Melatonin exhibits partial protective effects against gemcitabine- and cisplatin-induced kidney and reproductive injuries in mice.

Cisplatin has the potential to cause kidney and reproductive organ injuries, prompting the search for protective agents against cisplatin-induced toxicity. Melatonin, an antioxidant hormone, has shown promise in mitigating oxidative stress in various organs. However, its protective effects on cisplatin-induced kidney and reproductive injuries have not been extensively investigated. The aim of this study was to explore the potential protective effects of melatonin on cisplatin-induced kidney and reproductive injuries when administered in combination with gemcitabine in mice. Male C57BL/6 mice were subjected to a seven-week treatment with gemcitabine plus cisplatin, with or without melatonin intervention. The testis, epididymis, and kidney were assessed through histological analysis and measurement of blood parameters. Treatment with cisplatin led to a significant reduction in testicular weight, histological abnormalities, and alterations in reproductive hormone levels. Melatonin exhibited a slight protective effect on the testis, with higher doses of melatonin yielding better outcomes. However, melatonin did not reverse the effects of cisplatin on the epididymis. Administration of melatonin before and during treatment with cisplatin plus gemcitabine in mice demonstrated a modest protective effect on testicular injuries, while showing limited effects on epididymal injuries. Serum creatinine levels in the group treated with gemcitabine plus cisplatin treatment and high-dose melatonin approached those of the control group, indicating a protective effect on the kidney. These findings underscore the potential of melatonin as a protective agent against cisplatin-induced kidney and reproductive injuries and emphasize the need for further research to optimize its dosage and evaluate its long-term effects.

Downregulation of CRTAC1 in Urothelial Carcinoma Promotes Tumor Aggressiveness and Confers Poor Prognosis.

BACKGROUND: Cartilage acidic protein 1 (CRTAC1) is a glycosylated calcium-binding extracellular matrix protein. The oncological functions of CRTAC1 in urothelial carcinoma (UC) of the urinary bladder (UB) and upper urinary tract (UT) have not yet been elucidated. Based on the published UBUC transcriptome data, we re-evaluated the differential expression profile of calcium ion binding-related genes (GO:0005509), and we found that CRTAC1 was the most significantly downregulated gene in UBUC progression. Therefore, we analyzed the prognostic value and biological significance of CRTAC1 expression in UC. METHODS: We used immunohistochemistry to determine the CRTAC1 expression levels in 340 patients with UTUC and 295 patients with UBUC. The CRTAC1 expression was compared with the clinicopathological characteristics, and the prognostic impact of CRTAC1 on metastasis-free survival (MFS) and disease-specific survival (DSS) was evaluated. To study the biological functions of CRTAC1, the proliferation, migration, invasion, and tube formation abilities of UC-derived cells were evaluated. RESULTS: A low CRTAC1 expression significantly correlated with high tumor stage, high histological grade, perineural invasion, vascular invasion, nodal metastasis, and high mitotic rate (all p < 0.01). Moreover, the CRTAC1 immunoexpression status was an independent prognostic factor for MFS and DSS in UBUC and UTUC patients (all p < 0.001) in the multivariate analysis. The exogenous expression of CRTAC1 suppressed the cell proliferation, invasion, and angiogenesis, and downregulated the matrix metallopeptidase 2 (MMP2) level in BFTC909 and T24 cells. CONCLUSIONS: CRTAC1 may participate in progression of UC and serve as a prognostic marker for metastasis. Low CRTAC1 expression was significantly associated with aggressive UC characteristics and worse clinical outcomes. The inclusion of CRTAC1 immunoexpression in the standard pathological variables may optimize the risk stratification of patients.

New Hydronephrosis in the Native Kidney Is Associated with the Development of De Novo Urinary Bladder Urothelial Carcinoma in Patients with Post-Kidney Transplantation.

Increased malignancy after kidney transplantation (KT) is by far the most troublesome issue. Among these malignancies, urothelial carcinoma (UC) incidence is uniquely high in Taiwan. We want to know whether routine sonography to detect native hydronephrosis is associated with the development of de novo urinary bladder urothelial carcinoma (UBUC) in post-KT recipients. From 2003 to 2018, we retrospectively analyzed 1005 KT patients, 58 of whom were subsequently diagnosed with UBUC. The association between new native hydronephrosis and post-KT UBUC was analyzed with univariate and multivariate logistic regression analyses and a Kaplan-Meier plot. We excluded cases of people who had upper urinary tract urothelial carcinoma (UTUC) and were diagnosed prior to UBUC. There were 612 males (60.9%) and 393 females (39.1%), with a mean age of 48.2 ± 12.0 years old at KT. The mean follow-up period was 118.6 ± 70.2 months, and the diagnosis of UBUC from KT to UBUC was 7.0 ± 5.1 years. New native kidney hydronephrosis occurred more frequently in the UBUC group (56.4% versus 6.4%, p < 0.001) than the non-UBUC group. Multivariate analysis disclosed that native hydronephrosis is the only statistically significant factor for UBUC, with an odds ratio of 16.03 (95% CI, 8.66-29.68; p < 0.001). UBUC in post-KT patients with native hydronephrosis also showed a tendency toward multifocal lesions upon presentation (47.8%). Post-KT UBUC is characterized by pathologically aggressive and multiple foci lesions. Native kidney hydronephrosis may be a deciding factor of post-KT UBUC.

Fibulin-2: A potential regulator of immune dysfunction after bone trauma.

OBJECTIVES: To reveal the relationship between the fibulin-2 protein and immune dysfunction after bone trauma. METHODS: Individuals who were admitted to the study were divided into a bone trauma group, a recovered from bone trauma group and a volunteer without bone trauma group based on the reason for admission. Fibulin-2 levels in the three groups were compared. Fibulin-2-knockout (fibulin-2-/- ) mice and wild-type (WT) mice were used to detect susceptibility to infection. Hematoxylin and eosin (HE) staining and immunohistochemical staining were employed to observe pathological changes in each organ from fibulin-2-/- mice and WT mice. RESULTS: In total, 132 patients were enrolled in this study. The fibulin-2 level in the bone trauma group was lower than that in the recovered bone trauma group (3.39 ± 1.41 vs. 4.30 ± 1.38 ng/mL, t = 2.948, p < .05) and also lower than that in the volunteers without bone trauma group (3.39 ± 1.41 vs. 4.73 ± 1.67 ng/mL, t = 4.135, p < .05). Fibulin-2-/- mice are more prone to infection. Compared with those in WT mice, spleen function and thymus function in fibulin-2-/- mice were impaired. Immunohistochemical staining revealed that compared with those in WT mice, significantly fewer CD4+ T cells, CD8+ T cells, and CD19+ B cells were noted in the spleen and thymus of fibulin-2-/- mice. CONCLUSIONS: The plasma fibulin-2 level was lower in patients with bone trauma. Decreased fibulin-2 is associated with immune dysfunction after bone trauma.

Fibulin2: a negative regulator of BMSC osteogenic differentiation in infected bone fracture healing.

Bone fracture remains a common occurrence, with a population-weighted incidence of approximately 3.21 per 1000. In addition, approximately 2% to 50% of patients with skeletal fractures will develop an infection, one of the causes of disordered bone healing. Dysfunction of bone marrow mesenchymal stem cells (BMSCs) plays a key role in disordered bone repair. However, the specific mechanisms underlying BMSC dysfunction caused by bone infection are largely unknown. In this study, we discovered that Fibulin2 expression was upregulated in infected bone tissues and that BMSCs were the source of infection-induced Fibulin2. Importantly, Fibulin2 knockout accelerated mineralized bone formation during skeletal development and inhibited inflammatory bone resorption. We demonstrated that Fibulin2 suppressed BMSC osteogenic differentiation by binding to Notch2 and inactivating the Notch2 signaling pathway. Moreover, Fibulin2 knockdown restored Notch2 pathway activation and promoted BMSC osteogenesis; these outcomes were abolished by DAPT, a Notch inhibitor. Furthermore, transplanted Fibulin2 knockdown BMSCs displayed better bone repair potential in vivo. Altogether, Fibulin2 is a negative regulator of BMSC osteogenic differentiation that inhibits osteogenesis by inactivating the Notch2 signaling pathway in infected bone.

Sodium acetate ameliorates cisplatin-induced kidney injury in vitro and in vivo.

Cisplatin is an effective chemotherapeutic drug against tumors. Studies often report on the improvement of kidney injury by probiotics or short-chain fatty acids (SCFAs); however, the effects of SCFAs on cisplatin-induced kidney injury are rarely studied. The aim of this study is to evaluate the function of sodium acetate on preventing cisplatin-induced kidney injury. Cell viability was detected by MTT assay. SA-ß-gal staining was performed to investigate premature senescence. Reactive oxygen species (ROS) production was analyzed by H2DCFDA staining. Propidium iodide (PI) staining was analyzed by cell cycle. Protein expression was determined by Western blot assay. Annexin Ⅴ/PI staining was used to investigate cisplatin-induced apoptosis. Tumor growth and kidney injury were evaluated in C57BL/6 mice. Sodium acetate ameliorated cisplatin-induced premature senescence and ROS production in SV40 MES-13 glomerular cells, NRK-52E renal tubular cells, and NRK-49F renal fibroblast cells. Cisplatin-induced cell cycle arrest was inhibited by sodium acetate in SV40 MES-13 and NRK-49F cells. Sodium acetate alleviated cisplatin-induced apoptosis in vivo and in vitro but not cisplatin-induced fibrosis. Our study demonstrated that sodium acetate inhibited cisplatin-induced premature senescence, cell cycle arrest, and apoptosis by attenuating ROS production. This strategy may be useful in the treatment of cisplatin-induced kidney injury.

The Impact of Transoral Robotic Surgery on Erectile Dysfunction and Lower Urinary Tract Symptoms in Male Patients with Moderate-to-Severe Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA), lower urinary tract symptoms (LUTS), and erectile dysfunction (ED) are chronic conditions that seriously affect middle-aged men. This study aimed to evaluate the changes in the presence of these conditions after transoral robotic surgery (TORS) for OSA. This prospective observational study recruited 48 men with moderate-to-severe OSA (mean age 40.6 ± 8.1 years) who underwent TORS from October 2019 to November 2021 at a tertiary center. Baseline polysomnographic parameters, Epworth Sleepiness Scale (ESS), and demographic characteristics were measured. The evaluations of LUTS and ED were based on self-administered International Prostate Symptom Score (IPSS) and International Index of Erectile Function (IIEF-5) questionnaires, respectively, before TORS. The treatment outcomes were assessed three months postoperatively in the patients undergoing TORS due to moderate-to-severe OSA. There was significant Apnea-Hypopnea Index (AHI) reduction from 53.10 ± 25.77 to 31.66 ± 20.34 three months after undergoing TORS (p < 0.001). There was also a significant decrease in the total IPSS score (5.06 ± 5.42 at baseline to 2.98 ± 2.71 at three months postoperatively, p = 0.001), the storage domain, and the voiding domain (p < 0.05). The ED also improved significantly, as seen in the IIEF score (20.98 ± 3.32 to 22.17± 3.60, p = 0.007). The reduction of AHI was associated with changes in body weight and the lowest oxygen saturation (SpO2) levels during sleep (rho = 0.395, p = 0.005; rho = 0.526, p < 0.001, respectively). However, the reduction in AHI was not significantly associated with improvement in IPSS or IIEF scores (p > 0.05). For men with moderate-to-severe OSA, TORS can significantly improve the polysomnography parameters, sleep-related questionnaire scores, and quality of life, and alleviate ED and LUTS. AHI reduction is not a crucial factor for ED and LUTS improvement after TORS for OSA, especially in ED.

NPS-1034 Induce Cell Death with Suppression of TNFR1/NF-κB Signaling in Testicular Cancer.

Background and objectives: NPS-1034 with a dual inhibitory effect on Met and Axl kinase receptors has exhibited therapeutic potential in previous models. However, no study on treating testicular cancer (TC) cell lines with NPS-1034 has been established. Materials and Methods: In this study, a series of in vitro examinations of the apoptotic effect induced by NPS-1034 in TC cell lines was conducted to clarify the molecular interactions involved. Results: A decrease in cell viability rate was observed following NPS-1034 treatment, as shown in the MTT assay. Induction of the apoptotic effect was observed in TC cells as the sub-G1 and Annexin-PI populations increased in a dose-dependent manner. The involvement of the tumor receptor necrosis factor receptor 1 (TNFR1) pathway was later determined by the proteome array and western blotting. A reduction in TNFR1 and NF-κB downstream protein expressions, an upregulation of cleaved caspase-3 and -7, and a downregulation of survivin and claspin all reassured the underlying mechanism of the TNFR1 involved in the apoptotic pathway induced by NPS-1034. Conclusions: Our findings provide evidence for a potential underlying TNFR1 pathway involved in NPS-1034 treatment. This study should offer new insights into targeted therapy for TC.

A Clinical Diagnostic Study: Fibulin-2 is a Novel Promising Biomarker for Predicting Infection.

INTRODUCTION: Infection remains a major cause of morbidity and mortality in hospital. As uncontrolled early infection may develop into systemic infection and eventually progress to sepsis, it is important to address infection at an early stage. Furthermore, early detection and prompt diagnosis of infection are the basis of clinical intervention. However, as a result of the interference of complex aetiologies, including fever and trauma, problems regarding the sensitivity and specificity of current diagnostic indices remain, such as for C-reactive protein (CRP), procalcitonin (PCT), white blood cells (WBC), neutrophil ratio (NEU%), interleukin-6 (IL-6) and D-dimer. As a result, there is an urgent need to develop new biomarkers to diagnose infection. METHODS: From January to October 2021, consecutive patients in the emergency department (ED) were recruited to investigate the feasibility of fibulin-2 as a diagnostic indicator of early infection. Fibulin-2 concentrations in plasma were determined with enzyme-linked immunosorbent assay (ELISA). The performance of fibulin-2 for predicting infection was analysed by receiver operating characteristic (ROC) curves. RESULTS: We found that the plasma fibulin-2 level was elevated in patients with infection compared with those without infection. ROC curve analysis showed that the area under the curve (AUC) for fibulin-2 was 0.712. For all patients included, the diagnostic ability of fibulin-2 (AUC 0.712) performed as well as CRP (AUC 0.667) and PCT (AUC 0.632), and better than WBC (AUC 0.620), NEU% (AUC 0.619), IL-6 (AUC 0.561) and D-dimer (AUC 0.630). In patients with fever, fibulin-2 performed as well as PCT and better than the other biomarkers in infection diagnosis. In particular, fibulin-2 performed better than all these biomarkers in patients with trauma. CONCLUSION: Fibulin-2 is a novel promising diagnostic biomarker for predicting infection.

Chidamide and mitomycin C exert synergistic cytotoxic effects against bladder cancer cells in vitro and suppress tumor growth in a rat bladder cancer model.

Intravesical instillation (IVI) of Bacillus Calmette-Guerin (BCG) can prevent bladder cancer recurrence, but this agent has been out of stock in recent years. IVI of other agents, like chidamide, a histone deacetylase (HDAC) inhibitor, may have the potential to exert a therapeutic effect against bladder cancer by modifying the gene expression profiles associated with histone modifications that occur during cancer tumorigenesis. Here, we investigated the in vitro therapeutic effect of chidamide and/or mitomycin C in bladder cancer cell lines and screened related molecular pathways using an antibody array. We also quantitatively analyzed the synergistic effect of IVI of chidamide and mitomycin C in vivo in an N-methyl-N-nitrosourea (MNU)-induced rat bladder cancer model. The synergistic cytotoxic effect of chidamide plus mitomycin C was confirmed in both T24 and UMUC3 cells, with significantly greater induction of apoptosis elicited with chidamide plus mitomycin C than with either drug alone. The antibody array identified the Axl signaling pathway as the key target of the synergistic effect. Expression of Axl and its related downstream molecules, including claspin and survivin, was significantly suppressed. In the rat bladder cancer model, IVI of chidamide plus mitomycin C reduced tumor burden (Ki67 index) to a greater extent than either drug alone. Our results suggest that chidamide and mitomycin act synergistically to reduce MNU-induced bladder cancer. These findings provide new insights into a new and potentially effective approach to treating bladder cancer.

Clindamycin-loaded titanium prevents implant-related infection through blocking biofilm formation.

Implant-related infection is a disastrous complication. Surface modification of titanium is considered as an important strategy to prevent implant-related infection. However, there is no recognized surface modification strategy that can be applied in clinic so far. We explored a new strategy of coating. The clindamycin-loaded titanium was constructed by layer-by-layer self-assembly. The release of clindamycin from titanium was detected through high performance liquid chromatography. Different titanium was co-cultured with Staphylococcus aureus for 24 h in vitro, then the effect of different titanium on bacterial colonization and biofilm formation was determined by spread plate method and scanning electron microscopy. Cytotoxicity and cytocompatibility of clindamycin-loaded titanium on MC3T3-E1 cells were measured by CCK8. The antibacterial ability of clindamycin-loaded titanium in vivo was also evaluated using a rat model of osteomyelitis. The number of osteoclasts in bone defect was observed by tartrate-resistant acid phosphatase staining. Bacterial burden of surrounding tissues around the site of infection was calculated by tissue homogenate and colony count. Clindamycin-loaded titanium could release clindamycin slowly within 160 h. It reduced bacterial colonization by three orders of magnitude compare to control (p < .05) and inhibits biofilm formation in vitro. Cells proliferation and adhesion were similar on three titanium surfaces (p > .05). In vivo, clindamycin-loaded titanium improved bone healing, reduced microbial burden, and decreased the number of osteoclasts compared control titanium in the rat model of osteomyelitis. This study demonstrated that clindamycin-loaded titanium exhibited good biocompatibility, and showed antibacterial activity both in vivo and in vitro. It is promising and might have potential for clinical application.

Native Kidney Hydronephrosis Is Associated with Upper Urinary Tract Urothelial Carcinoma in Post-Kidney Transplantation Patients.

BACKGROUND: Upper urinary tract urothelial carcinoma (UTUC) is the most common malignancy occurring after kidney transplantation (KT) in Taiwan. The aim of this study was to investigate the association between native kidney hydronephrosis and UTUC in post-KT patients. METHODS: From 2003 to 2018, we conducted a retrospective cohort study that enrolled 1005 post-KT patients, 67 of whom were subsequently diagnosed with UTUC. We divided patients into two groups based on whether or not they had UTUC. Multivariate analysis and Kaplan-Meier plot were used to evaluate if native kidney hydronephrosis was associated with post-KT UTUC. RESULTS: The total cohort consisted of 612 men (60.9%) and 393 women (39.1%) with a mean age of 48.2 ± 12.0 at KT. The mean follow-up time was 118.6 ± 70.2 months, and mean time from KT to UTUC was 7.53 years. There was a significant gender difference with a female predominance among the UTUC patients (73.1% versus 26.9%, p < 0.001). Native kidney hydronephrosis occurred more frequently in the UTUC group (68.7% versus 4.8%, p < 0.001). Multivariate analysis showed that native kidney hydronephrosis and female gender were significantly associated with UTUC with odds ratios of 35.32 (95% CI, 17.99-69.36; p < 0.001) and 3.37 (95% CI, 1.55-7.29; p = 0.002), respectively. UTUC in the post-KT patients also showed aggressive pathological characteristics and a tendency toward bilateral lesions (41.8%). CONCLUSIONS: Native kidney hydronephrosis is significantly associated with post-KT UTUC patients in Taiwan. Native kidney hydronephrosis may be a deciding factor for standard nephroureterectomy and bladder cuff excision in selected patients. Nevertheless, almost half of the patients with kidney hydronephrosis do not present with UTUC at the end of our study.

Intravesical Instillation of Azacitidine Suppresses Tumor Formation through TNF-R1 and TRAIL-R2 Signaling in Genotoxic Carcinogen-Induced Bladder Cancer.

Azacitidine, an inhibitor of DNA methylation, shows therapeutic effects against several malignancies by inducing apoptosis and inhibiting tumor cell proliferation. However, the anti-tumor effects of azacitidine on urinary bladder urothelial carcinoma (UBUC), especially following intravesical instillation (IVI), are not established. Here, UBUC cell lines were used to analyze the in vitro therapeutic effects of azacitidine. Potential signaling pathways were investigated by antibody arrays and Western blotting. The N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced rat UBUC model was used for in vivo quantitative analysis of tumor burden. Azacitidine significantly inhibited DNMT expression in UBUC cell lines and reduced cell viability and clonogenic activity, as determined by MTT and colony formation assays, while also inducing significant cytotoxic effects in the form of increased sub-G1 and Annexin V-PI populations (all p < 0.05). Antibody arrays confirmed the in vitro suppression of TNF-R1 and the induction of TRAIL-R2 and their downstream signaling molecules. TNF-R1 suppression reduced claspin and survivin expression, while TRAIL-R2 activation induced cytochrome C and caspase 3 expression. Rats with BBN-induced bladder cancer had a significantly reduced tumor burden and Ki67 index following IVI of azacitidine (p < 0.01). Our study provides evidence for a reduction in BBN-induced bladder cancer by IVI of azacitidine through alterations in the TRAIL-R2 and TNF-R1 signaling pathways. These findings might provide new insights for further clinical trials.

Trends of Testicular Cancer Mortality-to-Incidence Ratios in Relation to Health Expenditure: An Ecological Study of 54 Countries.

Favorable testicular cancer mortality-to-incidence ratios (MIRs) are associated with health care disparities, including health care expenditures, but the trends of testicular MIR and health care disparity remain unclear. We evaluated changes in MIR as the difference between 2012 and 2018, termed delta MIR (δMIR). Health care expenditures and the human development index (HDI) were obtained from the World Health Organization and the Human Development Report Office of the United Nations Development Programme. The association between the variables was analyzed by Spearman's rank correlation coefficient. A total of 54 countries were included in the criteria of data quality reports and missing data. By continent, the most favorable MIR was in Oceania (0.03) while it was 0.36 in Africa. In these areas, the incidence rates were positively correlated to health care expenditure, but the mortality rates showed a reversed correlation. The MIR ranged from 0.01 to 0.34 and the δMIR ranged from -0.05 to 0.34. The favorable MIRs are correlated to high health care expenditure and HDI (all p < 0.001). Interestingly, favorable δMIRs tend to be seen in countries with relatively low health care expenditure and HDI (all p < 0.001). In conclusion, favorable testicular cancer MIRs are associated with high HDI and health care expenditure, but the improvement in MIR between 2012 and 2018 (δMIR) is negatively correlated with HDI and health care expenditure.

Gender differences in trends of bladder cancer mortality-to-incidence ratios according to health expenditure in 55 countries.

The association between bladder cancer mortality-to-incidence ratios (MIRs) and healthcare disparities has gender differences. However, no evidence supports gender as an issue in the association between changes in the MIR and health expenditures on bladder cancer. Changes in the MIR were defined as the difference in data from the years 2012 and 2018, which was named δMIR. Current health expenditures (CHE) and the human development index (HDI) were obtained from the World Health Organization and the Human Development Report Office. The association between variables was analyzed by Spearman's rank correlation coefficient. In total, 55 countries were analyzed according to data quality and the exclusion of missing data. Globally, the MIR changed according to the HDI level in both genders. Among the 55 countries studied, a high HDI and CHE were significantly associated with a favorable age-standardized rate-based MIR (ASR-based MIR) in both genders and the subgroups according to gender (for both genders, MIR vs. HDI: ρ = -0.720, p < 0.001; MIR vs. CHE per capita: ρ = -0.760, p < 0.001; MIR vs. CHE as a percentage of gross domestic product (CHE/GDP): ρ = -0.663, p < 0.001). Importantly, in females only, the CHE/GDP but neither the HDI score nor the CHE per capita was significantly associated with a favorable ASR-based δMIR (ASR-based δMIR vs. CHE/GDP: ρ = 0.414, p = 0.002). In the gender subgroups, the association between the HDI and the CHE was statistically significant for females and less significant for males. In conclusion, favorable bladder ASR-based MIRs were associated with a high CHE; however, improvement of the ASR-based δMIR data was more correlated with the CHE in females. Further investigation of the gender differences via a cohort survey with detailed information of clinical-pathological characteristics, treatment strategies, and outcomes might clarify these issues and improve therapeutic and/or screening strategies for bladder cancer.

Trends in the kidney cancer mortality-to-incidence ratios according to health care expenditures of 56 countries.

The incidence and mortality rates in kidney cancer (KC) are increasing. However, the trends for mortality have varied among regions over the past decade, which may be due to the disparities in medical settings, such as the availability of frequent imaging examinations and effective systemic therapies. The availability of these two medical options has been proven to be positively correlated with a favorable prognosis in KC and may be more common in countries with better health care systems and greater expenditures. The delicate association between the trends in clinical outcomes in KC and health care disparities warrant detailed observation. We applied a delta-mortality-to-incidence ratio (δMIR) for KC to compare two years as an index for the improvement in clinical outcomes and the mortality-to-incidence ratio (MIR) of a single year to evaluate their association with the Human Development Index (HDI), current health expenditure (CHE) per capita, and CHE as a percentage of gross domestic product (CHE/GDP) by using linear regression analyses. A total of 56 countries were included based on data quality reports and missing data. We discovered that the HDI, CHE per capita, and CHE/GDP were negatively correlated with the MIRs for KC (p < 0.001, p < 0.001, and p < 0.001, respectively). No significant association was observed between the δMIRs and the HDI, CHE per capita, and CHE/GDP among the included countries, and only the CHE/GDP shows a trend toward significance. Interestingly, the δMIRs related with an increase in relative health care investment include δCHE per capita and δCHE/GDP.

Platelet-rich plasma loaded with antibiotics as an affiliated treatment for infected bone defect by combining wound healing property and antibacterial activity.

To be faced with an infected bone defect and the need to accelerate bone union while controlling infection is a welcome challenge for orthopedists. Platelet-rich plasma (PRP) has been applied in tissue defects given their composition of growth factors however the weak antibacterial effects have limited the use of PRP in the clinical setting. Therefore, the aim of this study was to explore the feasibility of using PRP in a local antibiotic delivery system (PADS) with the characteristics of promoting wound healing of bone infection. PADS was prepared with the addition of antibiotics or no antibiotics as control after PRP was prepared by a two-step centrifugation procedure. Antibacterial tests showed zones of inhibition produced by antibiotics were not significantly different with antibiotics combined with PRP. HPLC analysis demonstrated that about 60% of the total vancomycin (VAN) and ceftazidime (CAZ) dose were released within 10 min, then the release rate gradually decreased. However, 90% clindamycin was released within 10 min. Interestingly, above 10 times the minimum inhibitory concentration was presented after 72 h. Additionally, ELISA and morphology studies of PADS indicated that loaded antibiotics could reduce the PRP-released growth factor concentration and disturb the structure of platelet-fibrin beams and fibrin network in a dose-dependent manner. Fortunately, the lower dose of antibiotics maintained their anti-microbial effect, meanwhile growth factors released from PADS, the structure of platelet-fibrin beams, fibrin network remained unaffected. In addition, a patient experiencing infected bone defect receiving this PADS treatment achieved union within the 15-month follow-up. Therefore, this novel PADS approach might represent a potential therapy for patients who have sustained infected bone defects.

Application of platelet-rich plasma in traumatic bone infections.

Introduction: Traumatic bone infection represents a clinical challenge for orthopedic surgeons. Traditional treatments include surgical debridement and antibiotic, but prolonged use of antibiotic may lead to colonization of resistant bacteria and other adverse reactions.Areas covered: Platelet-rich plasma (PRP), a biological product extracted from the peripheral blood of patients, has been widely used in the field of tissue repair in recent years. Because if its structural and antibacterial properties, PRP is an innovative option for the prevention and treatment of infections. This review assesses the recent scientific literature on PRP, specifically its in the treatment of infections. To this end, a literature review was conducted using the PubMed and Web of Science databases with the following keywords 'platelet-rich plasma (PRP)'; 'PRP AND traumatic bone infections'; 'PRP AND bone defect'; 'PRP AND antibiotics'; and 'PRP AND wound healing'.Expert opinion: This review focuses on the mechanism of action, preparation methods, clinical applications and other aspects related to PRP to provide a reference for its use in the treatment of traumatic bone infections, thereby enhancing the therapeutic effectiveness and improving the prognosis of patients.