Post-marketing safety of anti-IL-5 monoclonal antibodies (mAbs): an analysis of the FDA Adverse Event Reporting System (FAERS).

BACKGROUND: Anti-IL-5 monoclonal antibodies (mAbs) targeting IL-5 or IL-5 R α (including mepolizumab, benralizumab, and reslizumab) are widely used for inflammatory diseases such as asthma, eosinophilia, and polyangiitis. However, real-world data regarding its safety in a large sample population are incomplete. So, we evaluated the safety of anti-IL-5 mAbs by pharmacovigilance analyzes based on related adverse events (AEs) from the FDA Adverse Event Reporting System (FAERS). METHODS: In disproportionality analysis, four algorithms were employed to detect the signals of anti-IL-5 mAbs from the FAERS between 2016 and 2022. In addition, we also used MYSQL 8.0, Navicat Premium 15, and Microsoft EXCEL 2019 to analyze the signals of anti-IL-5 mAbs systematically. RESULTS: There are 9,476,351 reports collected from the FAERS database, of which 22,174 reports listed anti-IL-5 mAbs as the 'primary suspected (PS)' drug. A total of 59 (20 new signals, mepolizumab) and 62 (19 new signals, benralizumab) significant disproportionality preferred terms (PTs) conforming to the four algorithms were retained synchronously. Finally, we detected that the anti-IL-5 mAbs-induced AEs occurred in 31 organ systems (mepolizumab) and 30 organ systems (benralizumab). For mepolizumab and reslizumab, unexpected and new significant PTs of AEs were found, such as asthmatic crisis, chronic obstructive pulmonary disease (COPD), pneumonia, COVID-19, pneumothorax, adrenal insufficiency and so on. Notably, the risk signal of asthmatic crisis for mepolizumab was stronger than benralizumab (ROR 108.04 [95%CI, 96.09-121.47] vs 26.83 [95%CI, 18.91-38.06]). Comparing with mepolizumab and benralizumab, we found the proportion of serious adverse events in mepolizumab was both greater than benralizumab in each age group (≤20, 20-65, and ≥ 65). The median onset time of mepolizumab was 280 days (interquartile range [IQR] 1-367 days). CONCLUSION: Analysis of FAERS data identified anti-IL-5 mAbs-associated AEs, and our findings supported continuous clinical monitoring, pharmacovigilance, and further studies of anti-IL-5 mAbs. In addition, clinicians may be more aware of the limitations of use in package inserts of anti-IL-5 mAbs: Not for relief of acute bronchospasm or status asthmaticus. Because of some limitations in the FAERS such as self-reports from patients and other confounding factors, the safety of anti-IL-5 mAbs needed more studies in different dimensions, especially the risk of cancer.

Ocular adverse events of cenegermin used in neurotrophic keratopathy: an analysis of the FDA adverse event reporting system database.

BACKGROUND: Cenegermin, a recombinant human nerve growth factor, is an orphan drug approved for neurotrophic keratitis. The safety information on the label is incomplete, and the adverse reactions noted are mostly mild and tolerable. However, the occurrence of painful epithelial plagues and irreversible corneal deposits after cenegermin usage have been reported. Real-world data on long-term ocular safety are lacking. We aimed to assess the cenegermin-associated eye safety profile in the FDA pharmacovigilance database. METHODS: The signals of cenegermin-related ocular adverse events (AEs) from 2018 to 2022 were quantified using the reporting odds ratio (ROR) and information component (IC). The grading system was used to prioritize the signals. RESULTS: We identified 3288 cases of cenegermin-related ocular AEs and 56 positive ocular-related signals. Fifty unexpected signals of ocular AE were identified. Eye ulcer was classified as a designated medical event. Twenty AEs, including corneal perforation, eye infection, corneal deposits, and eye inflammation, were recognized as important medical event. The median onset time for ocular AEs was 6 days (interquartile range [IQR]: 1-29 days). CONCLUSION: This study revealed new cenegermin-related ocular AE signals. Clinical practice requires close monitoring to early identify and manage adverse reactions that may cause occurrence of serious irreversible consequences.

Design, optimization, and evaluation for a long-time-released transdermal microneedle delivery system containing estradiol.

Transdermal drug delivery systems (TDDS) have drawbacks such as poor absorption, low blood concentration, and delayed effects. Dissolving microneedle has sharp tips and short length, which overcome patients' pain and improve transdermal efficiency but has low mechanical strength and drug loading capacity. This study thereby proposes a microemulsion-encapsulated and long-time-released transdermal microneedle (MN) delivery system with estradiol (Es) as the model drug. The microemulsion (ME) was optimized by utilizing the pseudo-ternary phase diagram and D-optimal mixture design. The estradiol microemulsion-encapsulated microneedle (Es-ME-MN) was optimized by Box-Behnken design and prepared by freeze-thaw method. The Es-ME-MN obtained was characterized and evaluated through a large variety of studies. Es-ME-MN had sufficient mechanical strength to pierce skin and was safe enough, the length of which was 600 µm, and the Es content was 177.12 ± 0.72 µg/patch without drug-excipient chemical interaction. In vitro permeation study showed that Es-ME-MN has a higher transdermal efficiency and lower retention capacity than commercial estradiol patch and conventional MN. Es plasma concentration began to increase at 3 h and remained at 12.98-23.52 ng/mL until 72 h by pharmacokinetic experiments in the Es-ME-MN group. Es-ME-MN rapidly achieves effective blood concentrations through needle puncture and microemulsion delivery and maintains blood concentrations through the baseplate long-time release. Microemulsion-encapsulated, organic solvent-free, and long-time-released transdermal microneedle will make progress and provide a new idea for transdermal delivery of lipophilic drugs.

WITHDRAWN: Long-time-released Transdermal Microneedle Delivery System.

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A disproportionality analysis of adverse events associated to pertuzumab in the FDA Adverse Event Reporting System (FAERS).

BACKGROUND: Pertuzumab is widely used for the treatment of HER2 + breast cancer. But its safety in the real world should be continuously monitored. So, we evaluated the safety of pertuzumab by pharmacovigilance analyze based on related adverse events (AEs) from the FDA Adverse Event Reporting System (FAERS) and find whether potential or uncertain adverse events were present. METHODS: In disproportionality analysis, four algorithms were employed to detect the signals of pertuzumab from the FAERS between 2012 and 2022. In addition, we also used MYSQL 8.0, Navicat Premium 15, and Microsoft EXCEL 2019 to analyze the potential and high-ROR (reporting odds ratio) signals of pertuzumab. We also collected the onset times of pertuzumab-associated AEs. RESULTS: From January 2012 to December 2022, there are 39,190,598 AEs reported from the FAERS database, of which 14,707 AEs listed pertuzumab as the 'primary suspected (PS)' drug. A total of 115 (46 potential) significant disproportionality preferred terms (PTs) conforming to the four algorithms were retained. Finally, we detected that the pertuzumab-induced AEs occurred in 12 organ systems. For pertuzumab, unexpected and significant PTs of AEs were found, including but not limited to below PTs: haematotoxicity, cardiotoxicity, cardiomyopathy, mitral valve incompetence, tachycardia, intestinal perforation, hemorrhoids, erysipelas, dehydration, pneumonitis, skin toxicity, onychomadesis, cyanosis, and circulatory collapse. We found there were 9 strong signals (5 potential safety signals) and 68 medium intensity signals (21 potential safety signals) according to IC025 (information component). The potential strong signals (IC025 > 3.0) were myelosuppression, cardiotoxicity, cardiac dysfunction, ejection fraction decreased, interstitial lung disease, and onychomadesis. Excluding unreported or unreasonable onset time reports, a total of 2016 AEs reported onset time and the median onset time was 117 days (4, 96), as median (Q1, Q3). Notably, most of the all AEs (n = 1133, 56%) and cardiac-related events (n = 405, 53%) all occurred within one month after pertuzumab therapy. CONCLUSION: Analysis of FAERS data identified pertuzumab-associated AEs, and our findings supported continuous clinical monitoring, pharmacovigilance, and further studies of pertuzumab. A significant association was detected between pertuzumab and some potential adverse events which should be regarded with some care. We have to pay attention to the first month after pertuzumab therapy and prepare emergency measures, especially for the elderly and patients with cardiovascular diseases.

Medial malleolar window approach for varus-type tibial pilon fractures: a retrospective study.

PURPOSE: Choosing a suitable surgical approach is crucial and challenging for type C pilon fractures. This article aims to explore the clinical efficacy of the medial malleolar window approach for varus-type tibial pilon fractures. METHODS: A retrospective analysis was conducted on 38 patients with type C varus-type pilon fractures treated between May 2018 and June 2021. In total, 16 cases underwent surgical treatment through the medial malleolar window approach and 22 cases were treated with the traditional anteromedial approach combined with a posterior approach. The operation time, hospitalization time, fracture healing time, the American Orthopedic Foot and Ankle score, Visual Analogue Scale, and complications were recorded to comprehensively evaluate the clinical efficacy of the technique. Fracture reduction quality was evaluated using the criteria proposed by Burwell and Charnley. RESULTS: All patients were followed up. No patients presented delayed union or nonunion. Compared with the conventional approach, the medial malleolar window approach had the advantage of better clinical effect recovery and better fracture reduction (P < 0.05). Meanwhile, the medial malleolar window approach had a shorter operation time, although the statistics suggest no significant difference with the control group. No implant exposure or infection occurred. There was good wound healing at two weeks after surgery in all but two cases. Local wound edge necrosis developed in one case in the medial malleolar window approach group, and the wound could not be closed at one stage in another case in the conventional group because of excessive tension, requiring secondary closure. CONCLUSION: The medial malleolar window approach provides excellent exposure to type C pilon fractures, allowing for satisfactory fracture reduction and functional rehabilitation. The medial window approach is recommended for varus-type pilon fractures, which can effectively avoid a posterior incision and reduce the operation time.

Adding genistein or luteolin decreased the yield of citrinin and without reducing pigments in yam solid-fermentation by Monascus.

BACKGROUND: Chinese yam fermented by Monascus, namely red mold dioscorea (RMD), has the potential of treating diseases. However, the production of citrinin limits the application of RMD. In the present study, the fermentation process of Monascus was optimized by adding genistein or luteolin to reduce citrinin yield. RESULTS: The results showed that citrinin in 25 g of Huai Shan yam was reduced by 48% and 72% without affecting the pigment yield by adding 0.2 g of luteolin or genistein, respectively, to a 250-mL conical flask after fermentation for 18 days at 28 °C, whereas the addition of luteolin increased the content of yellow pigment by 1.3-fold. Under optimal conditions, citrinin in 20 g of iron bar yam decreased by 55% and 74% after adding 0.2 g of luteolin or genistein. Luteolin also increased yellow pigment content by 1.2-fold. Ultra HPLC coupled to quadrupole time-of-flight mass spectrometry was used for the preliminary analysis of Monascus fermentation products. It was found that the amino acid types in RMD are similar to those in yams, but there are fewer polysaccharides and fatty acids. CONCLUSION: The results obtained in the present study showed that the addition of genistein or luteolin could reduce citrinin on the premise of increasing pigment yield, which laid a foundation for the better use of yams in Monascus fermentation. © 2023 Society of Chemical Industry.

Post-traumatic cauda equina nerve calcification: A case report.

BACKGROUND: Post-traumatic cauda equina nerve calcification is extremely rare in clinical practice, and its etiology, pathogenesis, treatment and prognosis are unclear. There are few studies and reports on Post-traumatic cauda equina nerve calcification, and this review reports a case of Post-traumatic cauda equina nerve calcification for reference. CASE SUMMARY: A 52-year-old patient presented to our hospital with a history of lumbar spinal stenosis and a lumbar vertebral fracture caused by trauma. The patient's right lower limb had weakness in hip flexion, knee extension and plantarflexion with muscle strength grade 3, right ankle dorsiflexion and thumb dorsiflexion with muscle strength grade 0. The patient's skin sensation below the right knee plane disappeared. The patient's Computed tomography (CT) data showed signs of cauda equina nerve calcification and the terminal filaments in the plane of the third to fifth lumbar vertebrae. After treatment the patient's symptoms were slightly relieved. CONCLUSION: We provide an extremely rare case of Post-traumatic cauda equina nerve calcification and offer a conservative treatment plan. However, the etiology, mechanism and treatment of Post-traumatic cauda equina nerve calcification are still unclear. This requires scholars to conduct more research and exploration in this area.

Contribution of Quercetin to the Composition and Antioxidant Properties of Monascus Exopolysaccharides.

Exopolysaccharides are important metabolites of Monascus with healthy activities. However, the low production level limits their applications. Hence, the aim of this work was to increase the yield of exopolysaccharides (EPS) and optimize liquid fermentation by adding flavonoids. The EPS yield was optimized via both medium composition and culture conditions. The optional fermentation conditions achieved for EPS production of 7.018 g/L were 50 g/L sucrose, 3.5 g/L yeast extract, 1.0 g/L MgSO4·7H2O, 0.9 g/L KH2PO4, 1.8 g/L K2HPO4·3H2O, 1 g/L quercetin, and 2 mL/L Tween-80, with pH 5.5, inoculum size 9%, seed age 52 h, shaking speed 180 rpm, and fermentation culture 100 h, respectively. Furthermore, the addition of quercetin increased EPS production by 11.66%. The results also showed little citrinin residue in the EPS. The exopolysaccharides' composition and antioxidant capacity of quercetin-modified exopolysaccharides were then preliminarily investigated. The addition of quercetin changed the composition of the exopolysaccharides and the molecular weight (Mw). In addition, the antioxidant activity of Monascus exopolysaccharides was monitored using 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-Azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS+), and -OH. Monascus exopolysaccharides have good scavenging ability of DPPH and -OH. Furthermore, quercetin increased the scavenging ABTS+ ability. Overall, these findings provide a potential rationale for the application of quercetin in improving the EPS yield.

Diagnostic value of ultrasound evaluation of major salivary glands for Sjögren's syndrome based on the novel OMERACT scoring system.

OBJECTIVE: The novel Outcome Measures in Rheumatology Clinical Trials (OMERACT) scoring system was used to evaluate the diagnostic effectiveness of major salivary gland ultrasonography (SGUS) for Sjögren's syndrome (SS). MATERIALS AND METHODS: SGUS was performed on the parotid glands (PGs) and submandibular glands of 242 patients (145 patients with SS and 97 patients without SS) using the OMERACT scoring system (grade 0-3). We also evaluated the association of SGUS scores with unstimulated whole salivary flow rate (UWSF), stimulated whole salivary flow rate (SWSF), and labial salivary gland biopsy (LSGB) results. RESULTS: The SGUS scores were significantly higher for the SS group than for the non-SS group (p < 0.001). Using a cutoff value of 8 for the total score yielded the highest sensitivity (76%), specificity (90%), and area under the receiver operating characteristic curve (AUC, 0.828). The correlation between SGUS scores and salivary gland function was moderate to good. A cutoff value of 10 for the total score was more effective in predicting SWSF outcomes than UWSF outcomes (sensitivity: 73% > 58%, specificity: 98% > 87%, and AUC: 0.856 > 0.723). The association of OMERACT scores with LSGB results was fair to moderate. Among 61 anti-SSA-negative patients, 17 had positive PG scores (including ten SS and seven non-SS patients), and 44 had negative PG scores (including 37 non-SS and seven SS patients). CONCLUSION: The OMERACT scoring system had good sensitivity and excellent specificity, demonstrating excellent diagnostic potential for SS and efficacy in assessing salivary gland function. Negative SGUS results may help reduce unnecessary biopsies in anti-SSA-negative patients.

Safety and Efficacy of Combined Imbrication Axle Reconstruction and Z-Type Titanium Plate Fixation for Hinge Fracture Displacement During Open-Door Laminoplasty.

BACKGROUND: Open-door laminoplasty is a classical decompression method used to treat cervical spondylotic myelopathy. However, hinge fracture displacement (HFD) is a common occurrence during this procedure. The current study aimed to investigate the safety and efficacy of a combined imbrication axle reconstruction and Z-type titanium plate fixation method for HFD during open-door laminoplasty. METHODS: In total, 617 patients with cervical spondylotic myelopathy who underwent C3-C7 open-door laminoplasty from March 2015 to October 2018 were included in this retrospective study. Overall, 73 patients developed HFD during surgery. Of these, 43 underwent combined imbrication axle reconstruction and Z-type titanium plate fixation (IRZF group) and 30 underwent traditional titanium plate fixation (TF group). Data such as the operative time, intraoperative blood loss volume, and distribution of fractured hinges were recorded. Both groups were compared in terms of improvement in neurologic function, cervical curvature index, hinge fusion rate, incidence of C5 palsy, severity of axial symptoms, and development of complications. RESULTS: The operative time and intraoperative blood loss were slightly higher in the IRZF group than in the TF group; however, the differences were not significant (p > 0.05). Furthermore, there was no significant difference between the groups in terms of the number of fractured segments and the distribution of fractured hinges (p > 0.05). The cervical curvature index did not decline in the two groups (p > 0.05). The IRZF group had a higher hinge fusion rate than the TF group at 3 (79.6 vs. 57.1%) and 12 (93.9 vs. 74.3%) months postoperatively (p < 0.05). There was no significant difference in the incidence of C5 palsy between the two groups (9.3 vs. 6.7%; p > 0.05). However, the TF group had more severe axial symptoms than the IRZF group (p < 0.05). The neurologic function of the two groups increased postoperatively as per the Japanese Orthopaedic Association scoring system (p < 0.05). Nevertheless, there was no significant difference in terms of neurologic function at any observational time point (p > 0.05). One patient in the TF group with hinge nonunion underwent laminectomy due to lamina displacement into the spinal canal and nerve root compression. CONCLUSION: In patients with HFD, IRZF facilitates a more intimate contact between the lamina and the lateral mass and, therefore, achieves fractured hinge fusion without additional surgical trauma. This technical improvement can significantly promote neurologic recovery, decrease the severity of axial symptoms, and prevent the development of spinal cord or nerve root recompression.

Population Pharmacokinetic Analysis of Valsartan in Healthy Chinese Subjects.

The study was conducted to establish a population pharmacokinetic (PPK) model of valsartan in Chinese healthy subjects and investigate potential covariate impacts on the pharmacokinetics (PK) parameters. Data from a bioequivalence study with 78 Chinese healthy subjects were retrospectively analyzed to develop a PPK model of valsartan. Phoenix NLME 8.1 was used to build a PPK model and quantify the effects of covariates, such as demographic data and biochemical, on the PK parameters of valsartan. For the healthy Chinese population, valsartan conformed to the two-compartment model with an absorption lag time. In the final PPK model, food affected the absorption rate constant, while aspartate aminotransferase, alanine aminotransferase, and creatinine affected the clearance of the central compartment. The final PPK model was verified to be reproducible, and it can be used to evaluate the PK parameters. This is the first research describing the PPK profile of valsartan in healthy Chinese subjects, and it is expected to provide relevant PK parameters for further study of valsartan.

Effects of the cage height and positioning on clinical and radiographic outcome of lateral lumbar interbody fusion: a retrospective study.

BACKGROUND: The proper cage positioning and height in lateral lumbar interbody fusion (LLIF). This study evaluated their effects on clinical and radiographic outcome measures in patients undergoing LLIF. METHODS: This single-center retrospective study analyzed the characteristics and perioperative data of patients who underwent LLIF between January 2019 and December 2020. Radiographic (lumbar lordosis [LL], foraminal height, disc height [DH], segmental angle [SA], cross-sectional area [CSA] of thecal sac) and clinical (Oswestry Disability Index and Visual Analog Scale) outcomes were assessed preoperatively, postoperatively, and at the last follow-up. The effects of cage height and positioning on these parameters were also investigated. RESULTS: With a mean follow-up of 12.8 months, 47 patients with 70 operated level were analyzed. Data demonstrated that postsurgical clinical and radiographic outcome measures were significantly better than before surgery(P < 0.05). Cage height and positioning showed no significant difference with regarding to clinical outcome(P > 0.05). Subgroup analysis of the cage positioning showed that DH and SA were better restored by the final follow-up in patients with anteriorly placed cages than those with posteriorly placed cages (P < 0.05). Cages of posterior position showed significantly upgrading cage subsidence (P = 0.047). Cage height subgroup analysis showed that the preoperative forminal height, DH, and SA in the 11-mm cage group were significantly lower than in the 13-mm cage group; however, these parameters were comparable in the two groups postoperatively and at the final follow-up (P > 0.05). Furthermore, the postoperative and final follow-up degrees of DH, SA, and LL have improved in the 11-mm cage group more than the 13-mm cage group. The preoperative, postoperative, and final follow-up LL values in the 11-mm cage group were lower than in the 13-mm cage group(P < 0.01). CONCLUSIONS: Cage height and positioning did not affect the clinical outcomes in the present study. Cages in anterior position showed better restoration in DH, SA and decreased the incidence of cage subsidence. A comparable radiographic outcome can be achieved by inserting an appropriate cage height based on preoperative radiography.

ACR TI-RADS classification combined with number of nodules, halo features optimizes diagnosis and prediction of follicular thyroid cancer.

OBJECTIVES: To investigate the application value of The American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS) category combined with other ultrasound features of nodules in distinguishing follicular thyroid carcinoma (FTC) from thyroid follicular adenoma (FTA). METHODS: We collected and retrospectively analyzed clinical and ultrasound data for 118 and 459 patients with FTCs and FTAs, respectively, at our hospital. Next, we used ACR TI-RADS classification combined with other ultrasound features of nodules to distinguish FTC from FTA. Multivariate Logistic regression was used to screen independent risk factors for FTC, which were subsequently used to construct a nomogram for predicting FTC. RESULTS: ACR TI-RADS categories 4 and 5, unilateral multiple nodules, and halo thickness≥2 mm were independent risk factors for FTC. ACR TI-RADS category combined with number of nodules, halo features of the nodule was a significantly better prediction model for FTC diagnosis (AUC = 0.869) than that of ACR TI-RADS classification alone (AUC = 0.756). CONCLUTIONS: Clinicians need to pay attention to the halo of nodules when distinguishing FTA from FTC. Notably, ACR TI-RADS combined with other nodule ultrasound features has superior predictive performance in diagnosis of FTC compared to ACR TI-RADS classification alone, thus can provide an important reference value for preoperative diagnosis of FTC.

Combination of Body Mass Index and Fasting Blood Glucose Improved Predictive Value of New-Onset Prediabetes or Diabetes After Acute Pancreatitis: A Retrospective Cohort Study.

OBJECTIVES: We sought to evaluate whether combining body mass index (BMI) and fasting blood glucose (FBG) can refine the predictive value of new-onset prediabetes/diabetes after acute pancreatitis (NODAP). METHODS: In this retrospective cohort study, we used Kaplan-Meier analysis to compare differences in the NODAP rate among 492 patients with different BMI or FBG levels, or with the combination of these 2 factors mentioned above. RESULTS: In all, 153 of 492 (31.1%) eligible patients finally developed NODAP. According to univariate and multivariate analyses, BMI (hazard ratio, 2.075; 95% confidence interval, 1.408-3.060; P < 0.001) and FBG (hazard ratio, 2.544; 95% confidence interval, 1.748-3.710; P < 0.001) were important predictors of the incidence of NODAP. Subsequently, we divided 492 eligible patients into 3 groups according to the median BMI and FBG values, and found that the NODAP rate in the high-risk group was significantly higher than that in the medium-risk group ( P = 0.018) or the low-risk group ( P < 0.001). CONCLUSIONS: Body mass index and FBG are independent predictors of NODAP. The combination of BMI and FBG can refine the prediction of NODAP and identify candidates for clinical prevention.

Targeted fully endoscopic visualized laminar trepanning approach under local anaesthesia for resection of highly migrated lumbar disc herniation.

PURPOSE: To introduce a new fully endoscopic visualized laminar trepanning approach with a periendoscopic trephine under local anesthesia for resection of highly migrated lumbar disc herniation (LDH) and report the clinical outcomes of one year follow-up. METHODS: Twenty-one patients with highly migrated LDH who underwent percutaneous endoscopic lumbar discectomy via the laminar trepanning approach from June 2019 to August 2020 were retrospectively reviewed. Patient-Reported Outcomes Measurement Information System (PROMIS) Short Forms-Pain Interference (PI) and Physical Function (PF) were selected as outcome measures. The operating duration and complication were documented. RESULTS: The average age of the 21 patients (15 males, 6 females) was 37.8 ± 6.0 years (29-52 years). Disc migration originated from L4/5 in 19 patients, L5/S1 in two patients. The mean operative duration was 54.1 ± 9.0 minutes (42-79 min). All patients were followed up to 12 months after the operation. PROMIS PI T-scores decreased significantly from pre-operatively mean 68.6 ± 2.4 to 54.4 ± 1.9 (P < 0.001) and 47.1 ± 4.3 (P < 0.001) at six weeks and 12 months, respectively. PROMIS PF T-scores improved significantly from pre-operatively mean 26.7 ± 4.7 to 44.3 ± 4.2(P < 0.001) and 58.4 ± 4.0 (P < 0.001) at six weeks and 12 months, respectively. No complications and disc herniation recurrences occurred. CONCLUSION: The targeted full endoscopic laminar trepanning under local anesthesia with a visualized periendoscopic trephine offers a safe, efficient and cost-effective option for the resection of highly migrated LDH.

Comparison studies of ultrasound-guided botulinum toxin injection and balloon catheter dilatation in the treatment of neurogenic cricopharyngeal muscle dysfunction.

BACKGROUND: Cricopharyngeal muscle dysfunction (CPD) management has been challenging in clinical practice. OBJECTIVE: To compare the efficacy and safety of ultrasound-guided botulinum toxin injection and balloon catheter dilatation in treating CPD. METHODS: Forty patients with CPD were randomly divided into two groups, namely the botulinum toxin injection group (BTX group) and balloon dilatation group (BD group). Patients in the BTX group received a single ultrasound-guided injection of 50 units of botulinum toxin type A, while the BD group received dilatation therapy five times per week, consecutively for two weeks. Relative opening percentage of the upper esophageal sphincter (UES), the penetration-aspiration scale (PAS), and the Dysphagia Outcome Severity Scale (DOSS) were evaluated by a videofluoroscopic swallowing study (VFSS) at baseline, 1-month, and 3-months posttreatment. The Functional Oral Intake Scale (FOIS) and Standardized Swallowing Assessment (SSA) were also used to evaluate participants' swallowing function at baseline and the 1-week, 2-week, 1-month, and 3-month follow-ups. RESULTS: A generalized estimating equation (GEE) model revealed the significant main effect for time in UES, PAS, DOSS, FOIS, and SSA compared to baseline (P <0.05), while no group-by-time interactions (except for the PAS assessment) or main effect for treatment was detected among the above multiple variances. No systematic complications or severe adverse effects were noted. CONCLUSION: Both ultrasound-guided botulinum toxin type A injections and balloon dilatation therapy have been proven as safe and effective treatments for CPD patients. Future clinical trials with longer follow-up periods and more participants are warranted.

Detachable string magnetically controlled capsule endoscopy for detecting high-risk varices in compensated advanced chronic liver disease (CHESS1801): A prospective multicenter study.

BACKGROUND: Gastroesophageal varices is a serious complication of compensated advanced chronic liver disease (cACLD). Primary prophylaxis to reduce the risk of variceal hemorrhage is recommended if high-risk varices (HRV) are detected. We performed this study to compare the accuracy, patients' satisfaction and safety of detection of HRV by detachable string magnetically controlled capsule endoscopy (DS-MCCE) with esophagogastroduodenoscopy (EGD) as the reference. METHODS: We prospectively recruited participants with cACLD from 12 university hospitals (11 in China and one in the United Kingdom) between November 2018 and December 2019 (ClinicalTrials.gov, NCT03749954). All participants underwent DS-MCCE, followed by EGD within a week in a blinded fashion. Following endoscopy, and on the same day, participants were asked to fill in a satisfaction questionnaire regarding their experience. FINDINGS: A total of 105 eligible participants were enrolled. With EGD as the reference standard, the concordance index, sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio of DS-MCCE in diagnosis of HRV were 0•90 (95% confidence interval [CI]: 0•83-0•95), 92% (95% CI: 78-98%), 88% (95% CI: 78-95%), 80% (95% CI: 70-92%), 95% (95% CI: 90-100%), 7•91 (95% CI: 4•10-15•30), and 0•09 (95% CI: 0•03-0•30), respectively. The kappa score of 0•78 (95% CI: 0•65-0•90) suggested substantial agreement between DS-MCCE and EGD. Moreover, in participants undergoing EGD without sedation, the satisfaction of DS-MCCE was significantly better than that of EGD (p < 0•0001, d = 1•15 [95%CI: 0•88-1•42]). All participants confirmed the excretion of the capsule, and no adverse events occurred. INTERPRETATION: DS-MCCE is an accurate alternative to EGD for detecting HRV in cACLD, which is safe and associated with better satisfaction. FUNDING: A full list of funding can be found in the Funding Support section.

Full Endoscopic Lumbar Foraminoplasty with Periendoscopic Visualized Trephine Technique for Lumbar Disc Herniation with Migration and/or Foraminal or Lateral Recess Stenosis.

PURPOSE: To introduce a newly designed periendoscopic visualized trephine system for foraminoplasty in treating lumbar disc herniation with migration and/or foraminal or lateral recess stenosis, and report early clinical outcomes evaluated by the Patient-Reported Outcomes Measurement Information System (PROMIS). METHODS: A total of 25 patients who underwent transforaminal endoscopic lumbar discectomy with foraminoplasty using a periendoscopic visualized trephine from June 2019 to January 2020 were retrospectively reviewed. PROMIS pain interference and physical function were selected as outcome measures. RESULTS: The average age of the 25 patients (16 males, 9 females) was 32.0 ± 7.5 years (20-48 years). All patients were successfully followed up with the mean time of 10.1 ± 2.8 months (6-12 months). PROMIS pain interference scores decreased significantly from mean 67.0 ± 3.4 preoperatively to 37.5 ± 5.4 at the final follow-up (P < 0.01), and PROMIS physical function scores improved significantly from mean 29.2 ± 5.5 preoperatively to 59.3 ± 3.7 at the final follow-up (P < 0.01). No neural or vascular complication occurred. CONCLUSION: Full endoscopic lumbar foraminoplasty with a periendoscopic visualized trephine technique is safe and effective for treating lumbar disc herniation with migration and/or lateral recess or foraminal stenosis, with improved flexibility and convenience and decreased radiation exposure.