Evolution of ischemic stroke drug clinical trials in mainland China from 2005 to 2021

BackgroundTo assess the temporal changes in the characteristics of ischemic stroke drug clinical trials conducted in mainland China in 2005–2021.MethodsA statistical analysis of registered clinical trials on ischemic stroke was performed using the platform of the Center for Drug Evaluation of China National Medical Products Administration, the Chinese Clinical Trial Registry, and ClinicalTrials.gov websites.ResultsFrom January 1, 2005 to August 1, 2021, a total of 384 registered drug clinical trials on ischemic stroke were identified in mainland China. Over time, the number of trials gradually increased each year, with a significant growth in 2014, from 16 in 2013 to 42 in 2014. Phase IV trials (31.8%) accounted for the majority, followed by phase II (16.4%), phase I (10.9%), and phase III (8.6%). In terms of sponsorship, the proportion of investigator‐initiated trials (IITs) (60.7%) was higher than industry‐sponsored trials (ISTs) (39.3%). Additionally, trials involving traditional Chinese medicines (TCMs) (36.2%) accounted for the largest proportion, followed by trials involving antithrombotic therapy (19.5%) and cerebral protection agents (16.7%). Furthermore, over the past 17 years, the number of leading drug clinical trial units for ischemic stroke in mainland China has continuously increased. The leading principal units from Beijing, Shanghai, Guangdong, Jiangsu, and Liaoning accounted for the majority of the trials (67.4%).ConclusionIn the past 17 years, great progress has been made in the research and development (R&D) of drugs and clinical trials for ischemic stroke in mainland China. The most extensive progress was observed in TCMs, antithrombotic therapy, and cerebral protection agents. More clinical trials are needed to confirm whether the newly developed drugs can improve the clinical efficacy of ischemic stroke. Simultaneously, more pharmaceutical R&D efforts of innovative drugs are warranted.     

Role of pilocarpine use following laser peripheral iridotomy in eyes with refractory acute angle closure glaucoma: A case report and literature review

Rationale:Angle closure glaucoma (ACG) is one of the most emergent types of glaucoma in clinical practice. Laser peripheral iridotomy (LPI) could minimize pupillary block and prevent ACG from an acute attack. However, recurrent increase in intraocular pressure (IOP) may still occur despite successful LPI. The aim of this study is to highlight the importance of postLPI pilocarpine use and larger LPI size as well as to share some experiences of cataract surgery in patients with ACG.Patient concerns:A 63-year-old female was referred to our hospital for headache, and poor control of IOP in the right eye for 3 hours.Diagnoses:The patient was diagnosed ACG in the right eye. Recurrence of ACG in the right eye and new-onset and recurrent ACG in the left eye were noted during follow-up, despite successful LPI. The diagnosis was confirmed through slit lamp and gonioscope examination.Interventions:The LPI size was enlarged and pilocarpine use was maintained at 2% (1 drop 4 times a day) in both the eyes. Finally, cataract surgery was performed in both the eyes.Outcomes:No recurrence of ACG was noted during postLPI pilocarpine use in both the eyes. The postoperative IOP was stable for >6 months after cataract surgery without any surgical intervention or antiglaucoma medication use. No discomfort or major complication was observed.Conclusion:This report highlights the importance of postLPI pilocarpine use and larger LPI size in patients with refractory ACG.     

Intraocular lens power calculation after radical keratotomy and photorefractive keratectomy: A case report

Rationale:To report a rare case of calculating the IOL power in a cataract patient who underwent both radial keratotomy (RK) and photorefractive keratectomy (PRK).Patient concerns:A 48-year-old woman underwent bilateral RK at age 22 and bilateral PRK at age 46. She developed bilateral corneal haze and corneal endothelial inflammation and received steroids therapy for long time after PRK. Then she was referred to our hospital due to decreased vision in the both eyes.Diagnoses:The patient was diagnosed with binocular complicated cataract, corneal haze, high myopia and post corneal refractive surgery (RK and PRK).Interventions:The patient underwent bilateral phacoemulsification. The IOL power was calculated using SRK/T formula for RK and Haigis-L formula for PRK, respectively. We finally selected the Haigis-L formula and the intraocular lens (SN60WF) was implanted within the capsular bag.Outcomes:After the surgery, both eyes showed myopia drift, and the right eye continuously fluctuated in refractive results. However, by nearly 1 year later, refractive results in both eyes had stabilized, and no other complications had occurred.Lessons:IOL power in patients who undergo both RK and PRK can be reliably calculated using the Shammas-PL, Average of multiple formulas, or Barret True-K No History formulas. Haigis-L formula is not suitable. Such patients require at least three months after surgery to attain refractive stability in both eyes.     

Plasma exchange treats severe intrahepatic cholestasis caused by dacomitinib: A case report

Rationale:Dacomitinib-induced liver injury is often manifested by mild elevations of transaminases and bilirubin, and severe intrahepatic cholestasis caused by dacomitinib for simultaneous taking orally cytochrome P450 2D6 (CYP2D6) competitive substrates has been rarely reported.Patient concerns:The patient was a 69-year-old woman with non–small cell lung cancer (NSCLC) who was prescribed oral dacomitinib for a month; she was given oral loratadine due to “allergic rhinitis” and metoprolol extended action tablets due to “tachycardia” separately for a few days during the course of dacomitinib treatment. The patient developed liver damage, increased fatigue, yellow urine, and pruritus, with significantly elevated serum levels of bilirubin and glutamyltranspetidase.Diagnosis:Intrahepatic cholestasis, drug-induced liver injury, and NSCLC.Interventions:After admission, the patient was prescribed adenosylmethionine, acetylcysteine, ursodeoxycholic acid capsule, methylprednisolone and fenofibrate for a month, with progressive elevation of liver biochemical parameters. Through drug enzyme gene assays in the liver tissue after percutaneous liver biopsy, we found both CYP2D6*10/*10 and ATP-binding cassette subfamily B member 1 GG variants (rs1045642) positive. After the poor response to the conventional medication, the patient underwent plasma exchange.Outcomes:The patient was discharged after her liver parameters improved; the parameters remained normal at several follow-up visits, and she renewed the NSCLC regimens without dacomitinib after being evaluated by oncologists.Lessons:Dacomitinib can induce severe intrahepatic cholestasis. It is considered that patients with intermediate metabolic CYP2D6 are susceptible to drug-induced liver injury caused by dacomitinib; plasma exchange may be an effective treatment.     

Risk factors of perioperative complications and management with enhanced recovery after primary surgery in women with epithelial ovarian carcinoma in a single center

The present study aimed to evaluate the postoperative complications and the impact of an enhanced recovery programme in patients who underwent primary surgery (including extensive upper abdominal surgery) for epithelial ovarian carcinoma (EOC). All patients with stage I–IV ovarian carcinoma who underwent primary surgery were identified, and postoperative complications were evaluated and graded according to the Clavien-Dindo classification. Of 161 patients, 46 (28.57%) underwent surgical staging, 27 (16.77%) standard cytoreduction, 12 (7.45%) en bloc debulking and 76 (47.20%) extraradical debulking. A total of 157 patients (97.52%) achieved optimal tumor reduction (<1 cm). The mean postoperative hospitalization time was 17.33±11.29 days after completion of the initial postoperative chemotherapy (IPC), and the IPC interval was 16.22±10.09 days. A total of 13 patients (8.07%) had grade 3 complications (9 with wound dehiscence, 3 with digestive tract leakage and 1 with a bladder fistula). A total of 2 patients (1.24%) had grade 4–5 complications [1 patient with severe pneumonia returned to the intensive care unit (ICU) for tracheotomy and respiration rehabilitation; the other patient died of septicemia on day 19]. The multivariate analysis of the preoperative factors revealed that a human epididymis protein 4 (HE4) level of ≥717 pM (P=0.015) and Federation International of Gynecology and Obstetrics (FIGO) stage IV (P=0.004; compared with stage IIIC) were associated with grade 3–5 complications. The bootstrap analysis revealed that a cancer antigen 125 (CA125) level of ≥1,012 U/ml (P=0.034), a HE4 level of ≥717 pM (P=0.007) and FIGO stage IV (P=0.002; compared with stage IIIC) were significantly associated with grade 3–5 complications. Meanwhile, the multivariate analysis of the postoperative factors did not reveal any risk factors associated with grade 3–5 complications; the bootstrap analysis revealed that only transfer to the ICU after surgery (P=0.026) was significantly associated with grade 3–5 complications. In conclusion, the study found that application of enhanced recovery after surgery protocols is feasible in patients with EOC, especially in those undergoing advanced extensive upper abdominal surgery, and CA125, HE4 and FIGO stage IV were related with the occurrence of adverse perioperative outcomes.     

Effect of tissue inhibitor of metalloproteinases-3 genetics polymorphism on clinicopathological characteristics of uterine cervical cancer patients in Taiwan

Single nucleotide polymorphisms (SNPs) of tissue inhibitor of metalloproteinases-3 (TIMP-3) have been revealed to be related to various cancers. To date, no study explores the relationships between TIMP-3 polymorphisms and uterine cervical cancer. The purposes of this research were to investigate the associations among genetic variants of TIMP-3 and development and clinicopathological factors of uterine cervical cancer, and patient 5 years survival in Taiwanese women. The study included 123 patients with invasive cancer and 97 with precancerous lesions of uterine cervix, and 300 control women. TIMP-3 polymorphisms rs9619311, rs9862 and rs11547635 were checked and their genotypic distributions were determined by real-time polymerase chain reaction. It showed that women with genotypes CT/TT in rs9862 were found to display a higher risk of developing cervical cancer with moderate and poor cell differentiation. Moreover, it revealed that cervical cancer patients carrying genotypes CC in rs9619311 exhibited a poorer 5 years survival, as compared to those with TT/TC in Taiwanese women, using univariate analysis. In addition, pelvic lymph node metastasis was determined to independently predict 5 years survival in cervical cancer patients using multivariate analysis. Conclusively, TIMP-3 SNPs polymorphisms rs9619311 are related to cervical patient survival in Taiwanese women.     

Association between plasma Vitamin B5 levels and all‐cause mortality: A nested case‐control study

We aimed to evaluate the prospective association of vitamin B5 with all‐cause mortality and explore its potential modifiers in Chinese adults with hypertension. A nested, case‐control study was conducted in the China Stroke Primary Prevention Trial, including 505 deaths of all causes and 505 matched controls. The median follow‐up duration was 4.5 years. The primary outcome measure in this investigation was all‐cause mortality, which encompassed deaths for any reason. The mean plasma vitamin B5 concentration for cases (43.7 ng/mL) was higher than that in controls (40.9 ng/mL) (p = .001). When vitamin B5 was further assessed as quintiles, compared with the reference group (Q1: < 33.0 ng/mL), the risk of all‐cause mortality increased by 29% (OR = 1.29, 95% CI: 0.83‐2.01) in Q2, 22% (OR = 1.22, 95% CI: 0.77‐1.94) in Q3, 62% (OR = 1.62, 95% CI: 1.00‐2.62) in Q4, and 77% (OR = 1.77, 95% CI: 1.06‐2.95) in Q5. The trend test was significant (p = .022). When Q4‐Q5 were combined, a significant 41% increment (OR = 1.41, 95% CI: 1.03‐1.95) in all‐cause death risk was found compared with Q1‐Q3. The adverse effects were more pronounced in those with normal folate levels (p‐interaction = .019) and older people (p‐interaction = .037). This study suggests that higher baseline levels of plasma vitamin B5 are a risk factor for all‐cause mortality among Chinese patients with hypertension, especially among older adults and those with adequate folate levels. The findings, if confirmed, may inform novel clinical and nutritional guidelines and interventions to optimize vitamin B5 levels.     

Prognostic factors for acute posterior circulation cerebral infarction patients after endovascular mechanical thrombectomy: A retrospective study

This article was to analyze the factors influencing the prognosis of posterior circulation cerebral infarction (PCCI) patients, retrospectively.One hundred forty five patients diagnosed with PCCI in Nanyang Central Hospital between June 25, 2016 and October 14, 2019 were included and underwent cerebral vascular mechanical thrombectomy. The clinical data of those patients were collected. The patients were followed up for 3 months to observe the prognostic efficacy and explore the influencing factors for poor prognosis. The potential prognostic factors for PCCI patients after emergency endovascular mechanical thrombectomy were analyzed by univariate and multivariable logistic regression. The thermodynamic diagram was drawn to explore the associations between the prognostic factors.The risk of poor prognosis in PCCI patients receiving emergency endovascular mechanical thrombectomy was reduced by 0.552 time with every 1-point increase of the Alberta Stroke Program Early CT in posterior circulation score (odds ratio [OR] = 0.448, 95% confidence interval [CI]: 0.276–0.727). The risk of poor prognosis was increased by 0.827 time for each additional grade in the digital subtraction angiography-American Society of Intervention and Therapeutic Neuroradiology grading (OR = 1.827, 95% CI: 1.221–2.733, P = .003) and increased by 0.288 time for every 1-point increase in National Institutes of Health Stroke scale at 24 hours (OR = 1.288, 95% CI: 1.161–1.429). All P < .05.Alberta Stroke Program Early CT in posterior circulation score, digital subtraction angiography-American Society of Intervention and Therapeutic Neuroradiology grading, National Institutes of Health Stroke scale score at 24 hours were factors affecting the prognosis of PCCI patients undergoing emergency endovascular mechanical thrombectomy, which might provide evidence for endovascular treatment of PCCI.     

One-year efficacy of tenofovir alafenamide in patients with chronic hepatitis B: An observational study

Non-inferior antiviral efficacy and better renal safety have been reported in chronic hepatitis B patients with tenofovir alafenamide (TAF) treatment. The experience in real-world clinical practice is limited.We aimed to explore the efficacy after 1-year TAF treatment.A total of 148 patients (42 HBeAg-positive and 106 HBeAg-negative) with TAF treatment ≥1 year were included. Virological suppression (<20 IU/mL or undetectable), HBsAg level, alanine aminotransferase (ALT) normalization (≤36 U/L), and estimated glomerular filtration rate (eGFR) were analyzed at 1 year. Multivariate logistic regression analysis was performed to determine the associated factors for virological suppression and ALT normalization.Virological suppression was achieved in 83% and the 1-year median decline of hepatitis B virus DNA was 5.18 log IU/mL. ALT normalization occurred in 75.7%. HBsAg level decreased at a median of 0.27 log IU/mL with significant difference from baseline (P < .001). Baseline ALT (odds ratio [OR] 1.005, 95% confidence interval [CI] 1.000–1.010, P = .036) and hepatitis B virus DNA (OR 0.222, 95% CI 0.079–0.621, P = .004) were significant factors for 1-year virological suppression. Age (OR 1.064, 95% CI 1.003–1.130, P = .041) was associated with ALT normalization. Significant changes were observed in creatinine (mean increase 0.03 mg/dL, P = .011) and eGFR (mean decrease 2.6 mL/min/1.73 m², P = .004) after 1-year TAF treatment.One-year TAF treatment came to good virological response, modest ALT normalization rate and significant HBsAg decline. The observation of significant changes in eGFR warranted further studies.