•One-third of pediatric tumor patients require radiotherapy.•High pediatric radiotherapy utilization rate in a middle-income country.•Pediatric soft tissue sarcoma requires the highest radiotherapy ...utilization rate.•Palliative radiotherapy is frequently used for brainstem glioma patients.•Palliative radiotherapy is underutilized in childhood cancers.
Although the radiotherapy utilization rate (RUR) is determined for most adult cancers, it is seldom reported in childhood tumors, particularly in low- and middle-income countries (LMIC) where the majority of pediatric cancer patients reside. This study aims to investigate the real-life RUR for pediatric tumors in a large LMIC center.
The electronic files of patients treated at a single institution during 2010–2017 were reviewed and the RUR was defined as the percentage of patients who received at least one radiotherapy (RT) course from the total number of patients.
A total of 4390 out of 13,305 pediatric cancer patients received at least one RT course with a RUR of 33%. The curative, salvage, and palliative RURs were 27.8%, 2%, and 5.7%, respectively. There was a considerable variation in the RUR between various tumors, ranging from 0% in choroid plexus papilloma and other rare tumors to 100% in intracranial germinoma. Moreover, the RUR varied among different stages within each tumor type. Overall, 753 patients received 920 palliative RT courses (range 1–9) at a median dose of 30 Gy. The most commonly irradiated metastatic sites were the bone (34%) and the brain (9.8%).
This is the first analysis to provide valuable insights into the RUR for childhood tumors. Together with population-based pediatric cancer registries, this will help decipher pediatric RT needs and deficits. Additionally, the underutilization of palliative RT calls for multidisciplinary palliative care provision for pediatric cancer patients.
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•Canagliflozin mitigated methotrexate-induced cognitive impairment.•Canagliflozin suppressed neuroinflammation and inhibited TLR4/NF-κB/NLRP3 cascade.•Canagliflozin levelled off TNF-α ...and iNOS as well as CD86 immunoreactivity.•Canagliflozin strengthened CD163 immunoreactivity together with Arg-1 and TGF-β.•Canagliflozin succeeded in shifting microglial polarization towards M2 phenotype.
Methotrexate (MTX), a chemotherapeutic antimetabolite, has been linked to cognitive impairment in cancer patients. MTX-induced metabolic pathway disruption may result in decreased antioxidant activity and increased oxidative stress, influencing hippocampal neurogenesis and microglial activation. Nuclear factor-kappa B (NF-κB), an oxidative stress byproduct, has been linked to MTX toxicity via the activation of NLRP3 inflammasome signaling. Macrophage activation and polarization plays an important role in tissue injury. This differentiation may be mediated via either the Toll-like receptor 4 (TLR4) or NLRP3 inflammasome. Interestingly, Canagliflozin (CANA), a sodium-glucose cotransporter 2 (SGLT2) inhibitor has been recently reported to exert anti-inflammatory effects by modulating macrophage polarization balance. This study aimed to investigate CANA’s protective effect against MTX-induced cognitive impairment, highlighting the possible involvement of TLR4/ NF-κB crosstalk with NLRP3 inflammasome activation and macrophage polarization. Forty-eight Male Wistar rats were divided into 4 groups; (1) received saline orally for 30 days and intravenously on days 8 and 15. (2) received Canagliflozin (CANA; 20 mg/kg/day; p.o.) for 30 days. (3) received MTX (75 mg/kg, i.v.) on day 8 and 15, then they were injected with four i.p. injections of leucovorin (LCV): the first dose was 6 mg/ kg after 18 h, and the remaining doses were 3 mg/kg after 26, 42, and 50 h of MTX administration. (4) received MTX and LCV as in group 3 in addition to CANA as in group 2. MTX-treated rats showed cognitive deficits in spatial and learning memory as evidenced in the novel object recognition and Morris water maze tests. MTX exerted an oxidative effect which was evident by the increase in MDA and decline in SOD, GSH and GPx. Moreover, it exerted an inflammatory effect via elevated caspase-1, IL-1β and IL-8. CANA treatment restored cognitive ability, reduced MTX-induced oxidative stress and neuroinflammation via attenuation of TLR4/NF-κB/NLRP3 signaling, and rebalanced macrophage polarization by promoting the M2 phenotype. Hence, targeting molecular mechanisms manipulating macrophage polarization may offer novel neuroprotective strategies for preventing or treating MTX-induced immune modulation and its detrimental sequel.
Abstract
Background
Chronic Obstructive Pulmonary Disease (COPD) and Non-Alcholic Fatty Liver Disease (NAFLD) share common risk factors, such as reduced physical activity, and pathophysiological ...mechanisms including oxidative stress, low grade inflammation, and metabolic syndrome. COPD severity is also recognized as an independent risk factor of NAFLD. Interestingly, the literature reports a higher prevalence of all-cause liver disease in patients with COPD, but only a small number of patients with NAFLD. Therefore, the specific links between NAFLD and COPD need to be confirmed and further evaluated.
Aim of the Work
The aim of the study is to determine the possible association between Chronic Obstructive Lung Disease and Non-Alcoholic Fatty Liver Disease.
Patients and Methods
This cross-sectional study was conducted at outpatient clinics at Ain Shams Hospital during a Period 1 year. This study was performed on 60 Egyptian Patients divided into two groups as follow: Group 1:40 Patients diagnosed with COPD (Patients diagnosed by history of disease, smoking history and A ration of post bronchodilator FEV1 10 FVC of less than 70% of the predicted value). Group2: 20 Normal Healthy People (Control Group)
Results
There was no statistically significant difference with p-value >0.05 between both groups as regards age and sex, which indicated proper matching between groups. The present study showed that there was a statistically significant difference with p-value <0.05 between study groups as regards obstructive sleep apnea with high percentage of obstructive sleep apnea among cases. On the other hands, there was no statistically significant difference with p-value >0.05 between both groups as regards smoking and hypertension. The current study showed that there was no statistically significant difference with p-value >0.05 between study groups as regards systolic blood pressure, weight, height, waist circumference and BMI. On the other hand, there was a statistical significance difference with p-value <0.05 with higher mean of diastolic blood pressure among cases.
Conclusion
This study showed that NAFLD is associated with COPD. Physicians should be aware of possible liver comorbidities in COPD patients and that extrahepatic disease in NAFLD patients may vary more than previously thought. Further studies concerning the biochemical and metabolic mechanisms of NAFLD and COPD are required.
