Enhanced antitumour activity of doxorubicin and simvastatin combination loaded nanoemulsion treatment against a Swiss albino mouse model of Ehrlich ascites carcinoma

Doxorubicin (DOX) is the most commonly used anticancer drug; however, it has limited use because prolonged administration may result in severe cardiotoxicity. Simvastatin (SIM), generally prescribed for hypercholesterolaemia, has also shown salubrious results in the monotherapy or combinational drug therapy of different cancers in various models. Nanoparticle drug delivery systems are a novel way of improving therapeutics and also improving the absorption and specificity of drugs towards tumour cells. In this study, we exploited this technology to increase drug specificity and minimize imminent adverse effects. In this study, the antitumour activity of the combination formulas of DOX and SIM, either loaded in water (DOX‐SIM‐Solution) or nanoemulsions (NEs) (DOX‐SIM‐NE), was evaluated in a Swiss albino mouse model of Ehrlich ascites carcinoma. The anticancer effect was assessed by quantifying the change in body weight, mean survival time, and percent increase in lifespan (%ILS), determining haematological and serum biochemical parameters (liver function test, kidney function test and lipid profile parameters) as well as studying the histopathological alterations in liver tissues. We observed a clear increase in %ILS of the DOX‐SIM‐Solution group (265.30) that was double the %ILS of the DOX‐SIM‐NE group (134.70). However, DOX‐SIM‐NE had a non‐toxic effect on the haematological parameters, whereas DOX‐SIM‐Solution increased the levels of haemoglobin and lymphocytes. Furthermore, the encapsulation of SIM and DOX into NEs improved the levels of all serum biochemical parameters compared to the DOX‐SIM‐Solution. A reduction in the side effects of DOX‐SIM‐NE on the liver was also established using light microscopy, which revealed that the morphologies of the hepatocytes of the mice were less affected by administration of the DOX‐SIM‐NE treatment than with the DOX‐SIM‐Solution treatment. The study showed that incorporating SIM into the DOX‐loaded‐NE formulation remarkably improved its efficiency and simultaneously reduced its adverse effects.     

Complete penile disassembly in epispadias repair

International Urology and Nephrology - To report current results of complete penile disassembly technique in epispadias repair. In ten years, we have preformed 31 complete penile disassembly for...     

An assessment of cerebral venous thrombosis risk factors and associated clinical outcomes in Jazan region,Saudi Arabia

Objectives:To assess cerebral venous thrombosis risk factors, and associated clinical outcomes in Jazan region, Kingdom of Saudi Arabia.Methods:This study is a retrospective review of the medical records of patients diagnosed with cerebral venous thrombosis and admitted to King Fahad Central Hospital in Jazan between 2010 and 2019. Data concerning socio-demographics, clinical features, risk factors, laboratory, and imaging investigations were retrieved. Furthermore, data about cases management, and outcomes, including death, were collected and analysed.Results:A total of 51 medical records were identified. The majority of the patients were females (68.6%), and the mean age of the patients was 33.3 years, of which three patients were under 18 years old. The most frequently recorded symptom was headache (76.5%), followed by seizure (45.1%). The most commonly recorded risk factor was protein S deficiency (57%), followed by anaemia (51%). Venous infarction and haemorrhage were the most common acute complications (13.7%). The majority of the patients had a favourable prognosis where only 27.5% recovered with disability and only one patient died due to the disease.Conclusion:Clinical presentation of cerebral venous thrombosis in Jazan region is similar to other local and international studies. However, anaemia was recorded as a main risk factor for the disease, which might require further investigation to assess the possible association between prevalence of anaemia in Jazan region and the incidence of cerebral venous thrombosis.

Cerebral venous thrombosis (CVT) is a rare form of cerebrovascular disease in comparison with arterial stroke. CVT cases represent approximately 0.5-1% of all types of stroke which mainly occur in young and middle-aged adults.1 The data concerning the global epidemiology of CVT is currently limited.2 However, the incidence of CVT has been reported to vary between countries where the incidence might be higher as in Asian and the Middle Eastern countries in comparison to Australia and European countries.3According to a recent study conducted in Australia, the incidence of CVT was reported to reach 15.7 per 1,000,000 persons on a yearly basis. The incidence was higher among women and among those between 31-50 years old.4 In the Middle East, an Iranian study looked at the frequency of CVT between 2001 and 2004, and the annual frequency of CVT was 12.3 per one million.5 An older study, conducted in the city of Riyadh in Saudi Arabia between 1985 and 1994, identified 40 cases of CVT. Those identified were aged between 16 and 40.6 In addition, in a more recent study conducted in Jeddah and Al-Baha between 1990 and 2010, the number of detected cases of CVT was 111 where 19 of these were detected among children.7The CVT occurs when a thrombus develops as a result of a disturbance of the balance between the process of prothrombosis and thrombolysis.8,9 Risk factors for CVT can be categorised into transient and permanent risk factors. Permanent risk factors are hereditary thrombophilia, systemic diseases or miscellaneous factors, such as obesity. Transient risk factors can be subcategorised into sex-specific, iatrogenic, or miscellaneous risk factors, such as infection, head trauma or anaemia.8 The prevalence of CVT risk factors differs between countries. Infection, pregnancy, post-partum period, and dehydration have been reported to be more common in Asia and the Middle Eastern countries in comparison to European countries.8Patients with CVT exhibit variable clinical manifestations and complications, some of which can be life threatening. The most common clinical presentation is a headache, while some patients exhibit other signs and symptoms, such as seizure, decreased level of consciousness, vomiting, focal neurological deficit, or visual symptoms.8-10 Venous infarction and haemorrhage are frequently reported complications of CVT.11 Late presentation of CVT patients can increase the risk of disability and death. The mortality rate among CVT patients has been reported to vary between 4.3% and 6.8%.12Since CVT risk factors and vulnerable groups can vary between different populations, assessment of the distribution of risk factors among local populations can be clinically valuable. Studies assessing CVT prevalence and associated risk factors and clinical outcomes in Saudi populations are currently limited. Furthermore, data about CVT in Jazan region is currently lacking. This investigation aims to identify cases diagnosed with CVT in Jazan region and to evaluate the risk factors and associated clinical outcomes.     

The impact of neighborhoods and friendships on interracial anxiety among medical students and residents: A report from the medical student CHANGES study

Objective

To examine the experience of interracial anxiety among health professionals and how it may affect the quality of their interactions with patients from racially marginalized populations. We explored the influence of prior interracial exposure—specifically through childhood neighborhoods, college student bodies, and friend groups—on interracial anxiety among medical students and residents. We also examined whether levels of interracial anxiety change from medical school through residency.

Data Source

Web-based longitudinal survey data from the Medical Student Cognitive Habits and Growth Evaluation Study.

Study Design

We used a retrospective longitudinal design with four observations for each trainee. The study population consisted of non-Black US medical trainees surveyed in their 1st and 4th years of medical school and 2nd and 3rd years of residency. Mixed effects longitudinal models were used to assess predictors of interracial anxiety and assess changes in interracial anxiety scores over time.

Principal Findings

In total, 3155 non-Black medical trainees were followed for 7 years. Seventy-eight percent grew up in predominantly White neighborhoods. Living in predominantly White neighborhoods and having less racially diverse friends were associated with higher levels of interracial anxiety among medical trainees. Trainees' interracial anxiety scores did not substantially change over time; interracial anxiety was highest in the 1st year of medical school, lowest in the 4th year, and increased slightly during residency.

Conclusions

Neighborhood and friend group composition had independent effects on interracial anxiety, indicating that premedical racial socialization may affect medical trainees' preparedness to interact effectively with diverse patient populations. Additionally, the lack of substantial change in interracial anxiety throughout medical training suggests the importance of providing curricular tools and structure (e.g., instituting interracial cooperative learning activities) to foster the development of healthy interracial relationships.     

Early intervention in myelofibrosis and impact on outcomes: A pooled analysis of the COMFORT-I and COMFORT-II studies

Background

In a pooled analysis of the phase 3 Controlled Myelofibrosis Study With Oral JAK Inhibitor Treatment I (COMFORT-I) and COMFORT-II clinical trials, adult patients with intermediate-2 or high-risk myelofibrosis who received oral ruxolitinib at randomization or after crossover from placebo or best available therapy (BAT) had improved overall survival (OS).

Methods

This post hoc analysis of pooled COMFORT data examined relevant disease outcomes based on the disease duration (≤12 or >12 months from diagnosis) before ruxolitinib initiation.

Results

The analysis included 525 patients (ruxolitinib: ≤12 months, n = 84; >12 months, n = 216; placebo/BAT: ≤12 months, n = 66; >12 months, n = 159); the median age was 65.0–70.0 years. Fewer thrombocytopenia and anemia events were observed among patients who initiated ruxolitinib treatment earlier. At Weeks 24 and 48, the spleen volume response (SVR) was higher for patients who initiated ruxolitinib earlier (47.6% vs. 32.9% at Week 24, p = .0610; 44.0% vs. 26.9% at Week 48, p = .0149). In a multivariable analysis of factors associated with spleen volume reduction, a logistic regression model that controlled for confounding factors found that a significantly greater binary reduction was observed among patients with shorter versus longer disease duration (p = .022). At Week 240, OS was significantly improved among patients who initiated ruxolitinib earlier (63% [95% CI, 51%‒73%] vs. 57% [95% CI, 49%‒64%]; hazard ratio, 1.53; 95% CI, 1.01‒2.31; p = .0430). Regardless of disease duration, a longer OS was observed for patients who received ruxolitinib versus those who received placebo/BAT.

Conclusions

These findings suggest that earlier ruxolitinib initiation for adult patients with intermediate-2 and high-risk myelofibrosis may improve clinical outcomes, including fewer cytopenia events, durable SVR, and prolonged OS.

Plain Language Summary

• Patients with myelofibrosis, a bone marrow cancer, often do not live as long as the general population. These patients may also have an enlarged spleen and difficult symptoms such as fatigue.
• Two large clinical trials showed that patients treated with the drug ruxolitinib lived longer and had improved symptoms compared to those treated with placebo or other standard treatments.
• Here it was examined whether starting treatment with ruxolitinib earlier (i.e., within a year of diagnosis) provided benefits versus delaying treatment.
• Patients who received ruxolitinib within a year of diagnosis lived longer and experienced fewer disease symptoms than those whose treatment was delayed.