Hasil untuk "Therapeutics. Pharmacology"

M. Kramer, A. Feinstein

S. Ebrahim, F. Taylor, P. Brindle

This is one of a series of occasional articles on therapeutics for common or serious conditions, covering new drugs and old drugs with important new indications or concerns. The series advisers are Robin Ferner, honorary professor of clinical pharmacology, University of Birmingham and Birmingham City Hospital, and Albert Ferro, professor of cardiovascular clinical pharmacology, King’s College London. To suggest a topic for this series, please email us at practice@bmj.com.

C. Medina, M. Santos-Martinez, A. Radomski et al.

R. J. Solá, K. Griebenow

Daqiu Chen, Zixun Wang, Zhanxiong Xie et al.

BackgroundTirzepatide, a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, is highly effective for glycaemic control and weight reduction. However, its real-world cardiovascular adverse event reporting profile remains incompletely characterised.MethodsWe conducted a retrospective pharmacovigilance study using the FDA Adverse Event Reporting System (FAERS) from the second quarter of 2022 (FDA approval of tirzepatide) through the third quarter of 2025. Disproportionality analysis was performed using the Reporting Odds Ratio (ROR) with a concurrent full-database comparator (all other drugs reported in the same quarterly files). Because consumers submitted 92.3% of reports, primary inference was drawn from analyses restricted to healthcare professional (HCP) reports (physicians and pharmacists). Subgroup analyses stratified by age, sex, and body weight were conducted; weight-stratified analyses were confined to reports with documented body weight.ResultsA total of 103,693 unique tirzepatide reports were identified. Consumers accounted for 92.3% of submissions; body weight was documented in 5,881 reports (5.7%). In HCP-restricted analyses, tirzepatide was associated with persistently lower reporting odds for heart failure (ROR 0.18 [95% CI 0.07–0.43]). Similarly, no disproportionate reporting was detected for acute myocardial infarction (ROR 0.45 [0.19–1.08]), while remarkably, zero cases of angina or myocardial ischemia were reported in the HCP cohort. In contrast, no association was detected for atrial fibrillation (ROR 1.02 [0.58–1.80]) or tachycardia (ROR 1.01 [0.68–1.51]) in HCP reports. In weight-stratified analyses (full dataset, restricted to reports with documented weight), elevated RORs for tachycardia were observed in both weight groups (<95 kg: 1.91 [1.54–2.37]; ≥95 kg: 1.57 [1.20–2.05]); however, this finding was not replicated in the HCP-restricted analysis and should be interpreted with caution.ConclusionIn this real-world FAERS analysis using a concurrent full-database comparator and pre-specified stratification by reporter type, tirzepatide showed disproportionately low reporting of heart failure that was robust in HCP reports and across all subgroups. No reporting signal for atrial fibrillation, tachycardia, or ischemic events was detected after accounting for reporter bias. These findings provide pharmacovigilance evidence that complements the safety database of tirzepatide and generate hypotheses for ongoing cardiovascular outcome trials.

Man Li, Jinying Shi, Xiaodong Pan et al.

ABSTRACT Immune checkpoint regulators can improve neurological functions in Alzheimer's disease. However, it remains blurred whether these regulators may ameliorate temporal lobe epilepsy (TLE) and TLE‐related cognitive impairment. This study analyzed the bulk transcriptomic data of human TLE hippocampi by bioinformatics. The expression of the potential immune checkpoint regulators in the hippocampus was assessed by immunohistochemical staining; the preoperative seizure severity and postoperative cognitive function were evaluated by the National Hospital Seizure Severity Scale (NHS3) and Telephone Interview for Cognitive Status‐Modified (TICS‐m); the correlation between the target immune checkpoint regulators and TLE‐related cognitive impairment was examined by simple linear regression models and the area under the receiver operating characteristic curve (AUC). We first identified glucocorticoid‐induced tumor necrosis factor receptor ligand (GITRL) as a key immune checkpoint regulator in TLE patients, with an increased intensity of GITRL in epileptic hippocampus (n = 21) compared with that of the control (n = 3). The GITRL intensity was positively correlated with NHS3 score (r2 = 0.503, p < 0.001) and negatively with TICS‐m total score (r2 = 0.456, p < 0.001), specifically, TICS‐m memory score (r2 = 0.360, p = 0.004), TICS‐m language/attention score (r2 = 0.319, p = 0.008), and TICS‐m orientation score (r2 = 0.312, p = 0.008). The AUC showed that the GITRL intensity presented a good predictive performance in discerning patients with a TICS‐m score of ≥ 30 (AUC: 0.875, 95% CI, 0.721–1.00; p = 0.013). These findings highlight hippocampal GITRL as a potential predictive marker for TLE‐related cognitive impairment.

L. Slosky, M. Caron, L. Barak

G protein-coupled receptors (GPCRs) are the largest class of cell surface receptors in the genome and the most successful family of targets of FDA-approved drugs. New frontiers in GPCR drug discovery remain, however, as achieving receptor subtype selectivity and controlling off- and on-target side effects are not always possible with classic agonist and antagonist ligands. These challenges may be overcome by focusing development efforts on allosteric ligands that confer signaling bias. Biased allosteric modulators (BAMs) are an emerging class of GPCR ligands that engage less well-conserved regulatory motifs outside the orthosteric pocket and exert pathway-specific effects on receptor signaling. The unique ways that BAMs texturize receptor signaling present opportunities to fine-tune physiology and develop safer, more selective therapeutics. Here, we provide a conceptual framework for understanding the pharmacology of BAMs, explore their therapeutic potential, and discuss strategies for their discovery.

Zdenek Krejcik, David Kundrat, Jiri Klema et al.

Abstract Background Myelodysplastic neoplasms (MDS) are heterogeneous hematopoietic disorders characterized by ineffective hematopoiesis and genome instability. Mobilization of transposable elements (TEs) is an important source of genome instability leading to oncogenesis, whereas small PIWI-interacting RNAs (piRNAs) act as cellular suppressors of TEs. However, the roles of TEs and piRNAs in MDS remain unclear. Methods In this study, we examined TE and piRNA expression through parallel RNA and small RNA sequencing of CD34+ hematopoietic stem cells from MDS patients. Results Comparative analysis of TE and piRNA expression between MDS and control samples revealed several significantly dysregulated molecules. However, significant differences were observed between lower-risk MDS (LR-MDS) and higher-risk MDS (HR-MDS) samples. In HR-MDS, we found an inverse correlation between decreased TE levels and increased piRNA expression and these TE and piRNA levels were significantly associated with patient outcomes. Importantly, the upregulation of PIWIL2, which encodes a key factor in the piRNA pathway, independently predicted poor prognosis in MDS patients, underscoring its potential as a valuable disease marker. Furthermore, pathway analysis of RNA sequencing data revealed that dysregulation of the TE‒piRNA axis is linked to the suppression of processes related to energy metabolism, the cell cycle, and the immune response, suggesting that these disruptions significantly affect cellular activity. Conclusions Our findings demonstrate the parallel dysregulation of TEs and piRNAs in HR-MDS patients, highlighting their potential role in MDS progression and indicating that the PIWIL2 level is a promising molecular marker for prognosis. Graphical Abstract

Yang H, Yang Y, Huang Y et al.

Huan Yang, Yan Yang, Yihao Huang, Tao Liu, Yiheng Wang Department of Anesthesiology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, People’s Republic of ChinaCorrespondence: Yiheng Wang, Department of Anesthesiology, The First Affiliated Hospital, Hengyang Medical School, University of South China, 69 Chuanshan Road, Shigu District, Hengyang, Hunan, 421001, People’s Republic of China, Tel +867348578511, Email wyheng11@163.comPurpose: The 2,6-disubstituted alkylphenol ciprofol is a novel propofol analog for induction and maintenance of anesthesia. We aimed to compare the effects of ciprofol-based and propofol-based total intravenous anesthesia (TIVA) on postoperative recovery quality following hysteroscopic surgery.Patients and Methods: In this randomized non-inferiority trial, women scheduled for hysteroscopic surgery at a tertiary hospital were randomly assigned to the ciprofol or propofol groups. The patients were administered intravenous injections of ciprofol (0.4 mg/kg) or propofol (2.0 mg/kg) for anesthesia induction before a maintenance infusion at initial rates of 0.8 or 5.0 mg/kg/h, respectively. The primary outcome was the Quality of Recovery-15 scale (QoR-15) score at 24 h post-surgery, and a non-inferiority margin of − 8 was assumed. The secondary outcomes included hemodynamic changes, time to consciousness loss and recovery, incidences of injection pain, body movement, intraoperative respiratory adverse events, and postoperative adverse events.Results: The trial included 120 participants (60 per group). The total QoR-15 score 24 h after surgery in the ciprofol group was comparable to that in the propofol group (median [interquartile range]: 113.5 [111.0, 117.0] vs 112.5 [108.0, 117.0]; median difference [95% confidence interval]: − 1.0 [− 3.0, 2.0]). There were no significant differences in the five QoR-15 dimensions between the groups. The mean arterial pressure and heart rate during anesthesia induction and surgery were significantly higher in the ciprofol group than in the propofol group, whereas the incidence of injection pain was lower. In addition, there were no significant between-group differences in the time to loss of consciousness or awakening, incidences of intraoperative hypoxemia or laryngospasm, or incidences of postoperative nausea, vomiting, headache, dizziness, and drowsiness.Conclusion: Ciprofol is not inferior to propofol in terms of QoR score. Ciprofol administration is suitable for general anesthesia in female patients during hysteroscopic surgery.Keywords: ciprofol, propofol, postoperative recovery quality, hysteroscopic surgery

Wei Qin, Ping Nie, Xuejun Hui et al.

Diabetic kidney disease is one of the common complications in diabetic patients and has gradually become an important pathogenic factor in chronic kidney disease. Therefore, studying the mechanisms of its occurrence and development is of great significance for the prevention and treatment of diabetic kidney disease. Some researchers have pointed out that there is a phenomenon of hypoxia in diabetic kidney tissue and believe that hypoxia-inducible factor-1α is closely related to the occurrence and progression of diabetic kidney disease. Additionally, the homeostasis of zinc plays a key role in the body’s adaptation to hypoxic environments. However, the specific relationship among these three factors remains unclear. This article provides a detailed review of the multiple roles of hypoxia-inducible factor-1α in the pathogenesis of diabetic kidney disease, including: regulating angiogenesis, increasing the expression of erythropoietin, modulating oxidative stress through the PI3K/AKT and HIF-1α/HO-1 pathways, promoting inflammatory cell infiltration and the release of inflammatory factors to induce inflammatory responses, facilitating epithelial-mesenchymal transition, pathological angiogenesis, and promoting the release of fibrotic factors, ultimately leading to renal fibrosis. Furthermore, HIF-1α also participates in the occurrence and development of diabetic kidney disease through mechanisms such as regulating apoptosis, inducing mitochondrial autophagy, and vascular calcification. At the same time, this article clarifies the regulatory role of the trace element zinc on hypoxia-inducible factor-1α in diabetic kidney disease. This article provides references and insights for further research on the pathogenesis and progression of diabetic kidney disease.

Lin Tan, Jiayue Li, Dingcheng Sun et al.

Natural plant-derived active ingredients have gained increasing attention for their potential in the treatment of depression due to their safety and multi-target pharmacological activities. Saikosaponin A (SSA), a major bioactive saponin extracted from Bupleurum (a medicine and food homologous plant), has been reported to possess anti-inflammatory, neuroprotective, and antioxidative properties. In this study, we evaluated the antidepressant-like effects of SSA in a mouse model of chronic unpredictable mild stress (CUMS)-induced depression. Mice were subjected to CUMS, followed by daily administration of SSA (20 mg/kg, po for 6 weeks). Behavioral tests, including tail suspension test, open field test, elevated plus maze, and marble burying test, indicated that SSA significantly alleviated depressive-like and anxiety-like behaviors. Histopathological analysis by H&amp;E staining showed that SSA reduced hippocampal neuronal damage induced by chronic stress. Biochemical assays revealed that SSA normalized levels of neurotransmitters (5-HT, DA, and 5-HIAA), enhanced antioxidant enzyme activity (SOD, CAT, and GSH), and suppressed neuroinflammatory cytokine production (TNF-α, IL-1β, and IL-6). Mechanistically, SSA exerted its antidepressant effects by inhibiting the TLR4/NF-κB signaling pathway and upregulating BDNF expression. In PC12 cells, TLR4 overexpression attenuated SSA’s protective effects, whereas TLR4 silencing enhanced cellular resistance to corticosterone-induced damage. These findings suggest SSA alleviates CUMS-induced depression-like behaviors in mice by modulating neuroinflammation and oxidative stress through the TLR4/NF-κB/BDNF signaling axis, indicating its potential as a functional food-derived therapy for depression.

Zhiwei Jiang, Na Li, Qin Shao et al.

Abstract Cell aggregates that mimic in vivo cell–cell interactions are promising and powerful tools for tissue engineering. This study isolated a new, easily obtained, population of mesenchymal stem cells (MSCs) from rat hard palates named hard palatal‐derived mesenchymal stem cells (PMSCs). The PMSCs were positive for CD90, CD44, and CD29 and negative for CD34, CD45, and CD146. They exhibited clonogenicity, self‐renewal, migration, and multipotent differentiation capacities. Furthermore, this study fabricated scaffold‐free 3D aggregates using light‐controlled cell sheet technology and a serum‐free method. PMSC aggregates were successfully constructed with good viability. Transplantation of the PMSC aggregates and the PMSC aggregate‐implant complexes significantly enhanced bone formation and implant osseointegration in vivo, respectively. This new cell resource is easy to obtain and provides an alternative strategy for tissue engineering and regenerative medicine.

J. Bigby

Yuchan Huang, Yuchan Huang, Yuchan Huang et al.

Aquaporins (AQPs) are a family of transmembrane proteins expressed in various organ systems. Many studies have shown that the abnormal expression of AQPs is associated with gastrointestinal, skin, liver, kidneys, edema, cancer, and other diseases. The majority of AQPs are expressed in the digestive system and have important implications for the physiopathology of the gastrointestinal tract as well as other tissues and organs. AQP regulators can prevent and treat most gastrointestinal-related diseases, such as colorectal cancer, gastric ulcer, and gastric cancer. Although recent studies have proposed clinically relevant AQP-targeted therapies, such as the development of AQP inhibitors, clinical trials are still lacking and there are many difficulties. Traditional Chinese medicine (TCM) has been used in China for thousands of years to prevent, treat and diagnose diseases, and is under the guidance of Chinese medicine (CM) theory. Herein, we review the latest research on the regulation of AQPs by TCMs and their active components, including Rhei Radix et Rhizoma, Atractylodis macrocephalae Rhizoma, Salviae miltiorrhizae Radix et Rhizoma, Poria, Astragali radix, and another 26 TCMs, as well as active components, which include the active components include anthraquinones, saponins, polysaccharides, and flavonoid glycosides. Through our review and discussion of numerous studies, we attempt to explore the regulatory effects of TCMs and their active components on AQP expression in the corresponding parts of the body in terms of the Triple Energizer concept in Chinese medicine defined as “upper energizer, middle energizer, and lower energizer,”so as to offer unique opportunities for the development of AQP-related therapeutic drugs for digestive system diseases.

Li-Jiao Yan, Zhi-Jie Wang, Min Fang et al.

Objective: To evaluate the efficacy, clinical effectiveness, and safety of the Chinese herb Bupleuri radix for the treatment of acute uncomplicated respiratory tract infections (ARTIs).Methods: Four English and four Chinese databases were searched from their inception to June 2021. Randomized controlled trials (RCTs) assessing therapeutic effects of Bupleuri radix on ARTI were eligible for inclusion. The risk of bias for each trial was assessed using the Cochrane Risk of Bias Tool 2.0. RevMan 5.4 software was used for data analyses with effects estimated as risk ratios (RR) or mean differences (MD) with 95% confidence intervals (CI). The certainty of the evidence was assessed using the online GRADEpro tool.Results: Seven randomized trials involving 910 patients with acute upper respiratory tract infection (AURTI) were included. The review identified Bupleuri radix agents with four administration routes (oral, acupoint injection, intramuscular injection, nebulized inhalation). Bupleuri radix acupoint injection compared with placebo showed statistically significant effects in reducing fever resolution time (MD: −33.32 h, 95%CI: −35.71, −30.93), and in increasing the proportion of participants with fever resolved within 48 h from treatment onset (RR: 14, 95%CI: 1.96, 99.94). Bupleuri radix acupoint injection combined with usual care is more effective in reducing the temperature at day 1 from treatment onset (MD: −1.00°C, 95%CI: −1.19, −0.81) compared with usual care alone. Bupleuri radix pills showed similar antipyretic effects to acetaminophen. However, Bupleuri radix intramuscular injection plus vitamins failed to demonstrate an effect in reducing fever, when compared with ribavirin plus vitamins. It suggested that oral administration of Bupleuri radix solution for injections, pills, and Bupleuri radix decoction have a similar effect on improving global AURTI symptoms including two key symptoms (nasal discharge and cough), when compared with usual care alone. Only two trials reported whether or not there were any AEs and found no occurrence of adverse events in the herbal group.Conclusion: Low-certainty or very low-certainty evidence demonstrated that Bupleuri radix (solution for injections and pills) has an antipyretic effect on febrile patients with AURTI, but it has no effect on other AURTI symptoms. However, these findings need to be further confirmed by well-designed clinical trials with adequate sample sizes.Systematic review registration: (https://www.crd.york.ac.uk/prospero/#recordDetails), PROSPERO registration number: CRD42021234066.

Qiaoli Yu, Mingxue Ran, Yuqing Yang et al.

Sulfane sulfur is a class of compounds containing zero-valent sulfur. Most sulfane sulfur compounds are reactive and play important signaling roles. Key enzymes involved in the production and metabolism of sulfane sulfur have been characterized; however, little is known about how to change intracellular sulfane sulfur (iSS) levels. To accurately measure iSS, we optimized a previously reported method, in which reactive iSS reacts with sulfite to produce thiosulfate, a stable sulfane sulfur compound, before detection. With the improved method, several factors were tested to influence iSS in <i>Escherichia coli</i>. Temperature, pH, and osmotic pressure showed little effect. At commonly used concentrations, most tested oxidants, including hydrogen peroxide, tert-butyl hydroperoxide, hypochlorous acid, and diamide, did not affect iSS, but carbonyl cyanide m-chlorophenyl hydrazone increased iSS. For reductants, 10 mM dithiothreitol significantly decreased iSS, but <i>tris</i>(2-carboxyethyl)phosphine did not. Among different sulfur-bearing compounds, NaHS, cysteine, S₂O₃²⁻ and diallyl disulfide increased iSS, of which only S₂O₃²⁻ did not inhibit <i>E. coli</i> growth at 10 mM or less. Thus, with the improved method, we have identified reagents that may be used to change iSS in <i>E. coli</i> and other organisms, providing tools to further study the physiological functions of iSS.

Silvia Guzmán-Beltrán, Laura Elena Carreto-Binaghi, Claudia Carranza et al.

Tuberculosis (TB) is one of the highest infectious burdens worldwide. An excess of inflammation and inadequate antioxidant defense mechanisms are believed to lead to chronic inflammation and lung damage in tuberculosis (TB). However, circulating metabolites do not always replicate lung-associated biomarkers that define the pathobiology of the disease. The objective of this study was to determine the utility of exhaled breath condensate (EBC), a non-invasive and straightforward sample, to evaluate alveolar space-derived metabolites of redox state and inflammation. We assessed the levels of exhaled oxidant/antioxidant parameters (8-isoprostane, MDA, GSH), inflammatory markers, such as nucleosomes, cytokines (IL-2, IL-4, IL-6 and IL-8, IL-10, GM-CSF, TNF-α, and IFN-γ) and lipid mediators (PGE2, LTB4, RvD1, and Mar1), in patients with recently diagnosed pulmonary TB and healthy controls’ EBC and serum. The TB patients showed 36% lower GSH levels, and 2-, 1.4-, 1.1-, and 50-fold higher levels of 8-isoprostanes, nucleosomes, IL-6, and LTB4, respectively, in EBC. There was no correlation between EBC and serum, highlighting the importance of measuring local biomarkers. Quantitation of local inflammatory molecules and redox states in EBC would help find biomarkers useful for pharmacological and follow-up studies in pulmonary tuberculosis.

عباسعلی آهنگر, محمدحسین سالاری فر, ستاره مجاهدی رضائیان et al.

چکیدهمقدمه و اهداف اوتیسم یک اختلال عصبی-رشدی است که مهارت‌های شناختی و زبانی فرد را تحت تاثیر قرار می‌دهد. از آنجایی‌که زندگی اجتماعی انسان به توانایی-های شناختی و زبانی بسیار وابسته است، به‌کارگیری این توانایی‌ها عامل مهمی در رشد و پیشرفت انسان است. تولید و درک گفتمان روایتی به‌عنوان یکی از سطوح زبانی، مستلزم به‌کارگیری توانایی‌های شناختی و زبانی است. با توجه به این حقیقت ‌که خط سیر زمان و نحوه بیان آن یکی از مولفه‌های اصلی شکل‌گیری روایت به‌شمار می‌رود، مبحث زمان می‌تواند در گفتمان روایتی برای کودکان دارای اختلال اوتیسم چالش‌برانگیز باشد. بنابراین هدف پژوهش حاضر، بررسی بازنمایی برخی مولفه‌های زمان همچون نمود شامل نمود کامل و نمود ناقص و زمینه‌سازی شامل پیش‌زمینه و پس‌زمینه در گفتمان روایتی کودکان دارای اختلال اتیسم با عملکرد بالا است.مواد و روش هادر این پژوهش بررسی چگونگی بازنمایی مولفه‌های نمود و زمینه‌سازی در گفتمان روایتی کودکان دارای اختلال اوتیسم با عملکرد بالا و کودکان هنجار فارسی زبان بر اساس الگوی هیکمن و تقسیم‌بندی‌های رابرتس، برجسته دلفروز و جهانی صورت پذیرفت. به این منظور، 20 کودک اوتیسم با عملکرد بالا (پسر با سن تقویمی 7 تا 11 سال) و 20 کودک هنجار (پسر با سن تقویمی 7 تا 11 سال) در آزمون تولید گفتمان روایتی براساس دو داستان تصویری «اسب» و «گربه» ارائه شده توسط هیکمن شرکت داشتند. داده‌های گردآوری شده ابتدا بررسی و توصیف شد. سپس، با به‌کارگیری آزمون یو من-ویتنی مورد تجزیه و تحلیل قرار گرفت. یافته هایافته ها نشان داد تفاوت معناداری در بازنمایی مولفه نمود کامل و زمینه‌سازی توسط کودکان دارای اختلال اوتیسم با عملکرد بالا و کودکان هنجار وجود داشت(05/0= P). به بیان دیگر، کودکان دارای اختلال اوتیسم با عملکرد بالا کمتر از کودکان هنجار از نمود کامل استفاده کردند و همچنین، کودکان دارای اختلال اوتیسم با عملکرد بالا در هنگام روایت و انتقال اطلاعات اصلی به‌عنوان پیش‌زمینه عملکرد ضعیف‌تری را در مقایسه با کودکان هنجار به نمایش گذاشتند، در حالی‌که، این کودکان در مقایسه با کودکان هنجار اطلاعات حاشیه‌ای و جانبی یا پس زمینه بیشتری را تولید کردند.نتیجه‌گیریبه نظر می‌رسد عملکرد ضعیف کودکان دارای اختلال اوتیسم با عملکرد بالا در مقایسه با کودکان هنجاردر بازنمایی برخی مولفه‌های زمان همچون نمود و زمینه‌سازی در گفتمان روایتی با نقائص شناختی و زبانی آنها ارتباط دارد.

Hayahito Ishikawa, Masahiro Takeshima, Hiroyasu Ishikawa et al.

Abstract Pregabalin is a drug that can cause psychiatric symptoms via pregabalin withdrawal. Prior reports on pregabalin withdrawal have mainly focused on cases with pregabalin dependence or abuse, and little attention has been paid to patients who are prescribed regular doses of pregabalin. Herein, we report three cases of pregabalin withdrawal in patients without psychiatric disorders, taking regular doses of pregabalin, who developed psychiatric symptoms such as insomnia and anxiety after abrupt discontinuation of pregabalin. In addition, we conducted a systematic review of six case reports (previous studies) of pregabalin withdrawal under regular doses of pregabalin. Among the six cases, three patients had no comorbid mental or substance use disorders, the dose of pregabalin ranged from 150 to 600 mg/d, and the duration of pregabalin use ranged from a few weeks to many years. Of these six cases of pregabalin withdrawal, five had psychopathological symptoms, three had vegetative symptoms, and three had neurologic and physical complications. We concluded that since pregabalin withdrawal can occur even with regular doses and short‐term use, clinicians must carefully reduce pregabalin doses when reducing or discontinuing treatment, paying close attention to withdrawal symptoms. Our case series sheds light on the scant evidence from previous research on physical dependence in patients who are taking regular doses of pregabalin. Furthermore, our cases were also valuable in demonstrating that pregabalin withdrawal can occur even after a relatively short period of 2 months.

Evangelos Terpos, Marianna Politou, Theodoros N. Sergentanis et al.

We evaluated the antibody responses in 259 potential convalescent plasma donors for Covid-19 patients. Different assays were used: a commercial ELISA detecting antibodies against the recombinant spike protein (S1); a multiplex assay detecting total and specific antibody isotypes against three SARS-CoV-2 antigens (S1, basic nucleocapsid (N) protein and receptor-binding domain (RBD)); and an in-house ELISA detecting antibodies to complete spike, RBD and N in 60 of these donors. Neutralizing antibodies (NAb) were also evaluated in these 60 donors. Analyzed samples were collected at a median time of 62 (14–104) days from the day of first symptoms or positive PCR (for asymptomatic patients). Anti-SARS-CoV-2 antibodies were detected in 88% and 87.8% of donors using the ELISA and the multiplex assay, respectively. The multivariate analysis showed that age ≥50 years (<i>p</i> < 0.001) and need for hospitalization (<i>p</i> < 0.001) correlated with higher antibody titers, while asymptomatic status (<i>p</i> < 0.001) and testing >60 days after symptom onset (<i>p</i> = 0.001) correlated with lower titers. Interestingly, pseudotype virus-neutralizing antibodies (PsNAbs) significantly correlated with spike and with RBD antibodies by ELISA. Sera with high PsNAb also showed a strong ability to neutralize active SARS-CoV-2 virus, with hospitalized patients showing higher titers. Therefore, convalescent plasma donors can be selected based on the presence of high RBD antibody titers.