Search

Numerous studies have shown that vitamin D may play an important role in modulating the inflammatory process. This study aimed to evaluate the effect of vitamin D supplementation on inflammatory markers in patients with orthopedic disorders and obesity. Thirty-three obese subjects were included in the study and were divided into two groups based on their medical condition: acute orthopedic diseases and chronic orthopedic diseases. Inclusion criteria for the research included age 18-75 years, BMI > 30 kg/m 2 , vitamin D deficiency, and no previous vitamin D supplementation. Samples were collected before and after 3 months of 4000 IU/day vitamin D supplementation. The study used enzyme-linked immunosorbent assay (ELISA) and measured serum levels of markers such as chitinase-3-like protein 1 (YKL-40), interleukin 6 (IL-6), interleukin 17 (IL-17), tumor necrosis factor (TNF-α), and adiponectin. After 3 months of vitamin D supplementation, a statistically significant increase in vitamin D and IL-17 levels was observed in the group with acute orthopedic diseases. Similarly, after supplementation, a statistically significant increase in vitamin D, IL-6 and TNF-α levels was observed in the group with chronic orthopedic diseases. Moreover, after vitamin D supplementation, statistically significantly higher adiponectin levels were observed in the chronic orthopedic group than in the acute orthopedic group. Despite high-dose vitamin D supplementation, inflammatory markers increased in acute and chronic orthopedic conditions. Based on our study, vitamin D does not reduce inflammation in patients with orthopedic conditions and obesity.

Objectives: The purpose of this study was to determine the correlation between microscopic degeneration in the long head of the biceps tendon (LHBT) and the apoptotic process. Methods: This study included 26 consecutive patients who had undergone arthroscopic biceps tenodesis or tenotomy for symptomatic LHBT with or without concomitant rotator cuff tears (RCTs). Histological examination of the specimens under a light microscope was conducted after staining with hematoxylin, eosin, and the Alcian blue. Histopathological changes were assessed using the original Bonar score and the modified Bonar score and then correlated with the expression of the subsequent apoptosis markers: activated caspase-3 (casp3), tumor protein p53 (p53), and B-cell lymphoma 2 (BCL-2). Results: The mean original Bonar score was 8.65 (range 5-11), while the modified Bonar score was 7.61. There was no correlation between the original Bonar score and the age of the patients, but a positive correlation was found between the modified Bonar score and the age of the patients ( p = 0.0022). There was no correlation between the age of patients and the expression indexes of BCL-2 and casp3. However, the expression of the p53 index showed a positive correlation with patient aging ( p = 0.0441). Furthermore, there was no correlation observed between the expression of apoptotic indexes and both the original and modified Bonar scale. Conclusions: In LHB tendinopathy, the expression of apoptosis does not seem to directly correlate with the extent of degeneration, particularly in the late stages of tendinopathy. However, the transformations observed in collagen and ground substance were significantly associated with age, as well as tendinous tissue degeneration quantified according to modified Bonar score. The age of patients was also linked with the expression of the p53 index, as an increased apoptosis in the studied population.

Cyclin F (encoded by CCNF gene) has been reported to be implicated in the pathobiology of several human cancers. However, its potential clinical significance in clear cell renal cell carcinoma (ccRCC) remains unknown. The present study aimed to evaluate the potential significance of cyclin F, assessed by immunohistochemical (IHC) staining and molecular (bioinformatics) techniques, as a prognostic marker in ccRCC in relation to clinicopathological features and outcomes. IHC staining was performed using two independent ccRCC tissue array cohorts, herein called tissue macroarray (TMA)_1 and tissue microarray (TMA)_2, composed of 108 ccRCCs and 37 histologically normal tissues adjacent to the tumor (NAT) and 192 ccRCCs and 16 normal kidney samples, respectively. The mRNA expression data were obtained from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) public datasets, followed by bioinformatics analysis of biological mechanisms underlying prognosis. The relationship between immune cell infiltration level and CCNF expression in ccRCC was investigated using the Tumor Immune Estimation Resource 2.0 (TIMER2) and Gene Expression Profiling Interactive Analysis 2 (GEPIA2). Cyclin F expression was significantly elevated in ccRCC lesions compared to both NAT and normal renal tissues. Likewise, CCNF mRNA was markedly increased in ccRCCs relative to non-cancerous tissues. In all analyzed cohorts, tumors with features of more aggressive behavior were more likely to display cyclin F/CCNF-high expression than low. Furthermore, patients with high cyclin F/CCNF expression had shorter overall survival (OS) times than those with low expression. In addition, multivariable analysis revealed that cyclin F/CCNF-high expression was an independent prognostic factor for poor OS in ccRCC. Enrichment analysis for mechanistically relevant processes showed that CCNF and its highly correlated genes initiate the signaling pathways that eventually result in uncontrolled cell proliferation. CCNF expression was also correlated with immune cell infiltration and caused poor outcomes depending on the abundance of tumor-infiltrating immune cells in ccRCC. Our findings suggest that cyclin F/CCNF expression is likely to have an essential role in ccRCC pathobiology through regulating multiple oncogenic signaling pathways and affecting the tumor immune microenvironment and may serve as prognostic biomarker and promising therapeutic target in ccRCC., (© 2024. The Author(s).)

Background and Objectives : The objective of this retrospective study was to investigate the association between acetabulum fractures; the mechanism of injury; and variables such as BMI, duration of hospital stay, blood loss, and surgery time. By exploring these factors, we aim to enhance our understanding of them and their impact on the healing process and the subsequent management of pelvic fractures. Materials and Methods : This study included 67 of 136 consecutive patients who were admitted for pelvic ring fracture surgery between 2017 and 2022. The data were collected prospectively at a single trauma center. The inclusion criteria were acetabulum fractures and indications for operative treatment. The exclusion criteria were non-operative treatment for acetabular and pelvic ring fractures, fractures requiring primary total hip arthroplasty (THA), and periprosthetic acetabular fractures. Upon admission, all patients underwent evaluation using X-ray and computed tomography (CT) scans of the pelvis. Results : The present study found no statistically significant differences between the examined groups of patients with pelvic fractures in terms of BMI, surgery duration, length of hospital stay, and blood transfusion. However, two notable findings approached statistical significance. Firstly, patients who experienced a fall from height while sustaining a pelvic fracture required a higher number of blood transfusions (2.3 units) than those with other mechanisms of injury which was close to achieving statistical significance ( p = 0.07). Secondly, patients undergoing posterior wall stabilization required a significantly lower number of blood transfusions than those with other specific pelvic injuries (0.33 units per patient), approaching statistical significance ( p = 0.056). Conclusions : The findings indicated that factors such as BMI, time of surgery, blood loss, and the duration of hospital stay were not directly correlated with the morphology of acetabular fractures, the presence of additional trauma, or the mechanism of injury. However, in the studied group, the patients whose mechanism of trauma involved falling from height had an increased number of blood transfusions compared to other groups. Moreover, the patients who had surgery due to posterior wall acetabulum fracture had decreased blood transfusions compared to those with other Judet and Letournel types of fractures. Additionally, they had the shortest duration of surgery.

Background and Objectives : The negative effects of smoking on the musculoskeletal system were presented by many authors, although the relationship between smoking and osteoarthritis remains unclear. The aim of this paper was to investigate the negative effects of smoking on meniscal tissue in osteoarthritic knees by microscopic examination, by adapting the Bonar scoring system and its modifications. Materials and Methods : The study involved 34 patients with varus knees, from whom 65 samples of knee menisci were obtained. The mean age in the studied group was 65.385 years. The smoking status of the patients concluded that there were 13 smokers and 21 nonsmokers. Results : Among smokers, the mean classical Bonar score was 8.42 and the mean modified Bonar score was 6.65, while nonsmokers were characterized by scores of 8.51 and 7.35, respectively. There was a statistically significant negative correlation between the number of cigarettes and the collagen in the medial meniscus ( p = 0.0197). Moreover, in the medial meniscus, the modified Bonar score correlated negatively with the number of cigarettes ( p = 0.0180). Similarly, such a correlation was observed between the number of cigarettes and the modified Bonar score in the lateral meniscus ( p = 0.04571). Furthermore, no correlation was identified between the number of cigarettes and the classical Bonar score in the lateral meniscus. There was a statistically significant difference in the collagen variable value between the smokers and nonsmokers groups ( p = 0.04525). Conclusions : The microscopic investigation showed no differences in the menisci of smokers and nonsmokers, except for the collagen, which was more organized in smokers. Moreover, the modified Bonar score was correlated negatively with the number of cigarettes, which supports the role of neovascularization in meniscus pathology under the influence of tobacco smoking.

Background: The substances present in cigarette smoke have a negative impact on cellular integrity and metabolism, can reduce blood flow to tissues, and can disrupt collagen synthesis. Ultimately this can lead to cell death, which clinically may result in impaired tendon healing and the onset of chronic tendinopathy. Within the shoulder, the exact association between the extent of apoptosis in the long head of the biceps (LHB) tendon and harmful factors like cigarette smoke remains unclear., Objectives: The purpose of this study was to investigate the connection between smoking, the degree of apoptosis in LHB tendinopathy, and the long-term outcomes of surgical treatment., Design: Observational, retrospective study., Methods: This study included 22 consecutive patients who had undergone arthroscopic biceps tenodesis or tenotomy for symptomatic LHB tendinopathy with or without concomitant rotator cuff tears (RCT). The intra-articular LHB tendon remnants were histologically examined by measuring the level of expression of apoptotic cell markers such as BCL2, cleaved caspase 3, and p53. Pre- and postoperative clinical outcomes were analyzed by collecting patient report outcome measures such as the American Shoulder and Elbow Surgeons (ASES) score and the Visual Analogue Scale (VAS) for pain., Results: The smokers group had a mean pack-year history of 13.12 (SD = 9.94), mean number of cigarettes per day of 14.77 (SD = 4.64), and a mean smoking duration of 16.38 (SD = 10.1) years. Among the smoking indexes, the number of cigarettes per day showed a positive correlation with Snyder classification ( p = 0.0459, rho = 0.3682). Non-smokers and smokers did not show a statistically significant difference in the expression indexes of BCL2, cleaved caspase 3, or p53 ( p = 0.4216, p = 0.5449, p = 0.5613, respectively). However, the cleaved caspase 3 expression index showed a negative correlation with the severity of rotator cuff lesions in the total population ( p = 0.0193, rho = -0.4651)., Conclusions: While apoptotic processes in the LHB tendon were observed, no significant association was found between tobacco smoking, the extent of apoptosis, and clinical outcomes. However, the expression of the apoptotic marker cleaved caspase 3 correlated with the severity of rotator cuff pathology. Furthermore, active smoker status was associated with worse clinical outcomes in terms of pain following LHB tenodesis or tenotomy.

Withania somnifera , also known as Ashwagandha, has been used in traditional medicine for thousands of years. Due to the wide range of its activities, there has been interest in its possible beneficial effects on the human body. It is proved that, among others, Ashwagandha has anti-stress, anti-inflammatory, antimicrobial, anti-cancer, anti-diabetic, anti-obesity, cardioprotective, and hypolipidemic properties. Particularly interesting are its properties reported in the field of psychiatry and neurology: in Alzheimer's disease, Parkinson's disease, multiple sclerosis, depression, bipolar disorder, insomnia, anxiety disorders and many others. The aim of this review is to find and summarize the effect that Ashwagandha root extract has on the endocrine system and hormones. The multitude of active substances and the wide hormonal problems faced by modern society sparked our interest in the topic of Ashwagandha's impact on this system. In this work, we also attempted to draw conclusions as to whether W. somnifera can help normalize the functions of the human endocrine system in the future. The search mainly included research published in the years 2010-2023. The results of the research show that Ashwagandha can have a positive effect on the functioning of the endocrine system, including improving the secretory function of the thyroid gland, normalizing adrenal activity, and multidirectional improvement on functioning of the reproductive system. The main mechanism of action in the latter appears to be based on the hypothalamus-pituitary-adrenal (HPA) axis, as a decrease in cortisol levels and an increase in hormones such as luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in men were found, which results in stress level reduction and improvement in fertility. In turn, other studies prove that active substances from W. somnifera , acting on the body, cause an increase in the secretion of triiodothyronine (T3) and thyroxine (T4) by the thyroid gland and a subsequent decrease in the level of thyroid-stimulating hormone (TSH) in accordance with the hypothalamus-pituitary-thyroid (HPT) axis. In light of these findings, it is clear that Ashwagandha holds significant promise as a natural remedy for various health concerns, especially those related to the endocrine system. Future research may provide new insights into its mechanisms of action and expand its applications in both traditional and modern medicine. The safety and toxicity of Ashwagandha also remain important issues, which may affect its potential use in specific patient groups.

Objective: the aim of this study was to document the occurrence of THA after acetabulum surgery and examine the factors that predict its occurrence., Methods: This study included 77 consecutive patients who were admitted for acetabulum fracture surgery between 2012 and 2019. The inclusion criteria were acetabular fractures and indications for operative management. The exclusion criteria were acetabular fractures treated non-operatively, fractures requiring primary THA, and periprosthetic acetabular fractures. Data concerning demographics, date of injury, date of surgery, surgical approach, stabilization, and further reconstructive surgery were collected retrospectively. The number of patients who underwent THA and their risk factors were recorded. The minimum follow-up for each patient was 2 years of observation. A total of 77 patients with a mean age of 53 years were included., Results: At a mean follow-up of 2 years, THA was performed in 16 (20.8%) patients due to post-traumatic arthritis. An analysis of the surgical approaches showed that the Kocher-Langenbeck approach increased the risk of THA nearly 12 times compared with the ilioinguinal approach ( p = 0.016). Furthermore, the duration of the waiting period for surgery significantly impacted the occurrence of THA, with each additional day leading to an 89% increase in the risk of prosthesis usage ( p = 0.001)., Conclusions: This study suggests that acetabular fractures may lead to post-traumatic hip osteoarthritis. The surgical approach and the waiting time for surgery are potential factors that may predict secondary hip osteoarthritis and the need for subsequent THA. However, further investigations should be performed to establish predictors for secondary hip osteoarthritis, and especially to determine the impact of the surgical approach.

Sirtuins are a family of proteins with enzymatic activity. There are seven mammalian sirtuins (SIRT1-SIRT7) that are found in different cellular compartments. They are a part of crucial cellular pathways and are regulated by many factors, such as chemicals, environmental stress, and phytochemicals. Several in vitro and in vivo studies have presented their involvement in anti-inflammatory, antioxidant, and antiapoptotic processes. Recent findings imply that phytochemicals such as resveratrol, curcumin, quercetin, fisetin, berberine, and kaempferol may regulate the activity of sirtuins. Resveratrol mainly activates SIRT1 and indirectly activates AMPK. Curcumin influences mainly SIRT1 and SIRT3, but its activity is broad, and many pathways in different cells are affected. Quercetin mainly modulates SIRT1, which triggers antioxidant and antiapoptotic responses. Fisetin, through SIRT1 regulation, modifies lipid metabolism and anti-inflammatory processes. Berberine has a wide spectrum of effects and a significant impact on SIRT1 signaling pathways. Finally, kaempferol triggers anti-inflammatory and antioxidant effects through SIRT1 induction. This review aims to summarize recent findings on the properties of phytochemicals in the modulation of sirtuin activity, with a particular focus on biochemical aspects.

Cannabis-derived therapies are gaining popularity in the medical world. More and more perfect forms of cannabinoids are sought, which could be used in the treatment of many common diseases, including metabolic syndrome, whose occurrence is also increasing. The purpose of this review was to investigate the usefulness of cannabinoids, mainly cannabidiol (CBD), in individuals with obesity, impaired glucose and lipid metabolism, high blood pressure, and non-alcoholic fatty liver disease (NAFLD). We summarised the most recent research on the broad topic of cannabis-derived influence on metabolic syndrome components. Since there is a lot of work on the effects of Δ9-THC (Δ9-tetrahydrocannabinol) on metabolism and far less on cannabidiol, we felt it needed to be sorted out and summarised in this review. The research results on the use of cannabidiol in obesity are contraindicatory. When it comes to glucose homeostasis, it appears that CBD maintains it, sensitises adipose tissue to insulin, and reduces fasting glucose levels, so it seems to be a potential target in this kind of metabolic disorder, but some research results are inconclusive. CBD shows some promising results in the treatment of various lipid disorders. Some studies have proven its positive effect by decreasing LDL and increasing HDL as well. Despite their probable efficacy, CBD and its derivatives will likely remain an adjunctive treatment rather than a mainstay of therapy. Studies have also shown that CBD in patients with hypertension has positive effects, even though the hypotensive properties of cannabidiol are small. However, CBD can be used to prevent blood pressure surges, stabilise them, and have a protective effect on blood vessels. Results from preclinical studies have shown that the effect of cannabidiol on NAFLD may be potentially beneficial in the treatment of the metabolic syndrome and its components. Nevertheless, there is limited data on CBD and NAFLD in human studies. Because of the numerous confounding factors, the conclusions are unclear, and more research in this field is required., Competing Interests: The authors declare no conflict of interest.

The phenomena of ischemia and reperfusion are associated with the pathological background of cardiovascular diseases. Ischemia is initiated by ischemia reperfusion injury (IRI), which involves disruption of intracellular signaling pathways and causes cell death. The aim of this study was to assess the reactivity of vascular smooth muscle cells in the conditions of induced ischemia and reperfusion, and to determine the mechanisms leading to contractility disorders. This study was conducted using classical pharmacometric methods on an isolated model of the rat caudal artery. The experiment consisted of the analysis of the final and initial perfusate pressure measurements after induction of arterial contraction with phenylephrine in the presence of forskolin and A7 hydrochloride, two ligands modifying the contractility of vascular smooth muscle cells (VSMC). The pharmacometric analysis showed that in simulated reperfusion, cyclic nucleotides have a vasoconstrictive effect, and calmodulin has a vasodilating effect. The responsiveness of vascular smooth muscle cells to the vasopressor effects of α1-adrenomimetics during reperfusion may change uncontrollably, and the effects of secondary messengers may be counter physiological. Further studies are needed to evaluate the function of other second messengers on VSMCs in the process of ischemia and reperfusion.

This retrieval study included 43 Biolox delta explants (18 CoC, 25 CoP). Implants were examined macroscopically, whereby damage was evaluated using a semi quantitative scoring system. Confocal microscopy was used to examine wear related damage patterns of the articulating surfaces. Scanning electron microscopy (SEM) with energy-dispersive X-ray spectroscopy (EDS) was used to analyze wear marks on the implant surface and wear debris in periprosthetic tissue samples. Raman spectroscopy and X-ray diffraction (XRD) were used to quantify monoclinic zirconia fractions. On all components, in vivo wear resulted predominantly in different damage patterns caused by metal transfer. In CoC bearings stripe wear was additionally detected, and some implants underwent severe damage due to component breakage. The wear scores were higher for CoC components, with no differences between the scores for CoC heads and liners. Wear features caused comparable roughening on implants from CoC and CoP bearings. SEM studies demonstrated that most wear marks were caused by metal debris released from implant components. Grain pull-out was observed in stripe wear regions. Monoclinic phase shift was observed in a similar quantity on components from CoP and CoC bearings. The increase of monoclinic zirconia content around metal deposits was minimal and was more pronounced in areas of stripe wear. The results of this study indicate, that ZTA components in general undergo minimal wear in both, CoC and CoP bearings, however, it is more pronounced in the former. Metal deposits, as the most common wear feature, have no significant effect on monoclinic phase transition. STATEMENT OF SIGNIFICANCE: In this paper, we classify all damage patterns macroscopically according to an established scoring system and assess them regarding surface roughness (confocal microscopy) and monoclinic phase content (Raman spectroscopy) in order to derive the severity for patients. We compare hard-hard and hard-soft bearings and relate damage patterns with metal transfer based on SEM/EDS examinations. Furthermore, we work out correlations between patient-specific data, cause of revision and the physical condition of each individual sample Our cohort consists of 43 Biolox delta retrievals, a comparatively large quantity. In addition, we address current topics such as metal transfer and, based on the classification of damage patterns, provide incentives and/or meaningful focal points for further research., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Ltd.)

Background: An abnormally high body mass index is strongly associated with knee osteoarthritis. Usually, obese patients are excluded from clinical trials involving PRP intra-articular injections. Growth factors have been demonstrated to have a disease-modifying effect on KOA treatment, even though data on their influence on treatment effectiveness in obese patients are lacking., Purpose: To prospectively compare the level of selected growth factors including transforming growth factor-b (TGF-β), epidermal growth factor (EGF), fibroblast growth factor, insulin-like growth factor-1 (IGF-1), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and fibroblast growth factor-2 (FGF-2) in platelet-rich plasma (PRP) in obese patients and patients with normal BMI., Methods: A total of 49 patients were included in the study according to inclusion and exclusion criteria. The groups strongly differed in body mass index (median values 21.6 vs. 32.15). Concentrations of growth factors were measured with an enzyme-linked immunosorbent assay. Statistical significance was determined with the Mann-Whitney U test. The compliance of the distribution of the results with the normal distribution was checked using the Shapiro-Wilk test separately for both groups., Results: There were no statistically significant differences in median marker levels between groups. Statistically significant Pearson correlations were observed between IGF-1 serum level and age (weak negative, r = -0.294, p = 0.041) and gender (moderate positive, r = 0.392, 0.005)., Conclusions: BMI does not influence the level of selected growth factors in patients with knee osteoarthritis. Obese and non-obese patients had similar compositions of PDGF, TGF-β, EGF, FGF-2, IGF-1, and VEGF. PRP can be used in both groups with similar effects associated with growth factors' influence on articular cartilage., Competing Interests: The authors declare no conflict of interest.

Routine resection of the infrapatellar fat pad (IFP) during total knee arthroplasty (TKA) is controversial, as it may result in shortening of the patellar tendon (PT) and anterior knee pain. This prospective study examined whether IFP excision during TKA affects joint function, anterior knee pain, PT dimensions and sonographic structure. A total of 65 consecutive patients undergoing TKA for osteoarthritis were randomized into two groups: IFP was resected in one and retained in the other. Patients were examined preoperatively, at 6 weeks and 6 months postoperatively: pain (Numerical Rating Scale-NRS), range of motion (ROM) and knee function (Knee Injury and Osteoarthritis Outcome Score-KOOS score) were evaluated; sonographic examination determined the length, structure and vascularity of the PTs. In both groups there were postoperative improvements in NRS and KOOS scores, although IFP resection did not influence clinical outcomes or sonographic parameters. At 6 weeks and 6 months postoperatively for both groups there were no differences between NRS scores (Mann-Whitney test, p = 0.511 and p = 0.579), ROM scores (Mann-Whitney test, p = 0.331, p = 0.180) or all KOOS subscores. IFP excision had no effect on sonographic parameters. This study suggests that IFP resection during TKA does not influence postoperative functional outcomes, pain scores, patellar tendon length and thickness, or sonographic structure.

Complete loss of the meniscus inevitably leads to knee joint degeneration. Smoking is an important factor predicting poor outcome in orthopedics; however, data about its role in meniscus surgery are inconclusive. Smoking could be an important negative factor in isolated meniscus repair. The aim of this paper was to determine the influence of smoking on functional outcomes after isolated all-inside medial meniscus repair. This study included 50 consecutive patients with isolated, traumatic tear of the medial meniscus who underwent knee joint arthroscopy between 2016 and 2019. All-inside arthroscopic repair of the medial meniscus was performed in each case. All patients followed a uniform, postoperative rehabilitation protocol for 8 weeks. The follow-up examination was based on the functional scores at 3 and 6 months postoperatively. According to smoking status there were 17 smokers and 33 non-smokers. The mean number of cigarettes smoked per day was 11, for a mean of 7.4 years, and the mean pack-years index value was 4.9. There was no correlation between smoking years, number of cigarettes smoked per day, pack-years index, and functional outcomes. The arthroscopic inspection of the knee joints revealed cartilage lesions (≤IIº) in eight subjects, suggesting the secondary pathology to the meniscus tear. In this study, we found no evidence of an association between smoking indices and functional outcomes after all-inside repair of chronic medial meniscus tear. The nature of the chronic meniscal tear could be smoking-resistant owing to the poor blood supply to the sites in which these specific lesions occur.

Purpose: To prospectively compare the efficacy and safety of intra-articular injections of platelet-rich plasma (PRP) with hyaluronic acid (HA) and glucocorticosteroid (CS) control groups for knee osteoarthritis (KOA) in a randomized, triple-parallel, single-center clinical trial. Methods: A total of 75 patients were randomly assigned to one of three groups receiving a single injection of either leukocyte-poor platelet-rich plasma (25 knees), hyaluronic acid (25 knees), or glucocorticosteroid (25 knees). The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score was collected at baseline and 6, 12, and 26 weeks after treatment. Results: After 6 weeks of PRP administration, a decrease in the mean WOMAC value was observed in all three study groups. Three months after administration, the greatest decrease in the mean WOMAC value was obtained in the PRP group. The results in the HA and CS groups were similar (p = 0.681). In the one-way analysis of variance and post hoc analysis using the HSD Tukey test, a significantly greater improvement was shown by comparing the PRP and CS groups (p = 0.001), and the PRP and HA groups (p = 0.010). After intra-articular injection of CS, the reduction in pain was greatest 6 weeks after administration, and the mean value was the lowest among all groups. During subsequent visits, the value of the pain subscale increased, and after 6 months, it was the highest among the studied groups. Using the Wilcoxon paired test, no PRP effect was found to reduce stiffness at the 6-month follow-up (p = 0.908). Functional improvement was achieved in all groups, i.e., a decrease in the value of this subscale 6 months after administration. The largest decrease was seen in the group that received PRP (p < 0.001) and then in the HA group. The smallest decrease among the investigated methods was shown in the CS group. Conclusions: Intra-articular injections of PRP can provide clinically significant functional improvement for at least 6 months in patients with mild to moderate KOA which is superior to HA or CS injections.

Tumor necrosis factor α (TNFα) is one of the most important proinflammatory cytokines, which affects many processes associated with the growth and characteristics of endothelial, smooth muscle, and immune system cells. However, there is no correlation between most in vivo and in vitro studies on its role in endothelial cell proliferation and migration. In this study, we examined the effect of recombinant human (rh) TNFα produced in HEK293 cells on primary human coronary artery endothelial cells (pHCAECs) in the context of F-actin organization and such processes as migration and adhesion. Furthermore, we evaluated the possibility of the inhibition of the endothelial inflammatory response by the CRISPR-based regulation of TPM1 gene expression. We showed that TNFα-induced activation of pHCAECs was related to the reorganization of the actin cytoskeleton into parallel-arranged stress fibers running along the longer axis of pHCAECs. It allowed for the directed and parallel motion of the cells during coordinated migration. This change in F-actin organization promoted strong but discontinuous cell-cell contacts involved in signalization between migrating cells. Moreover, this form of intercellular connections together with locally increased adhesion was related to the formation of migrasomes and further migracytosis. Stabilization of the actin cytoskeleton through the CRISPR-based activation of endogenous expression of TPM1 resulted in the inhibition of the inflammatory response of pHCAECs following treatment with rh TNFα and stabilization of cell-cell junctions through reduced cleavage of vascular endothelial cadherin (VE-cadherin) and maintenance of the stable levels of α- and β-catenins. We also showed that CRISPR-based activation of TPM1 reduced inflammatory activation, proliferation, and migration of primary human coronary artery smooth muscle cells. Therefore, products of the TPM1 gene may be a potential therapeutic target for the treatment of proinflammatory vascular disorders., Competing Interests: MG, DG, and AG are the authors on a patent disclosing the intravascular stent, especially for coronary vessels which inner covering comprises monoclonal anti-VE-cadherin antibodies and a system of induction of tropomyosin-1 expression. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Gagat, Zielińska, Mikołajczyk, Zabrzyński, Krajewski, Klimaszewska-Wiśniewska, Grzanka and Grzanka.)

Background: The current standard of treatment of anterior cruciate ligament (ACL) is reconstruction (ACLR). This technique has some disadvantages: poor proprioception, donor site morbidity and the inability to restore joint kinematics. ACL repair could be an alternative treatment. The purpose of the study was to compare the stability and the function after ACL primary repair versus single-bundle ACLR., Methods: In a retrospective study, 12 patients underwent primary ACL repair with internal bracing, 15 patients underwent standard ACLR. Follow-up examinations were evaluated at up to 2 years postoperatively. One patient in the ACL repair group was lost to follow-up due to re-rupture. The absolute value of anterior tibial translation (ATT) and the side-to-side difference in the same patient (ΔATT) were evaluated using the GNRB arthrometer. The Lysholm knee scoring was obtained. Re-ruptures and other complications were recorded., Results: Anterior tibial translation (ATT) was significantly decreased in the ACL repair group compared with the ACLR group (5.31 mm vs. 7.18 mm, respectively; p = 0.0137). Arthrometric measurements demonstrated a mean side-to-side difference (ΔATT) 1.87 (range 0.2 to 4.9) mm significantly decreased compared to ACLR 3.36 (range 1.2-5.6 mm; p = 0.0107). The mean Lysholm score was 85.3 points in the ACL repair group and 89.9 in ACLR group. No significant differences between ACL repair and ACLR were found for the Lysholm score. There was no association between AP laxity and clinical outcomes. There were two complications in the internal bracing group: one patient had re-rupture and was treated by ACLR, another had limited extension and had arthroscopic debridement., Conclusions: Anterior tibial translation was significantly decreased after ACL repair. Additionally, the functional results after ACL repair with internal bracing were comparable with those after ACLR. It should be noted that the two complications occurred. The current study supports further development of ACL repair techniques.

The transient receptor potential (TRP) melastatin-like subfamily member 2 (TRPM2) is a non-selective calcium-permeable cation channel. It is expressed by many mammalian tissues, including bone marrow, spleen, lungs, heart, liver, neutrophils, and endothelial cells. The best-known mechanism of TRPM2 activation is related to the binding of ADP-ribose to the nudix-box sequence motif (NUDT9-H) in the C-terminal domain of the channel. In cells, the production of ADP-ribose is a result of increased oxidative stress. In the context of endothelial function, TRPM2-dependent calcium influx seems to be particularly interesting as it participates in the regulation of barrier function, cell death, cell migration, and angiogenesis. Any impairments of these functions may result in endothelial dysfunction observed in such conditions as atherosclerosis or hypertension. Thus, TRPM2 seems to be an attractive therapeutic target for the conditions connected with the increased production of reactive oxygen species. However, before the application of TRPM2 inhibitors will be possible, some issues need to be resolved. The main issues are the lack of specificity, poor membrane permeabilization, and low stability in in vivo conditions. The article aims to summarize the latest findings on a role of TRPM2 in endothelial cells. We also show some future perspectives for the application of TRPM2 inhibitors in cardiovascular system diseases.

Available biomarkers for pancreatic adenocarcinoma (PAC) are inadequate to guide individual patient prognosis or therapy. Therefore, herein we aimed to verify the hypothesis that differences in the expression of KIF11 and KIF14, i.e., molecular motor proteins being primarily implicated in cell division events could account for the differences in the clinical outcome of PAC patients. In-house immunohistochemistry was used to evaluate the protein expressions of KIF11 and KIF14 in PAC, whereas RNA-seq datasets providing transcript expression data were obtained from public sources. IHC and mRNA results were correlated with clinicopathological features and overall survival (OS). Furthermore, the genes co-expressed with KIF11 or KIF14 were predicted and functionally annotated. In our series, malignant ducts displayed more intense but less abundant KIF11 staining than normal-appearing ducts. The former was also true for KIF14, whereas the prevalence of positive staining was similar in tumor and normal adjacent tissues. Based on categorical immunoreactive scores, we found KIF11 and KIF14 to be frequently downregulated or upregulated in PAC cases, respectively, and those with elevated levels of either protein, or both together, were associated with better prognosis. Specifically, we provide the first evidence that KIF11 or KIF14 proteins can robustly discriminate between patients with better and worse OS, independently of other relevant clinical risk factors. In turn, mRNA levels of KIF11 and KIF14 were markedly elevated in tumor tissues compared to normal tissues, and this coincided with adverse prognosis, even after adjusting for multiple confounders. Tumors with low predicted KIF11 or KIF14 expression were seen to have enrichment for circadian clock, whereas those with high levels were enriched for the genomic instability-related gene set. KIF11 and KIF14 were strongly correlated with one another, and CEP55 , ASPM , and GAMT were identified as the main hub genes. Importantly, the combined expression of these five genes emerged as the most powerful independent prognostic indicator associated with poor survival outcome compared to classical clinicopathological factors and any marker alone. In conclusion, our study identifies novel prognostic biomarkers for PAC, which await validation.

Percutaneous acute Achilles tendon rupture suturing has become a leading treatment option in recent years. A common complication after this mini-invasive procedure is sural nerve injury, which can reduce the patients' satisfaction and final outcomes. High-resolution ultrasound is a reliable method for localizing the sural nerve, and it can be performed intra-operatively; however, the long-term results are yet unknown. The aim of the study was to retrospectively evaluate the long-term results of percutaneous Achilles tendon repair supported with real-time ultrasound imaging. We conducted 57 percutaneous sutures of acute Achilles tendon rupture between 2005 and 2015; 30 were sutured under sonographic guidance, while 27 were performed without sonographic assistance. The inclusion criteria were acute (less than 7 days) full tendon rupture, treatment with the percutaneous technique, age between 18 and 65 years, and a body mass index (BMI) below 35. The operative procedure was carried out by two surgeons, according to the surgical technique reported by Maffulli et al. In total, 35 patients were available for this retrospective assessment; 20 (16 men and 4 women) were treated with sonographic guidance, while 15 (12 men and 3 women) underwent the procedure without it. The mean follow-up was 8 years (range, 3-13 years). The sural nerve was localized 10 mm to 20 mm (mean, 15.8; SD, 3.02) laterally from the scar of the Achilles tendon tear. There was no significant difference between groups with respect to the FAOQ score ( P < 0.05). High-resolution ultrasounds performed intra-operatively can minimize the risk of sural nerve injury during percutaneous Achilles tendon repair.

Knee osteoarthritis (KOA) represents a clinical challenge due to poor potential for spontaneous healing of cartilage lesions. Several treatment options are available for KOA, including oral nonsteroidal anti-inflammatory drugs, physical therapy, braces, activity modification, and finally operative treatment. Intra-articular (IA) injections are usually used when the non-operative treatment is not effective, and when the surgery is not yet indicated. More and more studies suggesting that IA injections are as or even more efficient and safe than NSAIDs. Recently, research to improve intra-articular homeostasis has focused on biologic adjuncts, such as platelet-rich plasma (PRP). The catabolic and inflammatory intra-articular processes that exists in knee osteoarthritis (KOA) may be influenced by the administration of PRP and its derivatives. PRP can induce a regenerative response and lead to the improvement of metabolic functions of damaged structures. However, the positive effect on chondrogenesis and proliferation of mesenchymal stem cells (MSC) is still highly controversial. Recommendations from in vitro and animal research often lead to different clinical outcomes because it is difficult to translate non-clinical study outcomes and methodology recommendations to human clinical treatment protocols. In recent years, significant progress has been made in understanding the mechanism of PRP action. In this review, we will discuss mechanisms related to inflammation and chondrogenesis in cartilage repair and regenerative processes after PRP administration in in vitro and animal studies. Furthermore, we review clinical trials of PRP efficiency in changing the OA biomarkers in knee joint.

Aim: The purpose of this study was to investigate whether there is an association between smoking, the extent of the degeneration process in the biceps tendinopathy, including cells and extracellular matrix (ECM) alterations, and long-term surgical results., Methods: This study comprised 40 consecutive patients admitted for shoulder arthroscopy due to symptomatic biceps tendinopathy and classified into three groups based on smoking status: active smokers, former smokers, and non-smokers. According to the classical Bonar score criteria, the histopathologic evaluation of the harvested intra-articular portion of the tendon was done. The follow-up examination was based on the American Shoulder and Elbow Surgeons Score (ASES)., Results: A cohort of 32 patients was enrolled in the final follow-up examination; mean 37.56 months. Histopathological evaluation according to the classical Bonar score revealed degeneration of the tendinous tissue in each group but there was no correlation between the extent of degeneration, smoking indexes and the ASES. After revision of Bonar scale within the vascularity criterion, we found a correlation between the extent of degeneration of tendinous tissue, smoking data, ASES score, and the severity of rotator cuff injury., Conclusion: In this paper, we indicate the ambiguous role of the neovascularization in the biceps tendinopathy, and it was used for modification of the classical Bonar score. Consequently, recalculated, modified Bonar score was correlated positively with smoking indexes and functional outcomes. Furthermore, the morphological alterations of rotator cuff tendons also correlated positively with the extent of biceps tendon degeneration, measured according to the modified scoring system., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest., (© The Author(s), 2021.)

In the present study, we aimed to assess the selected components of cell cycle machinery, checkpoint, DNA repair, and synthesis, namely RRM2, cyclin F, and SPDL1 in pancreatic adenocarcinomas (PAC) by in-house immunohistochemistry (IHC) and bioinformatic analysis of public datasets, in terms of expression, correlation with clinicopathological parameters, and patient survival. Sixty eight patients with pancreatic ductal adenocarcinoma (PDAC) were included in our cohort study, and IHC was performed on tissue macroarrays. RNA-Seq-based transcriptome data for 177 PACs were retrieved from the Cancer Genome Atlas (TCGA). We found cyclin F, RRM2, and SPDL1 to be overexpressed at both protein and mRNA levels in tumor tissues compared to respective controls. Based on TCGA dataset, we have demonstrated that CCNF, RRM2, and SPDL1 are potent independent prognostic markers for poor overall survival, both by themselves and even more in combination with each other. Furthermore, high CCNF mRNA expression was associated with features of cancer progression. By contrast, overexpression of cyclin F or SPDL1 proteins denoted a good prognosis in PDAC patients; however, in the case of the former protein, the results did not reach statistical significance. Specifically, high levels of SPDL1 protein emerged as the most powerful independent prognostic factor associated with a better outcome. If validated, the CCNF/RRM2/SPDL1 three-gene panel developed in this study, as well as SPDL1 protein, may provide significant clinical implications for the prognosis prediction of PAC patients.

The purpose of this study was to investigate the association of smoking and functional outcomes after arthroscopic treatment of complex shoulder injuries: rotator cuff tears (RCTs) with biceps tendon (LHBT) tears. This retrospective case-control study has been conducted on a cohort of patients who underwent shoulder arthroscopy between 2015 and 2017 due to complex injury treatment. The outcomes were assessed using the American Shoulder and Elbow Surgeons Score (ASES), the University of California at Los Angeles (UCLA) Shoulder Score, need for non-steroid anti-inflammatory drugs (NSAIDs) consumption and the visual analog scale (VAS). Complications and changes in smoking status were also noted. A cohort of 59 patients underwent shoulder arthroscopy, due to complex LHBT pathology and RCTs, and were enrolled in the final follow-up examination; with mean duration of 26.03 months. According to smoking status, 27 of patients were classified as smokers, and the remaining 32 were non-smokers. In the examined cohort, 36 patients underwent the LHBT tenotomy and 23 tenodesis. We observed a relationship between smoking status and distribution of various RCTs ( p < 0.0001). The mean postoperative ASES and UCLA scores were 80.81 and 30.18 in the smoker's group and 84.06 and 30.93 in the non-smoker's group, respectively. There were no statistically significant differences in pre/postoperative ASES and postoperative UCLA scores between smokers and non-smokers ( p > 0.05). The VAS was significantly lower in the non-smokers' group ( p = 0.0021). Multi-tendon injuries of the shoulder are a serious challenge for surgeons, and to obtain an excellent functional outcome, we need to limit the negative risk factors, including smoking. Furthermore, there is a significant association between smoking and the occurrence of massive rotator cuff tears, and the pain level measured by the VAS. Simultaneous surgical treatment of RC and LHBT lesions in the smoker population allowed us to obtain the functional outcomes approximated to non-smokers in the long-term follow-up. Of course, we cannot assert that smoking is the real cause of all complications, however, we may assume that this is a very important, negative factor in shoulder arthroscopy.

The study aimed to evaluate the results after arthroscopic tenodesis and tenotomy of the biceps tendon (LHBT), coupled in tenotomy modality with a personalized postoperative rehabilitation protocol. The study included patients who underwent arthroscopic biceps tenotomy or tenodesis due to chronic biceps tendinopathy. Postoperatively, a standard rehabilitation program was prescribed to the tenodesis group and personalized was introduced in the tenotomy group, respectively. The outcomes were assessed using the American Shoulder and Elbow Surgeons scale (ASES), clinical tests that are dedicated to biceps tendinopathy, the occurrence of a Popeye deformity, night pain, and return to previous sporting activities. A cohort of 67 patients was enrolled in the final follow-up examination (mean 27 months) of which 40 patients underwent tenotomy (60%), and 27 patients (40%) underwent tenodesis. The mean ASES score improved from 48.1 to 87.8 in the tenotomy group and from 44 to 72.7 in the tenodesis group during the follow-up ( p < 0.0001). The tenotomy group had better mean postoperative ASES scores than the tenodesis group ( p < 0.0001). Positive clinical tests for biceps pathology were noticed more often in patients after LHB tenodesis ( p = 0.0541). The Popeye deformity occurred more often in the tenotomy group; however, no patient complained of the visual appearance of the arm contour ( p = 0.0128). Moreover, the frequency of night pain decreased in the tenotomy group ( p = 0.0059). Return to previous sporting activities was more frequent in the tenotomy group ( p = 0.0090). Arthroscopic biceps tenotomy is a reproducible, simple procedure, and augmented by a rapid rehabilitation protocol that provides promising clinical outcomes, reduces shoulder pain, and allows the patient to return to previous sporting activities, even in population older than 50 years.

Cartilage lesions have a multifactorial nature, and genetic factors are their strongest determinants. As biochemical and genetic studies have dramatically progressed over the past decade, the molecular basis of cartilage pathologies has become clearer. Several homeostasis abnormalities within cartilaginous tissue have been found, including various structural changes, differential gene expression patterns, as well as altered epigenetic regulation. However, the efficient treatment of cartilage pathologies represents a substantial challenge. Understanding the complex genetic background pertaining to cartilage pathologies is useful primarily in the context of seeking new pathways leading to disease progression as well as in developing new targeted therapies. A technology utilizing gene transfer to deliver therapeutic genes to the site of injury is quickly becoming an emerging approach in cartilage renewal. The goal of this work is to provide an overview of the genetic basis of chondral lesions and the different approaches of the most recent systems exploiting therapeutic gene transfer in cartilage repair. The integration of tissue engineering with viral gene vectors is a novel and active area of research. However, despite promising preclinical data, this therapeutic concept needs to be supported by the growing body of clinical trials.

Hematoma of the calf is a rare complication following anterior cruciate ligament reconstruction (ACLR). The golden standard method of its treatment is puncture and aspiration. More advanced procedures are needed in difficult cases, such as prolonged he-ma-tomas. Among the novel management choices is endoscopy with ultrasound guidance. The aim of the study was to present the management of a post-surgical hematoma of the calf using endoscopic and ultrasound-assisted surgery. A 48-year-old patient un-der-went arthroscopic ACLR grafted with hamstrings tendons (semitendinosus and gracilis). Due to a hematoma developing at the donor site, he experienced edema and paresthesiae of the calf and foot that enhanced over time. An open reoperation failed and symptoms recurred. A second reoperation was performed as an endoscopic and ultrasound-assisted mini-invasive procedure. Re-sults were assessed postoperatively using the IKDC 2000 and Lysholm questionnaires. An evident increase in IKDC 2000 Score (from 14.9 points after open surgery to 77.0 one week after endoscopic treatment) and Lysholm Scale (26 points after first surgery and 84 one week after endoscopic surgery) was observed after the mini-invasive procedure. Edema and paresthesiae of the affect-ed limb completely disappeared four weeks after endoscopy. No complications of the novel procedure were found. Accordingly, en-doscopic and ultrasound-assisted evacuation of a prolonged calf hematoma appears an effective minimally-invasive and tar-geted procedure.

Background: Breakage of joint arthroplasty components are rare, yet during an implant retrieval program we found several cases., Objective: In this study we examined the components to determine the causes and mechanisms of breakage of these implants., Methods: From our collection of 849 retrievals we selected 682 cases with metal parts (503 hip, 79 knee arthroplasties) and identified fractured components: seven hip resurfacing implants, five total hip replacement stems, one monopolar femoral head, and one modular revision femoral stem from. Implants were examined using optical and scanning electron microscopy; metallographic sections were prepared and samples of periprosthetic tissues underwent microscopic examination., Results: In the resurfacing components breakage occurred in small stems placed in the femoral neck due to necrosis of femoral heads, with no metal flaws detected. Fatigue breakage of femoral stems was caused by presence of material flaws in the CoCrMo alloy, and corrosion. The monopolar head failed in fatigue fracture mechanism, breakage was initiated in an undercut near the taper connection for femoral component. The modular stem from Ti alloy sustained fatigue fracture induced by corrosion caused by debris from previously revised stem; no material flaws were detected in this sample. In most cases periprosthetic tissues had a morphology typical for aseptic loosening., Conclusions: In our series failure was caused by material flaws, presence of stress raisers and localized corrosion. Our findings indicate that sharp edges and other features which can act as stress raisers should be avoided in newly designed implants. Corrosion induced fracture of the modular Ti stem indicates the need for a detailed debridement of periprosthetic tissues during revision arthroplasties.

Smoking has a damaging effect on the musculoskeletal system, which was presented by authors in the rotator cuff and Achilles tendons studies; however, there are a lack of data about the effect of smoking on disorders of the long head of the biceps tendon (LHBT), particularly at the microscopic level. The purpose of this study was to investigate the effect of the tobacco smoking on the histopathologic alterations of the LHBT. Thirty-six patients with preoperatively diagnosed tendinopathy of the LHBT were referred to the Orthopaedics Department. All patients underwent arthroscopic treatment with further macroscopic and microscopic evaluation of biceps tendon samples. The active and former smokers were characterised by more advanced degenerative process of the tendinous tissue; moreover, it was intensified in the group of former smokers. Subjects who smoke more than 20 cigarettes per day also had more advanced microscopic alterations. The most severe microscopic alterations occurred in the former smokers who used tobacco for more than 20 years. However, the non-smokers group revealed moderate degeneration in all LHBT samples. Tobacco smoking is an important risk factor of the LHBT disease, which essentially intensifies the degeneration of the tendinous tissue.

Tendinopathy of the long head of the biceps tendon is a difficult medical issue. Its pathogenesis and etiology is multifactorial and unclear. Tendinopathy is thought to be primarily degenerative in nature, as tendons are characterized by impaired regeneration and healing. Thirty-five patients with preoperatively diagnosed tendinopathy of long head of the biceps tendon were referred to the Orthopedics Department. All patients underwent an arthroscopic-assisted biceps tenodesis or tenotomy. The intra-articular portion of the long head of the biceps tendon was obtained from each of the patients who underwent arthroscopy. A macroscopic and microscopic evaluation of biceps tendon samples revealed degeneration among all specimens. This study demonstrates the prevalence of the degeneration process and the presence of marginal inflammation process in tendinopathy of the long head of biceps tendon. The role, that inflammation process plays in tendinopathy is important in the early phase and gradually becomes secondary to the developing degeneration. The inflammatory cells, occasionally seen in pathological tendons, could be an evidence of re-injury and recent healing response.