The Effect of Denosumab in Elderly Patients Regarding Bone Density and Fracture Risk

Background@#With an aging population, the importance of treating and diagnosing osteoporosis is increasing. Osteoporosis, previously known as a resorptive change primarily related to endocrinological mechanisms, is also being approached as a phenomenon of senile change. Denosumab is gaining popularity among osteoporosis medications due to its ability to increase bone mineral density (BMD) and the economic benefit arising from the 6-month cycle. In line with previous literature, this study aimed to examine the BMD-augmenting effect of denosumab through which it reduces fracture risk in individuals aged over 80 years. @*Methods@#We reviewed patients who received denosumab between 2018 and 2022 with a minimum clinical observation period of 12 months. BMD was measured every 12 months, and patients were classified per their period of denosumab use. Fracture risk was evaluated using the fracture risk assessment tool (FRAX) and fracture incidence during the observation period were assessed. @*Results@#Among 155 patients, a significant increase in BMD was observed at 3 sites: the lumbar spine, femoral neck, and total hip (p<0.001, p<0.001, and p=0.001, respectively). The patients were divided according to the length of clinical follow-up they received, and similar results were found in all subgroups. Fracture risk assessment was performed using FRAX and the incidence of fracture events during follow-up. FRAX significantly decreased in all subgroups except those who received 24 months of follow-up (p=0.003, p=0.41, p=0.001 in the 12, 24, and ≥36 months groups, respectively). @*Conclusions@#Denosumab use resulted in long-term BMD increase and reduced fracture risk in individuals aged 80 and above.

Isoflurane's Effect on Intraoperative Systolic Left Ventricular Performance in Cardiac Valve Surgery Patients

BACKGROUND: Isoflurane, a common anesthetic for cardiac surgery, reduced myocardial contractility in many experimental studies, few studies have determined isoflurane's direct impact on the left ventricular (LV) contractile function during cardiac surgery. We determined whether isoflurane dose-dependently reduces the peak systolic velocity of the lateral mitral annulus in tissue Doppler imaging (S′) in patients undergoing cardiac surgery. METHODS: During isoflurane-supplemented remifentanil-based anesthesia for patients undergoing cardiac surgery with preoperative LV ejection fraction greater than 50% (n = 20), we analyzed the changes of S′ at each isoflurane dose increment (1.0, 1.5, and 2.0 minimum alveolar concentration [MAC]: T1, T2, and T3, respectively) with a fixed remifentanil dosage (1.0 μg/min/kg) by using transesophageal echocardiography. RESULTS: Mean S′ values (95% confidence interval [CI]) at T1, T2, and T3 were 10.5 (8.8–12.2), 9.5 (8.3–10.8), and 8.4 (7.3–9.5) cm/s, respectively (P < 0.001 in multivariate analysis of variance test). Their mean differences at T1 vs. T2, T2 vs. T3, and T1 vs. T3 were −1.0 (−1.6, −0.3), −1.1 (−1.7, −0.6), and −2.1 (−3.1, −1.1) cm/s, respectively. Phenylephrine infusion rates were significantly increased (0.26, 0.22, and 0.47 μg/kg/min at T1, T2, and T3, respectively, P < 0.001). CONCLUSION: Isoflurane increments (1.0–2.0 MAC) dose-dependently reduced LV systolic long-axis performance during cardiac surgeries with a preserved preoperative systolic function.

Less Invasive Anterior Iliac Approach and Compression Osteosynthesis for the Treatment of High Anterior Column Fractures of the Acetabulum

BACKGROUND: Displaced anterior column fractures have increasingly been treated surgically by the ilioinguinal approach and fixation with lag screws and a buttress plate on the pelvic brim. However, a major disadvantage of the ilioinguinal approach is possible damage to the neurovascular bundle and the lymphatic structures in the intermediate part of the approach. This study aims to present a novel surgical technique of the less invasive anterior iliac approach and compression osteosynthesis for high anterior column fractures of the acetabulum. METHODS: In this retrospective case series, 19 patients treated operatively for isolated high anterior column fractures using the less invasive anterior iliac approach and compression osteosynthesis were included. Patient demographics, the cause of injury, associated injuries, time to surgical reconstruction, and operation time were collected from the medical records. The quality of reduction was assessed by postoperative standard radiographic views and computed tomography scans and graded according to Matta's criteria. Clinical and radiographic grades were assessed according to Matta's criteria at the last follow-up. RESULTS: This less invasive surgical technique was successful for reduction and fixation in all high anterior column fractures and provided sufficient stability to allow immediate mobilization of the patients after surgery. Twelve fractures were combined with the quadrilateral plate fracture and seven fractures did not involve the quadrilateral plate. According to Matta's criteria, anatomical reduction was obtained in 17 patients and imperfect reduction in two patients. Clinical results were excellent in 17 patients and good in two patients. Radiographic results were excellent in 17 patients and good in two patients. Ten patients had neurapraxia of the lateral femoral cutaneous nerve related to the approach, which was resolved completely in seven. One patient had deep vein thrombosis. CONCLUSIONS: Our less invasive surgical technique of the anterior iliac approach and compression osteosynthesis is a useful addition to the existing techniques in the treatment of high anterior column fractures of the acetabulum. Despite being a limited approach and fixation, this technique provides sufficient exposure for reducing and fixing the fracture and adequate stability to allow immediate mobilization of the patient after surgery.

First Coccygeal Vertebra Dislocation Treated by Open Reduction and Internal Fixation

STUDY DESIGN: Case report. OBJECTIVES: To report the effectiveness of open reduction and internal (screw) fixation treatment performed to treat dislocation of the first coccygeal vertebra. SUMMARY OF LITERATURE REVIEW: Most treatment methods for coccygeal dislocation were conservative treatment for acute coccygodynia and coccygectomy for chronic coccygodynia. MATERIALS AND METHODS: A 18-year-old female presented with severe coccygodynia due to a fall down the stairs. Computed tomography showed dislocation of the first coccygeal vertebra. We performed open reduction and internal fixation with a 4.0-mm shortthread cancellous screw with a washer, with no additional procedure for bone union. RESULTS: Union was achieved 10 weeks postoperatively. CONCLUSIONS: Open reduction and internal (screw) fixation can be a useful method for coccygeal vertebra dislocation.

Terminally Differentiating Eosinophils Express Neutrophil Primary Granule Proteins as well as Eosinophil-specific Granule Proteins in a Temporal Manner

Neutrophils and eosinophils, 2 prominent granulocytes, are commonly derived from myelocytic progenitors through successive stages in the bone marrow. Our previous genome-wide transcriptomic data unexpectedly showed that genes encoding a multitude of neutrophil primary granule proteins (NPGPs) were markedly downregulated during the end period of eosinophilic terminal differentiation when cord blood (CB) cluster of differentiation (CD) 34+ cells were induced to differentiate toward the eosinophil lineage during a 24-day culture period. Accordingly, this study aimed to examine whether NPGP genes were expressed on the way to eosinophil terminal differentiation stage and to compare their expression kinetics with that of genes encoding eosinophil-specific granule proteins (ESGPs). Transcripts of all NPGP genes examined, including proteinase 3, myeloperoxidase, cathepsin G (CTSG), and neutrophil elastase, reached a peak at day 12 and sharply declined thereafter, while transcript of ESGP genes including major basic protein 1 (MBP1) attained maximum expression at days 18 or 24. Growth factor independent 1 (GFI1) and CCAAT/enhancer-binding protein α (C/EBPA), transactivators for the NPGP genes, were expressed immediately before the NPGP genes, whereas expression of C/EBPA, GATA1, and GATA2 kinetically paralleled that of eosinophil granule protein genes. The expression kinetics of NPGPs and ESGPs were duplicated upon differentiation of the eosinophilic leukemia cell line (EoL-1) immature eosinophilic cells. Importantly, confocal image analysis showed that CTSG was strongly coexpressed with MBP1 in differentiating CB eosinophils at days 12 and 18 and became barely detectable at day 24 and beyond. Our results suggest for the first time the presence of an immature stage where eosinophils coexpress NPGPs and ESGPs before final maturation.

Single Low-Dose Radiation Induced Regulation of Keratinocyte Differentiation in Calcium-Induced HaCaT Cells

BACKGROUND: We are continually exposed to low-dose radiation (LDR) in the range 0.1 Gy from natural sources, medical devices, nuclear energy plants, and other industrial sources of ionizing radiation. There are three models for the biological mechanism of LDR: the linear no-threshold model, the hormetic model, and the threshold model. OBJECTIVE: We used keratinocytes as a model system to investigate the molecular genetic effects of LDR on epidermal cell differentiation. METHODS: To identify keratinocyte differentiation, we performed western blots using a specific antibody for involucrin, which is a precursor protein of the keratinocyte cornified envelope and a marker for keratinocyte terminal differentiation. We also performed quantitative polymerase chain reaction. We examined whether LDR induces changes in involucrin messenger RNA (mRNA) and protein levels in calcium-induced keratinocyte differentiation. RESULTS: Exposure of HaCaT cells to LDR (0.1 Gy) induced p21 expression. p21 is a key regulator that induces growth arrest and represses stemness, which accelerates keratinocyte differentiation. We correlated involucrin expression with keratinocyte differentiation, and examined the effects of LDR on involucrin levels and keratinocyte development. LDR significantly increased involucrin mRNA and protein levels during calcium-induced keratinocyte differentiation. CONCLUSION: These studies provide new evidence for the biological role of LDR, and identify the potential to utilize LDR to regulate or induce keratinocyte differentiation.

Epigallocatechin Gallate-Mediated Alteration of the MicroRNA Expression Profile in 5α-Dihydrotestosterone-Treated Human Dermal Papilla Cells

BACKGROUND: Dihydrotestosterone (DHT) induces androgenic alopecia by shortening the hair follicle growth phase, resulting in hair loss. We previously demonstrated how changes in the microRNA (miRNA) expression profile influenced DHT-mediated cell death, cell cycle arrest, cell viability, the generation of reactive oxygen species (ROS), and senescence. Protective effects against DHT have not, however, been elucidated at the genome level. OBJECTIVE: We showed that epigallocatechin gallate (EGCG), a major component of green tea, protects DHT-induced cell death by regulating the cellular miRNA expression profile. METHODS: We used a miRNA microarray to identify miRNA expression levels in human dermal papilla cells (DPCs). We investigated whether the miRNA expression influenced the protective effects of EGCG against DHT-induced cell death, growth arrest, intracellular ROS levels, and senescence. RESULTS: EGCG protected against the effects of DHT by altering the miRNA expression profile in human DPCs. In addition, EGCG attenuated DHT-mediated cell death and growth arrest and decreased intracellular ROS levels and senescence. A bioinformatics analysis elucidated the relationship between the altered miRNA expression and EGCG-mediated protective effects against DHT. CONCLUSION: Overall, our results suggest that EGCG ameliorates the negative effects of DHT by altering the miRNA expression profile in human DPCs.