Initial Experience of Long-Term Prophylaxis with Lanadelumab for Hereditary Angioedema in China: A Clinical Observation Study on Six Patients.

INTRODUCTION: Hereditary angioedema (HAE) is a rare genetic disorder caused by deficiency or dysfunction of C1-esterase inhibitor that is characterized by recurrent episodes of bradykinin-mediated edema. Lanadelumab has been the only available first-line therapy for long-term prophylaxis (LTP) of HAE in China since its approval in 2020. The present study aimed to investigate the clinical efficacy and safety of lanadelumab for LTP in Chinese patients. METHODS: A retrospective clinical data were collected for the 6 patients and used to examine the frequency of attack symptoms, disease-related loss of work days, and quality of life before and after LTP with lanadelumab. Health-related quality of life was assessed using the Dermatology Life Quality Index (DLQI) and the Angioedema Quality of Life Questionnaire (AE-QoL). RESULTS: Lanadelumab led to reductions of 97.8% and 98.5% in the attack rate and treated attack rate, respectively. All patients exhibited significant improvements in AE-QoL and DLQI scores (100% reduction rates) during the early treatment period (4 weeks and 2 weeks, respectively) and in missed work days/year (98.9% reduction rate). The efficacy of lanadelumab remained stable during COVID-19 vaccination and infection. No serious/severe treatment-emergent adverse events occurred during lanadelumab treatment. CONCLUSION: This study is the first report that demonstrates the clinical efficacy of lanadelumab and safety of LTP in HAE patients from Chinese mainland. A reasonable dosage plan can ensure a quick and long-lasting protective role of lanadelumab against HAE attacks, during COVID-19 pandemic period.

Efficacy and safety of insulin degludec biosimilar B01411 versus originator insulin degludec in Chinese patients with type 2 diabetes inadequately controlled on oral antidiabetic drugs: a multicenter, randomized, open-label, phase 3 study.

OBJECTIVE: To compare the efficacy and safety of insulin degludec biosimilar B01411 (HS-IDeg) with originator insulin degludec-Tresiba (NN-IDeg) in Chinese patients with type 2 diabetes mellitus (T2DM) who were inadequately controlled on oral antidiabetic drugs (OADs) for at least 3 months. METHODS: This multicenter, randomized, open-label, parallel-group, active-controlled, phase 3 study enrolled 362 participants with T2DM. Participants were stratified according to whether the insulin secretagogue (sulfonylurea or glinide) had been used before the screening and then randomized 1:1 to receive once-daily subcutaneous injections of HS-IDeg (n = 180) or NN-IDeg (n = 182) for 18 weeks. The primary endpoint was the change from baseline in glycated hemoglobin (HbA1c) to week 18. RESULTS: At week 18, the least squares (LS) mean change in HbA1c from baseline was -1.34% (95% CI -1.47 to -1.21) and -1.25% (95% CI -1.38 to -1.12) with HS-IDeg and NN-IDeg, respectively. The LS mean difference (HS-IDeg minus NN-IDeg) in HbA1c at week 18 was -0.09% (95% CI -0.28 to 0.10), demonstrating non-inferiority of HS-IDeg to NN-IDeg. Participants achieving HbA1c <7.0% at week 18 were 34.5% and 29.5% with HS-IDeg and NN-IDeg, respectively. Mean decreases in fasting plasma glucose and standard deviation of blood glucose were similar between both groups. Safety and tolerability, including hypoglycemia, adverse events, and weight change were similar between both groups. No severe hypoglycemia and no death occurred in the study. CONCLUSIONS: HS-IDeg and NN-IDeg demonstrated similar efficacy and safety over 18 weeks of treatment in Chinese patients with T2DM who had inadequate responses to OADs for at least 3 months.

Efficacy of Ixekizumab in Chinese Patients with Moderate-to-Severe Psoriasis and Special Body Area Involvement: Sub-analysis of a Randomized, Double-Blind, Multicenter Phase 3 Study.

INTRODUCTION: Special body area involvement is common in psoriasis and can be challenging to treat. We investigated the efficacy of ixekizumab (IXE) in Chinese patients with moderate-to-severe psoriasis and fingernail, scalp, or palmoplantar involvement. METHODS: A post-hoc sub-analysis of a phase 3 trial, in which patients were randomized to receive placebo, IXE 80 mg every 2 (IXE Q2W) or 4 (IXE Q4W) weeks. At Week 12, patients classified as IXE responders [static Physician's Global Assessment (sPGA) score of 0 or 1 [0,1)] were re-randomized (2:1) to IXE Q4W or placebo until Week 60. Efficacy was assessed by body-region specific parameters including Nail Psoriasis Severity Index (NAPSI), Psoriasis Scalp Severity Index (PSSI), and Palmoplantar Psoriasis Area Severity Index (PPASI). RESULTS: Of 438 patients, 99.1% (434) had ≥ 1 special area involvement [fingernail (76.5%, 335), scalp (97.3%, 426), palmoplantar (27.9%, 122)]. Significantly greater improvements from baseline in NAPSI score were observed with IXE Q4W and Q2W at Week 12 versus placebo (p < 0.001 for both). These improvements were further increased and sustained over 60 weeks in IXE Q4W and Q2W responders who were re-randomized to IXE Q4W, who achieved a 77.9% and 89.7% improvement from baseline, respectively, at Week 60. Significantly higher proportions of patients receiving IXE Q4W and Q2W achieved NAPSI 50 at Week 12 versus placebo (44.4%, 36.6% vs. 14.1%; p < 0.001 and < 0.01, respectively). Similarly, significantly higher proportions of patients receiving IXE Q4W and Q2W achieved PSSI 100 and PPASI 100 at Week 12 versus placebo (60.6% and 65.1% vs. 1.2%, and 67.4%, 84.3% vs. 21.4%, respectively; p < 0.001 for all comparisons). Improvements across all outcomes were sustained in patients re-randomized to IXE Q4W until Week 60. CONCLUSION: IXE led to a rapid onset of action and sustained efficacy over 60 weeks in Chinese patients with moderate-to-severe psoriasis and special body area involvement. CLINICALTRIALS: gov identifier, NCT03364309.

Three patients with new mutations in the EPCAM variant gene for congenital tufting enteropathy and a mutation review in China: a case report.

Background: Congenital tufting enteropathy (CTE) is a rare cause of intractable congenital diarrhea in children, always resulting in parenteral nutrition (PN) dependency. We aimed to report novel mutations in Chinese patients and to illustrate the clinical, histopathological, and molecular features of CTE in China. Case Description: We report three cases of CTE diagnosed with whole-exome sequencing (WES) and MOC31 [a monoclonal antibody of epithelial cell adhesion molecule (EPCAM)] immunohistochemistry. The main manifestations in the three patients were watery diarrhea and growth retardation. Upper endoscopy in three patients revealed villous atrophy of the duodenal mucosa. Histological examination revealed villus abnormalities and two patients with focal tufting. All of the three patients revealed a complete absence of EPCAM expression through MOC31 immunohistochemistry. Five novel mutations, including c.319delG, c.505_507delGAG, c.491+1G>C, c.60del (p.F20Lfs*17), and c.353G>A, in EPCAM were identified through molecular analysis. In our review, there were 18 different mutations in 11 patients from nine studies, with 12 mutations reported only once. In China, 73% of the patients were compound heterozygotes, and most of the pathogenic variants were in exon 3. All patients presented with congenital diarrhea and needed PN because of growth retardation, even when diarrhea was improved. Of the 11 patients, 3 (27%) died. Conclusions: CTE is rare and fatal, and lacks characteristic changes during endoscopy. Patients with CTE require early diagnosis via histological examination and genetic detection to improve survival.

Analysis of long-term outcome of modified gastric bypass for type 2 diabetes mellitus in Chinese patients.

BACKGROUND: Bariatric and metabolic surgery have been routinely performed following the rapid increase in obesity and metabolic diseases worldwide. Of all evolving procedures, Roux-en-Y gastric bypass (RYGB) is considered the gold standard for surgical treatment of patients with type 2 diabetes mellitus (T2DM) and obesity. RYGB was introduced in China nearly 20 years ago, but the number of RYGB surgeries only accounts for 3.1% of the total number of weight loss and metabolic surgeries in China, it's effect on Chinese people still needs further study. AIM: To investigate the effect and safety of a modified gastric bypass performed in Chinese patients with T2DM. METHODS: Patients with obesity and T2DM who underwent modified gastric bypass, with > 5-year follow-up data, were analyzed. RESULTS: All 37 patients underwent uneventful laparoscopic surgery, no patient was switched to laparotomy during the surgery, and no severe complications were reported. Average weight and body mass index of the patients reduced from 84.6 ± 17.3 (60.0-140.0) kg and 30.9 ± 5.0 (24.7-46.2) kg/m2 to 67.1 ± 12.2 (24.7-46.2) kg and 24.6 ± 3.9 (17.7-36.5) kg/m2, respectively, and fasting plasma glucose and glycated hemoglobin decreased from 7.4 ± 3.4 mmol/L and 8.2% ± 1.7% preoperatively to 6.5 ± 1.3 mmol/L and 6.5% ± 0.9% 5-years postoperatively, respectively. Only 29.7% (11/37) of the patients used hypoglycemic drugs 5-years postoperatively, and the complete remission rate of T2DM was 29.7% (11/37). Triglyceride level reduced significantly but high-density lipoprotein increased significantly (both P < 0.05) compared with those during the preoperative period. Liver and renal function improved significantly postoperatively, and binary logistic regression analysis revealed that the patients' preoperative history of T2DM and fasting C-peptide were significant prognostic factors influencing complete T2DM remission after RYGB (P = 0.006 and 0.012, respectively). CONCLUSION: The modified gastric bypass is a safe and feasible procedure for Chinese patients with obesity and T2DM, exhibiting satisfactory amelioration of weight problems, hyperglycemia, and combination disease.

Effectiveness and safety of glucose-lowering drugs as an adjunct to insulin therapy in Chinese patients with type 1 diabetes: a retrospective, observational study.

AIM: To assess the real-world impact of glucose-lowering drugs (GLDs) as an adjunct to insulin in Chinese patients with type 1 diabetes (T1DM). METHODS: This dual-center, observational, retrospective study included 121 T1DM patients receiving GLDs as adjuncts and 56 participants with insulin-only drugs as comparators. Glycated hemoglobin A1c (HbA1c), daily insulin dosage, fasting blood glucose (FBG), postprandial blood glucose (PBG), nocturnal blood glucose (NBG) and the difference in trough and peak blood glucose levels on the same day (Δ TP) were assessed at baseline and at the end of the study. RESULTS: In total, HbA1c decreased by 1.14% in the GLD+insulin group (p < 0.0001) and 0.36% in the insulin-only group (p = 0.0423, mean adjusted difference, -0.09% [95% CI, -0.55 to 0.37]). The total daily insulin concentration was reduced by 7.34 U per day in the GLD+insulin group vs. 5.55 U per day in the insulin-only group (mean adjusted difference, -2.32 U [95% CI, -4.97 to 0.33]). In particular, among patients with fasting C-peptide levels < 17 pmol/L, the total daily insulin concentration was significantly reduced by 9.22 U vs. 5.09 U per day (mean adjusted difference, -3.84 [95% CI, -6.85-0.84]; p = 0.0129). There were no notable differences in the other glycemic indices between the two groups. A gradual downward trend in changes in glycemic outcomes was observed among patients treated with various combinations of metformin, acarbose, and dipeptidyl peptidase 4 inhibitor (DPP-4i). Similar reductions in the daily insulin dose were also detected in most of the GLD+insulin group in addition to the DPP-4i-only group. No severe hypoglycemia was induced by additional GLDs. CONCLUSIONS: The use of additional GLDs tends to improve glycemic outcomes and reduce insulin requirements in patients with T1DM. These results indicate that the use of GLDs as an adjunctive therapy may have been an effective treatment strategy among adults with T1DM in China.

Varied clinical presentations of RP1L1 variants in Chinese patients: a study of occult macular dystrophy and vitelliform macular dystrophy.

BACKGROUND: Occult Macular Dystrophy (OMD), primarily caused by retinitis pigmentosa 1-like 1 (RP1L1) variants, is a complex retinal disease characterised by progressive vision loss and a normal fundus appearance. This study aims to investigate the diverse phenotypic expressions and genotypic correlations of OMD in Chinese patients, including a rare case of Vitelliform Macular Dystrophy (VMD) associated with RP1L1. METHODS: We analysed seven OMD patients and one VMD patient, all with heterozygous pathogenic RP1L1 variants. Clinical assessments included Best Corrected Visual Acuity (BCVA), visual field testing, Spectral Domain Optical Coherence Tomography (SD-OCT), multifocal Electroretinograms (mfERGs), and microperimetry. Next-generation sequencing was utilised for genetic analysis. RESULTS: The OMD patients displayed a range of phenotypic variability. Most (5 out of 7) had the RP1L1 variant c.133 C > T; p.R45W, associated with central vision loss and specific patterns in SD-OCT and mfERG. Two patients exhibited different RP1L1 variants (c.3599G > T; p.G1200V and c.2880G > C; p.W960C), presenting milder phenotypes. SD-OCT revealed photoreceptor layer changes, with most patients showing decreased mfERG responses in the central rings. Interestingly, a unique case of VMD linked to the RP1L1 variant was observed, distinct from traditional OMD presentations. CONCLUSIONS: This study highlights the phenotypic diversity within OMD and the broader spectrum of RP1L1-associated macular dystrophies, including a novel association with VMD. The findings emphasise the complexity of RP1L1 variants in determining clinical manifestations, underscoring the need for comprehensive genetic and clinical evaluations in macular dystrophies.

Efficacy and Safety of KRASG12C Inhibitor IBI351 Monotherapy in Patients With Advanced NSCLC: Results From a Phase 2 Pivotal Study.

INTRODUCTION: KRAS glycine-to-cysteine substitution at codon 12 (G12C) mutation is a well-recognized and increasingly promising therapeutic target with huge unmet clinical needs in NSCLC patients. IBI351 is a potent covalent and irreversible inhibitor of KRAS G12C. Here, we present the efficacy and safety of IBI351 from an open-label, single-arm, phase 2 pivotal study. METHODS: Eligible patients with NSCLC with KRAS G12C who failed standard therapy were enrolled. IBI351 was orally administered at a dose of 600 mg twice daily. The primary endpoint was confirmed objective response rate assessed by an independent radiological review committee (IRRC) as per Response Evaluation Criteria in Solid Tumors v1.1. Other endpoints were safety, IRRC-confirmed disease control rate, duration of response, progression-free survival (PFS), and overall survival. RESULTS: As of December 13, 2023, 116 patients were enrolled (Eastern Cooperative Oncology Group Performance Status 1: 91.4%; brain metastasis: 30.2%; prior treatments with both anti-PD-1 or anti-PD-L1 inhibitors and platinum-based chemotherapy: 84.5%). As per the IRRC assessment, the confirmed objective response rate was 49.1% (95% confidence interval [CI]: 39.7-58.6), and the disease control rate was 90.5% (95% CI: 83.7-95.2). The median duration of response was not reached whereas disease progression or death events occurred in 22 patients (38.6%), and the median PFS was 9.7 months (95% CI: 5.6-11.0). overall survival data was immature. Treatment-related adverse events (TRAEs) occurred in 107 patients (92.2%) whereas 48 patients (41.4%) had equal to or higher than grade three TRAEs. Common TRAEs were anemia (44.8%), increased alanine aminotransferase (28.4%), increased aspartate aminotransferase (27.6%), asthenia (26.7%) and presence of protein in urine (25.0%). TRAEs leading to treatment discontinuation occurred in nine patients (7.8%). In biomarker evaluable patients (n = 95), all patients had positive KRAS G12C in tissue whereas 72 patients were blood-positive and 23 were blood-negative for KRAS G12C. Patients with KRAS G12C in both blood and tissue had higher tumor burden at baseline (p < 0.05) and worse PFS (p < 0.05). Tumor mutation profiling identified tumor protein p53 (45.3%), serine/threonine kinase 11 (STK11) (30.5%), and kelch-like ECH-associated protein 1 (21.1%) as the most common genes co-mutated with KRAS G12C. Among 13 genes with mutation frequency equal to or higher than 5%, mutations of six genes (STK11, kelch-like ECH-associated protein 1, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma, DNA polymerase epsilon, SMAD family member 4, and BMP/retinoic acid-inducible neural-specific protein 3) were significantly associated with worse PFS (p < 0.05). Mutation in STK11 was also found to have a significant association with higher tumor burden at baseline and lower response rate (p < 0.05). CONCLUSIONS: IBI351 monotherapy demonstrated promising and sustained efficacy with manageable safety, supporting its potential as a new treatment option for KRAS G12C-mutant NSCLC.

Clinicopathological characteristics and prognosis of uterine sarcoma: a 10-year retrospective single-center study in China.

BACKGROUND: Uterine sarcoma is a rare and heterogeneous gynecological malignancy characterized by aggressive progression and poor prognosis. The current study aimed to investigate the relationship between clinicopathological characteristics and the prognosis of uterine sarcoma in Chinese patients. METHODS: In this single-center retrospective study, we reviewed the medical records of 75 patients with histologically verified uterine sarcoma treated at the First Affiliated Hospital of Xi'an Jiaotong University between 2011 and 2020. Information on clinical characteristics, treatments, pathology and survival was collected. Progression-free survival (PFS) and overall survival (OS) were visualized in Kaplan-Meier curves. Prognostic factors were identified using the log-rank test for univariate analysis and Cox-proportional hazards regression models for multivariate analysis. RESULTS: The histopathological types included 36 endometrial stromal sarcomas (ESS,48%), 33 leiomyosarcomas (LMS,44%) and 6 adenosarcomas (8%). The mean age at diagnosis was 50.2 ± 10.7 years. Stage I and low-grade accounted for the majority. There were 26 recurrences and 25 deaths at the last follow-up. The mean PFS and OS were 89.41 (95% CI: 76.07-102.75) and 94.03 (95% CI: 81.67-106.38) months, respectively. Univariate analysis showed that > 50 years, post-menopause, advanced stage, ≥ 1/2 myometrial invasion, lymphovascular space invasion and high grade were associated with shorter survival (P < 0.05). Color Doppler flow imaging positive signals were associated with shorter PFS in the LMS group (P = 0.046). The ESS group had longer PFS than that of the LMS group (99.56 vs. 76.05 months, P = 0.043). The multivariate analysis showed that post-menopause and advanced stage were independent risk factors of both PFS and OS in the total cohort and LMS group. In the ESS group, diagnosis age > 50 years and high-grade were independent risk factors of PFS, while high-grade and lymphovascular space invasion were independent risk factors of OS. CONCLUSION: In Chinese patients with uterine sarcoma, post-menopause and advanced stage were associated with a significantly poorer prognosis. The prognosis of ESS was better than that of LMS. Color Doppler flow imaging positive signals of the tumor helped to identify LMS, which needs to be further tested in a larger sample in the future.

A prognostic nomogram to predict the cancer-specific survival of patients with initially diagnosed metastatic gastric cancer: a validation study in a Chinese cohort.

BACKGROUND: Few studies have been designed to predict the survival of Chinese patients initially diagnosed with metastatic gastric cancer (mGC). Therefore, the objective of this study was to construct and validate a new nomogram model to predict cancer-specific survival (CSS) in Chinese patients. METHODS: We collected 328 patients with mGC from Northern Jiangsu People's Hospital as the training cohort and 60 patients from Xinyuan County People's Hospital as the external validation cohort. Multivariate Cox regression was used to identify risk factors, and a nomogram was created to predict CSS. The predictive performance of the nomogram was evaluated using the consistency index (C-index), the calibration curve, and the decision curve analysis (DCA) in the training cohort and the validation cohort. RESULTS: Multivariate Cox regression identified differentiation grade (P < 0.001), T-stage (P < 0.05), N-stage (P < 0.001), surgery (P < 0.05), and chemotherapy (P < 0.001) as independent predictors of CSS. Nomogram of chemotherapy regimens and cycles was also designed by us for the prediction of mGC. Thus, these factors are integrated into the nomogram model: the C-index value was 0.72 (95% CI 0.70-0.85) for the nomogram model and 0.82 (95% CI 0.79-0.89) and 0.73 (95% CI 0.70-0.86) for the internal and external validation cohorts, respectively. Calibration curves and DCA also demonstrated adequate fit and ideal net benefit in prediction and clinical applications. CONCLUSIONS: We established a practical nomogram to predict CSS in Chinese patients initially diagnosed with mGC. Nomograms can be used to individualize survival predictions and guide clinicians in making therapeutic decisions.

Safety and feasibility analysis of rapid daratumumab infusion in Chinese patients with multiple myeloma.

BACKGROUND: With the increasing use of daratumumab (DARA)-containing regimens for multiple myeloma (MM) patients in China, the standard infusion time of DARA is long, with the potential for infusion-related reactions (IRRs) and increased hospitalization and use of resources. Shortening the duration of DARA infusion helps to optimize the hospital stay and enhance the patient treatment experience. The current, commonly used 90-min rapid DARA infusion regimen may not be applicable to Chinese MM patients, and therefore, we explored a new 110-min rapid DARA infusion regimen aimed at reducing the treatment burden on patients to guarantee therapeutic safety. METHODS: MM inpatients treated with the DARA regimen were divided into two groups according to the number of times the DARA regimen was used: a standard infusion regimen for patients treated with the first two doses of DARA and a 110-min rapid infusion regimen for patients treated with more than two doses of DARA. Anti-allergy medications were routinely administered prior to the start of DARA infusion, patient consent, and authorization was obtained for all treatments, and statistical evaluation of the results was conducted via descriptive analyses, one-way ANOVA and chi-square tests. RESULTS: A total of 129 patients were included in this study: 68 in the standard infusion group, with 121 DARA infusions, and 129 in the rapid infusion group (patients who participated in the standard infusion subsequently participated in the rapid infusion), with 738 DARA infusions. The incidence of IRRs was 27.27% (36/121) in the standard infusion group and 1.35% (10/738) in the rapid infusion group, which were significantly different (p < 0.001). The incidence of IRRs after rapid infusion in other studies was <6%. The incidence of grade 1 IRRs in the rapid infusion group was 0.81% (6/738), the incidence of grade 2 IRRs was 0.54% (4/738), and there were no IRRs above grade 3; age, sex, and underlying disease had no effect on the choice of infusion method (p > 0.05). The mean infusion time after the occurrence of IRRs was also shorter in the rapid infusion group than in the standard infusion group (F = 24.781, p < 0.001). CONCLUSION: The 110-min rapid infusion DARA regimen is feasible and safe for use in Chinese MM patients.

Effects of sintilimab plus chemotherapy as first-line treatment on health-related quality of life in patients with advanced esophageal squamous cell carcinoma: results from the randomized phase 3 ORIENT-15 study.

Background: In ORIENT-15 study, sintilimab plus chemotherapy demonstrated significant improvement on overall survival (OS) versus placebo plus chemotherapy in first-line treatment of advanced esophageal squamous cell carcinoma (ESCC). Here, we report effect of sintilimab plus chemotherapy on health-related quality of life (HRQoL) in patients with advanced ESCC. Methods: From December 14, 2018 to August 28, 2022, HRQoL was evaluated in all randomized patients using European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 items (QLQ-C30), EORTC Quality of Life Questionnaire Oesophageal Cancer Module 18 items (QLQ-OES18), and visual analogue scale (VAS) of the EuroQol five-dimensional five-level questionnaire (EQ-5D-5L). Mean scores of each scale were described by treatment group through week 60. Least-squares mean (LSM) score change from baseline through week 24 were analyzed using the mixed-model repeated-measures method. Time to the first onset of deterioration (TTD) and OS for each scale were estimated. Clinical Trials Registration: NCT03748134. Findings: As of August 28, 2022, 689 of 690 enrolled patients were assessed for HRQoL analysis (sintilimab group: 340, placebo group: 349). Median follow-up was 32.2 months. Differences in LSM favored sintilimab over placebo for QLQ-C30 social functioning (LSM difference: 3.06, 95% CI: 0.55 to 5.57; P = 0.0170), pain (-2.24, 95% CI: -4.30 to -0.17; P = 0.0337), fatigue (-2.24, 95% CI: -4.46 to -0.02; P = 0.0479), constipation (-3.27, 95% CI -5.49 to -1.05; P = 0.0039), QLQ-OES18 pain (-1.77, 95% CI -3.11 to -0.43; P = 0.0097), trouble swallowing saliva (-2.09, 95% CI: -3.77 to -0.42; P = 0.0146), and choked when swallowing (-3.23, 95% CI: -5.60 to -0.86; P = 0.0076). TTD favored sintilimab over placebo for QLQ-OES18 dysphagia (Hazard ratio [HR]: 0.76, 95% CI: 0.61-0.94, P = 0.0104), and trouble swallowing saliva (HR: 0.48, 95% CI: 0.35-0.67, P < 0.0001). Improved OS were observed in patients with better performance in several functioning and symptom scales of QLQ-C30 and QLQ-QES18. Interpretation: The statistically significant differences of several HRQoL scales and improvements in delayed deterioration observed in our study further support the use of sintilimab plus chemotherapy as first-line treatment for advanced ESCC. Funding: This study was funded by Innovent Biologics and was co-funded by Eli Lilly.

Efficacy and Safety of Crisaborole Ointment 2% in Chinese Patients Aged ≥ 2 Years with Mild to Moderate Atopic Dermatitis.

INTRODUCTION: Atopic dermatitis (AD) is a chronic immuno-inflammatory skin disease. Crisaborole ointment, 2%, is a nonsteroidal phosphodiesterase 4 inhibitor approved for the treatment of mild to moderate AD. This post hoc analysis assesses the efficacy and safety of crisaborole in Chinese patients aged ≥ 2 years with mild to moderate AD. METHODS: We evaluated the efficacy and safety of crisaborole in Chinese patients from the vehicle-controlled, phase 3 CrisADe CLEAR study. Patients were randomly assigned 2:1 to receive crisaborole or vehicle twice daily, respectively, for 28 days. The primary endpoint was percent change from baseline in Eczema Area and Severity Index (EASI) total score at day 29. Key secondary endpoints were improvement in Investigator's Static Global Assessment (ISGA), ISGA success, and change from baseline in weekly average Peak Pruritus Numerical Rating Scale (PP-NRS) score. Adverse events were documented. RESULTS: Of 391 patients in the overall study, 237 were from China, 157 assigned to crisaborole and 80 assigned to vehicle. A greater reduction in percent change from baseline in EASI total score at day 29 was shown in the crisaborole vs. vehicle group (least squares mean [LSM]: -66.34 [95% (confidence interval) CI -71.55 to -61.12] vs. -50.18 [95% CI -58.02 to -42.34]). Response rates for achievement of ISGA improvement (43.2% [95% CI 35.4-51.1] vs. 33.4% [95% CI 22.5-44.2]) and ISGA success (31.7% [95% CI 24.3-39.0] vs. 21.5% [95% CI 12.1-30.9]) at day 29 were higher in the crisaborole vs. vehicle group. A greater reduction in change from baseline in weekly average PP-NRS score at week 4 was observed in the crisaborole vs. vehicle group (LSM: -1.98 [95% CI -2.34 to -1.62] vs. -1.08 [95% CI -1.63 to -0.53]). No new safety signals were observed. CONCLUSION: Crisaborole was effective and well tolerated in Chinese patients aged ≥ 2 years with mild to moderate AD. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04360187.

A Predictive Model for Graft Failure in Femtosecond Laser-Assisted Penetrating Keratoplasty Among Chinese Patients: A 2-Year Study.

INTRODUCTION: Graft failure is a major challenge in femtosecond laser-assisted penetrating keratoplasty (Fs-PKP). This study focuses on the development and validation of a clinical predictive model aimed at identifying the risk of graft failure in individuals undergoing Fs-PKP in China, offering a tailored approach to improve surgical outcomes. METHODS: This retrospective cohort study at Nanjing First Hospital involved 238 patients and followed the TRIPOD statement. The cohort was divided into a training set (n = 166) and a validation set (n = 72) in a 7:3 ratio. It analyzed 23 predictor variables related to recipient, donor, and surgical factors, defining graft failure as "visually significant and irreversible corneal stromal edema, haze, or scarring." A comprehensive nomogram was created using univariate and multivariate Cox regression analyses and assessed by concordance index (C-index), time-dependent receiver operating characteristics (ROC) curve, calibration plots, and decision curve analysis (DCA). RESULTS: Five critical risk factors were identified: recipients' history of systemic autoimmune disorders, ocular trauma, prior penetrating keratoplasty (PKP) history, donors' diabetes history, and the endothelial cell density of the donor cornea. The nomogram showed a C-index of 0.72 (95% CI 0.65-0.79) in the training group and 0.66 (95% CI 0.55-0.76) in the validation group, indicating robust predictive accuracy. Time-dependent ROC curves, calibration plots, and DCA consistently validated the model's reliability, predictive power, and clinical utility across both training and validation cohorts. CONCLUSIONS: Our study developed and validated a model incorporating five key factors, enhancing preoperative prediction and management for Chinese patients with Fs-PKP graft failure.

Germline RECQL gene mutations in Chinese patients with breast cancer.

Introduction: Breast cancer is the most common malignant tumor in women, seriously threatening health and survival. TP-dependent DNA helicase Q1 (RECQL) is a breast cancer susceptibility gene with possible familial links. However, RECQL gene mutations among Chinese women with breast cancer have not been evaluated. Therefore, this study assessed RECQL mutations and their relationships with clinicopathological and epidemiological characteristics in Chinese women with breast cancer. Method: Clinical information was also obtained via the hospital information system and a follow-up questionnaire. Peripheral venous blood (2 mL) was extracted from all patients and stored at -80°C for future use; the early venous blood samples were from our hospital's sample bank. RECQL gene sequencing were performed by the Shanghai Aishe Gene Company (China). Results: We found that a RECQL mutation is a susceptibility factor for breast cancer. Moreover, patients with RECQL mutations were more likely to have a family history of breast cancer than those without. Also, patients with RECQL variants of uncertain significance (VUS) were less likely to develop invasive ductal carcinoma than those without. In addition, unexplained RECQL mutations occurred more often in patients with human epidermal growth factor receptor 2+ breast cancer than in those with other subtypes. Discussion: These results provide a basis for creating screening criteria specific to Chinese women. However, the frequency of RECQL mutations was low, and the number of pathogenic mutations was too small and could not be analyzed. Thus, more extensive, long-term studies that include other functional experiments are needed to verify these results.

Fear of disease in patients with epilepsy - a network analysis.

Background: Disease-related fear among patients with epilepsy has significantly impacted their quality of life. The Disease-Related Fear Scale (D-RFS), comprising three dimensions, serves as a relatively well-established tool for assessing fear in these patients. However, certain problems potentially exist within the D-RFS's attribution of items, and its internal structure is still unclear. To establish an appropriate dimensional structure and gain deeper comprehension of its internal structure-particularly its core variables-is vital for developing more effective interventions aimed at alleviating disease-related fear among patients with epilepsy. Methods: This study employed a cross-sectional survey involving 609 patients with epilepsy. All participants underwent assessment using the Chinese version of the D-RFS. We used exploratory network analysis to discover a new structure and network analysis to investigate the interrelationships among fear symptom domains. In addition to the regularized partial correlation network, we also estimated the node and bridge centrality index to identify the importance of each item within the network. Finally, it was applied to analyze the differences in network analysis outcomes among epilepsy patients with different seizure frequencies. Results: The research findings indicate that nodes within the network of disease-related fear symptoms are interconnected, and there are no isolated nodes. Nodes within groups 3 and 4 present the strongest centrality. Additionally, a tight interconnection exists among fear symptoms within each group. Moreover, the frequency of epileptic episodes does not significantly impact the network structure. Conclusion: In this study, a new 5-dimension structure was constructed for D-RFS, and the fear of disease in patients with epilepsy has been conceptualized through a network perspective. The goal is to identify potential targets for relevant interventions and gain insights for future research.

The characteristics of suicide attempters in Chinese patients: Comparison of adolescents, youths, middle-aged and elderly.

BACKGROUND: Potential risk factors for suicide differ by age group. Therefore, this study aims to investigate the characteristics of patients with suicide attempts according to age group and any the relevant risk factors. METHODS: This study retrospectively reviewed the medical records of attempted suicide patients who were admitted to the emergency departments (ED) of the First Affiliated Hospital of Wenzhou Medical University between January 1, 2017, and December 31, 2021. Demographic information and clinical characteristics were collected. The participants were divided into four age groups and the characteristics of each group were compared. RESULTS: A total of 834 participants were included in this study. Suicide attempts were more prevalent in females, and the gender difference decreased with age. Having religious belief and less educated suicide attempts were concentrated in the elderly groups. Adolescents suicide attempts were more likely to occur in the spring, autumn and during non-office hours. Mental disorders were the major motivation for suicide among adolescents, and interpersonal and social problems were more prevalent among youths. Psychiatric medication was the leading suicidal substances among adolescents, while pesticides and herbicides were more prevalent in adults. The history of psychiatric diagnosis was more common in adolescents, while the history of somatic disorder was more prevalent in the elderly. CONCLUSION: This study confirmed differences in the demographic and clinical characteristics of patients in different age groups. Therefore, it is necessary to construct individualized intervention strategies for each age group based on the characteristics of the patients in order to reduce suicide.

Ibrutinib Efficacy, Safety, and Pharmacokinetics in Chinese Patients with Relapsed or Refractory Waldenström's Macroglobulinemia: A Multicenter, Single-Arm, Phase 4 Study.

INTRODUCTION: Waldenström's macroglobulinemia (WM) is a rare malignant B cell lymphoma which occurs in around 1-2% of all hematologic tumors. Ibrutinib was approved in China for WM on the basis of two global pivotal studies which enrolled no Chinese patients. The aim of this study was to determine the efficacy, safety, and pharmacokinetics of ibrutinib in Chinese patients with relapsed or refractory (r/r) WM. METHODS: This was an open-label, single-arm, multicenter phase 4 study conducted across five sites in China. Enrolled patients with clinicopathological confirmed WM received ibrutinib 420 mg once daily orally until disease progression or unacceptable toxicity. The primary endpoint was major response rate (MRR, partial response [PR], or better) according to the modified consensus criteria from the Sixth International Workshop on WM. RESULTS: Seventeen patients were enrolled; at data cutoff (March 19, 2022), MRR was 64.7% (90% confidence interval [CI] 42.0-83.4) and overall response rate was 100% (90% CI 83.8-100.0). One (5.9%) patient achieved very good PR, 10 (58.8%) achieved PR, and six (35.3%) achieved minor response. The median duration of response (PR or better) was 14.8 months (95% CI 10.8-not estimable [NE]). Median progression-free survival was 18.4 months (95% CI 12.9-NE). All patients experienced at least one treatment-emergent adverse event (TEAE) related to the study drug, and grade ≥ 3 TEAEs were reported in 13 (76.5%) patients. There were no TEAEs leading to dose reduction or death. The median model estimated maximum plasma concentration and area under the plasma concentration-time curve during 24 h after dosing at steady state were 40.5 ng/mL and 204 ng·h/mL, respectively. CONCLUSIONS: Ibrutinib demonstrated durable responses in Chinese patients with r/r WM. Treatment was well tolerated with no new safety signals compared with the pivotal global studies. Ibrutinib exposure was also comparable between Chinese and non-Chinese patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04042376.

Temporal associations of diabetes-related complications with health-related quality of life decrements in Chinese patients with type 2 diabetes: A prospective study among 19 322 adults-Joint Asia Diabetes Evaluation (JADE) register (2007-2018).

BACKGROUND: Patients with type 2 diabetes (T2D) are at high risk of developing multiple complications, affecting their health-related quality of life (HRQoL). Existing studies only considered impact of complication on HRQoL in the year of occurrence but not its residual impacts in subsequent years. We investigated temporal impacts of diabetes-related complications on HRQoL in a 12-year prospective cohort of ambulatory Chinese patients with T2D enrolled in the clinic-based Joint Asia Diabetes Evaluation (JADE) Register. METHODS: HRQoL utility measures were derived from EuroQol five-dimensional three-level questionnaire (EQ-5D-3L) questionnaires completed by 19 322 patients with T2D in Hong Kong (2007-2018). Temporal EQ-5D utility decrements associated with subtypes of cardiovascular-renal events were estimated using generalized linear regression model after stepwise selection of covariates with p < .01 as cutoff. RESULTS: In this cohort (mean ± SD age:61.2 ± 11.5 years, 55.3% men, median [interquartile range] duration of diabetes:10.1 [3.0-15.0] years, glycated hemoglobin [HbA1C ] 7.5 ± 1.5%), EQ-5D utility was 0.860 ± 0.163. The largest HRQoL decrements were observed in year of occurrence of hemorrhagic stroke (-0.230), followed by ischemic stroke (-0.165), peripheral vascular disease (-0.117), lower extremity amputation (-0.093), chronic kidney disease (CKD) G5 without renal replacement therapy (RRT) (-0.079), congestive heart failure (CHF) (-0.061), and CKD G3-G4 without RRT (-0.042). Residual impacts on HRQoL persisted for 2 years after occurrence of CHF or ischemic stroke and 1 year after hemorrhagic stroke or CKD G3-G4 without RRT. CONCLUSION: This is the first comprehensive report on temporal associations of HRQoL decrements with subtypes of diabetes-related complications in ambulatory Asian patients with T2D. These data will improve the accuracy of cost-effectiveness analysis of diabetes interventions at an individual level in an Asian setting.

Preliminary MRS study of critical values of relevant brain metabolites in elderly Chinese patients with post-stroke cognitive impairment.

Objective: Proton magnetic resonance spectroscopy (1H-MRS) was applied in this study to detect metabolite changes in the brain of post-stroke cognitive impairment (PSCI) and normal volunteers. The levels of N-acetylaspartate (NAA) and creatinine (Cr) and in the frontal lobe, hippocampus and cingulate gyrus were measured to distinguish patients with post-stroke cognitive impairment (PSCI) and normal control group (NC). The relationship between them and cognitive function was explored and a critical value of the metabolite ratio was predicted. This study may serve as a reference for the diagnosis of cognitive dysfunction after stroke. Methods: A total of 46 patients with PSCI (PSCI group, all patients are unilateral cerebral infarction or intracerebral haemorrhage) were screened by the Mini-Mental Status Examination (MMSE), and 35 healthy volunteers were selected as normal control group (NC group). The general information of gender, age, and education level was matched between the two groups. Two groups of subjects were examined using MRS and evaluated for cognitive function using the MMSE test and the Montreal Cognitive Assessment Scale (MoCA). The correlation between MRS and neurobehavioral scale (MMSE test and MoCA scale) was analysed, and the possible demarcation points of the brain metabolism of PSCI were evaluated. Result: The MMSE and MoCA scores of patients with PSCI were lower significantly when compared with those of the NC group (P < 0.05). The NAA/Cr values of the bilateral hippocampus, bilateral frontal lobe and bilateral anterior and posterior cingulate gyrus in the PSCI group were lower than those in the NC group (P < 0.05). The NAA/Cr cut-off value for the right frontal lobe was 1.533, and the NAA/Cr sensitivity, specificity and Youden index for the right frontal lobe were 0.943, 0.935, and 0.878. Conclusion: NAA/Cr values in the MRS bilateral frontal, bilateral hippocampus and bilateral anterior and posterior cingulate gyrus were reduced in the cognitively impaired post-stroke patients compared to the normal control group. MRS was also found to be correlated with the score of neurobehavioral scale (MMSE test and MoCA scale) and the combination of the two could evaluate cognitive dysfunction more comprehensively and objectively. NAA/Cr value of the right frontal lobe < 1.533 indicated that PSCI may occur. In accordance with this cut-off point, PSCI could be detected as early as possible and timely intervention could be carried out.