Cognitive enhancing effects of pazopanib in D­galactose/ovariectomized Alzheimer's rat model: insights into the role of RIPK1/RIPK3/MLKL necroptosis signaling pathway.

Necroptosis, a programmed form of necrotic cell death carried out by receptor-interacting serine/threonine protein kinase 1 (RIPK1) and RIPK3, has been found to be implicated in the pathogenesis of Alzheimer's disease (AD). An FDA-approved anti-cancer drug, pazopanib, is reported to possess potent inhibitory effect against necroptosis via interfering with RIPK1. So far, there are no existing data on the influence of pazopanib on necroptotic pathway in AD. Thus, this study was designed to explore the impact of pazopanib on cognitive impairment provoked by ovariectomy (OVX) together with D-galactose (D-Gal) administration in rats and to scrutinize the putative signaling pathways underlying pazopanib-induced effects. Animals were allocated into four groups; the first and second groups were exposed to sham operation and administered normal saline and pazopanib (5 mg/kg/day, i.p.), respectively, for 6 weeks, while the third and fourth groups underwent OVX then were injected with D-Gal (150 mg/kg/day, i.p.); concomitantly with pazopanib in the fourth group for 6 weeks. Pazopanib ameliorated cognitive deficits as manifested by improved performance in the Morris water maze besides reversing the histological abnormalities. Pazopanib produced a significant decline in p-Tau and amyloid beta (Aß) plaques. The neuroprotective effect of pazopanib was revealed by hampering neuroinflammation, mitigating neuronal death and suppressing RIPK1/RIPK3/MLKL necroptosis signaling pathway. Accordingly, hindering neuroinflammation and the necroptotic RIPK1/RIPK3/MLKL pathway could contribute to the neuroprotective effect of pazopanib in D-Gal/OVX rat model. Therefore, this study reveals pazopanib as a valuable therapeutic agent in AD that warrants future inspection to provide further data regarding its neuroprotective effect.

Conservative versus conventional oxygen therapy in type I acute respiratory failure patients in respiratory intensive care unit, Zagazig University.

The present study aimed to assess the effect of a conservative (permissive hypoxemia) versus conventional (normoxia) protocol for oxygen supplementation on the outcome of type I respiratory failure patients admitted to respiratory intensive care unit (ICU). This randomized controlled clinical trial was carried out at the Respiratory ICU, Chest Department of Zagazig University Hospital, for 18 months, starting in July 2018. On admission, 56 enrolled patients with acute respiratory failure were randomized in a 1:1 ratio into the conventional group [oxygen therapy was supplied to maintain oxygen saturation (SpO2) between 94% and 97%] and the conservative group (oxygen therapy was administered to maintain SpO2 values between 88% and 92%). Different outcomes were assessed, including ICU mortality, the need for mechanical ventilation (MV) (invasive or non-invasive), and ICU length of stay. In the current study, the partial pressure of oxygen was significantly higher among the conventional group at all times after the baseline reading, and bicarbonate was significantly higher among the conventional group at the first two readings. There was no significant difference in serum lactate level in follow-up readings. The mean duration of MV and ICU length of stay was 6.17±2.05 and 9.25±2.22 days in the conventional group versus 6.46±2.0 and 9.53±2.16 days in the conservative group, respectively, without significant differences between both groups. About 21.4% of conventional group patients died, while 35.7% of conservative group patients died without a significant difference between both groups. We concluded that conservative oxygen therapy may be applied safely to patients with type I acute respiratory failure.

The impact of COVID-19 pandemic on the health services provided by the Cardiothoracic Minia University Hospital in Egypt: A single-center retrospective observational study.

Background: The emergence of the new coronavirus (severe acute respiratory syndrome coronavirus 2, or SARS-CoV-2) in late 2019 resulted in a worldwide pandemic, which had severe consequences on the global health systems. There were drastic strains on the public health services. This, in turn, markedly affected patients with non-coronavirus disease (COVID-19) problems. Aim: This study aimed to evaluate the impact of COVID-19 infection on the health services provided to patients at the cardiothoracic university hospital, Minia University. Methods: A retrospective analysis of data about services provided to patients at Minia Cardiothoracic University hospital was obtained from pre-pandemic era (2018-2019) and during the pandemic time (2020-2021). The two sets of data were compared together. Data were collected about the number of patients who underwent different procedures such as Pulmonary Function Tests (PFTs), sleep studies or interventional chest procedures (bronchoscopy and thoracoscopy). Also, data were collected about the number of patients admitted in the chest ward, respiratory intensive care unit (ICU) or Coronary care unit and the number of patients who visited cardiothoracic, cardiology or chest outpatient clinics. Results: There is 81.4% reduction in the number of Pulmonary Function Testsperformed during the period 2020-2021 compared with the period 2018-2019, where the number of patients admitted to chest inward decreased by 66.4%. The number of sleep studies performed reduced by 61.5%, while the number of different outpatient clinical visits reduced to similar values (45.8% for cardiothoracic clinic, 45.4% for cardiology clinic and 40.5% for chest clinic). Regarding respiratory ICU admissions, the study reported a reduction of 35.7% and also Coronary care unit admissions decreased by 30.6%. Interventional pulmonary procedures had the lowest reduction rate (0.7%). Conclusion: Different health services were negatively affected by the emergence of COVID-19 era in both pulmonary and non-pulmonary fields.

Comparative Evaluation of Chest Ultrasonography and Computed Tomography as Predictors of Malignant Pleural Effusion: A Prospective Study.

Malignant pleural effusion (MPE) is a manifestation of advanced cancer that requires a prompt and accurate diagnosis. Ultrasonography (US) and computed tomography (CT) are valuable imaging techniques for evaluating pleural effusions; however, their relative predictive ability for a malignant origin remains debatable. This prospective study aimed to compare chest US with CT findings as predictors of malignancy in patients with undiagnosed exudative pleural effusion. Fifty-four adults with undiagnosed exudative pleural effusions underwent comprehensive clinical evaluation including chest US, CT, and histopathologic biopsy. Blinded radiologists evaluated the US and CT images for features suggestive of malignancy, based on predefined criteria. Diagnostic performance measures were calculated using histopathology as a reference standard. Of the 54 patients, 33 (61.1%) had MPEs confirmed on biopsy. No significant differences between US and CT were found in detecting parietal pleural abnormalities, lung lesions, chest wall invasion, or liver metastasis. US outperformed CT in identifying diaphragmatic pleural thickening ≥10 mm (33.3% vs. 6.1%, p < 0.001) and nodularity (45.5% vs. 3%, p < 0.001), whereas CT was superior for mediastinal thickening (48.5% vs. 15.2%, p = 0.002). For diagnosing MPE, diaphragmatic nodularity detected by US had 45.5% sensitivity and 100% specificity, whereas CT mediastinal thickening had 48.5% sensitivity and 90.5% specificity. Both US and CT demonstrate reasonable diagnostic performance for detecting MPE, with particular imaging findings favoring a malignant origin. US may be advantageous for evaluating diaphragmatic pleural involvement, whereas CT is more sensitive to mediastinal abnormalities.

Analysis of the current situation of pharmacogenomics in terms of educational and healthcare needs in Egypt and Lebanon.

Pharmacogenomics (PGx) is a practice that investigates the link between genetic differences and drug response in patients. This can improve treatment effectiveness and reduce harmful side effects. However, has yet to be adequately realized in developing nations. Three surveys were conducted between November 2022 to March 2023 in Egypt and Lebanon. The first survey assessed availability of PGx testing in different healthcare facilities; the second one assessed knowledge, interest and attitude toward learning about PGx among pharmacists and physicians; and the third one assessed interest in providing PGx education at academic levels. In Egypt, a few of the surveyed healthcare facilities are conducting some form of pharmacogenetic testing. In Lebanon, very few germline pharmacogenomic tests are offered in Greater Beirut's leading hospitals, and no other testing was recorded. PGx education attracts considerable interest, with 34.3% of pharmacists very interested and 48.8% interested. Similarly, 24.8% of total physicians were very interested while 44.8% were interested. Academic professionals in the surveyed institutions in both countries agreed on the need for educational programs in PGx and 78.2% agreed that there were good opportunities for implementing PGx testing. These findings clearly indicate the need to develop and implement educational programs in PGx in the Middle-East.

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