Tucatinib and stereotactic radiosurgery in the management of HER2 positive breast cancer brain metastases.

PURPOSE: HER2-positive breast cancer has a high risk of brain metastasis. Stereotactic radiosurgery (SRS) is standard of care for limited brain metastases. Tucatinib, a HER2-targeted tyrosine kinase inhibitor, has demonstrated intracranial efficacy in the HER2-CLIMB Trial. However, it is unknown whether tucatinib with SRS is safe or effective. METHODS: A retrospective analysis of HER2-positive breast cancer treated with SRS and tucatinib for brain metastases management was performed. All patients received tucatinib and SRS for the management of active brain metastases. The primary endpoint was local and distant brain tumor control. Secondary endpoints were intracranial progression free survival (CNS-PFS), systemic PFS, overall survival (OS), and neurotoxicity. RESULTS: A total of 135 lesions treated with SRS over 39 treatment sessions in 22 patients were identified. Median follow-up from tucatinib initiation was 20.8 months. Local brain control was 94% at 12-months and 81% at 24-months. Distant brain control was 39% at 12-months and 26% at 24-months. Median survival was 21.2 months, with 12- and 24-month OS rates of 84% and 50%, respectively. Median CNS-PFS was 11.3 months, with 12- and 24-month CNS-PFS rates of 44.9% at both time points. Median systemic PFS was not reached, with 12- and 24-month systemic PFS rates of 86% and 57%, respectively. Symptomatic radiation necrosis occurred in 6 (4%) lesions. No additional unexpected toxicities were noted. CONCLUSIONS: SRS in combination with tucatinib, capecitabine, and trastuzumab appears to be a safe and feasible treatment for HER2 + brain metastases. Further prospective evaluation of potential synergistic effects is warranted.

Effect of intrauterine infusion of autologous platelet-rich plasma in patients with refractory thin endometrium undergoing in vitro fertilization.

Introduction: Treatment of refractory thin endometrium during IVF is a relatively challenging problem, considering that optimal endometrium thickness is one of the critical factors for successful implantation and pregnancy. Autologous intrauterine platelet-rich plasma (PRP) infusion is an adjuvant therapeutic alternative for enhancing the endometrial thickness (EMT) and echo pattern. It was shown that PRP could expand EMT and improve pregnancy outcomes with its high content of growth factors and cytokines, and its role in the regulation of the immunological interaction between the embryo and the endometrium. The aim of the study is to evaluate the effect of autologous PRP in improving the ongoing pregnancy rate in patients with refractory thin endometrium undergoing IVF. Material and methods: A prospective study in Ain Shams University Hospital including 66 infertile women with a refractory thin endometrium below 7 mm by ultrasound on the day of human chorionic gonadotropin injection in fresh embryo transfer (ET) cycle, who did not respond to standard medical therapies after more than 2 cycles of previous medical therapy, and who were candidates for IVF cycle were given intrauterine PRP. Results: A significant increase in EMT was noted and enhancement of endometrial pattern after intrauterine PRP infusion in the days of ovum pick-up and ET. There was also a significant increase in ongoing pregnancy, chemical pregnancy, clinical pregnancy, and implantation rates, while the miscarriage rate decreased after PRP infusion. Conclusions: Intrauterine PRP infusion improved ongoing pregnancy, chemical pregnancy, clinical pregnancy, and implantation rates, in addition to EMT and pattern on the days of ovum pick-up and ET, while the miscarriage rate significantly decreased.

Emerging immunotherapeutic strategies for the treatment of breast cancer.

Immunotherapy has resulted in unprecedented gains in long-term outcomes for many cancer types and has revolutionized the treatment landscape of solid tumor oncology. Checkpoint inhibition in combination with chemotherapy has proven to be effective for the treatment of a subset of advanced triple-negative breast cancer in the first-line setting. This initial success is likely just the tip of the iceberg as there is much that remains unknown about how to best harness the immune system as a therapeutic strategy in all breast cancer subtypes. Therefore, numerous ongoing studies are currently underway to evaluate the safety and efficacy of immunotherapy in breast cancer. In this review, we will discuss emerging immunotherapeutic strategies for breast cancer treatment including the following: (1) Intratumoral therapies, (2) Anti-tumor vaccines, (3) B-specific T-cell engagers, and (4) Chimeric antigen receptor T-cell therapy, and (5) Emerging systemic immunotherapy strategies. For each topic, we will review the existing preclinical and clinical literature, discuss ongoing clinical trials, and highlight future directions in the field.

The presentation of brain metastases in melanoma, non-small cell lung cancer, and breast cancer and potential implications for screening brain MRIs.

PURPOSE: This study assessed the presentation and institutional outcomes treating brain metastases (BM) of breast cancer (BC), non-small cell lung cancer (NSCLC), and melanoma origin. METHODS: Patients with brain metastases treated between 2014 and 2019 with primary melanoma, NSCLC, and BC were identified. Overall survival (OS) was calculated from dates of initial BM diagnosis using the Kaplan-Meier method. RESULTS: A total of 959 patients were identified including melanoma (31%), NSCLC (51%), and BC (18%). Patients with BC were younger at BM diagnosis (median age: 57) than NSCLC (65) and melanoma patients (62, p < 0.0001). Breast cancer patients were more likely to present with at least 5 BM (27%) than NSCLC (14%) and melanoma (13%), leptomeningeal disease (23%, 6%, and 6%, p = 0.0004) and receive whole brain radiation therapy (WBRT) (58%, 37%, and 22%, p < 0.0001). There were no differences in surgical resection (24%, 24%, and 29%, p = 0.166). Median OS was shorter for BC patients (9.9, 10.3, and 13.7 months, p = 0.0006). CONCLUSION: Breast cancer patients were more likely to be younger, present with advanced disease, require WBRT, and have poorer OS than NSCLC and melanoma patients. Further investigation is needed to determine which BC patients are at sufficient risk for brain MRI screening.

Vitamin D and Hypoxia-Inducible Factor (HIF-1α) Serum Levels as Markers for Progression of Nephropathy in Type 2 Diabetic Patients.

BACKGROUND: Vitamin D is a locally acting hormone, which plays a major role in skeletal health. Previous studies reported an important role of vitamin D in modulation of inflammatory response. We aimed to investigate the role of vitamin D deficiency and hypoxia-inducible factor (HIF-1α) as markers for the progression of diabetic nephropathy in Saudi patients with type 2 diabetes mellitus (T2DM). METHODS: We included 174 Saudi patients with T2DM in addition to 60 healthy control subjects. Patients were classified according to urinary Albumin to Creatinine Ratio (ACR) into three groups: Group AI: ACR < 30 µg/mg, Group AII: ACR levels of 30 - 300 µg/mg and Group AIII: ACR > 300 µg/mg. We estimated fasting blood glucose, HbA1c, lipid profile, serum creatinine, hemoglobin concentration (Hb), estimated glomerular filtration rate (eGFR), urine albumin/creatinine ratio, serum 25 hydroxyvitamin D, calcium, parathyroid hormone (PTH), tumor necrosis factor (TNF-α), C- reactive protein (CRP), and hypoxia-inducible factor (HIF-1α). RESULTS: There was a significant difference among studied groups regarding serum levels of vitamin D, calcium, PTH, TNF-α, CRP, and HIF-1α levels. The level of vitamin D was lower in diabetic patients in comparison to the controls and was significantly related to the severity of renal nephropathy as indicated by the level of albumin in urine. Moreover, vitamin D levels showed significant negative correlation with the inflammatory markers: TNF-α, CRP, and HIF-1α levels. CONCLUSIONS: Vitamin D deficiency and elevated HIF-1α serum levels showed a significant correlation to progression of nephropathy in Saudi patients with T2DM.

Association of Vitamin D Deficiency, Dyslipidemia, and Obesity with the Incidence of Coronary Artery Diseases in Type 2 Diabetic Saudi Patients.

BACKGROUND: Diabetes mellitus type 2 (T2DM) is a chronic metabolic disease associated with vascular complications. We aimed to evaluate the relationship of vitamin D deficiency, dyslipidemia, and obesity with the incidence of coronary artery disease in type 2 diabetes mellitus. METHODS: The study included 200 Saudi adult subjects, aged 40 - 60 years, of both genders, attending King Abdulaziz Specialist Hospital in Taif city. Subjects were divided into four groups; 50 subjects each: Control group, type 2 diabetic, type 2 diabetic with coronary artery disease, and type 2 diabetic obese patients having body mass index (BMI) ≥ 30 kg/m2. Serum vitamin D (25-OH-D), fasting blood glucose (FBG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglycerides (TG), and glycosylated hemoglobin (HbA1c) levels were estimated. RESULTS: Serum vitamin D and HDL-C in the three diabetic patient groups were significantly decreased (p < 0.001) compared to the control group. Among patient groups, the levels in the diabetic coronary and diabetic obese patients were significantly decreased as compared to the diabetic patient group (p < 0.001). FBG levels, HbA1c%, TC, TG, LDL-C levels, and BMI in all diabetic patient groups were significantly higher (p < 0.001) in comparison to control. Significant negative correlations were observed between serum vitamin D and FBG, HbA1c%, TC, TG, LDL-C levels, and BMI whereas positive correlations with HDL-C in all diabetic patient groups. CONCLUSIONS: The deficiency status of 25-OH-D is associated with dyslipidemia in type 2 Saudi diabetic patients, specifically those complicated with obesity and coronary artery diseases.

Seroprevalence of IgM and IgG Against SARS-CoV-2 after Two Doses of Pfizer-BioNTech COVID-19 Vaccine in Women with Breast Cancer.

BACKGROUND: This study evaluates the seroprevalence of immunoglobulin M (IgM) and G (IgG) antibodies against SARS-CoV-2 after two doses of Pfizer-BioNTech COVID-19 vaccination from women with breast cancer in Jazan city Kingdom of Saudi Arabia, antibody detections were performed one month and three months after the administration of the second dose. METHODS: Overall, 103 breast cancer patients were included. Individuals who had had two doses of Pfizer-BioNTech vaccine, patients who were earlier diagnosed with COVID-19 infection, had not finalized immunization plan, or who received the second dose recently were excluded from the study. The antibodies detection test was run according to the manufacturer's directions of Viva Diag™ SARS-CoV-2 IgM/IgG Rapid Test (COVID-19 IgM/IgG Rapid Test). RESULTS: This study included 62 (60.2%) and 41 (39.8%) patients with invasive ductal carcinoma and invasive lobular carcinoma, respectively. The age, median and interquartile range (IQR) was 54.0 (26) years. Regarding reactivity of antibodies, after one month IgM antibody showed 64 (62.1%) positive and 39 (37.9%) negative while IgG antibody showed positive results in all patients. After three months IgM antibody showed 44 (42.7%) positive and 59 (57.3%) negative, while IgG showed 87 (84.5%) positive and 16 (15.5%) negative. There were significant differences in the IgM and IgG seropositivity. There were 19.3% patients with ductal carcinoma who were positive and then turned negative versus 17.7% who were positive and then turned negative, respectively (p < 0.001). There were significant differences in IgM antibody positivity among different age groups. CONCLUSIONS: Our results recommend the importance of screening for an antibody response for breast cancer patient after immunization in order to reveal persons who need early and late extra enhancing vaccine dose. Upcoming studies recommended to estimate different methods that raise cancer patients' immune response.

Capecitabine and stereotactic radiation in the management of breast cancer brain metastases.

BACKGROUND: Little is known about the safety and efficacy of concurrent capecitabine and stereotactic radiotherapy in the setting of breast cancer brain metastases (BCBM). METHODS: Twenty-three patients with BCBM underwent 31 stereotactic sessions to 90 lesions from 2005 to 2019 with receipt of capecitabine. The Kaplan-Meier method was used to calculate overall survival (OS), local control (LC), and distant intracranial control (DIC) from the date of stereotactic radiation. Imaging was independently reviewed by a neuro-radiologist. RESULTS: Median follow-up from stereotactic radiation was 9.2 months. Receptor types of patients treated included triple negative (n = 7), hormone receptor (HR)+/HER2- (n = 7), HR+/HER2+ (n = 6), and HR-/HER2+ (n = 3). Fourteen patients had stage IV disease prior to BCBM diagnosis. The median number of brain metastases treated per patient was 3 (1 to 12). The median dose of stereotactic radiosurgery (SRS) was 21 Gy (range: 15-24 Gy) treated in a single fraction and for lesions treated with fractionated stereotactic radiation therapy (FSRT) 25 Gy (24-30 Gy) in a median of 5 fractions (range: 3-5). Of the 31 stereotactic sessions, 71% occurred within 1 month of capecitabine. No increased toxicity was noted in our series with no cases of radionecrosis. The 1-year OS, LC, and DIC were 46, 88, and 30%, respectively. CONCLUSIONS: In our single institution experience, we demonstrate stereotactic radiation and capecitabine to be a safe treatment for patients with BCBM with adequate LC. Further study is needed to determine the potential synergy between stereotactic radiation and capecitabine in the management of BCBM.

Trastuzumab Emtansine (T-DM1) and stereotactic radiation in the management of HER2+ breast cancer brain metastases.

BACKGROUND: Due to recent concerns about the toxicity of trastuzumab emtansine (T-DM1) with stereotactic radiation, we assessed our institutional outcomes treating HER2-positive breast cancer brain metastases (BCBM) with T-DM1 and stereotactic radiation. METHODS: This is a single institution series of 16 patients with HER2-positive breast cancer who underwent 18 stereotactic sessions to 40 BCBM from 2013 to 2019 with T-DM1 delivered within 6 months. The Kaplan-Meier method was used to calculate overall survival (OS), local control (LC), distant intracranial control (DIC), and systemic progression-free survival (sPFS) from the date of SRS. A neuro-radiologist independently reviewed follow-up imaging. RESULTS: One patient had invasive lobular carcinoma, and 15 patients had invasive ductal carcinoma. All cases were HER2-positive, while 10 were hormone receptor (HR) positive. Twenty-four lesions were treated with stereotactic radiosurgery (SRS) to a median dose of 21 Gy (14-24 Gy). Sixteen lesions were treated with fractionated stereotactic radiation (FSRT) with a median dose of 25 Gy (20-30Gy) delivered in 3 to 5 fractions. Stereotactic radiation was delivered concurrently with T-DM1 in 19 lesions (48%). Median follow up time was 13.2 months from stereotactic radiation. The 1-year LC, DIC, sPFS, and OS were 75, 50, 30, and 67%, respectively. There was 1 case of leptomeningeal progression and 1 case (3%) of symptomatic radionecrosis. CONCLUSIONS: We demonstrate that stereotactic radiation and T-DM1 is well-tolerated and effective for patients with HER2-positive BCBM. An increased risk for symptomatic radiation necrosis was not noted in our series.

Breast cancer subtype predicts clinical outcomes after stereotactic radiation for brain metastases.

PURPOSE: We investigated the prognostic ability of tumor subtype for patients with breast cancer brain metastases (BCBM) treated with stereotactic radiation (SRT). METHODS: This is a retrospective review of 181 patients who underwent SRT to 664 BCBM from 2004 to 2019. Patients were stratified by subtype: hormone receptor (HR)-positive, HER2-negative (HR+/HER2-), HR-positive, HER2-positive (HR+/HER2+), HR-negative, HER2-positive (HR-/HER2+), and triple negative (TN). The Kaplan-Meier method was used to calculate overall survival (OS), local control (LC), and distant intracranial control (DIC) from the date of SRT. Multivariate analysis (MVA) was conducted using the Cox proportional hazards model. RESULTS: Median follow up from SRT was 11.4 months. Of the 181 patients, 47 (26%) were HR+/HER2+, 30 (17%) were HR-/HER2+, 60 (33%) were HR+/HER2-, and 44 (24%) were TN. Of the 664 BCBMs, 534 (80%) received single fraction stereotactic radiosurgery (SRS) with a median dose of 21 Gy (range 12-24 Gy), and 130 (20%) received fractionated stereotactic radiation therapy (FSRT), with a median dose of 25 Gy (range 12.5-35 Gy) delivered in 3 to 5 fractions. One-year LC was 90%. Two-year DIC was 35%, 23%, 27%, and 16% (log rank, p = 0.0003) and 2-year OS was 54%, 47%, 24%, and 12% (log rank, p < 0.0001) for HR+/HER2+, HR-/HER2+, HR+/HER2-, and TN subtypes, respectively. On MVA, the TN subtype predicted for inferior DIC (HR 1.62, 95% CI 1.00-2.60, p = 0.049). The modified breast-Graded Prognostic Assessment (GPA) significantly predicted DIC and OS (both p < 0.001). CONCLUSIONS: Subtype is prognostic for OS and DIC for patients with BCBM treated with SRT.

Assessment of organizational culture types, leadership styles and their relationships within governmental and non-governmental hospitals in Gaza Strip of Palestine.

BACKGROUND: The subjects of organizational culture and leadership have been studied several times in various fields. However, studies have tried to determine the relationship between corporate culture and leadership as it is still indistinguishable, or more evidence is needed. The paper describes the perceptions of the staffs about the hospitals' organizational culture types and their managers' leadership styles in these hospitals and the relationships that may exist between these domains. METHOD: This is a cross-sectional descriptive study involving 400 participants from three governmental and two non-governmental hospitals during the period from June to December 2018. The target population included all categories of staff working at hospitals as physicians, nurses, paramedics and administrators. RESULTS: The largest number of participants was 82.5 % from government hospitals while 17.5 % were from non-governmental hospitals. Clan and hierarchy-driven cultures were the top-defined forms of organizational culture at hospitals in the Gaza Strip. In all types of organizational culture, the non-governmental hospitals which all are small size hospitals have higher perceptions' means than the governmental ones that have different sizes. Managers' styles in the investigated hospitals were transformational and transactional. The study's results showed significant positive associations by Pearson's Correlations and effect by linear multiple regression analysis between styles of transformation and transactional leaderships and types of organizational cultures. DISCUSSION AND CONCLUSION: The study addressing the main concepts showed positive relations and also impacts between two of the leadership styles and organizational culture types, apart from the Laissez-faire style. This paper has been successful in contributing to the research on this topic and providing indications for understanding certain domains of the hospital industry in Palestine.

The Use of Dual Energy X-Ray Bone Density Scan in Assessment of Alveolar Cleft Grafting Using Bone Marrow Stem Cells Concentrate/Platelet-Rich Fibrin Regenerative Technique.

OBJECTIVES: To determine the densitometric quality of regenerated bone at the site of bone marrow and platelet-rich membrane grafting technique at unilateral alveolar cleft region using dual energy x-ray bone density scan (DEXA). METHODS: The present prospective cohort study included 16 unilateral alveolar cleft patients who were selected randomly from the outpatient maxillofacial surgery clinic and suffered from unilateral alveolar cleft. Bone marrow aspirate and platelet-rich fibrin (PRF) (bone marrow stem cells + PRF) were used as the grafting material. Six months of follow-up have been conducted for all patients' including clinical and radiographic assessments with (DEXA scan). RESULTS: Sixteen unilateral patients with a mean age of 12.56 ±â€Š1.71 years were included in the sample and the majority of patients were females with a frequency of 56.2 percent. The current research revealed no infection or wound dehiscence. After surgery, the pain and edema scores were reasonable. Our findings showed that, after 6 months of regenerative graft, the average bone mineral density of the cleft side DEXA scan value was 1.56 ±â€Š0.32 gm/cm2, compared to 1.51 ±â€Š0.488 gm/cm2 on the normal side of the noncleft scan. There was no statistically significant difference in DEXA bone mineral content measurements between the cleft and standard sides (P = 0.461). CONCLUSIONS: The bone marrow stem cells + PRF regenerative graft technique has been successfully integrated, and the DEXA scan approach for measuring regenerated grafted bone mineral content was found to be appropriate for simple and inexpensive follow-up of alveolar cleft lip patients.

Evaluation of invasive breast cancer samples using a 12-chemokine gene expression score: correlation with clinical outcomes.

BACKGROUND: A unique 12-chemokine gene expression score (CS) accurately predicted the presence of tumor-localized, ectopic lymph node-like structures (TL-ELNs) and improved overall survival (OS) in primary colorectal cancer and metastatic melanoma. We analyzed the correlation between CS, clinicopathological variables, molecular data, and 366 survival in Moffitt Cancer Center's Total Cancer Care (TCC) patients with non-metastatic breast cancer. METHODS: Affymetrix gene expression profiles were used to interrogate the CS by the principal component method. Breast tumors were classified as high or low score based on median split, and correlations between clinicopathologic variables, PAM50 molecular subtype, and ELN formation were analyzed using the TCC dataset. Differences in overall survival (OS) and recurrence-free survival (RFS) in the larger KM Plot breast cancer public datasets were compared using Kaplan-Meier curves. RESULTS: We divided the Total Cancer Care (TCC) breast cancer patients into two groups of high or low CS. Mean CS was 0.24 (range, 2.2-2.1). Patients with higher CS were more likely to be white (172 vs. 159; p = 0.03), had poorly differentiated tumors (112 vs. 59; p <0.0001), ER/PR negative (41 vs. 26) and HER2 positive (36 vs. 19; p = 0.001), and contain TL-ELNs. Higher CS scores were also seen in the basal and HER2+ molecular subtypes. In the KM Plot breast cancer datasets higher CS patients demonstrated superior OS (HR = 0.73, p = 0.008) and RFS (HR 0.76, p = <0.0001), especially in basal and HER2+ patients. CONCLUSIONS: High CS breast tumors tend to be higher grade, basal or HER2+, and present more frequently in Caucasians. However, this group of patients also shows the presence of TL-ELNs within the tumor microenvironment and has better survival outcomes. The CS is a novel tool that can identify breast cancer patients with tumors of a unique intratumoral immune composition and better prognosis. Whether or not the CS is a predictive response marker in breast cancer patients undergoing immunotherapy remains to be determined.

The CXCR1/2 ligand NAP-2 promotes directed intravascular leukocyte migration through platelet thrombi.

Thrombosis promotes leukocyte infiltration into inflamed tissues, leading to organ injury in a broad range of diseases; however, the mechanisms by which thrombi guide leukocytes to sites of vascular injury remain ill-defined. Using mouse models of endothelial injury (traumatic or ischemia reperfusion), we demonstrate a distinct process of leukocyte recruitment, termed "directed intravascular migration," specifically mediated by platelet thrombi. Single adherent platelets and platelet aggregates stimulated leukocyte shape change at sites of endothelial injury; however, only thrombi were capable of inducing directed intravascular leukocyte migration. Leukocyte recruitment and migration induced by platelet thrombi occurred most prominently in veins but could also occur in arteries following ischemia-reperfusion injury. In vitro studies demonstrated a major role for platelet-derived NAP-2 (CXCL-7) and its CXCR1/2 receptor in regulating leukocyte polarization and motility. In vivo studies demonstrated the presence of an NAP-2 chemotactic gradient within the thrombus body. Pharmacologic blockade of CXCR1/2 as well as genetic deletion of NAP-2 markedly reduced leukocyte shape change and intrathrombus migration. These studies define a distinct process of leukocyte migration that is initiated by homotypic adhesive interactions between platelets, leading to the development of an NAP-2 chemotactic gradient within the thrombus body that guides leukocytes to sites of vascular injury.

Cleft Lip and Palate Research Trends in Saudi Arabia: A Bibliometric Analysis.

As Saudi Arabia advances in medical education and patient care, assessing its contribution to cleft lip and palate (CLP) research is vital. This bibliometric analysis aims to map the trends, collaborations, and impact of Saudi research in CLP. Utilizing the Web of Science database, this study conducted a comprehensive bibliometric analysis of CLP research related to Saudi Arabian publications. The analysis included data extraction and assessment of publications, citations, H-index, and international collaborations using advanced bibliometric tools and software. A total of 89 CLP-related articles in Saudi Arabia were retrieved. The findings indicated a steady increase in publications and citations over the years, reflecting growing interest and recognition of CLP's challenges in the Saudi healthcare context. King Abdulaziz University and King Saud University emerged as leading contributors. International collaboration was evident, with significant partnerships with countries like the USA, Canada, the UK, and others. The Cleft Palate-Craniofacial Journal and the Saudi Dental Journal were identified as the most influential journals in disseminating Saudi CLP research. The study highlights a positive growth trajectory in Saudi CLP research, marked by increased publications, citations, and international collaborations. It underscores the importance of continuous research and the need for enhanced efforts to further the understanding and treatment of CLP. Future studies should consider including a broader range of databases to provide a more comprehensive global view of CLP research trends.

Evaluation of Students' Proficiency in Removing Gutta-Percha Prior to Fiber Post Placement: A Retrospective Study.

INTRODUCTION: This retrospective study focuses on dental students' proficiency in removing gutta-percha during fiber post space preparation, which is important for maintaining apical seal integrity in endodontically treated teeth. Emphasizing the significance of preventing further reinfection. The primary objective of this study was to assess the proficiency of undergraduate dental students in the manipulation of gutta-percha during fiber post preparation, specifically focusing on the psychomotor skills involved. In addition, the study aims to determine the predictive value of these skills on the ultimate clinical outcomes of the procedure, with particular emphasis on variations attributable to tooth type. MATERIALS AND METHODS: The analysis encompassed 290 periapical radiographs obtained from endodontically treated teeth, all of which had undergone fiber post placement by undergraduate students at the College of Dentistry, Taibah University, Saudi Arabia. Postoperatively, the length of the remaining gutta-percha was measured by two experts in the field, and subsequent outcomes were classified into three categories: optimal, suboptimal, and inadequate, based on the extent of gutta-percha remaining. RESULTS: Students showed optimal removal rates ranging from 33.3% to 73.1%. Among the studied sample, upper anterior teeth were the highest included teeth (n=117, 40%). Remarkably, lower anterior teeth were more prone to suboptimal and inadequate gutta-percha remaining lengths (n=24, 33%). However, the chi-square test revealed no statistically significant difference in students' psychomotor skills while removing the gutta-percha and preparing the teeth to receive fiber posts across tooth types (p-value > 0.05). CONCLUSION: With the limitations of this study, more than half of the included cases show that undergraduate students of the College of Dentistry at Taibah University, Saudi Arabia, possess an optimum level of psychomotor skills in removing gutta-percha while preparing the teeth for receiving fiber posts. This study suggests enhancing the preclinical training of students by considering more training on different tooth types in relation to dental arches.

Silymarin ameliorates diazinon-induced subacute nephrotoxicity in rats via the Keap1-Nrf2/heme oxygenase-1 signaling pathway.

PURPOSE: The goal of the current study was to clarify the potential molecular mechanism underlying the protective effects of silymarin (SIL) administration against diazinon-induced subacute nephrotoxicity, with a special emphasis on the role of the Kelch-like-associated protein-1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2)-heme oxygenase-1 (HO-1) signaling pathway in minimizing the oxidative stress induced by diazinon (DZN). METHODS: Five equal groups of thirty adult male Wistar rats were created at random. Group 1 (G1) was maintained under typical control conditions and administered saline intragastrically (I/G) once daily for 4 weeks; G2 was administered olive oil I/G for 4 weeks; G3 was I/G administered silymarin daily for 4 weeks; G4 was I/G administered diazinon daily for 4 weeks. G5 was I/G administered silymarin daily 1 h before the I/G administration of the diazinon for 4 weeks. Blood samples were collected at the end of the experiment for the determination of complete blood cell count, and kidney function tests. Kidney specimens were collected for the evaluation of the oxidative markers, mRNA gene expression, protein markers, and histopathological examination. RESULTS: SIL reduced the renal dysfunction caused by DZN by restoring urea and creatinine levels, as well as oxidative indicators. Although the expression of Keap-1 was also elevated, overexpression of Nrf2 also enhanced the expression of HO-1, a crucial target enzyme of Nrf2. CONCLUSIONS: SIL is hypothesized to potentially aid in the prevention and management of nephrotoxicity caused by DZN.

Alveolar Oral Layer Repair by Periosteal Grafts versus Maxillary Flaps and Gingivoperiosteoplasty: Techniques and Follow-up to Adolescence.

Background: Alveolar periosteoplasty during primary repair of cleft lip is still a topic of debate due to the fear exacerbating maxillary retrusion. The authors present their experience with early closure of alveolar clefts. The study aims to analyze gingivoperiosteoplasty (GPP) by comparing the use of locoregional flaps versus distant grafts for reconstruction of the lower layer of the primary palate cleft. Methods: Seventeen infants underwent 22 alveolar cleft repairs. After nasal floor repair by nasal mucoperiosteum, the oral layer was repaired by maxillary or gingival periosteal flaps in seven patients with alveolar clefts less than or equal to 6 mm wide, and tibial or pericranial periosteal grafts in 10 patients with wider clefts. At teenage years, crossbites in three flap-GPP and three graft-GPP patients were compared with nine older adolescents without primary GPP. Results: Alveolar clefts were perfectly sealed. Radiographs during the early 3 postoperative years showed new bone formation more posteriorly extended in patients who underwent graft-GPP. Teeth eruption and alveolar rigidity at the mixed dentition age eliminated the need for secondary bone grafting. The anterior crossbites in adolescent patients ranged between -2 and -14 mm; crossing was relatively smaller in patients with a younger age and without cleft palate. The mean crossbite was 7.2 mm in the six teenagers and 9.6 mm in the control cases. Conclusions: Graft-GPP may be a good alternative to flap-GPP, particularly for wide alveolar cleft repair. Maxillary retrusion is aggravated in patients with cleft palate and older age at assessment. GPP may not increase crossbite.

A nephrologist dream of peritoneal dialysis catheter with zero migration: A multicenter prospective study.

INTRODUCTION: PD catheter tip migration is a common complication and a significant cause of catheter malfunction. In this perspective, we present our experience with a new catheter and a new technique that involves the use of a new triple cuff PD catheter and a low entry site in an attempt to prevent PD catheter migration. METHODS: A total of 503 incident PD patients have been studied in more than one PD center over a period of 5 years. RESULTS: During the 5-year follow up we recorded zero percent catheter migration. Other technical complications were poor drainage in 3.4%, omental wrap in 2.8%, early leakage in 3.4%, and catheter replacement in 2.4%. By the end of the study, the one-year PD catheter survival was 97.6%. CONCLUSION: Our new triple cuff PD catheter and our low-entry approach seem to be effective in preventing PD catheter migration and minimizing other mechanical complications.

Bcl-xL-inhibitory BH3 mimetics can induce a transient thrombocytopathy that undermines the hemostatic function of platelets.

BH3 mimetics are a new class of proapo-ptotic anticancer agents that have shown considerable promise in preclinical animal models and early-stage human trials. These agents act by inhibiting the pro-survival function of one or more Bcl-2-related proteins. Agents that inhibit Bcl-x(L) induce rapid platelet death that leads to thrombocytopenia; however, their impact on the function of residual circulating platelets remains unclear. In this study, we demonstrate that the BH3 mimetics, ABT-737 or ABT-263, induce a time- and dose-dependent decrease in platelet adhesive function that correlates with ectodomain shedding of the major platelet adhesion receptors, glycoprotein Ibα and glycoprotein VI, and functional down-regulation of integrin α(IIb)ß(3). Analysis of platelets from mice treated with higher doses of BH3 mimetics revealed the presence of a subpopulation of circulating platelets undergoing cell death that have impaired activation responses to soluble agonists. Functional analysis of platelets by intravital microscopy revealed a time-dependent defect in platelet aggregation at sites of vascular injury that correlated with an increase in tail bleeding time. Overall, these studies demonstrate that Bcl-x(L)-inhibitory BH3 mimetics not only induce thrombocytopenia but also a transient thrombocytopathy that can undermine the hemostatic function of platelets.