1.Ethnic Differences in the Safety and Efficacy of Tenecteplase Versus Alteplase for Acute Ischemic Stroke: A Systematic Review and Meta-Analysis
Jin Hean KOH ; Claire Yi Jia LIM ; Lucas Tze Peng TAN ; Ching-Hui SIA ; Kian Keong POH ; Vijay Kumar SHARMA ; Leonard Leong Litt YEO ; Andrew Fu Wah HO ; Teddy WU ; William Kok-Fai KONG ; Benjamin Yong Qiang TAN
Journal of Stroke 2024;26(3):371-390
Background:
and Purpose Tenecteplase is a thrombolytic agent with pharmacological advantages over alteplase and has been shown to be noninferior to alteplase for acute ischemic stroke in randomized trials. However, evidence pertaining to the safety and efficacy of tenecteplase in patients from different ethnic groups is lacking. The aim of this systematic review and metaanalysis was to investigate ethnicity-specific differences in the safety and efficacy of tenecteplase versus alteplase in patients with acute ischemic stroke.
Methods:
Following an International Prospective Register of Systematic Reviews (PROSPERO)- registered protocol (CRD42023475038), three authors conducted a systematic review of the PubMed/MEDLINE, Embase, Cochrane Library, and CINAHL databases for articles comparing the use of tenecteplase with any thrombolytic agent in patients with acute ischemic stroke up to November 20, 2023. The certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. Two independent authors extracted data onto a standardized data collection sheet. A pairwise meta-analysis was conducted in risk ratios (RR).
Results:
From 34 studies (59,601 participants), the rate of complete recanalization was significantly higher (P<0.01) in Asian (RR: 1.91, 95% confidence interval [CI]: 1.30 to 2.80) versus Caucasian patients (RR: 0.99, 95% CI: 0.87 to 1.14). However, Asian patients (RR: 1.18, 95% CI: 0.87 to 1.62) had significantly higher (P=0.01) rates of mortality compared with Caucasian patients (RR: 1.10, 95% CI: 1.00 to 1.22). Caucasian patients were also more likely to attain a modified Rankin Scale (mRS) score of 0 to 2 at follow-up (RR: 1.14, 95% CI, 1.10 to 1.19) compared with Asian (RR: 1.00, 95% CI, 0.95 to 1.05) patients. There was no significant difference in the rate of symptomatic intracranial hemorrhage (P=0.20) and any intracranial hemorrhage (P=0.83) between Asian and Caucasian patients.
Conclusion
Tenecteplase was associated with significantly higher rates of complete recanalization in Asian patients compared with Caucasian patients. However, tenecteplase was associated with higher rates of mortality and lower rates of mRS 0 to 2 in Asian patients compared with Caucasian patients. It may be beneficial to study the variations in response to tenecteplase among patients of different ethnic groups in large prospective cohort studies.
2.Identification of sumoylated targets in proliferating mouse spermatogonia and human testicular seminomas.
Margarita VIGODNER ; Benjamin LUCAS ; Stav KEMENY ; Tamar SCHWARTZ ; Rebecca LEVY
Asian Journal of Andrology 2020;22(6):569-577
Spermatogenesis is regulated by a complex network of posttranslation modifications. Sumoylation (a modification by small ubiquitin-like modifiers, or SUMO proteins) was identified as an important cellular event in different cell types. SUMO proteins are highly expressed in the testis, and their role during spermatogenesis has begun to be elucidated. Given the important role of sumoylation in the regulation of mitosis and cancer progression in other tissues, the aim of the current study was to identify the targets of SUMO in proliferating mouse spermatogonia and human seminoma tissues and to initially examine the level of sumoylation in relation to the proliferative activity of the tissues. Using freshly purified spermatogonia and C18-4 spermatogonia cell line, mass spectrometry analysis identified several SUMO targets implicated into the proliferation of spermatogonia (such as heat shock protein 60 [HSP60] and prohibitin). Tissue array and western blot approaches showed that SUMO expression is a prominent feature of human seminomas and that the proliferative activity of the tumor tissues was positively correlated with the level of SUMO expression. Downregulation of sumoylation with si-RNA was not sufficient to significantly affect the proliferation of C18-4 spermatogonia; however, SUMO overexpression increased the proliferation rate of the cells. These data suggest that cells are more sensitive to an elevated level of SUMO, and that this situation may lead to an upregulated cellular proliferation and, possibly, cancer. Mass spectrometry analysis identified around a hundred SUMO targets in seminoma samples. Notably, many of the identified proteins (such as proliferating cell nuclear antigen [PCNA], DNA topoisomerase 2-alpha [Top2A], prohibitin, 14-3-3 protein, and others) were implicated in oncogenic transformation and cancer progression.
3.Torsion of the spermatic cord in adults: a multicenter experience in adults with surgical exploration for acute scrotal pain with suspected testicular torsion.
Van Thi DANG ; Benjamin PRADERE ; Anne Mauger DE VARENNES ; Nadia Ali BENALI ; Maxime VALLÉE ; William BERCHICHE ; Bastien GONDRAN-TELLIER ; Gaelle MARGUE ; Clément MICHIELS ; Charles GAILLARD ; Tristan GREVEZ ; Florian BARDET ; Maud HULIN ; Anthony MANUGUERRA ; Ugo PINAR ; Caroline PLASSAIS ; Margeux FELBER ; William WANDOREN ; Kévin KAULANJAN ; Ines DOMINIQUE ; Marc SBIZERRA ; Emilien Seizilles DE MAZANCOURT ; Xavier MATILLON ; Igor DUQUESNE ; Maxime CHABENES ; Victor GAILLARD ; Lucas FRETON ; Francois LANNES ; Zine-Eddine KHENE
Asian Journal of Andrology 2022;24(6):575-578
Acute scrotal pain (ASP) requiring surgical exploration is common in the pediatric population, but little has been reported on this subject with regard to the adult population. The aim of this study was to investigate the demographic and clinical characteristics and outcomes of scrotal explorations performed on adult patients. Patients over 21 years of age who underwent surgical exploration for ASP with suspected testicular torsion (TT) at 14 French hospitals between January 2005 and December 2019 were included in this study. The main outcome measures were demographic characteristics, pathology found during scrotal exploration, and perioperative outcomes. Logistic regression was used to perform univariate and multivariate analyses to identify predictors of TT. Data for 1329 men were analyzed. The median age was 30 (interquartile range [IQR]: 25-35; range: 21-89) years. Regarding the clinical examination, 867 (65.2%) patients presented with an elevation of the testicle, 613 (46.1%) patients with scrotal edema or erythema, and 211 (15.9%) patients with nausea or vomiting. Operative findings identified TT in only 684 (51.5%) patients, epididymo-orchitis in 112 (8.4%) patients, a tumor in 16 (1.2%) patients, and no causes in 475 (35.7%) patients. Orchiectomy for nonviable testes was required in 101 (7.6%) patients. In multivariate analysis, an elevation of the testicle, erythema/swelling, and the presence of nausea/vomiting were found to be associated with the occurrence of TT. Testicular torsion is not exclusive to children and adolescents, so must be considered in males of any age with acute scrotal findings. However, one-third of scrotal explorations in adults did not lead to a diagnosis.
Adolescent
;
Male
;
Adult
;
Child
;
Humans
;
Spermatic Cord Torsion/surgery*
;
Spermatic Cord
;
Retrospective Studies
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Pain/surgery*
;
Nausea/complications*
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Vomiting/complications*
;
Scrotum/surgery*
4.Safety attitudes, burnout and well-being among healthcare workers during the COVID-19 pandemic: an Indo-Pacific regional cross-sectional study.
Abhiram KANNEGANTI ; Benjamin Yong Qiang TAN ; Nik Hisamuddin NIK AB RAHMAN ; Aloysius Sheng-Ting LEOW ; Max DENNING ; Ee Teng GOH ; Lucas Jun HAO LIM ; Ching-Hui SIA ; Ying Xian CHUA ; James KINROSS ; Melanie TAN ; Li Feng TAN ; Yi Min WAN ; Arvind SHARMA ; Rivan DANUAJI ; R N KOMAL KUMAR ; Chew Keng SHENG ; Cheah Phee KHENG ; Sarah Shaikh ABDUL KARIM ; Mohd Najib ABDUL GHANI ; Suhaimi MAHMUD ; Yiong Huak CHAN ; Vijay Kumar SHARMA ; Kang SIM ; Shirley Beng SUAT OOI
Singapore medical journal 2023;64(11):667-676
INTRODUCTION:
The coronavirus disease 2019 (COVID-19) pandemic has had an unprecedented impact in Asia and has placed significant burden on already stretched healthcare systems. We examined the impact of COVID-19 on the safety attitudes among healthcare workers (HCWs), as well as their associated demographic and occupational factors, and measures of burnout, depression and anxiety.
METHODS:
A cross-sectional survey study utilising snowball sampling was performed involving doctors, nurses and allied health professions from 23 hospitals in Singapore, Malaysia, India and Indonesia between 29 May 2020 and 13 July 2020. This survey collated demographic data and workplace conditions and included three validated questionnaires: the Safety Attitudes Questionnaire (SAQ), Oldenburg Burnout Inventory and Hospital Anxiety and Depression Scale. We performed multivariate mixed-model regression to assess independent associations with the SAQ total percentage agree rate (PAR).
RESULTS:
We obtained 3,163 responses. The SAQ total PARs were found to be 35.7%, 15.0%, 51.0% and 3.3% among the respondents from Singapore, Malaysia, India and Indonesia, respectively. Burnout scores were highest among respondents from Indonesia and lowest among respondents from India (70.9%-85.4% vs. 56.3%-63.6%, respectively). Multivariate analyses revealed that meeting burnout and depression thresholds and shifts lasting ≥12 h were significantly associated with lower SAQ total PAR.
CONCLUSION
Addressing the factors contributing to high burnout and depression and placing strict limits on work hours per shift may contribute significantly towards improving safety culture among HCWs and should remain priorities during the pandemic.
Humans
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Cross-Sectional Studies
;
Pandemics
;
COVID-19/epidemiology*
;
Burnout, Psychological
;
Health Personnel