Successful medical management of a pituitary macroadenoma with features of resistant acromegaly and hyperprolactinemia using pasireotide.

BACKGROUND: The somatostatin analog, pasireotide, is used for the treatment of acromegaly after the failure of surgery and/or first-line medical treatment. CASE PRESENTATION: A 48-year-old male reported that during a workup for obesity in his home country, hyperprolactinemia was diagnosed and a 3.5 × 3.5 cm pituitary macroadenoma was identified on pituitary MRI. He received cabergoline for 6 months; then he was lost to follow-up. He presented at our Endocrine clinic 2 years later for treatment of obesity (BMI 49.5 kg/m2). Biochemical workup revealed that in addition to hyperprolactinemia (7,237 [normal: 85-323 mIU/L), he had acromegaly, evident by elevated insulin-like growth factor 1 (IGF-1) level (450 [normal: 88-210 µg/L]), and a positive growth hormone suppression test, secondary hypothyroidism, and secondary hypogonadism. Pituitary MRI showed that the adenoma encased parts of the left and right internal carotid arteries and encroached on the optic chiasm. Surgical excision was therefore not feasible. He was treated with cabergoline and later, long-acting release (LAR) octreotide. Prolactin levels were reduced with cabergoline, but IGF-1 levels did not respond to octreotide, and it was discontinued. The patient abandoned radiotherapy after two sessions. He was started on LAR pasireotide 40 mg every 4 weeks and continued on cabergoline 0.5 mg per week. His biochemical response was dramatic, with a near normalization of IGF-1 levels in 3 months. After 6 months from starting pasireotide, we increased cabergoline dose from 0.5 mg/week to 3 mg/week. Three months later, IGF-1 level was normalized. The patient developed type 2 diabetes as a side effect of pasireotide; however, this was well-controlled with medications. CONCLUSIONS: The case suggests that pasireotide can provide marked biochemical improvement in acromegaly after the failure of both cabergoline monotherapy and cabergoline plus octreotide. This further confirms a potentially efficacious treatment regimen in treatment-resistant acromegaly with hyperprolactinemia.

Phytochemical analysis and evaluation of its antioxidant, antimicrobial, and cytotoxic activities for different extracts of Casuarina equisetifolia.

BACKGROUND: Casuarina equisetifolia belongs to the Casuarina species with the most extensive natural distribution, which contain various phytochemicals with potential health benefits. This study aimed to investigate the chemical composition and biological activities of different extracts of Casuarina equisetifolia. METHODS: The n-hexane extract was analyzed for its unsaponifiable and fatty acid methyl esters fractions, while chloroform, ethyl acetate, and butanol extracts were studied for their phenolic components. Six different extracts of C. equisetifolia needles were evaluated for their total phenolic content, total flavonoid content, and their antioxidant, antimicrobial, and cytotoxic activities. RESULTS: The n-hexane extract contained mainly hydrocarbons and fatty acid methyl esters, while ten phenolic compounds were isolated and identified in the chloroform, ethyl acetate, and butanol extracts. The methanolic extract exhibited the highest total phenolic and flavonoid content, highest antioxidant activity, and most potent cytotoxic activity against HepG-2 and HCT-116 cancer cell lines. The ethyl acetate extract showed the most significant inhibition zone against Staphylococcus aureus and Bacillus subtilis. CONCLUSION: Casuarina equisetifolia extracts showed promising antioxidant, antimicrobial, and cytotoxic activities. Overall, Casuarina equisetifolia is a versatile tree with a variety of uses, and its plant material can be used for many different purposes.

Factors Affecting the Satisfaction of Women Employees in Health Sector: A Perception Study in Saudi Arabia.

Purpose: Broad evidence points out that women workers in Saudi Arabia face a range of inequitable work practices despite continued efforts for gender equality. The study aims to assess the satisfaction of Saudi women working in the health sector among certain factors in the work environment, factors that enable them to gain opportunities and benefits and make decisions. Patients and Methods: This is a cross-sectional study, which involved the use of closed-ended surveys on 261 Saudi women working in the healthcare sector. Results: Most of the females were aged between 25 and 34 years (59%) and more than half of them worked in the governmental sector (53%). Fifty-eight percent of the females hold clinical jobs, 25% of the administrative jobs were 37% of them have more than 19 years of working experience. The finding showed a significant association between female workers in health sector satisfaction with factors related to the workplace environment, training, and development, and their involvement in decision-making. Conclusion: Most women felt empowered when they received equitable tasks and were able to reach managerial-level positions in their organizations. Establishing a positive work environment characterized by opportunities has the potential to enhance women workers' satisfaction.

A Phase I/II Study of GSK525762 Combined with Fulvestrant in Patients with Hormone Receptor-positive/HER2-negative Advanced or Metastatic Breast Cancer.

PURPOSE: Endocrine-based therapy is the initial primary treatment option for hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer (mBC). However, patients eventually experience disease progression due to resistance to endocrine therapy. Molibresib (GSK525762) is a small-molecule inhibitor of bromodomain and extraterminal (BET) family proteins (BRD2, BRD3, BRD4, and BRDT). Preclinical data suggested that the combination of molibresib with endocrine therapy might overcome endocrine resistance. This study aimed to investigate the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy [objective response rate (ORR)] of molibresib combined with fulvestrant in women with HR+/HER2- mBC. PATIENTS AND METHODS: In this phase I/II dose-escalation and dose-expansion study, patients received oral molibresib 60 or 80 mg once daily in combination with intramuscular fulvestrant. Patients enrolled had relapsed/refractory, advanced/metastatic HR+/HER2- breast cancer with disease progression on prior treatment with an aromatase inhibitor, with or without a cyclin-dependent kinase 4/6 inhibitor. RESULTS: The study included 123 patients. The most common treatment-related adverse events (AE) were nausea (52%), dysgeusia (49%), and fatigue (45%). At a 60-mg dosage of molibresib, >90% of patients experienced treatment-related AE. Grade 3 or 4 treatment-related AE were observed in 47% and 48% of patients treated with molibresib 60 mg and molibresib 80 mg, respectively. The ORR was 13% [95% confidence interval (CI), 8-20], not meeting the 25% threshold for proceeding to phase II. Among 82 patients with detected circulating tumor DNA and clinical outcome at study enrollment, a strong association was observed between the detection of copy-number amplification and poor progression-free survival (HR, 2.89; 95% CI, 1.73-4.83; P < 0.0001). CONCLUSIONS: Molibresib in combination with fulvestrant did not demonstrate clinically meaningful activity in this study.

Improvement of adult female acne with a novel weekly estradiol loaded peel off mask. A split face, placebo controlled study.

BACKGROUND: Adult female acne is characterized by a relapsing eruption of acne in individuals who are 25 years or older. It usually shows slower response to the traditional adolescent acne treatments. Usually, androgens promote acne by stimulating sebum production, while estrogens have the opposite effect by reducing sebum output when present in adequate quantities. Estradiol is the female sex hormone with the highest absolute serum levels and the highest estrogenic activity during a woman's reproductive years. Peel-off facial masks were suggested to intensify the effect of the added active ingredient through forming an occlusive film after drying. OBJECTIVES: to study the safety and efficacy of weekly topical estradiol 0.05% in the treatment of adult acne in females. METHODS: Twenty female patients with adult acne were subjected to once weekly application of estradiol 0.05% and placebo masks to either side of the face for 8 weeks. Acne lesion count was performed at baseline, at each visit and 8 weeks after end of treatment. RESULTS: At the end of the treatment period, the treated side showed significant improvement of comedones, papules and pustules. Although, lesions count increased 2 months after stopping treatment, they were still significantly less on the estradiol side compared to placebo. No side effects were reported. LIMITATIONS: The limited number of patients studied and the limited follow-up period. The estradiol effect was not studied on cellular and molecular levels. CONCLUSIONS: Topical estradiol peel off mask can be a promising convenient, safe and effective treatment for adult acne in women.

Artificial intelligence in the detection and classification of dental caries.

STATEMENT OF PROBLEM: Automated detection of dental caries could enhance early detection, save clinician time, and enrich treatment decisions. However, a reliable system is lacking. PURPOSE: The purpose of this study was to train a deep learning model and to assess its ability to detect and classify dental caries. MATERIAL AND METHODS: Bitewings radiographs with a 1876×1402-pixel resolution were collected, segmented, and anonymized with a radiographic image analysis software program and were identified and classified according to the modified King Abdulaziz University (KAU) classification for dental caries. The method was based on supervised learning algorithms trained on semantic segmentation tasks. RESULTS: The mean score for the intersection-over-union of the model was 0.55 for proximal carious lesions on a 5-category segmentation assignment and a mean F1 score of 0.535 using 554 training samples. CONCLUSIONS: The study validated the high potential for developing an accurate caries detection model that will expedite caries identification, assess clinician decision-making, and improve the quality of patient care.

Investigating the promising SARS-CoV-2 main protease inhibitory activity of secoiridoids isolated from Jasminum humile; in silico and in Vitro assessments with structure-activity relationship.

The proteolytic enzyme 3 C-like protease (3Clpro or Mpro) is considered the most important target for SARS-CoV-2 which could be attributed to its crucial role in viral maturation and/or replication. Besides, natural phytoconstituents from plant origin are always promising lead compounds in the drug discovery area. Herein, the previously isolated and identified seven compounds from Jasminum humile (J. humile) were examined in vitro and in silico against the SARS-CoV-2 Mpro. First, the Vero E6 cells were utilized to pursue the potential of the investigated compounds (both in fractions and individual isolates) using the MTT assay. The total extract (T1) displayed the most significant activity against SARS-CoV-2 with IC50 = 29.36 µg/mL. Besides, the fractions (Fr1 and Fr3) showed good activity against the SARS-CoV-2 with IC50 values of 70.42, and 73.09 µg/mL, respectively. Then, the SARS-CoV-2 Mpro inhibitory assay was utilized to emphasize the inhibitory potential of the investigated isolates. MJN, JMD, and IJM candidates displayed prominent Mpro inhibitory potentials with IC50 = 30.44, 30.24, and 56.25 µM, respectively. Moreover, molecular docking of the identified seven compounds against the Mpro of SARS-CoV-2 showed that the five secoiridoids achieved superior results. MJN, JSM, IJM, and JMD showed higher affinities towards the Mpro target compared to the co-crystallized antagonist. Furthermore, the most active complexes (MJN, JSM, IJM, and JMD-Mpro) were subjected to MD simulations run for 150 ns and MM-GBSA calculations, compared to the co-crystallized inhibitor (O6K-Mpro). Finally, the SAR study clarified that JMD achieved the best anti-SARS-CoV-2 Mpro activity followed by MJN.Communicated by Ramaswamy H. Sarma.

HIGHLIGHTSSeven isolates from J. humile, besides different extracts, were examined both in vitro and in silico.Anti-SARS-CoV-2 using the MTT assay and anti-SARS-CoV-2 Mpro inhibitory assay were performed.Compounds MJN, JMD, and IJM displayed prominent SARS-CoV-2 Mpro inhibition.Molecular docking, molecular dynamics simulations, and MM-GBSA calculations were carried out.SAR study was conducted on the isolated compounds.

AR visualizations in laparoscopy: surgeon preferences and depth assessment of vascular anatomy.

Introduction: This study compares five augmented reality (AR) vasculature visualization techniques in a mixed-reality laparoscopy simulator with 50 medical professionals and analyzes their impact on the surgeon. Material and methods: ​​The different visualization techniques' abilities to convey depth were measured using the participant's accuracy in an objective depth sorting task. Demographic data and subjective measures, such as the preference of each AR visualization technique and potential application areas, were collected with questionnaires. Results: Despite measuring differences in objective measurements across the visualization techniques, they were not statistically significant. In the subjective measures, however, 55% of the participants rated visualization technique II, 'Opaque with single-color Fresnel highlights', as their favorite. Participants felt that AR could be useful for various surgeries, especially complex surgeries (100%). Almost all participants agreed that AR could potentially improve surgical parameters, such as patient safety (88%), complication rate (84%), and identifying risk structures (96%). Conclusions: More studies are needed on the effect of different visualizations on task performance, as well as more sophisticated and effective visualization techniques for the operating room. With the findings of this study, we encourage the development of new study setups to advance surgical AR.

The respiratory and hemodynamic effects of alveolar recruitment in cirrhotic patients undergoing liver resection surgery: A randomized controlled trial.

Background and Aims: Extensive surgical retraction combined with general anesthesia increase alveolar collapse. The primary aim of our study was to investigate the effect of alveolar recruitment maneuver (ARM) on arterial oxygenation tension (PaO2). The secondary aim was to observe its effect on hemodynamics parameters in hepatic patients during liver resection, to investigate its impact on blood loss, postoperative pulmonary complications (PPC), remnant liver function tests, and on the outcome. Material and Methods: Adult patients scheduled for liver resection were randomized into two groups: ARM (n = 21) and control (C) (n = 21). Stepwise ARM was initiated after intubation and was repeated post-retraction. Pressure-control ventilation mode was adjusted to deliver a tidal volume (Vt) of 6 mL/kg and an inspiratory-to-expiratory time (I:E) ratio of 1:2 with an optimal positive end-expiratory pressure (PEEP) for the ARM group. In the C group, a fixed PEEP (5 cmH2O) was applied. Invasive intra-arterial blood pressure (IBP), central venous pressure (CVP), electrical cardiometry (EC), alanine transaminase (ALT, U/L), and aspartate aminotransferase (AST, U/L) blood levels were monitored. Results: ARM increased PEEP, dynamic compliances, and arterial oxygenation, but reduced ventilator driving pressure compared to group C (P < 0.01). IBP, cardiac output (CO), and stroke volume variation were not affected by the higher PEEP in the ARM group (P > 0.05) but the CVP increased significantly (P = 0.001). Blood loss was not different between the ARM and C groups (1700 (1150-2000) mL vs 1110 (900-2400) mL, respectively and P = 0.57). ARM reduced postoperative oxygen desaturation; however, it did not affect the increase in remnant liver enzymes and was comparable to group C (ALT, P = 0.54, AST, P = 0.41). Conclusions: ARM improved intraoperative lung mechanics and reduced oxygen desaturation episodes in recovery, but not PPC or ICU stay. ARM was tolerated with minimal cardiac and systemic hemodynamic effects.

Inhaled Sedation with Volatile Anesthetics for Mechanically Ventilated Patients in Intensive Care Units: A Narrative Review.

Inhaled sedation was recently approved in Europe as an alternative to intravenous sedative drugs for intensive care unit (ICU) sedation. The aim of this narrative review was to summarize the available data from the literature published between 2005 and 2023 in terms of the efficacy, safety, and potential clinical benefits of inhaled sedation for ICU mechanically ventilated patients. The results indicated that inhaled sedation reduces the time to extubation and weaning from mechanical ventilation and reduces opioid and muscle relaxant consumption, thereby possibly enhancing recovery. Several researchers have reported its potential cardio-protective, anti-inflammatory or bronchodilator properties, alongside its minimal metabolism by the liver and kidney. The reflection devices used with inhaled sedation may increase the instrumental dead space volume and could lead to hypercapnia if the ventilator settings are not optimal and the end tidal carbon dioxide is not monitored. The risk of air pollution can be prevented by the adequate scavenging of the expired gases. Minimizing atmospheric pollution can be achieved through the judicious use of the inhalation sedation for selected groups of ICU patients, where the benefits are maximized compared to intravenous sedation. Very rarely, inhaled sedation can induce malignant hyperthermia, which prompts urgent diagnosis and treatment by the ICU staff. Overall, there is growing evidence to support the benefits of inhaled sedation as an alternative for intravenous sedation in ICU mechanically ventilated patients. The indication and management of any side effects should be clearly set and protocolized by each ICU. More randomized controlled trials (RCTs) are still required to investigate whether inhaled sedation should be prioritized over the current practice of intravenous sedation.

Diagnostic accuracy of global longitudinal strain in prediction of severity and extent of coronary artery stenosis in patients with acute coronary syndrome.

BACKGROUND: 2 D Speckle tracking echocardiography (STE) is a non-invasive, angle-independent, semiautomatic and objective technique that quantitatively assesses global and regional longitudinal systolic strain and provides a single bull's eye map for segmental wall strain of the left ventricle. OBJECTIVES: assessment of the accuracy of global longitudinal strain (GLS) using STE in the detection of resting myocardial ischaemia and its severity compared with visual assessment of wall motion score index by conventional 2 D echo. PATIENTS AND METHODS: 100 patients who presented with ACS were included. Wall motion score index (WMSI) was calculated in a 16-segment model and compared with GLS assessed in left ventricle 17 segments and calculated automatically by summation of regional longitudinal peak systolic strain (RLS) using STE. Quantitative coronary angiography was performed on clinical indication and significant stenosis was defined as a 70% reduction of the arterial lumen. RESULTS: 56 patients (56%) of patients were males with a mean age of 58.3 years. GLS showed a significant positive correlation between ejection fraction (EF) and GLS (p < 0.05), (r value 0.514) and a good significant negative correlation between WMSI and GLS (p < 0.05), (r value 0.593). And a good significant correlation between GLS and both severity of the lesion and the number of affected vessels was found (p < 0.05). ROC curves showed the cut-off point of GLS was (-15.9) for predicting lesion ≥70% with 88.1% sensitivity, 90.2% specificity respectively. CONCLUSION: GLS has higher specificity, sensitivity, and diagnostic accuracy for the detection of the severity of lesion and number of the vessel affected than WMSI.

Correlation between obstructive sleep apnea and ventricular function: a cross-sectional hospital-based study.

BACKGROUND: Obstructive sleep apnoea (OSA) is a major cause of cardiovascular morbidity and mortality worldwide. Previous studies showed high prevalence of OSA in heart failure. We aimed to evaluate the association of OSA with cardiac dysfunction and the importance of myocardial performance index (Tei) in identifying cardiac dysfunction. METHODS: Participants with OSA and sinus rhythm were included, while participants with arrhythmia, debilitating disease, or significant valvular heart disease were excluded. Thirty participants were enrolled, consecutively allocated in a single group, and underwent nocturnal polysomnography, electrocardiogram, and transthoracic echocardiography. RESULTS: The prevalence of hypertension, diabetes, and smoking in the study population was 50%, 30%, and 23.3%, respectively. The mean body mass index and apnoea-hypopnoea index (AHI) of the study population was 40.11 ± 7.5 kg/m2 and22.12 ± 13.54 events/h, respectively. There were statistically significant differences between mild, moderate, and severe OSA regarding the left ventricular end diastolic diameter, left ventricular end systolic diameter, ejection fraction, and fractional shortening (p = 0.006, p = 0.002, p = 0.014 and p = 0.011),respectively. There were statistically significant regular positive correlations between the AHI and the right and left Tei (r = 0.447, p = 0.001 and r = 0.391, p = 0.003),respectively. CONCLUSIONS: The prevalence of OSA was more in patients with comorbidities especially hypertension and diabetes. OSA was significantly associated with ventricular remodelling and cardiac dysfunction. A significant regular positive correlation was observed between the severity of OSA and worsening cardiac function as measured by Tei. Echocardiographic evaluation of the right and left ventricles and the right and left Tei could be considered as potentially valid, reproducible, and clinically applicable non-invasive methods for estimation of ventricular global function in patients with OSA.

Designing a new fast solution to control isolation rooms in hospitals depending on artificial intelligence decision.

Decreasing the COVID spread of infection among patients at physical isolation hospitals during the coronavirus pandemic was the main aim of all governments in the world. It was required to increase isolation places in the hospital's rules to prevent the spread of infection. To deal with influxes of infected COVID-19 patients' quick solutions must be explored. The presented paper studies converting natural rooms in hospitals into isolation sections and constructing new isolation cabinets using prefabricated components as alternative and quick solutions. Artificial Intelligence (AI) helps in the selection and making of a decision on which type of solution will be used. A Multi-Layer Perceptron Neural Network (MLPNN) model is a type of artificial intelligence technique used to design and implement on time, cost, available facilities, area, and spaces as input parameters. The MLPNN result decided to select a prefabricated approach since it saves 43% of the time while the cost was the same for the two approaches. Forty-five hospitals have implemented a prefabricated solution which gave excellent results in a short period of time at reduced costs based on found facilities and spaces. Prefabricated solutions provide a shorter time and lower cost by 43% and 78% in average values respectively as compared to retrofitting existing natural ventilation rooms.

Phantom study on surgical performance in augmented reality laparoscopy.

PURPOSE: Only a few studies have evaluated Augmented Reality (AR) in in vivo simulations compared to traditional laparoscopy; further research is especially needed regarding the most effective AR visualization technique. This pilot study aims to determine, under controlled conditions on a 3D-printed phantom, whether an AR laparoscope improves surgical outcomes over conventional laparoscopy without augmentation. METHODS: We selected six surgical residents at a similar level of training and had them perform a laparoscopic task. The participants repeated the experiment three times, using different 3D phantoms and visualizations: Floating AR, Occlusion AR, and without any AR visualization (Control). Surgical performance was determined using objective measurements. Subjective measures, such as task load and potential application areas, were collected with questionnaires. RESULTS: Differences in operative time, total touching time, and SurgTLX scores showed no statistical significance ([Formula: see text]). However, when assessing the invasiveness of the simulated intervention, the comparison revealed a statistically significant difference ([Formula: see text]). Participants felt AR could be useful for various surgeries, especially for liver, sigmoid, and pancreatic resections (100%). Almost all participants agreed that AR could potentially lead to improved surgical parameters, such as operative time (83%), complication rate (83%), and identifying risk structures (83%). CONCLUSION: According to our results, AR may have great potential in visceral surgery and based on the objective measures of the study, may improve surgeons' performance in terms of an atraumatic approach. In this pilot study, participants consistently took more time to complete the task, had more contact with the vascular tree, were significantly more invasive, and scored higher on the SurgTLX survey than with AR.

Diagnostic Validity and Reliability of Low-Dose Prospective ECG-Triggering Cardiac CT in Preoperative Assessment of Complex Congenital Heart Diseases (CHDs).

For the precise preoperative evaluation of complex congenital heart diseases (CHDs) with reduced radiation dose exposure, we assessed the diagnostic validity and reliability of low-dose prospective ECG-gated cardiac CT (CCT). Forty-two individuals with complex CHDs who underwent preoperative CCT as part of a prospective study were included. Each CCT image was examined independently by two radiologists. The primary reference for assessing the diagnostic validity of the CCT was the post-operative data. Infants and neonates were the most common age group suffering from complex CHDs. The mean volume of the CT dose index was 1.44 ± 0.47 mGy, the mean value of the dose-length product was 14.13 ± 5.4 mGy*cm, and the mean value of the effective radiation dose was 0.58 ± 0.13 mSv. The sensitivity, specificity, PPV, NPV, and accuracy of the low-dose prospective ECG-gated CCT for identifying complex CHDs were 95.6%, 98%, 97%, 97%, and 97% for reader 1 and 92.6%, 97%, 95.5%, 95.1%, and 95.2% for reader 2, respectively. The overall inter-reader agreement for interpreting the cardiac CCTs was good (κ = 0.74). According to the results of our investigation, low-dose prospective ECG-gated CCT is a useful and trustworthy method for assessing coronary arteries and making a precise preoperative diagnosis of complex CHDs.

A Phase I Study of the Non-Receptor Kinase Inhibitor Bosutinib in Combination with Pemetrexed in Patients with Selected Metastatic Solid Tumors.

Src is overexpressed in various cancers, including 27% of non-small cell lung cancer NSCLC, and is correlated with poor clinical outcomes. We hypothesize that Src kinase inhibitors, including Bosutinib, may exhibit clinical synergy in combination with the antifolate drug pemetrexed. In this Phase I, dose-escalation, safety, and maximum tolerated dose (MTD)-determining study, 14 patients with advanced metastatic solid tumors that had progressed on "standard of care" chemotherapy were enrolled in a 3 + 3 dose escalation study. Oral Bosutinib was administered once daily beginning on day 1, where the first cohort started at an oral dose of 200 mg daily with pemetrexed 500 mg/m2 IV on a three-week schedule. The study's primary objective was to determine the dose-limiting toxicity (DLT), the MTD of Bosutinib in combination with pemetrexed, and the type and frequency of adverse events associated with this treatment. Twelve patients were evaluable for response, including ten patients with adenocarcinoma of the lung, one patient with metastatic adenocarcinoma of the appendix, and one patient with urothelial carcinoma. The median number of Bosutinib and pemetrexed cycles received was 4 (range, 1-4). The MTD of oral Bosutinib in this combination was 300 mg daily. Two patients (17%) had a partial response (PR), and seven patients (58%) showed stable disease (SD) as the best response after the fourth cycle (end of treatment). One patient had disease progression after the second cycle, while three patients had disease progression after the fourth cycle. The two responders and the two patients with the longest stable disease duration or stabilization of disease following progression on multiple systemic therapies demonstrated Src overexpression on immunohistochemical staining of their tumor. The median progression-free survival (PFS) was 6.89 months (95% CI (3.48, 30.85)), and the median overall survival (OS) was 11.7 months (95% CI (3.87, 30.85)). Despite the limitations of this Phase I study, there appears to be potential efficacy of this combination in previously treated patients.

Triplet (FOLFOXIRI) Versus Doublet (FOLFOX or FOLFIRI) Regimen as First Line Treatment in Metastatic Colorectal Carcinoma, a Prospective Phase II, Randomized Controlled Trial.

BACKGROUND: The outcomes of treatment of metastatic colorectal cancer (mCRC) is still unsatisfactory. Several trials approved that, the upfront treatment with triplet regimen included fluorouracil, leucovorin, irinotecan and oxaliplatin improved the outcomes of patients with metastatic disease as compared to standard doublet regimen. The objective of our study is evaluating the impact of upfront treatment with triplet (FOLFOXIRI) regimen on both oncological outcomes (response rate and survival) and patients' tolerability in comparison to the standard doublet regimen. METHODS: We randomly enrolled 64 patients with a newly diagnosed unresectable mCRC to receive either FOLFOXIRI (experimental arm) or FOLFIRI or FOLFOX4 (control arm) biweekly up to 12 cycles. The primary endpoints are overall response rate (RR) and patients' tolerability. The secondary endpoints are the progression free and overall survival. RESULT: There was a significantly increase in RR (59% vs 37%) and complete remission rate (CR) (6.3% and 3.1%, respectively (P = 0.045) for the triplet therapy group compared to control group.  Consequently, an increased rate of secondary resection of metastasis (21.9% vs 3.1% respectively; P=0.023). The FOLFOXIRI regimen was associated with higher rate of grade 3/4 toxicity but not statistically significant except febrile neutropenia (6.2%; P=0.03). There was numerical prolongation in the median PFS in the FOLFOXIRI group on compared to control group but not significantly (9 versus 8 months; P=0.11). The median OS was 20 and 22 months in FOLFOXIRI arm and control arm respectively with no statistically significant difference (P=0.57). CONCLUSION: FOLFOXIRI had a higher efficacy and higher conversion rate to secondary resection over the doublet regimen as an upfront treatment option, coupled with a manageable adverse event, but failed to improve the survival outcomes.

Cytotoxic effects of extracts obtained from plants of the Oleaceae family: bio-guided isolation and molecular docking of new secoiridoids from Jasminum humile.

CONTEXT: Traditionally, Oleaceae plants are used to treat many diseases, such as rheumatism, hypercholesterolaemia, or ulcers. OBJECTIVES: To investigate the cytotoxic potential of Jasminum humile L., Jasminum grandiflorum L., and Olea europaea L. (Oleaceae) extracts against selected human cancer cells lines, followed by a phytochemical investigation of the most potent one. MATERIALS AND METHODS: The 95% ethanol extracts of aerial parts of three oleaceous plants were examined for their cytotoxicity against HepG-2, MCF-7, and THP-1 cell lines using MTT assay and doxorubicin (positive control). J. humile was bio-selected and submitted to bio-guided fractionation. Chromatographic workup of ethyl acetate and n-butanol fractions afforded two new compounds; 1-methoxyjasmigenin (1) and 1-methyl-9-aldojasmigenin (2), along with five known ones (3-7). Structures were unambiguously elucidated using 1D/2D NMR and ESI-HRMS. Isolated compounds were assessed for their anti-proliferative potential, and both selectivity index and statistical significance were determined. Molecular docking was conducted against the Mcl-1 receptor using (AZD5991) as a standard. RESULTS: Jasmoside (5) was the most potent anticancer compound showing IC50 values of 66.47, 41.32, and 27.59 µg/mL against HepG-2, MCF-7, and THP-1 cell lines, respectively. Moreover, isojasminin (4) exhibited IC50 values of 33.49, 43.12, and 51.07 µg/mL against the same cell lines, respectively. Interestingly, 5 exhibited the highest selectivity index towards MCF-7 and THP-1, even greater than doxorubicin. Molecular docking results were in full agreement with the MTT assay and the proposed SAR. CONCLUSION: In this study, two new compounds were purified. The biological activity highlighted jasmoside (5) as a lead anticancer drug for further future investigation.

Sleep Deprivation & Amphetamine Induced Psychosis.

Objectives: To explore the relationship between sleep deprivation and amphetamine-induced psychosis. Methods: The patient group included 78 patients with a diagnosis of amphetamine (Captagon)-induced psychosis. The control group included 49 patients with no current or past history of amphetamine (Captagon)-induced psychosis. All study subjects underwent the following: a demographic sheet, a structured clinical interview for SM-IV (SCID 1), a drug use questionnaire, a questionnaire to explore any relationship between sleep deprivation and Captagon-induced psychosis, routine medical investigation, and urine screening for detection of drugs. Results: The patient group showed significantly higher both regular and maximum daily doses of Captagon. Patients showed more periods of sleep deprivation with the use of Captagon in comparison to controls, especially with the increase of the Captagon dose. Patients believed that the occurrence and termination of sleep deprivation were the cause of the start and end of psychotic experiences (more so than the increase and decrease or stoppage of Captagon doses). Conclusion: sleep deprivation plays an essential role in the development of psychotic symptoms in patients who are using Captagon.

Nanoemulsions of Jasminum humile L. and Jasminum grandiflorum L. Essential Oils: An Approach to Enhance Their Cytotoxic and Antiviral Effects.

Unprecedented nanoemulsion formulations (NE) of Jasminum humile and Jasminum grandiflorum essential oils (EO) were prepared, and examined for their cytotoxic and antiviral activities. NE characterization and stability examination tests were performed to ensure formula stability. The antiviral activity was determined against hepatitis A (HAV) and herpes simplex type-1 (HSV-1) viruses using MTT assay, while the cytotoxic potential was determined against liver (HepG-2), breast (MCF-7), leukemia (THP-1) cancer cell lines and normal Vero cells. Statistical significance was determined in comparison with doxorubicin as cytotoxic and acyclovir as antiviral standard drugs. GC-MS analysis indicated twenty four compounds in the EO of J. humile and seventeen compounds in the EO of J. grandiflorum. Biological investigations of pure EOs revealed weak cytotoxic and antiviral effects. Nevertheless, their NE formulations exhibited high biological value as cytotoxic and antiviral agents. NE formulations also showed feasible selectivity index for the viral-infected and cancer cells (especially HepG-2) than normal Vero cells. Both nanoemulsions showed lower IC50 than standard doxorubicin against HepG-2 (26.65 and 22.58 vs. 33.96 µg/mL) and MCF-7 (36.09 and 36.19 vs. 52.73 µg/mL), respectively. The study results showed the dramatic effect of nanoemulsion preparation on the biological activity of EOs and other liposoluble phytopharmaceuticals.