0.346; p < .05; SEE = 0.347 ng/ml). BAP was positively correlated with double product (DP) (r = 0.742; p = .006), RBC (r = 0.650; p = .022), HGB (r = 0.637; p = .026), mean arterial pressure (MAP) (r = 0.622; p = .031), diastolic blood pressure (DBP) (r = 0.612; p = .034), body height (r = 0.603; p = .038), IKEPT (r = 0.565; p = .056), and systolic blood pressure (SBP) (r = 0.538; p = .071). BAP, a dependent variable, was the most closely correlated with DP (r2 = 0.550; p < .01; SEE = 9.161 U/l). TAP was also significantly associated with DP (r = 0.775; p = .003), with the association being stronger than between BAP and DP (r2 = 0.600; p < .01; SEE = 1000.5 beats/min*mm Hg). CONCLUSIONS: In relatively healthy the oldest-old nursing home women without inflammation, total body weight was the best predictor of bone resorption shown by the CTX-I concentration, whereas the rate pressure product (DP) turned out to best predict osteoblastic activity determinable from serum alkaline phosphatase activity. The results of the study suggest that the activity of serum TAP and BAP can be enhanced by different mechanisms.