Preparation and in vivo evaluation of nano sized cubosomal dispersion loaded with Ruta graveolens extracts as a novel approach to reduce asthma-mediated lung inflammation.

Asthma is a chronic disease affecting people of all ages. Asthma medications are associated with adverse effects restricting their long-term usage, demanding newer alternative therapies. This study aimed to investigate the anti-asthmatic properties of Ruta graveolens extract and its prepared nano-cubosomal dispersion (Ruta-ND). Firstly, the R. graveolens methanolic extract exhibited higher anti-inflammatory activity on Lipopolysaccharide (LPS)-activated BEAS-2B cells. To ensure best bioavailability and hence best cellular uptake, R. graveolens extract was loaded in nano-cubosomal dispersion (ND). Then, the anti-asthmatic effects of Ruta extract and ND were simultaneously evaluated in rats' model with ovalbumin-induced allergic asthma. R. graveolens extract and Ruta-ND subsided asthma score and improved lung function by restoring FEV1/FVC ratio to the expected values in control rats. Also, it showed strong antioxidant and anti-inflammatory activities manifested by lowering levels of malondialdehyde (MDA), IL-4, IL-7, TGF-ß, and Ig-E, and increasing levels of superoxide dismutase (SOD) and INF-γ in bronchoalveolar lavage fluid. Our research findings also indicate autophagy induction and apoptosis inhibition by Ruta extract and Ruta-ND. Finally, the HPLC MS/MS phytochemical profiling of R. graveolens extract evident production of various alkaloids, flavonoids, coumarins, and other phenolics with reported pharmacological properties corresponding to/emphasize our study findings. In conclusion, R. graveolens exhibited promise in managing Ova-induced allergic asthma and could be developed as an alternative anti-allergic asthma drug.

Development of a Novel, Ecologically Friendly Generation of pH-Responsive Alginate Nanosensors: Synthesis, Calibration, and Characterisation.

Measurement of the intracellular pH is particularly crucial for the detection of numerous diseases, such as carcinomas, that are characterised by a low intracellular pH. Therefore, pH-responsive nanosensors have been developed by many researchers due to their ability to non-invasively detect minor changes in the pH of many biological systems without causing significant biological damage. However, the existing pH-sensitive nanosensors, such as the polyacrylamide, silica, and quantum dots-based nanosensors, require large quantities of organic solvents that could cause detrimental damage to the ecosystem. As a result, this research is aimed at developing a new generation of pH-responsive nanosensors comprising alginate natural polymers and pH-sensitive fluorophores using an organic, solvent-free, and ecologically friendly method. Herein, we successfully synthesised different models of pH-responsive alginate nanoparticles by varying the method of fluorophore conjugation. The synthesised pH nanosensors demonstrated a low MHD with a relatively acceptable PDI when using the lowest concentration of the cross-linker Ca+2 (1.25 mM). All the pH nanosensors showed negative zeta potential values, attributed to the free carboxylate groups surrounding the nanoparticles' surfaces, which support the colloidal stability of the nanosensors. The synthesised models of pH nanosensors displayed a high pH-responsiveness with various correlations between the pH measurements and the nanosensors' fluorescence signal. In summation, pH-responsive alginate nanosensors produced using organic, solvent-free, green technology could be harnessed as potential diagnostics for the intracellular and extracellular pH measurements of various biological systems.

Taste Masking of Promethazine Hydrochloride Using l-Arginine Polyamide-Based Nanocapsules.

Promethazine hydrochloride (PMZ), a potent H1-histamine blocker widely used to prevent motion sickness, dizziness, nausea, and vomiting, has a bitter taste. In the present study, taste masked PMZ nanocapsules (NCs) were prepared using an interfacial polycondensation technique. A one-step approach was used to expedite the synthesis of NCs made from a biocompatible and biodegradable polyamide based on l-arginine. The produced NCs had an average particle size of 193.63 ± 39.1 nm and a zeta potential of −31.7 ± 1.25 mV, indicating their stability. The NCs were characterized using differential scanning calorimetric analysis and X-ray diffraction, as well as transmission electron microscopy that demonstrated the formation of the NCs and the incorporation of PMZ within the polymer. The in vitro release study of the PMZ-loaded NCs displayed a 0.91 ± 0.02% release of PMZ after 10 min using artificial saliva as the dissolution media, indicating excellent taste masked particles. The in vivo study using mice revealed that the amount of fluid consumed by the PMZ-NCs group was significantly higher than that consumed by the free PMZ group (p < 0.05). This study confirmed that NCs using polyamides based on l-arginine and interfacial polycondensation can serve as a good platform for the effective taste masking of bitter actives.

Non-resectable Malignant Peritoneal Mesothelioma Treated with Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) Plus Systemic Chemotherapy Could Lead to Secondary Complete Cytoreductive Surgery: A Cohort Study.

BACKGROUND: Diffuse malignant peritoneal mesothelioma (DMPM) is an aggressive primary peritoneal neoplasia. At diagnosis, few patients are eligible for a recommended cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Among neoadjuvant strategies, pressurized intraperitoneal aerosol chemotherapy (PIPAC) combined with systemic chemotherapy has been recently proposed. This study evaluated this strategy in a cohort of DMPM patients. METHODS: Patients with DMPM and primary or recurrent non-resectable diseases who received at least one PIPAC procedure in alternation with systemic chemotherapy were included in this retrospective study to analyze oncologic outcomes. RESULTS: Overall, 26 DMPM patients were treated with at least one PIPAC, including 20 patients with no previous CRS. Of 22 patients (85%) who had symptoms, 9 had perceptible ascites. Overall, 79 PIPAC procedures were performed, with half of the patients receiving three PIPAC procedures or more. Among eight patients (31%), 10 adverse events (13% of procedures) were reported, including two severe complications, both corresponding to digestive perforations. Improvement of symptoms was reported for 32% of the patients, whereas control of ascites was noted in 46%. All but one procedure among 14 patients (54%) secondarily treated by CRS-HIPEC were considered complete resections. After a median follow-up period of 29.6 months (95% confidence interval [CI], 17.6-not reached [NR]), the median overall survival period was 12 months (95% CI 11.1-NR). The median progression-free survival (PFS) was significantly better among the patients who underwent resection than among those who did not (33.5 vs 7.4 months; hazard ratio [HR], 0.18; 95% CI 0.06-0.755; p < 0.001). CONCLUSIONS: For patients with initially non-resectable DMPM, PIPAC is feasible for treatment with neoadjuvant intent and could facilitate complete secondary resection.

Smart Pellets for Controlled Delivery of 5-Fluorouracil.

This work aimed to develop a new one-pot and readily scaled-up formulation capable of retaining 5-fluorouracil and prolonging its release to obtain a site-specific medication delivery for the potential treatment of colorectal cancer. Six polymer-based formulations were successfully produced using a thermal bulk polymerization method and loaded with 5-fluorouracil, which is a chemotherapeutic agent used in the treatment of colorectal carcinoma. The pellets produced were characterized by measuring the glass transition temperature, tensile strength, Young's modulus, and tensile elongation at break. Studies on in vitro swelling and release were carried out in phosphate-buffered saline to evaluate the behaviour of the developed system. The Young's modulus, glass transition temperature, and tensile strength all increased significantly as the crosslinker concentration increased, but the fracture strain value reduced significantly. The in vitro swelling profile of the produced formulations was significantly reduced by increasing crosslinking density. Less than 27% cumulative drug release was achieved for all formulations after 5 h of starting the release study. The highest cumulative drug release reached after 24 h was 69%. The developed drug delivery system demonstrated the ability to delay the release of 5-fluorouracil in upper gastrointestinal tract-mimicking conditions, while permitting its release in a controlled way afterward, which makes it promising for the potential delivery of 5-fluorouracil to the colon.

Medication errors in Najran, Saudi Arabia: Reporting, responsibility, and characteristics: A cross-sectional study.

Background: Medication error is a preventable adverse effect of medical care, whether or not it is evident or harmful to the patient. Disclosure of medication errors and improvement of patient safety are inexorably related, and they provide one of the strongest reasons to report and disclose errors, including near misses in which no harm comes to the patient. This study aimed to identify medication errors at the southern province of Saudi Arabia. Methods: A cross-sectional retrospective study was conducted by reviewing all medical records in the King Khaled Hospital in Najran, Saudi Arabia. Medication errors related information were extracted from the electronic medical system for the duration between 2018 and 2020. Results: During the study period of 2018 to 2020, a total of 4860 medication errors were identified. More than half of the reported medication errors (66.9%) were linked to ordering, prescribing, or transcribing medications. The most commonly reported medication errors connected to ordering/prescribing/transcribing were inappropriate dosage, dosage units, and therapeutic duplication of medication. The most commonly reported medication errors linked to administration were missing documentation during administration, not performing independent double-checks during the administration of high alert medications, and the administration of look-alike sound-alike (LASA) medications. The intensive care unit (ICU), female medical ward, and male medical ward were the most commonly reported locations for medication errors. Pharmacists detected more than half of the reported medication errors. Physicians were found to be responsible for 66.0% of reported medication errors, followed by nurses. Conclusion: Medication errors are common in hospital settings in Saudi Arabia's southern provinces. Efforts should be made to improve drug ordering, prescribing, and transcription in hospital settings. To guarantee optimum practices, the entire medical team should take responsibility for the patient's optimal medication administration.

Knowledge and awareness of the general population and healthcare providers about retinoblastoma: It is time to know the glow.

Retinoblastoma is the most frequent primary intraocular tumour in childhood. Early detection of retinoblastoma is the key to successful management with a higher chance of survival. This study aims to assess the knowledge of the general population and healthcare providers about retinoblastoma in term of presentation, risk factors, timing for diagnosis, and complications. A cross-sectional study using an online survey was conducted in three Arab countries (Jordan, Saudi Arabia, and Iraq) between 28 August and 16 September 2020. The questionnaire tool was constructed based on an extensive literature review to explore the study's aim and objectives. Logistic regression was used to identify predictors of better knowledge about retinoblastoma. A total of 3676 participants were involved in the study (Jordan = 2654, Saudi Arabia = 604, and Iraq = 418). The average retinoblastoma knowledge score for the whole study population was 6.25 (SD = 4.12) out of 21, representing 29.8% (out of the maximum possible total score). Participants aged above 50 years old, married individuals, those with a secondary education level, those who work as professionals in industry, those who have more than four children, and those who reported that they were not in direct contact with a large number of children were less likely to be knowledgeable about retinoblastoma presentation, risk factors, the timing for diagnosis, and complications (P < .05). Early detection is the cornerstone for decreasing morbidity and mortality among children with retinoblastoma. However, the awareness and knowledge about retinoblastoma are very limited in our study population. Efforts should be directed at increasing awareness of both the general population and healthcare providers regarding retinoblastoma. Policymakers are responsible for improving knowledge and awareness about retinoblastoma to facilitate early detection of the disease by conducting awareness campaigns in addition to improve screening skills of healthcare providers and providing them with proper screening and diagnostic tools.

Formulation of sublingual promethazine hydrochloride tablets for rapid relief of motion sickness.

The delivery of antihistaminic agents via the oral route is problematic, especially for elderly patients. This study aimed to develop a sublingual formulation of promethazine hydrochloride by direct compression, and to mask its intensely bitter taste. Promethazine hydrochloride (PMZ) sublingual tablets prepared by direct compression were optimized using Box-Behnken full factorial design. The effect of a taste-masking agent (Eudragit E 100, X1), superdisintegrant (crospovidone; CPV, X2) and lubricant (sodium stearyl fumarate; SSF, X3) on sublingual tablets' attributes (responses, Y) was optimized. The prepared sublingual tablets were characterized for hardness (Y1), disintegration time (Y2), initial dissolution rate (IDR; Y3) and dissolution efficiency after 30 min (Dissolution Efficiency (DE); Y4). The obtained results showed a significant positive effect of the three independent factors on tablet hardness (P < 0.05), and the interactive effect of Eudragit E 100 and CPV on tablet hardness was significant. Disintegration time was mainly affected by Eudragit E 100 and CPV concentrations. Moreover, IDR was employed to assess the taste masking effect, lower values were obtained at higher Eudragit E 100 concentration despite it was statistically insignificant (p > 0.05). Optimized formulation that was suggested by the software was composed of: Eudragit E 100 (X1) = 2.5% w/w, CPV (X2) = 4.13% w/w, and SSF (X3) = 1.0% w/w. The observed values of the optimized formula were found to be close to the predicted optimized values. The Differential Scanning Calorimetric (DSC) studies indicated no interaction between PMZ and tablet excipients.

Prognostic impact of combined progression index based on peritoneal grading regression score and peritoneal cytology in peritoneal metastasis.

AIMS: The peritoneal regression grading score (PRGS) and peritoneal cytology (PC) assess response to chemotherapy in peritoneal metastasis (PM) in a setting of palliative treatment by pressurized intraperitoneal aerosol chemotherapy (PIPAC). Progression has been defined as an increase of PRGS between first and third PIPAC procedures (iPRGS). iPRGSand positive peritoneal cytology were not associated with prognostic impact. These results may be explained by a lack of statistical power. Also, it is not known whether the mean or the highest PRGS among taken peritoneal biopsies bears the highest clinical value. We therefore conducted the largest prospective study to investigate the prognostic impact of PGRS, PC, and their combination, designated as combined progression index (CPI). METHODS AND RESULTS: Patients with PM who underwent >3 PIPAC (n = 112) between December 2016 and February 2019 were prospectively included. A significant difference in OS and PFS according to CPI (used highest value of PRGS) was found (OS: CPI-, 83.3, 95% CI [49.8; NA] vs. CPI+, 48.1, 95% CI [38.5; 66.4] months; and PFS (respectively, 59.7, 95% CI [43.0; 96.0] vs. 33.7, 95% CI [30.4; 44.2] months). PRGS or PC had no independent prognostic impact. CPI+ was an independent predictor of worse prognosis, in OS (HR = 5.24, 95% CI [2.07; 13.26]), and PFS (HR = 4.41, 95% CI [1.40; 13.88]). CONCLUSIONS: The CPI based on highest PRGS and PC was found to be independently associated with a worse prognosis for OS and for PFS in the setting of peritoneal metastasis. These results indicate that it should be of interest to systematically take peritoneal fluid for cytological examination and to implement the CPI in the therapeutic decision-making process in the context of PIPAC.

Long-term results of laparoscopic cytoreductive surgery and HIPEC for the curative treatment of low-grade pseudomyxoma peritonei and multicystic mesothelioma.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) provide long-term survival for low-grade pseudomyxoma peritonei (PMP) and multicystic peritoneal mesothelioma (MM). Feasibility of laparoscopic CRS-HIPEC has been reported for selected patients but data regarding long-term outcomes are missing to assess the oncological interest. This study aimed to report long-term outcomes for low-grade PMP and MM treated by laparoscopic approach. METHODS: From a prospectively maintained CRS-HIPEC database, all patients who underwent laparoscopic CRS-HIPEC with curative intent were analyzed. Selection criteria for laparoscopic approach were low-grade PMP or MM, with pathological confirmation prior to CRS-HIPEC, ASA 2, age < 75 years, no extrap-eritoneal disease, Peritoneal Cancer Index (PCI) < 10, and a limited history of abdominal surgery. RESULTS: Between March 2009 and June 2017, 43 patients were scheduled for laparoscopic CRS and HIPEC. Laparoscopic CRS and HIPEC was completed (LSC) in 32 patients and 11 patients were converted to open surgery (CONV). Median age was 44.5 years (17.13-71.4) in the LSC group and 54.9 years (22.5-70.5) in the CONV group (p = 0.086). Median BMI was not different between groups, 21.2 and 23.9 for LSC and CONV groups, respectively (p = 0.267). There were 21 and 11 patients in the LSC group, and 8 and 3 in the CONV group, with PMP and MM, respectively (p = 0.794). Median PCI was 2.5 (0-9) and 7 (1-15) in the LSC and CONV groups, respectively (p = 0.004). There was no difference in the completeness of cytoreduction score (p = 0.256). After a median follow-up of 31.6 months (95% CI 19.3-36.4), 2 patients in the LSC group and 2 patients in the CONV group presented with peritoneal recurrence. CONCLUSION: For selected patients with low aggressive peritoneal disease, laparoscopic CRS-HIPEC provides interesting long-term outcomes.

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) might increase the risk of anastomotic leakage compared to HIPEC: an experimental study.

BACKGROUND: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) and hyperthermic intraperitoneal chemotherapy (HIPEC) are technics proposed to treat patients with peritoneal carcinomatosis, in different settings. There is some concern about an over-risk of anastomotic leakage (AL) with PIPAC jeopardizing a combination with cytoreductive surgery. This study used a healthy swine model to compare the postoperative AL rate between PIPAC and HIPEC with digestive resection and to analyze macrocirculation and microcirculation parameters. METHODS: Segmental colonic resection with a handsewn anastomosis was performed on 16 healthy pigs; 8 pigs had a PIPAC procedure with 7.5 mg/m2 cisplatin (PIPAC group), and 8 pigs had a closed HIPEC procedure with 70 mg/m2 cisplatin and 42 °C as the target intraperitoneal temperature (HIPEC group). Pigs were kept alive for 8 days, then sacrificed and autopsied to look for AL, which was defined as local abscess or digestive fluid leakage when pressure was applied to the anastomosis. Food intake, weight, and core temperature were monitored postoperatively. Macrocirculation (heart rate, systolic blood pressure) and microcirculation parameters (percentage of perfused vessels, perfused vessels density, DeBacker score) were evaluated intraoperatively at five timepoints. Results were compared between pigs with AL and those without. RESULTS: The HIPEC group had no AL, but 3 of 8 pigs (37.5%) had AL in the PIPAC group (p = 0.20). Heart rate and core temperature showed perioperative increases in the HIPEC group. Intraoperatively, heart rate was higher in the HIPEC group at the two last timepoints (123 vs. 93 bpm, p = 0.031, and 110 vs. 85 bpm, p = 0.010, at timepoints 3 and 4, respectively). Other macrocirculatory and microcirculatory parameters showed no significant differences. CONCLUSION: In this healthy swine model, PIPAC might have increased AL incidence compared to HIPEC. This potential over-risk did not seem to be related to changes in the microcirculation. PIPAC should probably not be used with digestive resection and should be avoided in cases of perioperative serosal injury.

PIPAC versus HIPEC: cisplatin spatial distribution and diffusion in a swine model.

Purpose: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a novel approach for delivering intraperitoneal chemotherapy and offers perspective in the treatment of peritoneal carcinomatosis. Concept is based on a 12 mmHg capnoperitoneum loaded with drug changed in microdoplets. It was postulated to guarantee a more homogeneous drug distribution and tissular uptake than hyperthermic intraperitoneal chemotherapy (HIPEC). The aim of this study was to compare cisplatin peritoneal distribution and pharmacokinetic between HIPEC and PIPAC procedures in a healthy swine model.Methods: Two groups of eight pigs underwent either HIPEC with cisplatin (70 mg/m2) at 43 °C for 60 min, or PIPAC with cisplatin (7.5 mg/m2) for 30 min. Postoperatively, peritoneal areas were biopsied allowing peritoneal cavity cartography. Tissular and plasmatic cisplatin concentrations were analyzed.Results: Cisplatin distribution was heterogeneous in both the groups with higher concentrations obtained closed to the delivery sites. Median total platinum peritoneal concentration by pig was higher in the HIPEC group than in the PIPAC group (18.0 µg/g versus 4.3 µg/g, p < .001) but the yield was 2.2 times better with PIPAC. Platinum concentrations were higher in the HIPEC group in all stations. At each time-point, cisplatin plasmatic concentrations were higher in the HIPEC group (p < .001) but beneath the toxicity threshold.Conclusions: With doses used in clinical practice, HIPEC guaranteed a higher cisplatin peritoneal uptake than PIPAC in this swine model. Spatial drug distribution was heterogeneous with both technics, with hotspots closed to the drug delivery sites. Nevertheless, considering the dose ratio, IP drug uptake yield was better with PIPAC.

Middle East Respiratory Syndrome (MERS) and novel coronavirus disease-2019 (COVID-19): From causes to preventions in Saudi Arabia.

Saudi Arabia is one of the countries that has been affected by COVID-19. At the beginning of March 2020, it revealed a steadily rising number of laboratory-confirmed cases. By 20th May 2020, 59,854 infected cases had been confirmed, with 329 deaths. To prevent a further outbreak of COVID-19, this article discusses the current understanding of COVID-19 and compares it with the outbreak of Middle East Respiratory Syndrome (MERS) in 2012 in Saudi Arabia. It also discusses the causes, transmission, symptoms, diagnosis, treatments and prevention measures to identify an applicable measure to control COVID-19.

Pressurised intraperitoneal aerosol chemotherapy: rationale, evidence, and potential indications.

Pressurised intraperitoneal aerosol chemotherapy (PIPAC) was introduced as a new treatment for patients with peritoneal metastases in November, 2011. Reports of its feasibility, tolerance, and efficacy have encouraged centres worldwide to adopt PIPAC as a novel drug delivery technique. In this Review, we detail the technique and rationale of PIPAC and critically assess its evidence and potential indications. A systematic search was done to identify all relevant literature on PIPAC published between Jan 1, 2011, and Jan 31, 2019. A total of 106 articles or reports on PIPAC were identified, and 45 clinical studies on 1810 PIPAC procedures in 838 patients were included for analysis. Repeated PIPAC delivery was feasible in 64% of patients with few intraoperative and postoperative surgical complications (3% for each in prospective studies). Adverse events (Common Terminology Criteria for Adverse Events greater than grade 2) occurred after 12-15% of procedures, and commonly included bowel obstruction, bleeding, and abdominal pain. Repeated PIPAC did not have a negative effect on quality of life. Using PIPAC, an objective clinical response of 62-88% was reported for patients with ovarian cancer (median survival of 11-14 months), 50-91% for gastric cancer (median survival of 8-15 months), 71-86% for colorectal cancer (median survival of 16 months), and 67-75% (median survival of 27 months) for peritoneal mesothelioma. From our findings, PIPAC has been shown to be feasible and safe. Data on objective response and quality of life were encouraging. Therefore, PIPAC can be considered as a treatment option for refractory, isolated peritoneal metastasis of various origins. However, its use in further indications needs to be validated by prospective studies.

Ninety-day post-operative morbidity and mortality using the National Cancer Institute's common terminology criteria for adverse events better describe post-operative outcome after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

BACKGROUND: The post-operative morbidity and mortality after CRS-HIPEC has been widely evaluated. However, there is a major discrepancy between rates reported due to different metrics and time of analysis used. OBJECTIVE: To evaluate the legitimacy of 90-day morbidity and mortality based on the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) v4.0 classification as criteria of quality for cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). METHODS: A prospective database of all patients undergoing CRS-HIPEC for peritoneal carcinomatosis between 2004 and 2015 was queried for 90-day morbidity and mortality and survival. RESULTS: Among 881 patients, the 90-day major complication rate based on NCI-CTCAE classification and Clavien-Dindo's classification were 51% (n = 447 patients) and 25% (n = 222 patients), respectively. Among patients who presented with a 90-day complication based on the NCI-CTCAE classification, 50% (n = 225 patients) presented a medical complication not reported by Clavien-Dindo's classification. After surgery, 24 patients (2.7%) died of post-operative complications, for only 10 (42%) of them the death occurred within 30-day after surgery. Occurrence of major complication based on either NCI-CTCAE classification, Clavien-Dindo's classification or the medical complication not reported by Clavien-Dindo's classification all negatively impacts the overall survival. CONCLUSION: Among commonly reported morbidity's classification, 90-day morbidity based on NCI-CTCAE classification represents a legitimate metric of CRS-HIPEC quality. Post-operative morbidity after CRS-HIPEC should be reported using 90-day NCI-CTCAE classification.

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Carcinomatosis in the Elderly: A Case-Controlled, Multicenter Study.

OBJECTIVE: This study was designed to identify factors associated with morbidity and mortality in patients older than 70 years who underwent cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal carcinomatosis (PC). BACKGROUND: Major surgery is associated with higher morbidity and mortality in elderly patients. For PC, CRS and HIPEC is the only current potential curative therapy, but the risks inherent to this patient population have called its benefits into question. METHODS: We retrospectively analyzed a multi-center database from 1989 to 2015. All patients who underwent CRS and HIPEC for PC were selected and patients older than 70 years were matched 1:4 with a younger cohort according to cancer origin, peritoneal cancer index (PCI), and completeness of cytoreduction. Major morbidity and mortality were analyzed. RESULTS: Of 2328 patients, 188 patients older than aged 70 years were matched with 704 younger patients. Patients older than aged 70 years demonstrated a higher American Society of Anesthesiologist score (≥ASA III 10.8 vs. 6.6 %, p = 0.008). There was no difference in overall 90-day morbidity (≥70: 45.7 % vs. <70: 44.5 %; p = 0.171); however, patients older than 70 years had significantly more cardiovascular complications (13.8 vs. 9.2 %, p = 0.044). Differences between the older and younger cohorts failed to reach significance for 90-day mortality (5.4 and 2.7 %, respectively; p = 0.052), and failure-to-rescue (11.6 and 6.1 %, respectively; p = 0.078). In multivariate analysis, PCI > 7 (95 % CI 1.051-5.798, p = 0.038) and HIPEC duration (95 % CI 1.106-6.235, p = 0.028) were independent factors associated with morbidity in elderly patients. CONCLUSIONS: CRS and HIPEC appear feasible for selected patients older than aged 70 years, albeit with a higher risk of medical complications associated with increased mortality.

Artificial intelligence in prosthodontics.

Artificial Intelligence (AI) is gaining popularity worldwide owing to its significant impact in science and innovation. The role of AI in prosthodontics has increased significantly in recent years. AI is used for diagnosis, decision-making, prognosis, treatment planning and prediction of outcomes. Integration of AI into prosthodontics can enhance the accuracy and precision of dental practice. However, limited datasets are a major constraint in its practical applications.

The Prevalence of Risk Factors for Cardiovascular Diseases in Najran Region, Saudi Arabia.

The primary goal of this study was to investigate the knowledge, prevalence, and risk factors of cardiovascular diseases among individuals in the Najran region of Saudi Arabia. In the Najran region of Saudi Arabia, an online cross-sectional survey was conducted. Between September and October 2023, a self-administered questionnaire was distributed to a random sample of the general population aged 18 and up. The survey instrument asked about history and exposure, physician-diagnosed illnesses, cardiovascular diseases (CVDs), medication use, and other risk factors. This research had a total of 2046 individuals. Around one-fifth of the study participants reported that they or a family member suffered from CVD, and arrhythmia was the most commonly reported; blood tests, cardiac catheterization, and ECG were the most commonly reported tests performed for CVD patients, around one-tenth of CVD patients reported that they do not have any chronic diseases other than CVD, and the vast majority of the patients confirmed their regular medical appointments. This is one of the first studies to investigate the knowledge, prevalence, and use of CVD drugs among individuals in the Najran region of Saudi Arabia. The study participants' lack of knowledge about CVD could lead to ineffective preventive measures and poor patient outcomes. The study's findings underscore the crucial need for more extensive and efficient educational initiatives that consider the targeted population's talents, attitudes, and perceptions.

24 Factorial Design Formulation Optimization and In vitro Characterization of Desloratadine Nanosuspension Prepared Using Antisolvent Precipitation.

INTRODUCTION: Desloratadine, a second-generation antihistaminic drug, is poorly watersoluble and requires amelioration of the dissolution rate to improve its pharmacokinetics properties. METHOD: This study investigated the impact of polymer, surfactant types, and concentration on the particle size, zeta potential, and dissolution efficiency of nanosuspensions formulated through the solvent antisolvent precipitation method. To optimize the delivery of Desloratadine nanosuspension, we used Minitab software and a 4-factor, 2-level full factorial design. Physicochemical properties and drug release studies were conducted to evaluate the suggested nanosuspension formulations. The optimization goals included minimizing particle size and zeta potential while maximizing dissolution efficiencies. RESULT: The selected optimal nanosuspension demonstrated favourable values, including a particle size of 478.63 ± 15.67 nm, a zeta potential of -36.24 ± 3.21 mV, and dissolution efficiencies in double distilled water and buffer of 90.29 ± 3.75 % and 93.70 ± 3.67 %, respectively. The optimized formulation was subjected to additional analysis using X-ray powder diffraction (XPRD), scanning and transmission electron microscopy (SEM and TEM), and Fourier-transform infrared spectroscopy (FTIR). CONCLUSION: The optimized nanosuspension formulation also underwent further studies under optimal lyophilization conditions, revealing the effectiveness of mannitol as a cryoprotectant at a concentration of 8%.

Oral bioavailability enhancement of doxazosin mesylate: Nanosuspension versus self-nanoemulsifying drug delivery systems.

Background and purpose: Doxazosin mesylate (DOX) is an antihypertensive drug that possesses poor water solubility and, hence, poor release properties. Both nanosuspensions and self-nanoemulsifying drug delivery systems (SNEDDS) are becoming nanotechnology techniques for the enhancement of water solubility of different drugs. Experimental approach: The study's goal was to identify the best drug delivery system able to enhance the release and antihypertensive effect of DOX by comparing the physical characteristics such as particle size, zeta potential, entrapment efficiency, release rate, and main arterial blood pressure of DOX-loaded nanosuspensions and SNEDDS in liquid and solid form. Key results: DOX nanosuspension preparation had a particle size of 385±13 nm, poly-dispersity index of 0.049±3, zeta potential of 50 ± 4 mV and drug release after 20 min (91±0.43 %). Liquid SNEDDS had a droplet size of 224±15 nm, poly-dispersity index of (0.470±0.01), zeta potential of -5±0.10 mV and DR20min of 93±4 %. Solid SEDDS showed particle size of 79±14 nm, poly-dispersity index of 1±0.00, a zeta potential of -18 ±0.26 mv and DR20min of 100 ±2.72 %. Conclusion: Finally, in terms of the mean arterial blood pressure lowering, solid SNEDDS performed better effect than both liquid SNEDDS and nanosuspension (P >0.05).