Gabapentinoids for chemotherapy-induced peripheral neuropathy: systematic review and meta-analysis.

INTRODUCTION: Chemotherapy-induced peripheral neuropathy (CIPN) affects patients' quality of life and treatment effectiveness. Gabapentinoids, like gabapentin and pregabalin, are often used for CIPN treatment, but their efficacy and safety remain uncertain. This study reviews and analyses randomised controlled trial data on this topic. MATERIALS/METHODS: We searched PubMed, Embase and Cochrane CENTRAL until 29 August 2022 for studies on gabapentinoid use in CIPN. Meta-analysis was performed using RevMan V.5.4 and the Metafor package in R. Outcomes included pain scores, quality of life and adverse drug events. RESULTS: For the prevention setting, our meta-analysis shows that pregabalin did not significantly improve average pain (standardised mean difference (SMD) -0.14, 95% CI -0.51 to 0.23; I2=26% (95% CI 0% to >98%)) or quality of life (mean difference (MD) 2.5, 95% CI -4.67 to 9.67; p=0.49) in preventing CIPN compared with placebo. However, it showed a potential trend towards reducing the worst pain (SMD -0.28, 95% CI -0.57 to 0.01; I2=0% (95% CI 0% to 98%; p=0.06)). For the treatment setting, some studies have shown a potential therapeutic effect of gabapentinoids. However, the results are not consistent between studies. Given the studies' heterogeneity, a meta-analysis in treatment setting was not performed. CONCLUSION: There is limited evidence to support the use of gabapentinoids in CIPN. In prevention setting, gabapentinoids do not significantly prevent CIPN. In treatment setting, studies have been inconsistent in their conclusions, lacking definitive benefits over placebo. More comprehensive and higher quality research is needed in the future. PROSPERO REGISTRATION NUMBER: CRD42022361193.

Changing Incidence and Characteristics of Photokeratoconjunctivitis During the COVID-19 Pandemic.

Introduction: Photokeratoconjunctivitis (PKC) is primarily caused by welding. However, inappropriate use of germicidal lamps, which have been widely used following the COVID-19 outbreak, can also cause PKC. Our goal in this study was to investigate the incidence of and changes in the causes of PKC during the coronavirus 2019 (COVID-19) pandemic. Methods: We conducted a single-center, retrospective observational study. The health records of patients who visited the emergency department in a tertiary care hospital from January 1, 2018-December 31, 2021 and were diagnosed with PKC, were reviewed. We then conducted an analysis to compare the characteristics of PKC before and after COVID-19 began and the features of PKC caused by welding and germicidal lamps. Results: There were 160 PKC cases with a clear etiology before the COVID-19 pandemic and 147 cases during the COVID-19 pandemic. No significant differences in age and gender were detected between the two groups. The incidence of PKC induced by the use of germicidal lamps during the COVID-19 pandemic was significantly higher (10.2%) than the incidence before the pandemic (3.1%). The ratio of females to males in the germicidal lamp subgroup was significantly higher than the ratio in the welding subgroup. Limitations included incomplete information due to the retrospective nature of the study, underestimation of incidence, and possible recall bias. Conclusion: In the era of COVID-19, clinicians should be aware of the hazards of germicidal lamps. Although the COVID-19 pandemic seems to show signs of easing, new infectious diseases that require protective measures could still emerge in the future. Therefore, injuries related to germicidal lamps deserve more public health attention.

Quetiapine Significantly Improves the Effectiveness of Radiotherapy in Combating Hepatocellular Carcinoma Progression in a Hep3B Xenograft Mouse Model.

BACKGROUND/AIM: In hepatocellular carcinoma (HCC) treatment, radiotherapy (RT) stands as a pivotal approach, yet the emergence of radioresistance poses a formidable challenge. This study aimed to explore the potential synergy between quetiapine and RT for HCC treatment. MATERIALS AND METHODS: A Hep3B xenograft mouse model was used, the investigation tracked tumor progression, safety parameters, and molecular mechanisms. RESULTS: The findings revealed a synergistic anti-HCC effect when quetiapine was coupled with RT that prolonged tumor growth time and a significantly higher growth inhibition rate compared to the control group. Safety assessments indicated minimal pathological changes, suggesting potential of quetiapine in mitigating RT-induced alterations in liver and kidney functions. Mechanistically, the combination suppressed metastasis and angiogenesis-related proteins, while triggering the activation of apoptosis-related proteins via targeting Epidermal growth factor receptor (EGFR)-mediated signaling. CONCLUSION: The potential of the quetiapine and RT combination is emphasized, offering enhanced anti-HCC efficacy, a safety profile, and positioning quetiapine as a radiosensitizer for HCC treatment.

TALE-based organellar genome editing and gene expression in plants.

KEY MESSAGE: TALE-based editors provide an alternative way to engineer the organellar genomes in plants. We update and discuss the most recent developments of TALE-based organellar genome editing in plants. Gene editing tools have been widely used to modify the nuclear genomes of plants for various basic research and biotechnological applications. The clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 editing platform is the most commonly used technique because of its ease of use, fast speed, and low cost; however, it encounters difficulty when being delivered to plant organelles for gene editing. In contrast, protein-based editing technologies, such as transcription activator-like effector (TALE)-based tools, could be easily delivered, expressed, and targeted to organelles in plants via Agrobacteria-mediated nuclear transformation. Therefore, TALE-based editors provide an alternative way to engineer the organellar genomes in plants since the conventional chloroplast transformation method encounters technical challenges and is limited to certain species, and the direct transformation of mitochondria in higher plants is not yet possible. In this review, we update and discuss the most recent developments of TALE-based organellar genome editing in plants.

Risk of Bleeding Following Non-Vitamin K Antagonist Oral Anticoagulant Use in Patients With Acute Ischemic Stroke Treated With Alteplase.

Importance: Current guidelines advise against intravenous alteplase therapy for treatment of acute ischemic stroke in patients previously treated with non-vitamin K antagonist oral anticoagulants (NOACs). Objective: To evaluate the risk of bleeding and mortality after alteplase treatment for acute ischemic stroke among patients treated with NOACs compared to those not treated with NOACs. Design, Setting, and Participants: This nationwide, population-based cohort study was conducted in Taiwan using data from Taiwan's National Health Insurance Research Database from January 2011 through November 2020 and included 7483 patients treated with alteplase for acute ischemic stroke. A meta-analysis incorporating the results of the study with those of previous studies was performed, and the review protocol was prospectively registered with PROSPERO. Exposures: NOAC treatment within 2 days prior to stroke, compared to either no anticoagulant treatment or warfarin treatment. Main Outcomes and Measures: The primary outcome was intracranial hemorrhage after intravenous alteplase during the index hospitalization (the hospitalization subsequent to alteplase administration). Secondary outcomes were major bleeding events and mortality during the index hospitalization. Propensity score matching was used to control potential confounders. Logistic regression was used to estimate the odds ratio (OR) of outcome events. Meta-analysis was performed using a random-effects model. Results: Of the 7483 included patients (mean [SD] age, 67.4 [12.7] years; 2908 [38.9%] female individuals and 4575 [61.1%] male individuals), 91 (1.2%), 182 (2.4%), and 7210 (96.4%) received NOACs, warfarin, and no anticoagulants prior to their stroke, respectively. Compared to patients who were not treated with anticoagulants, those treated with NOACs did not have significantly higher risks of intracranial hemorrhage (risk difference [RD], 2.47% [95% CI, -4.23% to 9.17%]; OR, 1.37 [95% CI, 0.62-3.03]), major bleeding (RD, 4.95% [95% CI, -2.56% to 12.45%]; OR, 1.69 [95% CI, 0.83-3.45]), or in-hospital mortality (RD, -4.95% [95% CI, -10.11% to 0.22%]; OR, 0.45 [95% CI, 0.15-1.29]) in the propensity score-matched analyses. Furthermore, the risks of bleeding and mortality were not significantly different between patients treated with NOACs and those treated with warfarin. Similar results were obtained in the meta-analysis. Conclusions and Relevance: In this cohort study with meta-analysis, compared to no treatment with anticoagulants, treatment with NOACs prior to stroke was not associated with a higher risk of intracranial hemorrhage, major bleeding, or mortality in patients receiving intravenous alteplase for acute ischemic stroke.

Association between chronic pain and acute coronary syndrome in the older population: a nationwide population-based cohort study.

BACKGROUND: Chronic pain (CP) may increase the risk of acute coronary syndrome (ACS); however, this issue in the older population remains unclear. Therefore, this study was conducted to clarify it. METHODS: We used the Taiwan National Health Insurance Research Database to identify older patients with CP between 2001 and 2005 as the study cohort. Comparison cohort was the older patients without CP by matching age, sex, and index date at 1:1 ratio with the study cohort in the same period. We also included common underlying comorbidities in the analyses. The risk of ACS was compared between the two cohorts by following up until 2015. RESULTS: A total of 17241 older patients with CP and 17241 older patients without CP were included in this study. In both cohorts, the mean age (± standard deviation) and female percentage were 73.5 (± 5.7) years and 55.4%, respectively. Spinal disorders (31.9%) and osteoarthritis (27.0%) were the most common causes of CP. Older patients with CP had an increased risk for ACS compared to those without CP after adjusting for all underlying comorbidities (adjusted sub-distribution hazard ratio [sHR] 1.18; 95% confidence interval: 1.07-1.30). The increasement of risk of ACS was more when the follow-up period was longer (adjusted sHR of < 3 years: 1.8 vs. <2 years: 1.75 vs. <1 year: 1.55). CONCLUSIONS: CP was associated with an increased risk of ACS in the older population, and the association was more prominent when the follow-up period was longer. Early detection and intervention for CP are suggested in this population.

Clinical Effect of Moisturized Skin Care on Radiation Dermatitis of Head and Neck Cancer.

BACKGROUND/AIM: Radiation therapy (RT) for head and neck cancer may cause severe radiation dermatitis (RD) resulting in RT interruption and affecting disease control. A few studies address skin moisture changes during RT for head and neck cancer. The purpose of this study was to explore the effect of moisturized skin care (MSC) on severity of RD. PATIENTS AND METHODS: The study includes newly diagnosed head and neck cancer patients undergoing RT. Participants were divided into MSC group and routine skin care (RSC) group based on patient's preferred decision. Skin moisture in the four quadrants of the neck was measured weekly before and after RT. RD was assessed with the Radiation Induced Skin Reaction Assessment Scale (RISRAS) and the Radiation Therapy Oncology Group (RTOG) acute skin toxicity grading criteria. RESULTS: A total of 54 patients were enrolled, of which 49 patients were suitable for the statistical analysis. There was a statistically significant difference in the RISRAS total score since the 5th week after RT between the groups. The severity of RD was less (B=0.814, p=0.021) and the onset was later (B=-0.384, p=0.006) in the MSC group when compared to the RSC group. Skin moisture decreased with cumulative radiation dose. In the upper neck, the MSC group had a slower rate of skin moisture decrease compared to the RSC group (right upper neck: B=0.935, p=0.007; left upper neck: B=0.93, p=0.018). CONCLUSION: MSC can effectively reduce the severity and delay the onset of RD, while slows down skin moisture decrease during RT.

A Novel Isotope-labeled Small Molecule Probe CC12 for Anti-glioma via Suppressing LYN-mediated Progression and Activating Apoptosis Pathways.

Background: Glioblastoma multiforme (GBM) is the most lethal malignancy in brain, which is surrounded by the blood-brain barrier (BBB), which limits the efficacy of standard treatments. Developing an effective drug that can penetrate the blood-brain barrier (BBB) remains a critical challenge in the fight against GBM. CC12 (NSC749232) is an anthraquinone tetraheterocyclic homolog with a lipophilic structure that may facilitate penetration of the brain area. Methods: We used temozolomide sensitive and resistance GBM cells and animal model to identify the CC12 delivery, anti-tumor potential and its underlying mechanism. Results: Importantly, toxicity triggered by CC12 was not associated with the methyl guanine-DNA methyl transferase (MGMT) methylation status which revealed a greater application potential compared to temozolomide. Alexa F488 cadaverine-labelled CC12 successfully infiltrated into the GBM sphere; in addition, 68Ga-labeled CC12 was also found in the orthotopic GBM area. After passing BBB, CC12 initiated both caspase-dependent intrinsic/extrinsic apoptosis pathways and apoptosis-inducing factor, EndoG-related caspase-independent apoptosis signaling in GBM. RNA sequence analysis from The Cancer Genome Atlas indicated that LYN was overexpressed in GBM is associated with poorer overall survival. We proved that targeting of LYN by CC12 may diminish GBM progression and suppress it downstream factors such as signal transduction and activator of extracellular signal-regulated kinases (ERK)/transcription 3 (STAT3)/nuclear factor (NF)-κB. CC12 was also found to participate in suppressing GBM metastasis and dysregulation of the epithelial-mesenchymal transition (EMT) through inactivation of the LYN axis. Conclusion: CC12, a newly developed BBB-penetrating drug, was found to possess an anti-GBM capacity via initiating an apoptotic mechanism and disrupting LYN/ERK/STAT3/NF-κB-regulated GBM progression.