BACKGROUND: Disease-modifying therapies have been approved for the treatment of relapsing multiple sclerosis (RMS). The present study aims to examine the safety of teriflunomide in Chinese patients with RMS. METHODS: This non-randomized, multi-center, 24-week, prospective study enrolled RMS patients with variant (c.421C>A) or wild type ABCG2 who received once-daily oral teriflunomide 14 mg. The primary endpoint was the relationship between ABCG2 polymorphisms and teriflunomide exposure over 24 weeks. Safety was assessed over the 24-week treatment with teriflunomide. RESULTS: Eighty-two patients were assigned to variant ( n  = 42) and wild type groups ( n  = 40), respectively. Geometric mean and geometric standard deviation (SD) of pre-dose concentration (variant, 54.9 [38.0] μg/mL; wild type, 49.1 [32.0] μg/mL) and area under plasma concentration-time curve over a dosing interval (AUC tau ) (variant, 1731.3 [769.0] μg∙h/mL; wild type, 1564.5 [1053.0] μg∙h/mL) values at steady state were approximately similar between the two groups. Safety profile was similar and well tolerated across variant and wild type groups in terms of rates of treatment emergent adverse events (TEAE), treatment-related TEAE, grade ≥3 TEAE, and serious adverse events (AEs). No new specific safety concerns or deaths were reported in the study. CONCLUSION: ABCG2 polymorphisms did not affect the steady-state exposure of teriflunomide, suggesting a similar efficacy and safety profile between variant and wild type RMS patients. REGISTRATION NCT04410965, https://clinicaltrials.gov .
Humans ; Crotonates/adverse effects* ; Toluidines/adverse effects* ; Nitriles ; Hydroxybutyrates ; Female ; Male ; Adult ; ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics* ; Middle Aged ; Multiple Sclerosis, Relapsing-Remitting/genetics* ; Prospective Studies ; Young Adult ; Neoplasm Proteins/genetics* ; East Asian People

[Abstract] [Objective] To assess the effect of a centrifugal haemocyte separator on platelet counts in patients with neurological immune-mediated disorders during/after therapeutic plasma exchange (TPE). [Methods] This study included 189 patients (108 females and 81 males) who were treated in the department of neurology at Huashan Hospital, Fudan University, from March 2021 to March 2022. A total of 820 TPE treatments were carried out. Each patient received 2 to 5 TPEs, with each TPE amounting to the patient's plasma volume. The peripheral blood cell counts of the patients were evaluated before TPE and after 2 to 5 TPEs. [Results] The duration of a single TPE in this study was 94(84,107) minutes, and the actual volume of a single TPE replacement was 2 456(2 142, 2 785) mL. The number of patients who underwent TPE for 2, 3, 4, and 5 sessions was 17, 28, 18, and 126, respectively. The platelet (PLT) counts of the patients before and after the TPE were 195×10⁹/L (range:150 to 245) and 220×10⁹/L (range:170 to 270), respectively (P<0.05). Consequently, the overall PLT counts exhibited a significant decrease from baseline following TPE, yet the PLT counts remained within the normal range after TPE. Spearman's correlation analysis indicated that platelet loss did not correlate with the duration of TPE (ρ=0.037), the age of the patient (ρ=0.015), or the volume of the single replacement fluid (ρ=0.034), P>0.05, weakly correlated with the number of TPE sessions (ρ=0.017), and moderately correlated with the PLT counts before TPEs (ρ=0.446). [Conclusion] The TPE procedure exhibited a measurable impact on the patients' platelet levels, but the platelet counts remained within the normal range, therefore did not interfere with the patients' subsequent treatment protocols. The decrease in platelet level was correlated with the baseline platelet level before treatment and the number of TPE sessions.

AIM: To assess the efficacy of Quyin Koufuye in different types of psoriasis vulgaris and analyzes the relationship between efficacy and various disease-related factors, as well as its complementary role in biologic therapy. METHODS: This study included a total of 396 patients with psoriasis. Based on the patient history, participants were categorized into the biologics group (n=98), Quyin Koufuye-assisted biologics group (n=62), and Quyin Koufuye monotherapy group (n=236). Patient history data were collected, including gender, duration of illness, disease type, initial site of onset, degree of itching, recurrence status and time, smoking habits, joint pain, family history of psoriasis, nail damage, treatment plan, and PASI/BSA scores. A retrospective analysis was conducted to identify factors influencing the efficacy of Quyin Koufuye and to analyze its combined effects with biologics. RESULTS: Combining Quyin Koufuye with biologics significantly boosted the PASI90 response rate to 72.6% (P=0.014). Responders to PASI50 with Quyin Koufuye experienced longer recurrence intervals (> 6 months) than non-responders (50% vs. 33.6%, P= 0.045). Influencing factors included psoriasis-affected body surface area (OR=0.960, P=0.000), prolonged smoking history (OR=2.10, P=0.046), and psoriasis type (OR=2.47, P=0.015). CONCLUSION: This study underscores the synergy of Quyin Koufuye and biologics in treating psoriasis, particularly for longer recurrence intervals-factors like smoking history, psoriasis type, and affected body surface area impact Quyin Koufuye's efficacy.

Methods: Preoperatively, all 160 patients with OVCFs underwent pressure-pain threshold (PPT), temporal summation (TS), conditioned pain modulation (CPM), and imaging assessments. Pain intensity and pain-related disability were evaluated before and after PVP. Results: Preoperatively, patients with OVCFs had lower PPTs in both local pain and pain-free areas and lower CPM and higher TS in pain-free areas than healthy participants (p<0.05). Unlike patients with acute fractures, patients with subacute/chronic OVCFs showed higher TS with or without lower CPM in the pain-free area compared with healthy participants (p<0.05). Postoperatively, RBP occurred in 17 of 160 patients (10.6%). All preoperative covariates with significant differences between the RBP and non-RBP groups were subjected to multivariate logistic regression, showing that intravertebral vacuum cleft, posterior fascia edema, numeric rating pain scale scores for low back pain at rest, and TS were independently associated with RBP (p<0.05). Conclusions Augmented central pain processing may occur in patients with OVCFs, even in the subacute stage, and this preexisting CS may be associated with RBP. Preoperative assessment of TS in pain-free areas may provide additional information for identifying patients who may be at risk of RBP development, which may be beneficial for preventing this complication.

Humans ; Gemcitabine ; Neoplasms

BACKGROUND: This study aimed to develop a comprehensive instrument for evaluating and ranking clinical practice guidelines, named Scientific, Transparent and Applicable Rankings tool (STAR), and test its reliability, validity, and usability. METHODS: This study set up a multidisciplinary working group including guideline methodologists, statisticians, journal editors, clinicians, and other experts. Scoping review, Delphi methods, and hierarchical analysis were used to develop the STAR tool. We evaluated the instrument's intrinsic and interrater reliability, content and criterion validity, and usability. RESULTS: STAR contained 39 items grouped into 11 domains. The mean intrinsic reliability of the domains, indicated by Cronbach's α coefficient, was 0.588 (95% confidence interval [CI]: 0.414, 0.762). Interrater reliability as assessed with Cohen's kappa coefficient was 0.774 (95% CI: 0.740, 0.807) for methodological evaluators and 0.618 (95% CI: 0.587, 0.648) for clinical evaluators. The overall content validity index was 0.905. Pearson's r correlation for criterion validity was 0.885 (95% CI: 0.804, 0.932). The mean usability score of the items was 4.6 and the median time spent to evaluate each guideline was 20 min. CONCLUSION The instrument performed well in terms of reliability, validity, and efficiency, and can be used for comprehensively evaluating and ranking guidelines.
Reproducibility of Results ; Surveys and Questionnaires ; Practice Guidelines as Topic ; Humans

OBJECTIVES: To explore the changes of elbow flexor muscle strength after musculocutaneous nerve injury and its correlation with needle electromyography (nEMG) parameters. METHODS: Thirty cases of elbow flexor weakness caused by unilateral brachial plexus injury (involving musculocutaneous nerve) were collected. The elbow flexor muscle strength was evaluated by manual muscle test (MMT) based on Lovett Scale. All subjects were divided into Group A (grade 1 and grade 2, 16 cases) and Group B (grade 3 and grade 4, 14 cases) according to their elbow flexor muscle strength of injured side. The biceps brachii of the injured side and the healthy side were examined by nEMG. The latency and amplitude of the compound muscle action potential (CMAP) were recorded. The type of recruitment response, the mean number of turns and the mean amplitude of recruitment potential were recorded when the subjects performed maximal voluntary contraction. The quantitative elbow flexor muscle strength was measured by portable microFET 2 Manual Muscle Tester. The percentage of residual elbow flexor muscle strength (the ratio of quantitative muscle strength of the injured side to the healthy side) was calculated. The differences of nEMG parameters, quantitative muscle strength and residual elbow flexor muscle strength between the two groups and between the injured side and the healthy side were compared. The correlation between elbow flexor manual muscle strength classification, quantitative muscle strength and nEMG parameters was analyzed. RESULTS: After musculocutaneous nerve injury, the percentage of residual elbow flexor muscle strength in Group B was 23.43% and that in Group A was 4.13%. Elbow flexor manual muscle strength classification was significantly correlated with the type of recruitment response, and the correlation coefficient was 0.886 (P<0.05). The quantitative elbow flexor muscle strength was correlated with the latency and amplitude of CMAP, the mean number of turns and the mean amplitude of recruitment potential, and the correlation coefficients were -0.528, 0.588, 0.465 and 0.426 (P<0.05), respectively. CONCLUSIONS The percentage of residual elbow flexor muscle strength can be used as the basis of muscle strength classification, and the comprehensive application of nEMG parameters can be used to infer quantitative elbow flexor muscle strength.
Humans ; Elbow ; Electromyography ; Musculocutaneous Nerve ; Elbow Joint/physiology* ; Muscle, Skeletal ; Muscle Strength ; Peripheral Nerve Injuries