Abstract: Breast cancer is the most widespread cancer in women with rising incidence, prevalence, and mortality in developed regions. Most breast cancers (80%) are estrogen receptor–positive, indicating that disease progression could be controlled by estrogen inhibition in the breast tissue. However, drug resistance limits the benefits of this approach. Combinatorial treatment could overcome the resistance and improve the outcome of breast cancer treatment. In the current study, we prepared letrozole-(LTZSPs) and quercetin-loaded spanlastics (QuSPs) using different edge activators—Tween 80, Brij 35, and Cremophor RH40—with different concentrations. The spanlastics were evaluated for their average particles size, surface charge, and percent encapsulation efficiency. The optimized formulations were further examined using transmission electron microscopy, Fourier transform infrared spectroscopy, in vitro drug release and ex vivo skin permeation studies. The prepared spherical LTZSPs and QuSPs had average particle sizes ranged between 129–310 nm and 240–560 nm, respectively, with negative surface charge and high LTZ and Qu encapsulation (94.3–97.2% and 97.9–99.6%, respectively). The in vitro release study of LTZ and Qu from the selected formulations showed a sustained drug release for 24 h with reasonable flux and permeation through the rat skin. Further, we evaluated the in vitro cytotoxicity, cell cycle analysis, and intracellular reactive oxygen species (ROS) of the combination therapy of letrozole and quercetin either in soluble form or loaded in spanlastics against MCF-7 breast cancer cells. The LTZSPs and QuSPs combination was superior to the individual treatments and the soluble free drugs in terms of in vitro cytotoxicity, cell cycle analysis, and ROS studies. These results confirm the potential of LTZSPs and QuSPs combination for transdermal delivery of drugs for enhanced breast cancer management.

Autoimmune inflammatory arthritides (AIA), such as psoriatic arthritis and rheumatoid arthritis, are chronic systemic conditions that affect multiple joints of the body. Recently, total-body (TB) PET/CT scanners exhibiting superior technical characteristics (total-body coverage, geometric sensitivity) that could benefit AIA evaluation, compared with conventional PET/CT systems, have become available. The objectives of this work were to assess the performance of an ultra-low-dose, ¹⁸F-FDG TB PET/CT acquisition protocol for evaluating systemic joint involvement in AIA and to report the association of TB PET/CT measures with joint-by-joint rheumatologic examination and standardized rheumatologic outcome measures. Methods: Thirty participants (24 with AIA and 6 with osteoarthritis) were prospectively enrolled in this single-center, observational study. All participants underwent a TB PET/CT scan for 20 min starting at 40 min after intravenous injection of 78.1 ± 4.7 MBq of ¹⁸F-FDG. Qualitative and quantitative evaluation of ¹⁸F-FDG uptake and joint involvement were performed from the resulting images and compared with the rheumatologic assessments. Results: TB PET/CT enabled the visualization of ¹⁸F-FDG uptake at joints of the entire body, including those of the hands and feet, in a single bed position, and in the same phase of radiotracer uptake. A range of pathologies consistent with AIA (and non-AIA in the osteoarthritis group) were visualized, and the feasibility of extracting PET measures from joints examined by rheumatologic assessments was demonstrated. Of 1,997 evaluable joints, there was concordance between TB PET qualitative assessments and joint-by-joint rheumatologic evaluation in the AIA and non-AIA cohorts for 69.9% and 91.1% joints, respectively, and an additional 20.1% and 8.8% joints, respectively, deemed negative on rheumatologic examination showed PET positivity. On the other hand, 10.0% and 0% joints in the AIA and non-AIA cohorts, respectively, were positive on rheumatologic evaluation but negative on TB PET. Quantitative measures from TB PET in the AIA cohort demonstrated a moderate-to-strong correlation (Spearman ρ = 0.53-0.70, P < 0.05) with the rheumatologic outcome measures. Conclusion: Systemic joint evaluation in AIA (and non-AIA) is feasible with a TB PET/CT system and an ultra-low-dose protocol. Our results provide the foundation for future larger studies to evaluate the possible improvements in AIA joint assessment via the TB PET/CT technology.

Background: Remarkable progress has been made in the treatment of pediatric acute lymphoblastic leukemia (ALL), with survival rates reaching > 80% in high-income countries. In Egypt, the outcome of treatment of ALL has been less favorable. Aim: To evaluate the clinicolaboratory characteristics in patients admitted at Sohag Cancer Center and to assess the outcome and the prognostic factors affecting it. Methods: This retrospective study included 79 pediatric ALL patients, from January 2010 to December 2014, who were treated according to modified Total therapy study XIIIB high-risk ALL of St. Jude Children's Research Hospital (SJCRH). Results: 52% were males with a median age of 6 years. 58.2% were stratified as HR, 69.6% had precursor B-ALL, 39.2% presented with total leucocytic count (TLC) (≥ 50x109/L), and 11.3% had CNS leukemia. Complete remission (CR) was achieved in 87.3%. Regarding treatment outcome, induction failure was reported in 5.1%, relapse in 24.1%, deaths in CR in 7.2%, and continuous complete remission in 59.5%. The median follow-up was 42 months, 4 years OS, EFS, and DFS were 64.1 ± 5.6, 57 ± 5.7, and 63.3 ± 5.8% respectively. TLC and bone marrow aspirate postinduction were the only significant prognostic factors affecting EFS. Conclusions: The modified TXIIIB of SJCRH was effective in improving ALL outcomes in our center, however, survival rates were much lower than internationally reported results with only initial TLC and response postinduction having a significant effect on EFS and DFS.

Background. Intrathecal fentanyl in spinal anesthesia improves intra- and postoperative analgesia. Dexmedetomidine
is a fascinating adjuvant with regards to neuraxial anesthesia in children experiencing surgery for abdominal malignancy.
Patients and Methods. After endorsement by the institutional reviewing board (IRB) and guardians’ written informed
consent, this research was carried out on 60 pediatric malignancy patients scheduled for major abdominal
surgery. Children were randomly distributed into three groups (20 patients each): Group C: given 2mL of bupivacaine
0.5% (0.4 mg/kg) intrathecally, injected gradually over 20 seconds. Group F: the same as group C, plus fentanyl
0.2 lg/kg. Group D: the same as group C, plus dexmedetomidine 0.2 lg/kg. Pain at zero, two, four, six, 12, 18, and
24 hours postoperatively was evaluated by Face, Legs, Activity, Crying, and Consolability (FLACC) score. First analgesic
request and postoperative unfavorable effects were recorded for 24 hours postoperatively. Results. A significant
decrease was recognized in the mean FLACC score in groups D and F at six, eight, and 12 hours postoperatively,
in contrast to group C (P0.05). First analgesic request was significantly prolonged in group D (7.6760.57 hours),
in contrast to groups F and C (5.4061.09 hours and 4.2363.27 hours, respectively, P < 0.04). Paracetamol utilization
was significantly decreased in group D (316.67628.86 mg), in contrast to group C (391.00652.00 mg, P < 0.03),
without a significant difference between group F (354.44646.67 mg) and groups D and C (P > 0.05). Conclusions.
Adding dexmedetomidine and fentanyl to intrathecal bupivacaine improved postoperative analgesia following
abdominal surgery for cancer in children, with better overall analgesia of dexmedetomidine compared with
fentanyl.
Key Words: Intrathecal; Fentanyl; Dexmedetomidine; Bupivacaine; Pediatric Major Abdominal Cancer Surgery