Search Results (17)

Background/Objectives: Femoral neck and proximal femur fractures in the elderly can result from low-energy trauma due to osteoporotic changes and contribute significantly to increased morbidity and mortality. Despite various treatment options, closed reduction and internal fixation (CRIF) with intramedullary nails has become the predominant approach. While a minimally invasive approach reduces complications and speeds recovery, this outcome is not always feasible in practice. The primary surgical goal remains achieving a stable and precise fracture reduction, favoring CRIF when possible. Our study aims to evaluate the clinical, radiological, and functional outcomes of patients operated on using the Wide-Awake Local Anesthesia No Tourniquet (WALANT) technique. Methods: Patients who underwent surgery for intertrochanteric femur fractures between June 2019 and June 2021 were analyzed. Patients who were between 75 and 90 years old and had undergone surgery with a proximal femoral nail (PFN) were included in the study. Patients were excluded if they required general anesthesia, if an acceptable reduction could not be achieved with the PFN, if they did not attend the last follow-up examination, or if the follow-up period was <4 years. Patients were functionally assessed using the Harris hip score at the 6th month and at the last follow-up and using the visual analog scale at the surgery, at the 4th hour after surgery, and at the time of discharge. For radiological assessment, the classification of reduction quality and the measurement of the tip–apex distance were used. Results: Forty patients (22F/18M) were included in the study. Their mean age was 83.0 ± 2.9 years. The mean time from trauma to surgery was 6.8 ± 2.3 h. Patients were mobilized on average 1.53 ± 0.8 h after surgery, and the mean hospitalization time was 27.4 ± 8.1 h. No statistically significant decrease in hemoglobin value was observed before or after surgery (p = 0.476). The Harris hip score was 73.3 ± 3.2 at the 6th month postoperatively and 74.9 ± 2.5 at the last follow-up (p = 0.296). The reduction quality was found to be poor in only two patients. Conclusions: The WALANT technique’s promising results in terms of pain management, blood loss control, and early mobilization show that it is a viable alternative to conventional anesthesia methods in geriatric hip fractures. Full article

Background: Intra-articular calcaneal fracture (CF) treatment is associated with a high risk of complications, but closed reduction and internal fixation (CRIF) is a minimally invasive alternative for treatment. Methods: Forty-eight patients treated with CRIF and CALCAnail^® due to intra-articular CF between 2016 and 2021 were analyzed to check union time, complication rate, and functionality after the intervention. Functional and pain outcomes were assessed, including the Maryland Foot Score (MFS), American Orthopedic Foot & Ankle Society (AOFAS) scale questionnaires, and the numerical pain scale (NRS) at mid-term follow-ups 2–5 years after the intervention. Results: Intervention increased median Böhler’s angle from 21.5° to 32° (p < 0.01). The median bone union time was 12 weeks. The risk of malunion was higher in patients with Sanders type 4 (RR = 2.28; 95% CI 1.11–4.72) and those operated on later than the 2nd day after injury (RR = 2.1; 95% CI 1.08–4.09). Patients with at least one of the comorbidities (nicotinism, diabetes, obesity) had a higher risk of intensive pain (NRS > 3) 2–5 years after surgery (RR = 1.69; 95% CI 1.06–2.68), and 84% were satisfied with their treatment. Other complications included complex regional pain syndrome in two patients (4%), malunion in three (6%), and surgical site infection in two (4%). The MFS had a median score of 85 points, while that of the AOFAS was 82 points. Conclusions: CRIF, with the use of the CALCAnail^® implant, allows doctors to restore anatomical relationships around the subtalar joint, resulting in good clinical and functional results. Full article

Background/Objectives: Mitochondrial oxidative phosphorylation (OXPHOS) has been exploited as a therapeutic target in cancer treatments because of its crucial role in tumorigenesis. CR6-interacting factor 1 (CRIF1), a mitochondrial ribosomal subunit protein, is essential for the regulation of mitochondrial OXPHOS capacity. However, the mechanism of CRIF1 in triple-negative breast cancer (TNBC) cells remains unclear. Methods/Results: We showed that the downregulation of CRIF1 reduced cell proliferation in the TNBC cell lines MDA-MB-468, MDA-MB-231, and, especially, BT549. In addition, wound scratch and Transwell assays showed that CRIF1 deficiency inhibited the migration and invasion of BT549 cells. CRIF1 downregulation resulted in the suppression of mitochondrial bioenergetics in BT549 cells, specifically affecting the inhibition of OXPHOS complexes I and II. This was evidenced by a decrease in the mitochondrial oxygen consumption rate and the depolarization of the mitochondrial membrane potential. Damage to mitochondria resulted in a lower adenosine triphosphate level and an elevated production of mitochondrial reactive oxygen species. In addition, CRIF1 deficiency decreased hypoxia-inducible factor 1α accumulation, NADPH synthesis, and TP53-induced glycolysis and apoptosis regulator (TIGAR) expression in BT549 cells. These events contributed to G0/G1-phase cell cycle inhibition and the upregulation of the cell cycle protein markers p53, p21, and p16. Transfection with a TIGAR overexpression plasmid reversed these effects and prevented CRIF1 downregulation-induced proliferation and migration reduction. Conclusions: These results indicate that blocking mitochondrial OXPHOS synthesis via CRIF1 may have a therapeutic antitumor effect in BT549 TNBC cells. Full article

To clarify the effects of newly developed controlled-release iodine fertilizer (CRIF) on enhancing lettuce (Lactuca sativa L.) iodine accumulation, improving the physiological traits, and reducing iodine leaching from soil, a greenhouse pot experiment was conducted. Polymer-coated iodate (PCIO), polymer-coated iodide (PCI), and two conventional iodine fertilizers—iodate (CIO) and iodide (CI)—were applied at a rate of 15 mg iodine per kg soil. The study found that the coating of iodine fertilizers had no significant effects on the biomass of lettuce. The iodine concentration in lettuce leaves subjected to PCIO treatment was elevated by 50.1% and 45.5%, respectively, in comparison to leaves treated with CIO and PCI. The soil-to-leaf transfer factor (TF_leaf, dry weight basis) for plants treated with PCIO was significantly higher than that of PCI-treated plants. PCIO also significantly reduced iodine leaching by 46.3% compared to CIO. In lettuce leaves with PCIO treatment, the enzymatic activities of superoxide dismutase (SOD) and catalase (CAT) significantly increased by 50.8% and 27.6%, respectively. Likewise, malo-naldehyde (MDA) levels decreased by 23.2% compared to the control samples. PCIO also demonstrated advantages in enhancing the quality of the lettuce. In conclusion, the application of controlled-release iodine fertilizer could be a highly effective and eco-friendly approach to cultivating iodine-rich vegetables. Full article

The treatment for humeral shaft fractures (HSFs) is still controversial, consisting of a wide variety of orthopedic osteosynthesis materials that imply different grades of invasiveness. The aim of this study is to investigate the correlation between inflammatory blood-derived markers and the magnitude of the surgical procedure in young and middle-aged patients who sustained these fractures. Observational, retrospective research was conducted between January 2018 and December 2023. It followed patients diagnosed with recent HFSs (AO/OTA 12−A and B) and followed operative treatment. They were split in two groups, depending on the surgical protocol: group A, operated by closed reduction and internal fixation (CRIF) with intramedullary nails (IMNs), and group B, operated by open reduction and internal fixation (ORIF) with dynamic compression plates (DCPs). Statistically significant differences (p < 0.05) between the two groups could be observed in injury on the basis of surgery durations, surgical times, pre- and postoperative neutrophil-per-lymphocyte ratio (NLR), postoperative platelet-per-lymphocyte ratio (PLR), monocyte-per-lymphocyte ratio (MLR), systemic inflammatory index (SII), systemic inflammatory response index (SIRI) and aggregate inflammatory systemic index (AISI). The multivariate regression model proposed revealed that NLR > 7.99 (p = 0.007), AISI > 1668.58 (p = 0.008), and the surgical times (p < 0.0001) are strongly correlated to the magnitude of the surgical protocol followed. Using receiver operating characteristic (ROC) curve analysis, a balanced reliability was determined for both postoperative NLR > 7.99 (sensitivity 75.0% and specificity 75.6) and AISI > 1668.58 (sensitivity 70.6% and specificity 82.2%). Postoperative NLR and AISI as inflammatory markers are highly associated with the magnitude of surgical trauma sustained during humeral shaft fracture osteosynthesis in a younger population. Full article

The aim of this study was to assess surgical treatment in metacarpal shaft fractures of the second to fifth ray to determine the functional outcomes and complications in open reduction and internal fixation (ORIF) versus closed reduction and internal fixation (CRIF). This was a retrospective study that included patients with metacarpal shaft fractures of the second to fifth rays who were treated surgically between 1 January 2007 and 31 December 2019. Functional outcomes were scored using the QuickDASH and Eq5D score. A total of 231 treated patients were included. Single fractures were seen in 180 patients, and multiple fractures in 51 patients. ORIF was applied in 141 patients and CRIF in 90 patients. The functional outcomes were not significantly different between the groups. Complications were found in 41 (29%) of the ORIF patients and 15 (17%) of the CRIF patients. The functional outcomes after single or multiple metacarpal shaft fractures were similar in the ORIF and CRIF patients. ORIF showed significantly more complications, such as functional impairment and infections and a higher reoperation rate. In conclusion, CRIF is as safe as ORIF for the surgical treatment of metacarpal shaft fractures in terms of its functional outcome and slightly preferable due to its lower complication rate. Full article

Sterile inflammation is a natural response of the organism in the absence of microorganisms, which is triggered in correspondence with the degree of tissue damage sustained after a surgical procedure. The objective of this study was to explore the values of postoperative hematological-derived biomarkers in assessing the sterile inflammatory response magnitude related to the invasiveness of the surgical reduction technique used for subtrochanteric fractures (STFs) treatment. A retrospective, observational cohort research was conducted between January 2021 and October 2023 that included a total of 143 patients diagnosed with acute subtrochanteric fractures who underwent long Gamma Nail (LGN) fixation. According to the surgical reduction technique used, they were divided into two groups: group 1, which consisted of those with a closed reduction and internal fixation (CRIF); and group 2, which consisted of those with an open reduction internal fixation (ORIF). Between groups, statistically significant differences (p < 0.05) were found in relation to days to surgery, length of hospital stay (LOHS), duration of surgery, postoperative hemoglobin (HGB) levels, neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), monocyte–lymphocyte ratio (MLR), systemic inflammation index (SII), systemic inflammation response index (SIRI), and aggregate inflammation systemic index (AISI). The receiver operating characteristics (ROC) curve analysis revealed that all ratios presented a high diagnostic ability (p < 0.0001) with NLR > 6.95 being the most reliable (sensitivity 94.8% and specificity 70.6%). Moreover, the multivariate regression model confirmed that sterile immune response after orthopedic interventions can be assessed in an almost equal and non-dependent manner using these biomarkers. Postoperative NLR, PLR, MLR, SII, SIRI, and AISI ratios are closely correlated to the sterile inflammatory response magnitude, due to the extent of surgical dissection performed during internal fixation procedures of subtrochanteric femur fractures. Full article

The treatment for hip fractures consists of a wide variety of orthopedic implants ranging from prosthesis to intramedullary nails. The purpose of this study is to determine the correlation between blood-count-derived biomarkers such as the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), the monocyte-to-lymphocyte ratio (MLR) and the systemic immune-inflammation index (SII) and the level of aggression sustained by elderly patients during these surgical procedures. A total of 129 patients aged over 70 and diagnosed with acute hip fractures who underwent surgical treatment between November 2021 and February 2023 were included in our observational retrospective cohort study. Two groups were formed depending on the anatomic location of the fracture for statistical comparison: group 1 with extracapsular fractures, who received a closed reduction internal fixation (CRIF) with a gamma nail (GN) as treatment, and group 2 with intracapsular fractures, who received a bipolar hemiarthroplasty (BHA) as treatment. The length of hospital stay (LHS), duration of surgery, preoperative days, pre- and postoperative red blood count (RBC) and hemoglobin (HGB) levels and postoperative NLR, PLR and SII were significantly different between the two groups (p < 0.05). Furthermore, the multivariate analysis indicated that the postoperative NLR (p = 0.029), PLR (p = 0.009), SII (p = 0.001) and duration of surgery (p < 0.0001) were independently related to the invasiveness of the procedures. The ROC curve analysis demonstrated that a postoperative SII > 1564.74 is a more reliable predictor of surgical trauma in terms of specificity (58.1%) and sensitivity (56.7%). Postoperative SII as a biomarker appears to be closely correlated with surgical trauma sustained by an older population with hip fractures. Full article

Mitochondrial oxidative phosphorylation (OXPHOS) system dysfunction in cancer cells has been exploited as a target for anti-cancer therapeutic intervention. The downregulation of CR6-interacting factor 1 (CRIF1), an essential mito-ribosomal factor, can impair mitochondrial function in various cell types. In this study, we investigated whether CRIF1 deficiency induced by siRNA and siRNA nanoparticles could suppress MCF-7 breast cancer growth and tumor development, respectively. Our results showed that CRIF1 silencing decreased the assembly of mitochondrial OXPHOS complexes I and II, which induced mitochondrial dysfunction, mitochondrial reactive oxygen species (ROS) production, mitochondrial membrane potential depolarization, and excessive mitochondrial fission. CRIF1 inhibition reduced p53-induced glycolysis and apoptosis regulator (TIGAR) expression, as well as NADPH synthesis, leading to additional increases in ROS production. The downregulation of CRIF1 suppressed cell proliferation and inhibited cell migration through the induction of G0/G1 phase cell cycle arrest in MCF-7 breast cancer cells. Similarly, the intratumoral injection of CRIF1 siRNA-encapsulated PLGA nanoparticles inhibited tumor growth, downregulated the assembly of mitochondrial OXPHOS complexes I and II, and induced the expression of cell cycle protein markers (p53, p21, and p16) in MCF-7 xenograft mice. Thus, the inhibition of mitochondrial OXPHOS protein synthesis through CRIF1 deletion destroyed mitochondrial function, leading to elevated ROS levels and inducing antitumor effects in MCF-7 cells. Full article

Background: This review aims to identify what angulation may be accepted for the conservative treatment of pediatric radial neck fractures and how the range of motion (ROM) at follow-up is influenced by the type of fracture treatment. Patients and Methods: A PRISMA-guided systematic search was performed for studies that reported on fracture angulation, treatment details, and ROM on a minimum of five children with radial neck fractures that were followed for at least one year. Data on fracture classification, treatment, and ROM were analyzed. Results: In total, 52 studies (2420 children) were included. Sufficient patient data could be extracted from 26 publications (551 children), of which 352 children had at least one year of follow-up. ROM following the closed reduction (CR) of fractures with <30 degrees angulation was impaired in only one case. In fractures angulated over 60 degrees, K-wire fixation (Kw) resulted in a significantly better ROM than intramedullary fixation (CIMP; Kw 9.7% impaired vs. CIMP 32.6% impaired, p = 0.01). In more than 50% of cases that required open reduction (OR), a loss of motion occurred. Conclusions: CR is effective in fractures angulated up to 30 degrees. There may be an advantage of Kw compared to CIMP fixation in fractures angulated over 60 degrees. OR should only be attempted if CR and CRIF have failed. Full article

It has widely been accepted that food restriction (FR) without malnutrition has multiple health benefits. Various calorie restriction (CR) and intermittent fasting (IF) regimens have recently been reported to exert neuroprotective effects in traumatic brain injury (TBI) through variable mechanisms. However, the evidence connecting CR or IF to neuroprotection in TBI as well as current issues remaining in this research field have yet to be reviewed in literature. The objective of our review was therefore to weigh the evidence that suggests the connection between CR/IF with recovery promotion following TBI. Medline, Google Scholar and Web of Science were searched from inception to 25 February 2022. An overwhelming number of results generated suggest that several types of CR/IF play a promising role in promoting post-TBI recovery. This recovery is believed to be achieved by alleviating mitochondrial dysfunction, promoting hippocampal neurogenesis, inhibiting glial cell responses, shaping neural cell plasticity, as well as targeting apoptosis and autophagy. Further, we represent our views on the current issues and provide thoughts on the future direction of this research field. Full article

Paclitaxel (taxol), a chemotherapeutic agent, remains the standard of care for the lethal triple-negative breast cancer (TNBC). However, over 50% of TNBC patients become resistant to chemotherapy and, to date, no solution is available. CR6-interacting factor 1 (CRIF1) is reported to act as a negative regulator of the cell cycle by interacting with cyclin-dependent kinase 2 (CDK2). In our study, two selective CRIF1–CDK2 interface inhibitors were used to investigate whether they could exert anti-proliferative activity on the TNBC cell lines. When combined with taxol treatment, these two inhibitors can advance the cells from G0/G1 to S and G2/M phases, producing irreparable damage to the cells, which then undergo apoptosis. Moreover, they enhanced the reduction in cell proliferation induced by taxol in TNBC cells, thereby improving sensitivity to taxol in these cell lines. Importantly, the inhibitors did not regulate the cell cycle in normal cells, indicating their high selectivity towards TNBC cells. Overall, the resistance to the anti-proliferative effects induced by taxol can be significantly reduced by the combined treatment with selective CRIF1–CDK2 interface inhibitors, making a conceptual advance in the CDK-related cancer treatment. Full article

Although inflammation and fibrosis, which are key mechanisms of chronic kidney disease, are associated with mitochondrial damage, little is known about the effects of mitochondrial damage on the collecting duct in renal inflammation and fibrosis. To generate collecting duct-specific mitochondrial injury mouse models, CR6-interacting factor-1 (CRIF1) ^flox/flox mice were bred with Hoxb7-Cre mice. We evaluated the phenotype of these mice. To evaluate the effects on unilateral ureteral obstruction (UUO)-induced renal injury, we divided the mice into the following four groups: a CRIF1^flox/flox (wild-type (WT)) group, a CRIF1^flox/flox-Hob7 Cre (CRIF1-KO) group, a WT-UUO group, and a CRIF1-KO UUO group. We evaluated the blood and urine chemistries, inflammatory and fibrosis markers, light microscopy, and electron microscopy of the kidneys. The inhibition of Crif1 mRNA in mIMCD cells reduced oxygen consumption and membrane potential. No significant differences in blood and urine chemistries were observed between WT and CRIF1-KO mice. In UUO mice, monocyte chemoattractant protein-1 and osteopontin expression, number of F4/80 positive cells, transforming growth factor-β and α-smooth muscle actin staining, and Masson’s trichrome staining were significantly higher in the kidneys of CRIF1-KO mice compared with the kidneys of WT mice. In sham mice, urinary 8-hydroxydeoxyguanosine (8-OHDG) was higher in CRIF1-KO mice than in WT mice. Moreover, CRIF1-KO sham mice had increased 8-OHDG-positive cell recruitment compared with WT-sham mice. CRIF1-KO-UUO kidneys had increased recruitment of 8-OHDG-positive cells compared with WT-UUO kidneys. In conclusion, collecting duct-specific mitochondrial injury increased oxidative stress. Oxidative stress associated with mitochondrial damage may aggravate UUO-induced renal injury. Full article

Elevated plasma homocysteine levels can induce vascular endothelial dysfunction; however, the mechanisms regulating homocysteine metabolism in impaired endothelial cells are currently unclear. In this study, we deleted the essential mitoribosomal gene CR6 interacting factor 1 (CRIF1) in human umbilical vein endothelial cells (HUVECs) and mice to induce endothelial cell dysfunction; then, we monitored homocysteine accumulation. We found that CRIF1 downregulation caused significant increases in intracellular and plasma concentrations of homocysteine, which were associated with decreased levels of folate cycle intermediates such as 5-methyltetrahydrofolate (MTHF) and tetrahydrofolate (THF). Moreover, dihydrofolate reductase (DHFR), a key enzyme in folate-mediated metabolism, exhibited impaired activity and decreased protein expression in CRIF1 knockdown endothelial cells. Supplementation with folic acid did not restore DHFR expression levels or MTHF and homocysteine concentrations in endothelial cells with a CRIF1 deletion or DHFR knockdown. However, the overexpression of DHFR in CRIF1 knockdown endothelial cells resulted in decreased accumulation of homocysteine. Taken together, our findings suggest that CRIF1-deleted endothelial cells accumulated more homocysteine, compared with control cells; this was primarily mediated by the disruption of DHFR expression. Full article

Although previous studies continuously report an increased risk of hearing loss in diabetes patients, the impact of the disease on the inner ear remains unexplored. Herein, we examine the pathophysiology of diabetes-associated hearing impairment and cochlear synaptopathy in a mouse model of diabetes. Male B6.BKS(D)-Lepr^db/J (db/db, diabetes) and heterozygote (db/+, control) mice were assigned into each experimental group (control vs. diabetes) based on the genotype and tested for hearing sensitivity every week from 6 weeks of age. Each cochlea was collected for histological and biological assays at 14 weeks of age. The diabetic mice exerted impaired hearing and a reduction in cochlear blood flow and C-terminal-binding protein 2 (CtBP2, a presynaptic ribbon marker) expression. Ultrastructural images revealed severely damaged mitochondria from diabetic cochlea accompanied by a reduction in Cytochrome c oxidase subunit 4 (COX4) and CR6-interacting factor 1 (CRIF1). The diabetic mice presented significantly decreased levels of platelet endothelial cell adhesion molecule (PECAM-1), B-cell lymphoma 2 (BCL-2), and procaspase-9, but not procaspase-8. Importantly, significant changes were not found in necroptotic programmed cell death markers (receptor-interacting serine/threonine-protein kinase 1, RIPK1; RIPK3; and mixed lineage kinase domain-like pseudokinase, MLKL) between the groups. Taken together, diabetic hearing loss is accompanied by synaptopathy, microangiopathy, damage to the mitochondrial structure/function, and activation of the intrinsic apoptosis pathway. Our results imply that mitochondrial dysfunction is deeply involved in diabetic hearing loss, and further suggests the potential benefits of therapeutic strategies targeting mitochondria. Full article