Immune checkpoint inhibitor-induced aplastic anaemia: Case series and large-scale pharmacovigilance analysis.

Introduction: Impressive advances in immunotherapy especially immune checkpoint inhibitors have made great progress in treating multiple cancers but can also cause serious even incurable immune-related adverse events, mostly found in colitis, dermatitis, hepatitis, and thyroiditis patients. Rare autoimmune hematologic toxicities have been reported in the literature, but are poorly described. Aplastic anaemia induced by immune checkpoint inhibitors is a life-threatening autoimmune disease; however, only a few cases have been reported in the literature. Objective: To characterize and evaluate Aplastic anaemia associated with different ICI regimens in public database and review the literature. Methods: We described a case series of patients experiencing Aplastic anaemia while on immune checkpoint inhibitors. We also mined the Food and Drug Administration's Adverse Event Reporting System and used reporting odds ratio, the proportional reporting ratio, the Bayesian confidence propagation neural network and the multi-item gamma Poisson shrinker algorithms to achieve the data of the suspected adverse events of Aplastic anaemia-induced by immune checkpoint inhibitors between January 2011 and June 2022. Results: Thirteen patients with Aplastic anaemia events while on immune checkpoint inhibitors were included in our case series, and seven of them had a fatal outcome. In FAERS, a total of 38 individual case safety reports (immune checkpoint inhibitors) with different ICI regimens were retrieved, of which 25 (65.79%) were reported as monotherapy and 13 (34.2%) had a fatal outcome. The reporting odds ratio was significant for nivolumab (reporting odds ratio 3.05, 95%CI 1.73-5.38), pembrolizumab (reporting odds ratio 2.33, 95%CI 1.16-4.67), avelumab (reporting odds ratio 12.63, 95%CI 3.15-50.62) and ipilimumab/nivolumab (ROR 2.57, 95%CI 1.15-5.72). Conclusion: There is a significant reporting signal of Aplastic anaemia with several ICI agents. Clinicians should raise awareness and monitor this potentially fatal adverse event.

Assessment of the abstract reporting of systematic reviews of dose-response meta-analysis: a literature survey.

BACKGROUND: There is an increasing number of published systematic reviews (SR) of dose-response meta-analyses (DRMAs) over the past decades. However, the quality of abstract reporting of these SR-DRMAs remains to be understood. We conducted a literature survey to investigate the abstract reporting of SR-DRMAs. METHODS: Medline, Embase, and Wiley online Library were searched for eligible SR-DRMAs. The reporting quality of SR-DRMAs was assessed by the modified PRISMA-for-Abstract checklist (14 items). We summarized the adherence rate of each item and categorized them as well complied (adhered by 80% or above), moderately complied (50 to 79%), and poorly complied (less than 50%). We used total score to reflect the abstract quality and regression analysis was employed to explore the potential influence factors for it. RESULTS: We included 529 SR-DRMAs. Eight of 14 items were moderately (3 items) or poorly complied (5 items) while only 6 were well complied by these SR-DRMAs. Most of the SR-DRMAs failed to describe the methods for risk of bias assessment (30.2, 95% CI: 26.4, 34.4%) and the results of bias assessment (48.8, 95% CI: 44.4, 53.1%). Few SR-DRMAs reported the funding (2.3, 95% CI: 1.2, 3.9%) and registration (0.6, 95% CI: 0.1, 1.6%) information in the abstract. Multivariable regression analysis suggested word number of abstracts [> 250 vs. ≤ 250 (estimated ß = 0.31; 95% CI: 0.02, 0.61; P = 0.039)] was positively associated with the abstract reporting quality. CONCLUSION: The abstract reporting of SR-DRMAs is suboptimal, substantial effort is needed to improve the reporting. More word number may benefit for the abstract reporting. Given that reporting of abstract largely depends on the reporting and conduct of the SR-DRMA, review authors should also focus on the completeness of SR-DRMA itself.

Associations between Ambient Temperature and Acute Myocardial Infarction.

BACKGROUND: The associations between incidence of acute myocardial infarction (AMI) and the ambient temperature were mixed in prior studies. METHODS: Data of 2033 consecutive admissions of AMI in a central tertiary hospital in North China from 1st Jan 2003 to 31st Dec 2011 were collected. The weather data in this period were from the local meteorological department. Based on the ambient temperature information, we defined several ambient temperature indices, including daily average temperature, extremely low temperature, and daily temperature range, then characterized the independent associations between them and the incidence of AMI. RESULTS: The daily average temperature one day before was independently associated with AMI incidence rate: a rise of 5°C of the daily average temperature led to a 5% decrease in AMI admissions. Daily average temperature and temperature range two days before were independently associated with AMI incidence rate: a rise of 5°C of the daily average temperature led to a fall of 6% in AMI admissions, and a rise of 2°C of the daily temperature range led to a rise of 4% in AMI admission. CONCLUSION: Low ambient temperature has substantial association with AMI, and can play an important role in warning and forecasting the incidence.

Primary health care in China: is China's health reform reform for the whole nation?

BACKGROUND: Good primary health care can enhance national health status at relatively low cost. The barefoot doctor model in China was once considered to have been a successful health care policy. It was a model which was followed by other low-developed or developing countries. In recent decades, the Chinese government promulgated a number of new policies and health reforms to improve its health care system. AIM: This paper aimed to highlight the great significance of primary health care and appeal to the policymakers to change the priority to primary health care in order to be able to guarantee universal health care for the whole nation at least at primary care level. METHOD: This study discussed Chinese primary health care by reviewing its history and development. FINDING: Chinese government's efforts do not seem to be leading to a completely successful outcome for all the people of China as a result of the substantial imbalance of investments between tertiary level hospitals and grass-root level health care institutions. The government appears to have neglected the importance of primary health care in the implementation of health systems and resources.

Genetic predisposition of stroke: understanding the evolving landscape through meta-analysis.

Stroke, either ischemic or hemorrhagic, is the leading cause of death and morbidity worldwide. Identifying the risk factors is a prerequisite step for stroke prevention and treatment. It is believed that a major portion of the currently unidentified risk factors is of genetic origin. Consistent with this idea, numerous potential risk alleles for stroke have been reported, however, the genetic evidence so far is not conclusive. The major goal of this review is to update the current knowledge about the genetic predisposition to the common multifactorial stroke, and to provide a bird's-eye view of this fast moving field. We selectively review and meta-analyze the related English literatures in public domain (PubMed) from 2000 onward, including the original reports and meta-analyses, to evaluate the genetic risk factors of common multifactorial stroke. The results indicated that we reviewed and meta-analyzed original reports and existing meta-analyses that studied the genetic predisposition to the common multifactorial stroke. Some original reports and meta-analyses were specific for ischemic stroke and others were for hemorrhagic stroke only. We also evaluated the major evolving issues in this field and discussed the future directions. In conclusion, strong evidences suggest that genetic risk factors contribute to common multifactorial stroke, and many genetic risk genes have been implicated in the literatures. However, not a single risk allele has been conclusively approved.

A time course study about gene expression of post-thermal injury with DNA microarray.

BACKGROUND: Burn injury is one of the most common and devastating forms of trauma in daily life. However, the exact sequence of events after burn injury remains unknown. OBJECTIVE: This study aims to investigate gene expression alterations after burn injury. METHODS: Microarray data set GSE8056 was downloaded from the Gene Expression Omnibus (GEO) database, including 12 samples, equally distributed in four groups: normal skin tissue as control and damaged tissues 1-3 days after burn (early period); 4-7 days after burn (middle period); and more than 7 days after burn (late period). Packages in R language were utilized to pre-process the data and filter out the differentially expressed genes (DEGs). Functional annotation of all three groups of DEGs was conducted by using clusters of orthologous groups analysis. The DEGs shared by all three groups were picked out and analyzed with STRING to set up a protein-protein interaction network. CFinder was chosen to implement module analysis, and expression analysis systematic explorer was then adopted to reveal the dysfunctional pathways for each module. RESULTS: A total of 727, 782, and 445 DEGs were identified in the early, middle, and late period after burn, and 234 DEGs were identified as continually differentially expressed throughout all time periods, including genes encoding proinflammatory cytokines, such as interleukin (IL)-6, IL-8, and IL-1ß, and genes associated with cell proliferation. Three modules associated with cell proliferation and inflammatory responses were generated from the protein-protein interaction network. CONCLUSION: Our findings are beneficial for understanding the progression of the wound healing response after burn.

Multicenter study on adult growth hormone level in postoperative pituitary tumor patients.

The objective of this study is to observe the adult growth hormone level in postoperative pituitary tumor patients of multi-centers, and explore the change of hypophyseal hormones in postoperative pituitary tumor patients. Sixty patients with pituitary tumor admitted during March, 2011-March, 2012 were selected. Postoperative hypophyseal hormone deficiency and the change of preoperative, intraoperative, and postoperative growth hormone levels were recorded. Growth hormone hypofunction was the most common hormonal hypofunction, which took up to 85.0 %. Adrenocortical hormone hypofunction was next to it and accounted for 58.33 %. GH + ACTH + TSH + Gn deficiency was the most common in postoperative hormone deficiency, which took up to 40.00 %, and GH + ACTH + TSH + Gn + AVP and GH deficiencies were next to it and accounted for 23.33 and 16.67 %, respectively. The hormone levels in patients after total pituitary tumor resection were significantly lower than those after partial pituitary tumor resection, and the difference was statistically significant; growth hormone and serum prolactin levels after surgery in two groups were decreased, and the difference was statistically significant. The incidence rate of growth hormone deficiency in postoperative pituitary tumor patients is high, which is usually complicated with deficiency of various hypophyseal hormones. In clinical, we should pay attention to the levels of the hypopnyseal hormones, and take timely measures to avoid postoperative complications.

Emodin inhibits inducible nitric oxide synthase in a rat model of craniocerebral explosive injury.

To investigate the effects of emodin on blast-induced traumatic brain injury (bTBI) in a rat model. Eighty rats were randomly divided into 2 groups (the control group and the emodin-treated group; N = 40 per group) and were used to establish the model of blast-induced traumatic brain injury. Ten minutes after the explosion, an isotonic saline solution (10 mg/kg) or emodin (10 mg/kg) were administered via an intraperitoneal injection to the control group and the emodin-treated group, respectively. At each time point (pre-explosion, 2, 6, 12, 24 h after explosion), 2 rats were used for the pathological assessment and 6 rats were used for the biochemical assessment. The concentration of nitric oxide (NO) and the expression and activity of inducible nitric oxide synthase (iNOS) were measured at each time point by spectrophotometry and western blot analysis. Light and electron microscopy showed that the brain damage in the emodin-treated group was less serious than that observed in the control group. The concentration of NO in the emodin-treated group was lower compared with the control group (p < 0.05). Western blot analysis showed that protein expression in the emodin-treated group was lower than the control group (p < 0.05). Emodin can alleviate brain damage after bTBI by inhibiting iNOS. These findings suggest that emodin has a protective effect against bTBI. One possible mechanism may occur by inhibiting the expression and activity of iNOS and consequently decreasing the concentration of NO.

Epileptiform Discharges and Frontal Paroxysmal EEG Abnormality Act as Predictive Marker for Subsequent Epilepsy in Children With Complex Febrile Seizures.

Using electroencephalography (EEG) for diagnosing subsequent epilepsy in children after febrile seizure (FS) is not common. The present study investigates the relationship between epileptiform discharges and subsequent epilepsy, and looks for the predictive marker for this disorder. A total of 378 children with complex FS and whose EEG showed epileptiform discharges or normal EEG were included. Development of FS was compared between those with epileptiform discharges and those with normal EEG. Risk factors were analyzed using multivariate logistic regression to clarify their effects on subsequent epilepsy. The association between generalized or focal EEG localization, and between frontal epileptiform discharges and subsequent epilepsy, were analyzed. Among 378 patients with complex FS, 51 showed epileptiform discharges. History of epilepsy, frontal seizure, number of FS, and prolonged seizure were the risk factors for epileptiform discharge. Subsequent epilepsy was significantly frequent in patients with more than 2 risk factors (odds ratio [OR] = 17; 95% confidence interval [CI] = 4.1-29.6). Prolonged seizure (OR = 4.98; 95% CI = 1.63-13.29), FS number (OR = 2.96; 95% CI = 1.23-10.51), and family history of epilepsy (OR = 2.67; 95% CI = 1.05-7.63) were significantly correlated with subsequent epilepsy. Of 9 patients with paroxysms in the frontal region, 8 (88.9%) developed epilepsy. There was concordance between frontal epileptiform discharges and subsequent epilepsy (κ = .901). In conclusion, epileptiform discharges are risk factors for subsequent epilepsy. Frontal paroxysmal EEG is a marker for subsequent epilepsy.

Anticonvulsant and sedative effects of paederosidic acid isolated from Paederia scandens (Lour.) Merrill. in mice and rats.

This study was designed to evaluate the anticonvulsant and sedative effects of paederosidic acid isolated from Paederia scandens (Lour.) Merrill. in mice and rats. In the present study, anticonvulsant activities of paederosidic acid were evaluated by maximal electroshock and pentylenetetrazole-induced seizures in male mice. Then, pentobarbital sodium-induced sleeping time and locomotor activity tests in mice were used to evaluate the sedative effects of paederosidic acid. Finally, the mechanism of paederosidic acid was explored by evaluating the contents of Glu and GABA in the brain, and Western blot was used to measure GAD65 expression in the mouse brain. Paederosidic acid (5, 10, 20, and 40 mg/kg, ip) had significant anticonvulsant and sedative effects. Moreover, paederosidic acid increased brain gamma-aminobutyric acid and decreased glutamic acid in the brain, and it up-regulated expressions of GAD 65. In conclusion, our results suggest that paederosidic acid may be a promising future therapeutic agent for treatment of epilepsy.