The influence of simvastatin on osteoblast functionality in the presence of titanium dioxide particles In-vitro.

OBJECTIVE: Leaching of particles from dental titanium implant surfaces into preimplant microenvironment causes detrimental effects on bone cells. The current study investigated influence of simvastatin in mitigating adverse pro-inflammatory effects of titanium dioxide (TiO2) micro (MP) and nano (NP) particles on hFOB 1.19 cells in vitro. DESIGN: Viability of hFOB 1.19 cells following exposure to varying concentrations of TiO2 MPs and NPs and simvastatin were measured by XTT assay. hFOB 1.19 cells were treated with 100 µg/mL of TiO2 MPs, 100 µg/mL of TiO2 NPs, 0.1 µM simvastatin, 100 µg/mL of TiO2 MPs+ 0.1 µM simvastatin and 100 µg/mL of TiO2 NPs+ 0.1 µM simvastatin. After 24 h, ROS was measured by flow cytometry. On day 14, real-time PCR analysis for pro-inflammatory cytokines and bone formation markers was done for TNFα, IL1ß, osteocalcin, ALP, and Col1 markers; while ALP and RANKL/OPG ratio were determined by colorimetric and ELISA assays respectively. Further, mineralization study using Alizarin Red S staining (ARS) and calcium quantification were performed. RESULTS: Exposure of hFOB to TiO2 MPs and NPs generated ROS and reduced cell viability significantly, with upregulation of pro-inflammatory markers TNFα and IL1ß and downregulation of bone formation markers OC and increased RANKL/OPG ratio and lowered degree of mineralization. Treatment with 0.1 µM of simvastatin treatment reversed the effects by mitigating oxidative stress, dampening pro-inflammatory markers, upregulation of bone formation markers, lowering RANKL/OPG ratio and increasing degree of mineralization. CONCLUSION: Simvastatin possesses antioxidant, anti-inflammatory, and pro-osteogenic properties that may support bone healing around titanium implants.

Impact of Bone Morphogenetic Protein 7 and Prostaglandin receptors on osteoblast healing and organization of collagen.

PURPOSE: This study seeks to investigate the impact of co-administering either a Prostaglandin EP2 receptor agonist or an EP1 receptor antagonist alone with a low dose BMP7 on in vitro healing process, collagen content and maturation of human osteoblasts. METHODOLOGY: Human osteoblast cells were used in this study. These cells were cultured and subjected to different concentrations of Prostaglandin EP2 receptor agonist, EP1 receptor antagonist, BMP7, Control (Ct) (Vehicle alone), and various combinations treatments. Cell viability at 24, 48 and 72 hours (h) was evaluated using the XTT assay. A wound healing assay was conducted to observe the migration ability of human osteoblast cells. Additionally, Sirius red staining and Fourier-Transform Infrared Spectroscopy Imaging (FT-IR) was employed to analyze various parameters, including total protein concentration, collagen production, mature collagen concentration, and mineral content. RESULTS: The combination of low dose BMP7 and Prostaglandin EP2 receptor agonist resulted to the lowest cell viability when compared to both the Ct and individual treatments. In contrast, the Prostaglandin EP1 receptor antagonist alone showed the highest cellular viability at 72 h. In the wound healing assay, the combined treatment of low dose BMP7 with the Prostaglandin EP2 receptor agonist and EP1 receptor antagonist showed a decrease in human osteoblast healing after 24 h. Analysis of FT-IR data indicated a reduction in total protein content, collagen maturity, collagen concentration and mineral content in combination treatment compared to the single or Ct treatments. CONCLUSION: The combination of a Prostaglandin EP2 receptor agonist or an EP1 receptor antagonist when combined with low dose BMP7 significantly hinders both human osteoblast healing and collagen maturity/concentration in comparison to low dose BMP7 treatment alone.

Does intravesical Bacillus Calmette-Guérin for bladder cancer protect from COVID-19?

INTRODUCTION: The study aimed to correlate the history of intravesical BCG as well as infantile BCG immunization with the incidence and severity of COVID-19 infection. METHODS: Retrospective data collection of patients with high-risk non muscle invasive bladder cancer (NMIBC) from two Canadian centers. Data collection included a history of BCG instillation, infantile immunization, and the development of COVID-19 infection. Admission and/ or mortality because of COVID-19 was reported. RESULTS: We could include data from 348 patients: including 188 and 160 patients from Ontario and British Columbia respectively. COVID-19 affected 15% of these patients. Intravesical BCG was used in 44% of these patients. Intravesical BCG and/or infantile BCG immunization did not correlate with the incidence of COVID-19 infection. CONCLUSIONS: Previous intravesical BCG and/ or a history of infantile BCG vaccination were not more/ less frequent in patients who had COVID-19 infection.

Endophytic to total tumour volume ratio: An added variable to patients with T1b/T2 renal tumours undergoing partial nephrectomy.

INTRODUCTION: Partial nephrectomy is the standard of care to patients with small renal masses. It is still encouraged to larger tumours whenever feasible. The aim of this study is to look for the endophytic to total tumour volume ratio as an added variable to study the complexity of partial nephrectomy to patients with T1b/ T2 renal tumours. METHODS: Retrospective data collection of patients that had partial nephrectomy for T1b/T2 renal tumours by a single surgeon was done. Radiological re-assessment for the CT images to measure the endophytic to total tumour volume ratio was done. RESULTS: The mean age of the patients was 63 years. The study included 25 males and 11 females. All cases were managed by open surgery using retroperitoneal transverse lateral lumbotomy and warm ischemia was used in all patients. The mean tumour volume was 74 cc, the mean endophytic tumour volume was 29 cc. The mean percentage of endophytic to total tumour volume was 42%. CONCLUSIONS: Partial nephrectomy is safe for most of the patients with good performance status, having large renal masses. More complex surgery can be predicted in patients with endophytic to total tumour volume greater than 42%.

Evaluation of salivary Thy-1 in health, periodontitis, and obesity.

OBJECTIVES: Thy-1 (CD90) is a glycosylphosphatidyl-anchored protein belonging to the immunoglobulin family and is known to control mesenchymal stromal cells differentiation into osteoblasts or adipocytes. The study aimed to investigate the salivary levels of Thy-1 in health, periodontitis, obesity, and any potential association. MATERIALS AND METHODS: Seventy-one participants were divided into four groups: healthy (H), subjects with periodontitis (P), obese individuals (O), and obese individuals having periodontitis (PO). Unstimulated whole saliva was collected from participants who were evaluated for periodontal parameters. The levels of Thy-1 were measured with a commercially available ELISA kit. The data were statistically analyzed. RESULTS: A significant difference in salivary Thy-1 levels among different groups was observed. Periodontitis patients had the maximum, and obese individuals had the minimum Thy-1 levels. Significant differences between H and P, H and PO, P and O, and O and PO were observed. Overall correlations between Thy-1 and periodontal parameters and a positive correlation with pocket depth in group PO were noted. CONCLUSION: Thy-1 could be detected in the saliva of all study participants. It is implied that a local inflammatory condition like periodontitis elevates the salivary levels of Thy-1 with, and without obesity.

History of infantile BCG immunization did not predict lamina propria invasion and/or high-grade in patients with non-muscle invasive bladder cancer.

OBJECTIVE: To evaluate the utility of infantile BCG vaccination history in predicting stage and grade of tumours in non-muscle invasive bladder cancer (NMIBC). MATERIALS AND METHODS: We retrospectively analyzed data from patients from a single center who were diagnosed with new NMIBC and underwent transurethral resection of bladder tumour (TURBT) between 2017 and 2022. We assessed BCG immunization status with various demographics and comorbidities, as well as tumour recurrence, progression, stage, and grade. RESULTS: A total of 188 patients met the inclusion criteria for our study. The mean age of patients at the time of diagnosis was significantly lower in those that had been immunized with BCG (71 ± 9) than those who had not (77 ± 10) (p < 0.0001). History of BCG immunization did not correlate with sex, history of diabetes mellitus (DM), prior history of intravesical BCG treatment, and tumour recurrence, progression, stage, and grade. CONCLUSIONS: History of infantile BCG vaccination did not correlate with the depth of invasion and/or the grade in patients with non-muscle invasive bladder cancer. Patients that received infantile BCG vaccination were significantly younger at the time of diagnosis of NMIBC.

The 14-Kilodalton Human Growth Hormone Fragment a Potent Inhibitor of Angiogenesis and Tumor Metastasis.

The 14-kilodalton human growth hormone (14 kDa hGH) N-terminal fragment derived from the proteolytic cleavage of its full-length counterpart has been shown to sustain antiangiogenic potentials. This study investigated the antitumoral and antimetastatic effects of 14 kDa hGH on B16-F10 murine melanoma cells. B16-F10 murine melanoma cells transfected with 14 kDa hGH expression vectors showed a significant reduction in cellular proliferation and migration associated with an increase in cell apoptosis in vitro. In vivo, 14 kDa hGH mitigated tumor growth and metastasis of B16-F10 cells and was associated with a significant reduction in tumor angiogenesis. Similarly, 14 kDa hGH expression reduced human brain microvascular endothelial (HBME) cell proliferation, migration, and tube formation abilities and triggered apoptosis in vitro. The antiangiogenic effects of 14 kDa hGH on HBME cells were abolished when we stably downregulated plasminogen activator inhibitor-1 (PAI-1) expression in vitro. In this study, we showed the potential anticancer role of 14 kDa hGH, its ability to inhibit primary tumor growth and metastasis establishment, and the possible involvement of PAI-1 in promoting its antiangiogenic effects. Therefore, these results suggest that the 14 kDa hGH fragment can be used as a therapeutic molecule to inhibit angiogenesis and cancer progression.

Accuracy of Rapid Emergency Medicine Score and Sequential Organ Failure Assessment Score in predicting acute paraphenylenediamine poisoning adverse outcomes.

Paraphenylenediamine (PPD) is a commonly used xenobiotic in hair dying, causing deleterious outcomes in acute poisoning. Although many epidemiological studies and case reports explained their clinical presentations and fatal consequences, no studies have evaluated the early determinants of adverse outcomes. Therefore, the present study aimed to assess the initial predictors of acute PPD poisoning adverse outcomes, focusing on the discriminatory accuracy of the Rapid Emergency Medicine Score (REMS) and Sequential Organ Failure Assessment (SOFA) score. A retrospective cohort study included all acute PPD-poisoned patients admitted to three Egyptian emergency hospitals from January 2020 to January 2022. Data was gathered on admission, including demographics, toxicological, clinical, scoring systems, and laboratory investigations. Patients were categorized according to their outcomes (mortality and complications). Ninety-seven patients with acute PPD poisoning were included, with a median age of 23 years, female predominance (60.8%), and suicidal intention (95.9%). Out of all patients, 25.77% died, and 43.29% had complicated outcomes. Respiratory failure was the primary cause of fatalities (10.30%), while acute renal failure (38.14%) was a chief cause of complications. The delay time till hospitalization, abnormal electrocardiogram, initial creatine phosphokinase, bicarbonate level, REMS, and SOFA scores were the significant determinants for adverse outcomes. The REMS exhibited the highest odds ratio (OR = 1.91 [95% confidence interval (CI): 1.41-2.60], p < 0.001) and had the best discriminatory power with the area under the curve (AUC) = 0.918 and overall accuracy of 91.8% in predicting mortality. However, the SOFA score had the highest odds ratio (OR = 4.97 [95% CI: 1.16-21.21], p = 0.001) and only yielded a significant prediction for complicated sequels with AUC = 0.913 and overall accuracy of 84.7%. The REMS is a simple clinical score that accurately predicts mortality, whereas the SOFA score is more practicable for anticipating complications in acute PPD-poisoned patients.

Partial Nephrectomy for T1b/T2 Renal Mass: An Added Shift from Radical Nephrectomy.

The aim of our study was to show our short-term experience in managing large renal masses (cT1b/T2) through partial nephrectomy (PN) over the last 3 years. Retrospective data collection for all patients managed by PN for renal masses larger than 4 cm over the last 3 years. Epidemiological data were collected. Surgical data including surgical and ischemic times as well as intra and postoperative complications were collected. Pre- and postoperative estimated glomerular filtration rate (eGFR) data were collected and correlated as well as postoperative complications and recurrence. We could identify 47 patients managed by PN for radiologically confirmed >4 cm renal masses. The mean age of the patients was 55.7 ± 13.4, including 29 males and 18 females. Masses were T1b and T2 in 40 and 7 patients, respectively. The mean tumor size was 6.2 ± 1.5 cm. Using renal nephrometry score; 8, 28, and 11 had low, moderate, and high complexity, respectively. Renal cell carcinoma (RCC) was identified in 42 patients. Five patients out of 42 cancerous cases (12%) had pathological T3 RCC. The mean preoperative and postoperative eGFR were 89.09 ± 12.41 and 88.50 ± 10.50, respectively (P 0.2). The median follow-up was 14 months and within that short time, no patient had evidence for cancer recurrence. PN for large renal masses is safe in experienced hands and should be attempted in a higher percentage of patients, regardless of the tumor complexity. No cancer recurrence or deterioration of renal function was observed within our short-term follow-up.

Successful Surgical Management of Locally Advanced Renal Cell Carcinoma Invading Spleen and Pancreas.

Over the last two decades, the treatment of metastatic RCC has changed significantly, and the role of surgery is being debated. A 50-year-old man presented with pain in his left loin. An ultrasound, followed by a CT scan, revealed a 17.5 cm left renal mass invading the left suprarenal gland, spleen, and pancreatic tail. Radical nephrectomy through chevron incision under epidural block with general anesthesia was performed. The entire mass was removed en bloc. The estimated blood loss was 300 mL, and no blood transfusions were performed. The operation took approximately 2 h. Histological examination revealed clear cell renal carcinoma with extension into the spleen, pancreatic tail, and diaphragmatic fibers with negative resection margin. The patient discharged after a 3-day uneventful hospital stay. Aggressive surgical removal of a locally invasive renal cell carcinoma is feasible and should be considered in patients with good performance status and no or minimal distant metastases.

Radical cystectomy for bladder urothelial carcinoma with aggressive variant histology.

PURPOSE: The aim of this study is to report our experience in managing bladder cancer in patients with variant pathology. METHODS: Retrospective data collection for all patients managed by radical cystectomy over the last 3 years for a variant pathol-ogy was completed. We specifically included micropapillary and nested variants. RESULTS: Ten patients were identified, with eight having micropapillary carcinoma (MPC) and two having nested vari-ants. Nine patients were male. The median age was 75. The two patients with nested variant were 56 and 62 years old, respec-tively, whereas all patients with MPC were over the age of 70. Upon cystectomy of all micropapillary cases, three patients (37.5%) had positive lymph node invasion and the final patholo-gy was T2 (two patients), T3 (two patients), and T4 (four patients). Barring a grade III complication Clavien-Dindo classi-fication due to wound dehiscence that necessitated secondary surgical closure, there were no specific perioperative complica-tions. Given the urethral invasion, cystourethrectomy was per-formed on the female patient. Within a median 13-month fol-low-up, three patients developed local recurrence, including two urethral and one new lateral pelvic mass. CONCLUSIONS: Considering the muscle invasive nature of micropapillary and nested bladder cancer, aggressive surgical management should not be postponed. Moreover, due to notable prevalence of concurrent and/or recurrent urethral involvement, initial urethrectomy or early and frequent postoperative ure-throscopy should be provided. Patients with variant histology bladder cancer may benefit from early radical cystectomy when compared to bladder sparing protocols and prostate sparing cystectomy treatment options.

The efficacy of salivary Histatin-1 protein in wound closure of nicotine treated human periodontal ligament fibroblast cells - In vitro study.

OBJECTIVES: The aims of this study were to investigate the efficacy of Histatin-1 in wound closure as well as effects on gene expression of nicotine-treated human Periodontal Ligament Fibroblast cells (HPDL) in vitro. DESIGN: HPDL grown in 2.5% culture medium treated with 10 ng/ml Histatin - 1 in the presence/absence of 0.5 µM nicotine were subjected to wound assay and migration was studied at 0 h, 6 h, 12 h and 24 h. Cells grown in 2.5% medium served as control. Cell migration was studied by wound gap and transwell migration assays. The effect of Histatin-1 on expression of matrix metalloproteinase 8 (MMP-8), insulin-like growth factor 1 (IGF-1), transforming growth factor beta (TGF-ß), collagen type I (COL1) and plasminogen activator inhibitor 1 (PAI-1) were studied. RESULTS: Histatin-1 treatment significantly decreased percentage wound gap at 12 h (62.96 ± 3.22 vs 79.23 ± 1.73; p < 0.05) and at 24 h (38.78 ± 7.59 vs 75.21 ± 4.94; p < 0.001) compared with controls. In nicotine+Histatin-1 treated cells, wound gap decreased to 70.2 ± 2.9% (p < 0.01) at 24 h compared to nicotine alone in which 82 ± 1.64% of wound gap was retained. Transwell migration assays showed significant migration of HPDL with Histatin-1 (p < 0.05). Gene expression demonstrated significant upregulation for IGF-1, TGF ß, COL1 and PAI-1 with Histatin-1. CONCLUSION: Histatin-1 significantly mitigated the effect of nicotine in wound healing assay involving HPDL fibroblast cells at 24 h. Histatin-1 aided wound closure is attributed to the upregulation of IGF-1, TGF ß, COL1, and PAI-1 genes.

Adverse pathological outcomes of patients with de novo muscle invasive bladder cancer in Northern Ontario.

OBJECTIVE: This study aimed to investigate the clinical and pathological characteristics of patients with de novo muscle-invasive bladder cancer (MIBC) who underwent radical cystectomy in Northern Ontario. METHODS: This is a retrospective cross-sectional study of patients with de novo T2 MIBC who underwent radical cystectomy over a 2-year-period in Thunder Bay Regional Health Sciences Centre. Clinical and pathological characteristics of Trans Urethral Resection of Bladder Tumors and cystectomy specimens were analyzed. RESULTS: Of the 59 patients aged 67 ± 8.8 years, predominated by males (80%), 27.1% were younger than age 60. After surgery, upstaging was noted in 59.3% (T3 in 27.1% and T4 in 32.2%) while node positive was noted in 36% of patients. Prostate adenocarcinoma was incidentally discovered in 20 (34%) of patients with 50% considered significant (Gleason score ≥ 7). Downstaging was found in those who had neoadjuvant chemotherapy (p = 0.001). CONCLUSIONS: The high prevalence of younger ages (less than 60), a high rate of upstaging, the presence of high-grade incidental prostate cancer, and lymph node positives in T2 de novo MIBC in Northern Ontario, warrants further investigation of potential causes and risk factors at individual, public, and population health levels in the region.

Aristolochic acid: What urologists should know.

To the Editor, Aristolochic acid is one of major causes for upper tract urothelial carcinoma, especially in younger population. While it is mentioned as a cause in guidelines, little is actually known about the toxin by urologists. We are aiming in our letter to provide some direct and clear information to ourselves that would help us to know more about that toxin and how it can adversely affect our patients [...].

Radical cystectomy for clinical T4b urothelial carcinoma: An Ontario, single-center experience.

INTRODUCTION: Guidelines surrounding the management of T4b muscle-invasive bladder cancer (MIBC) with radical cystectomy (RC) are limited and lack clarity. Our objective was to analyze our single-center experience to provide additional insight into the role of RC. METHODS: We performed a retrospective data analysis using clinical, radiological, and pathological information for all patients managed by RC for cT4b MIBC at the Thunder Bay Regional Health Sciences Centre (July 2015 to July 2020). Patients that had MIBC as their first diagnosis were termed the de novo group and patients that were initially diagnosed as having non-MIBC were termed the progressive group. RESULTS: Nineteen consecutive patients (16 males and three females), with a median age of 68 years, managed by two urologists over the last five years, met study criteria. Eleven (58%) of the patients had de novo MIBC while eight (42%) presented with progressive disease. All patients had dysuria as a presenting symptom. Only one (5%) patient received neoadjuvant chemotherapy. There were low rates of perioperative transfusion (11%), bowel resections (5%), postoperative transfusions (0%), ileus (32%), urine leak (16%), and wound dehiscence (5%). Fourteen patients (74%) had positive lymph nodes. All patients had adjuvant chemotherapy. The one-year recurrence rate in these patients was 53%, with 32% of recurrence being distant metastasis. The one-year survival rate was 95%. CONCLUSIONS: Patients in the de novo and progressive arms of our cohort had similar rates of surgical complications and disease recurrence. We found operative morbidity and disease control to be reasonable, suggesting RC can be considered more often in the management of T4b MIBC patients.

Micropapillary bladder cancer: an added indication to prophylactic urethrectomy.

There is little research on the role of urethrectomy during cystectomy in patients with micropapillary bladder cancer (MPBC). We present two cases of MPBC cystectomy and suggest that urethrectomy be performed concurrently as a preventive measure. The first case involved a woman who had a mixed solid and papillary bladder tumour. An anterior pelvic exenteration was performed as well as a total urethrectomy. The T4a micropapillary variant tumour was confirmed by pathology. The second case involved a man with T1 MPBC who was treated with a BCG induction course. A recurrent muscle-invasive MPBC was discovered during follow-up. During the radical cystoprostatectomy, the urethra was spared. T2 MPBC was discovered through pathology. He had a urethrectomy 6 months later due to urethral bleeding, and the pathology revealed micropapillary cancer of the urethra.

Bacillus Calmette-Guerin vaccine and bladder cancer incidence: Scoping literature review and preliminary analysis.

BACKGROUND: The Bacillus Calmette-Guerin (BCG) vaccine has long been used for the prevention of tuberculosis (TB) around the world. BCG is also used as an immunotherapy agent for the treatment of non-muscle invasive urinary bladder cancer. This scoping literature review and preliminary data analysis aims to summarize the literature correlating infantile BCG vaccination with the incidence of future bladder cancer. METHODS: Studies were identified by a formal literature search of MEDLINE and Cochrane Central Registrar of Controlled Trials following PRISMA guidelines. Preliminary data analysis was conducted on publicly accessible data summarizing the impact of gender, BCG vaccination, and socio-economic effects on crude and age-standardized rates of bladder cancer. RESULTS: As part of our analysis, preliminary regression models demonstrated BCG vaccination status, gender, and socio-economic status to have statistically significant effects on crude and age-standardized rates of bladder cancer incidence. BCG vaccination was associated with a 35-37% lower age-standardized rate of bladder cancer incidence. CONCLUSIONS: There is very little literature examining the relationship between prior BCG vaccination and rates of bladder cancer incidence. Our limited data analysis indicates that a relationship does exist between infantile BCG vaccination and later bladder cancer development, although extensive future investigation is needed in this area.