A Novel Formononetin Derivative Promotes Anti-ischemic Effects on Acute Ischemic Injury in Mice

Natural flavonoids, formononetin and ononin, possess antioxidant, antibacterial, anti-inflammatory and neuroprotective effects. Many complications caused by SARS-CoV-2 make patients difficult to recover. Flavonoids, especially formononetin and ononin, have the potential to treat SARS-CoV-2 and improve myocardial injury. However, their poor water solubility, poor oral absorption, high toxicity, and high-cost purification limit industrial practical application. Succinylation modification provides a solution for the above problems. Formononetin-7-O-β-(6″-O-succinyl)-D-glucoside (FMP), a new compound, was succinyl glycosylated from formononetin by the organic solvent tolerant bacteria Bacillus amyloliquefaciens FJ18 in a 10.0% DMSO (v/v) system. The water solubility of the new compound was improved by over 106 times compared with formononetin, which perfectly promoted the application of formononetin and ononin. The conversion rate of formononetin (0.5 g/L) was almost 94.2% at 24 h, while the yield of formononetin-7-O-β-(6″-O-succinyl)-D-glucoside could achieve 97.2%. In the isoproterenol (ISO)-induced acute ischemia mice model, the myocardial injury was significantly improved with a high dose (40 mg/kg) of formononetin-7-O-β-(6″-O-succinyl)-D-glucoside. The lactate dehydrogenase level was decreased, and the catalase and superoxide dismutase levels were increased after formononetin-7-O-β-(6″-O-succinyl)-D-glucoside treatment. Thus, formononetin-7-O-β-(6″-O-succinyl)-D-glucoside has high water solubility, low toxicity, and shows significant antimyocardial ischemia effects.

Predictors of intubation and mortality in COVID-19 patients: a retrospective study

Background Estimating the risk of intubation and mortality among COVID-19 patients can help clinicians triage these patients and allocate resources more efficiently. Thus, here we sought to identify the risk factors associated with intubation and intra-hospital mortality in a cohort of COVID-19 patients hospitalized due to hypoxemic acute respiratory failure (ARF). Results We included retrospectively a total of 187 patients admitted to the subintensive and intensive care units of the University Hospital “Maggiore della Carità” of Novara between March 1st and April 30th, 2020. Based on these patients’ demographic characteristics, early clinical and laboratory variables, and quantitative chest computerized tomography (CT) findings, we developed two random forest (RF) models able to predict intubation and intra-hospital mortality. Variables independently associated with intubation were C-reactive protein (p < 0.001), lactate dehydrogenase level (p = 0.018) and white blood cell count (p = 0.026), while variables independently associated with mortality were age (p < 0.001), other cardiovascular diseases (p = 0.029), C-reactive protein (p = 0.002), lactate dehydrogenase level (p = 0.018), and invasive mechanical ventilation (p = 0.001). On quantitative chest CT analysis, ground glass opacity, consolidation, and fibrosis resulted significantly associated with patient intubation and mortality. The major predictors for both models were the ratio between partial pressure of arterial oxygen and fraction of inspired oxygen, age, lactate dehydrogenase, C-reactive protein, glycemia, CT quantitative parameters, lymphocyte count, and symptom onset. Conclusions Altogether, our findings confirm previously reported demographic, clinical, hemato-chemical, and radiologic predictors of adverse outcome among COVID-19-associated hypoxemic ARF patients. The two newly developed RF models herein described show an overall good level of accuracy in predicting intra-hospital mortality and intubation in our study population. Thus, their future development and implementation may help not only identify patients at higher risk of deterioration more effectively but also rebalance the disproportion between resources and demand.

Prognostic evaluation of immune thrombocytopenia outcomes in Egyptian children: a retrospective single-center experience

Immune thrombocytopenia (ITP) is the most common cause of thrombocytopenia in children. This retrospective study was designed to analyze presenting features of ITP cases in Benha, evaluate outcomes in children and determine prognostic factors. This research was accepted by Research Ethics Committee (REC) of Faculty of Medicine, Benha University (chairman: Prof. Nermeen Adly Mahmoud). Ethics comittee refrence number MS 40-3/2019. Records of 308 children with ITP in Benha University Hospitals and Benha Children Hospital haematology clinics between May 2014 and January 2021 were retrospectively analyzed. Socio-demographic, clinical, and laboratory data of the studied children such as age, gender, the type of residence, the date of diagnosis, complaints at presentation, preceding vaccination or infection, the type of bleeding, initial platelet count, LDH (lactate dehydrogenase) level, initial treatment, and outcomes were recorded. A total of 308 children diagnosed with ITP were included, clinical courses were determined as newly diagnosed and chronic in 71.4% and 28.6%, respectively. The median age of patients at diagnosis was 5 ± 3.4 years. The male/female ratio was 1.14. The median age at diagnosis was significantly higher in chronic ITP patients (p < 0.001); patients ≥ 10 years were more likely to develop chronic ITP than younger ones (p = 0.029). Regarding residency, seasonality, type of bleeding and history of preceding infection or vaccination, the difference was not statistically significant. Initial platelet counts > 20 × 109 were significantly more prevalent in chronic ITP (p < 0.001). LDH level at presentation was significantly higher in chronic cases (p = 0.046). Initial lines of treatment were the following: steroids, IVIG, and IVIG with steroids (in 88%, 5.2%, and 2.9% of the cases, respectively). A total of 3.9% of the children did not receive any treatment. There was no significant difference in the outcomes between the initial lines of treatment (p = 0.105). In our study, age > 10 years, female gender, higher platelet count and high LDH level at presentation were found to increase the probability of chronic ITP.

Salivary Lactate Dehydrogenase in Relationship to the Severity of Hypoxic-Ischemic Encephalopathy among Newborn Infants

Introduction. Hypoxic-ischemic encephalopathy (HIE) is defined as a neurological complication that results from perinatal asphyxia. Previous studies had investigated various markers to early detect HIE; however, these markers appeared to have several drawbacks, especially in resource-limited settings. Aim. This study aimed at evaluating the predictive value of the salivary lactate dehydrogenase level as a potential predictor of hypoxic-ischemic encephalopathy for newborns. Materials and Methods. We included 30 neonates with HIE due to perinatal asphyxia and 30 healthy newborns that serve as controls, admitted at the intensive care unit for neonates and maternity ward at Ismailia area Clinics and Hospitals. We measured the LDH levels by using saliva samples that were collected for neonates maximum by 12 h after birth. Results. It was found that patients with HIE had a statistically significant higher salivary LDH level (1927 ± 390.3 IU/L) than patients without HIE (523.6 ± 142.8 IU/L) ( p < 0.001 ). Moreover, salivary LDH showed a good discriminative ability where the AUC was 0.966 regarding salivary LDH (95% CI: 0.917–1.0) ( p < 0.001 ). The best cutoff value was 1420 IU/L or more which showed the best results in predicting the occurrence of HIE with 98.3% and 97.6% sensitivity and specificity, respectively. Conclusion. Salivary LDH can be considered as a useful noninvasive laboratory marker that can accurately predict HIE incidence among neonates with asphyxia within 12 hours from birth. The cases in the HIE group were assigned into three stages according to the Sarnat and Sarnat staging system: stage I: mild (irritable, normal, or hypertonia and poor feeding); stage II: moderate (lethargy, hypotonia, and frequent seizure); stage III: severe (coma, flaccid, absent reflexes, and frequent seizure). There is a positive association between LDH levels and the severity of HIE.

Clinical Spectrum and Neuroimagistic Features in Hospitalized Patients with Neurological Disorders and Concomitant Coronavirus-19 Infection

In the first months of the COVID-19 pandemic, several research studies focused on understanding the damage to the respiratory and circulatory systems. However, the evidence of neurological manifestations as part of the clinical spectrum of the disease has increased. The aim of this retrospective study was to determine the potential association of neurological disorders with concomitant COVID-19 infection. We reviewed 101 patients (mean age, 70.05 years; 62.37% men) diagnosed with different neurological disorders and COVID-19 who were referred to the Department of Neurology between March 2020 and May 2021. The protocol included demographic, clinical, and neuroimagistic features, biochemical evaluation data, and prognosis. In the first group of patients with non-severe COVID-19 infection (<50% lung damage), we enrolled 75 cases (mean age, 69.13 years; 65.33% men), and the second group, with 26 patients (mean age, 72.69 years; 53.84% men), developed severe COVID-19 infection (>50% lung damage). Severe COVID-19 infection was significantly correlated with an increased highly sensitive C-reactive protein level (hsCRP) (p < 0.05), lactate dehydrogenase level (LDH) (p < 0.05), erythrocyte sedimentation rate (ESR) (p < 0.05), D-dimer (p < 0.05), fibrinogen level (p < 0.05), and blood glucose (p < 0.05) when compared to the first group. These biochemical parameters were increased in both groups, but the levels were much higher in the second group. Headaches (72.27%) and dizziness (14.85%) were present in the early stage of infection. Cerebrovascular events were also reported: ischemic stroke (48% vs. 57.69%; p < 0.05), cerebral hemorrhage (4.95%), and cerebral venous sinus thrombosis (1.98%). Encephalitis (1.98%) and Guillain–Barré Syndrome (1.98%) were found but less frequently. Cranial nerve abnormalities were statistically more common in the non-severe group: anosmia (32% vs. 26.92%; p < 0.05), dysgeusia/ageusia (48% vs. 42.30%; p < 0.05), impaired eye movement (1.33% vs. 0%), and facial nerve palsy (2.66% vs. 0%). Seizures (13.33% vs. 11.53%; p < 0.05) and a depressed level of consciousness (31.68%) occurred commonly. We detected the neuropsychiatric symptoms of anxiety (23.76%) and depression (14.85%). Mortality was increased in both groups but was much higher in the second group (46.15% vs. 21.33%). Neurological complications during COVID-19 infection are common in hospitalized patients, but the mechanism of these complications is not fully understood, representing a continuous challenge for neurologists.

Safety and Tolerability of a 90-minute Infusion of Originator and Biosimilar Rituximab in Rituximab- Naïve Patients

This study aimed to investigate the safety and tolerability of 90-min rapid infusion of rituximab, originator or biosimilar (Truxima), for rituximab-naïve patients with hematologic malignancy. We undertook a retrospective review of records of 118 patients (81 originator rituximab and 37 Truxima) with hematologic malignancy who had received rituximab rapid infusion from the first cycle of chemotherapy with corticosteroid premedication administration. Most patients had high Ann Arbor stage (80.9%), high International Prognostic Index risk (69.1%), favorable performance status (98.3%), and high lactate dehydrogenase level (78.8%). The patients received a collective total of 717 rapid rituximab infusions, with an average of 6 infusions per patient (range, 1-8). The incidence of infusion-related reactions (IRRs) of any grade and grade 3/4 during first infusion was 21.2% and 0.8%, respectively. No episode of grade 3/4 IRR was observed during the second and subsequent rituximab infusions. Severity and type of IRRs in Truxima administration were comparable to those of originator rituximab. This study suggests that 90-minute rituximab infusion with the first dose of chemotherapy was well tolerated. In terms of IRR, safety profiles of Truxima were comparable to that of originator rituximab, suggesting that Truxima might replace originator rituximab in a rapid infusion setting.

The Association between Serum Lactate Dehydrogenase Level and In-hospital Death due to Pulmonary Embolism

Background: Few studies are evaluating the prognostic value of lactate dehydrogenase (LDH) in patients with pulmonary embolism (PE). We analyzed the possible power of serum LDH levels to predict in-hospital mortality.Methods: In this cross-sectional study 217 patients with confirmed PE diagnosis with CT angiography and available serum LDH level at first 24-hours upon admission were included.Results: The mean age of patients was 63.04±16.81 years old, 23 patients (10.6%) died during hospitalization. Multivariate analysis showed that only LDH, WBC were independent predictors of in-hospital mortality, however, this association was not significant.Conclusion: LDH can be a good prognostic marker for predicting in-hospital death in patients with pulmonary embolism.