Purpose: Approximately 50%-74% of patients with metastatic human epidermal growth factor receptor 2 (HER2)–positive breast cancer do not respond to trastuzumab, with 75% of treated patients experiencing disease progression within a year. The combination of pyrotinib and capecitabine has showed efficacy in these patients. This study evaluates the efficacy and safety of pyrotinib combined with metronomic vinorelbine for trastuzumab-pretreated HER2-positive advanced breast cancer patients. Materials and Methods: In this phase 2 trial, patients aged 18-75 years with HER2-positive advanced breast cancer who had previously failed trastuzumab treatment were enrolled to receive pyrotinib 400 mg daily in combination with vinorelbine 40mg thrice weekly. The primary endpoint was progression-free survival (PFS), while secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. Results: From October 21, 2019, to January 21, 2022, 36 patients were enrolled and received at least one dose of study treatment. At the cutoff date, 20 experienced disease progression or death. With a median follow-up duration of 35 months, the median PFS was 13.5 months (95% confidence interval [CI], 8.3 to 18.5). With all patients evaluated, an ORR of 38.9% (95% CI, 23.1 to 56.5) and a DCR of 83.3% (95% CI, 67.2 to 93.6) were achieved. The median OS was not reached. Grade 3 adverse events (AEs) were observed in 17 patients, with diarrhea being the most common (27.8%), followed by vomiting (8.3%) and stomachache (5.6%). There were no grade 4/5 AEs. Conclusion Pyrotinib combined with metronomic vinorelbine showed promising efficacy and an acceptable safety profile in HER2-positive advanced breast cancer patients after trastuzumab failure.

Purpose: Approximately 50%-74% of patients with metastatic human epidermal growth factor receptor 2 (HER2)–positive breast cancer do not respond to trastuzumab, with 75% of treated patients experiencing disease progression within a year. The combination of pyrotinib and capecitabine has showed efficacy in these patients. This study evaluates the efficacy and safety of pyrotinib combined with metronomic vinorelbine for trastuzumab-pretreated HER2-positive advanced breast cancer patients. Materials and Methods: In this phase 2 trial, patients aged 18-75 years with HER2-positive advanced breast cancer who had previously failed trastuzumab treatment were enrolled to receive pyrotinib 400 mg daily in combination with vinorelbine 40mg thrice weekly. The primary endpoint was progression-free survival (PFS), while secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. Results: From October 21, 2019, to January 21, 2022, 36 patients were enrolled and received at least one dose of study treatment. At the cutoff date, 20 experienced disease progression or death. With a median follow-up duration of 35 months, the median PFS was 13.5 months (95% confidence interval [CI], 8.3 to 18.5). With all patients evaluated, an ORR of 38.9% (95% CI, 23.1 to 56.5) and a DCR of 83.3% (95% CI, 67.2 to 93.6) were achieved. The median OS was not reached. Grade 3 adverse events (AEs) were observed in 17 patients, with diarrhea being the most common (27.8%), followed by vomiting (8.3%) and stomachache (5.6%). There were no grade 4/5 AEs. Conclusion Pyrotinib combined with metronomic vinorelbine showed promising efficacy and an acceptable safety profile in HER2-positive advanced breast cancer patients after trastuzumab failure.

Purpose: Approximately 50%-74% of patients with metastatic human epidermal growth factor receptor 2 (HER2)–positive breast cancer do not respond to trastuzumab, with 75% of treated patients experiencing disease progression within a year. The combination of pyrotinib and capecitabine has showed efficacy in these patients. This study evaluates the efficacy and safety of pyrotinib combined with metronomic vinorelbine for trastuzumab-pretreated HER2-positive advanced breast cancer patients. Materials and Methods: In this phase 2 trial, patients aged 18-75 years with HER2-positive advanced breast cancer who had previously failed trastuzumab treatment were enrolled to receive pyrotinib 400 mg daily in combination with vinorelbine 40mg thrice weekly. The primary endpoint was progression-free survival (PFS), while secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. Results: From October 21, 2019, to January 21, 2022, 36 patients were enrolled and received at least one dose of study treatment. At the cutoff date, 20 experienced disease progression or death. With a median follow-up duration of 35 months, the median PFS was 13.5 months (95% confidence interval [CI], 8.3 to 18.5). With all patients evaluated, an ORR of 38.9% (95% CI, 23.1 to 56.5) and a DCR of 83.3% (95% CI, 67.2 to 93.6) were achieved. The median OS was not reached. Grade 3 adverse events (AEs) were observed in 17 patients, with diarrhea being the most common (27.8%), followed by vomiting (8.3%) and stomachache (5.6%). There were no grade 4/5 AEs. Conclusion Pyrotinib combined with metronomic vinorelbine showed promising efficacy and an acceptable safety profile in HER2-positive advanced breast cancer patients after trastuzumab failure.

Hemophilia is a hereditary coagulation disorder, in which patients often suffer from joint dysfunction due to recurrent joint bleeding, with the knee joint being particularly susceptible to involvement, thereby significantly impairing their ability to walk.Gait analysis, as an objective, quantitative, and comprehensive assessment tool, can be employed to accurately evaluate the walking function of patients and provide a scientific basis for the rehabilitation management of individuals with hemophilia.With the deepening of medical research, the role of gait analysis in the rehabilitation management of hemophilia is increasingly being recognized.This review article summarizes the application of gait analysis in the rehabilitation management of hemophilia, including changes in gait parameters, kinematic and kinetic characteristics of joints in patients with hemophilia, as well as the relationships between these parameters and the severity of the disease and treatment outcomes in hemophilia patients, exploring the role of gait analysis in the rehabilitation management of hemophilia to better apply it in clinical practice.

Objective:To study the current status of longitudinal extrauterine growth restriction (EUGR) in extremely preterm infants (EPIs) and to develop a prediction model based on clinical data from multiple NICUs.Methods:From January 2017 to December 2018, EPIs admitted to 32 NICUs in North China were retrospectively studied. Their general conditions, nutritional support, complications during hospitalization and weight changes were reviewed. Weight loss between birth and discharge > 1SD was defined as longitudinal EUGR. The EPIs were assigned into longitudinal EUGR group and non-EUGR group and their nutritional support and weight changes were compared. The EPIs were randomly assigned into the training dataset and the validation dataset with a ratio of 7∶3. Univariate Cox regression analysis and multiple regression analysis were used in the training dataset to select the independent predictive factors. The best-fitting Nomogram model predicting longitudinal EUGR was established based on Akaike Information Criterion. The model was evaluated for discrimination efficacy, calibration and clinical decision curve analysis.Results:A total of 436 EPIs were included in this study, with a mean gestational age of (26.9±0.9) weeks and a birth weight of (989±171) g. The incidence of longitudinal EUGR was 82.3%(359/436). Seven variables (birth weight Z-score, weight loss, weight growth velocity, the proportion of breast milk ≥75% within 3 d before discharge, invasive mechanical ventilation ≥7 d, maternal antenatal corticosteroids use and bronchopulmonary dysplasia) were selected to establish the prediction model. The area under the receiver operating characteristic curve of the training dataset and the validation dataset were 0.870 (95% CI 0.820-0.920) and 0.879 (95% CI 0.815-0.942), suggesting good discrimination efficacy. The calibration curve indicated a good fit of the model ( P>0.05). The decision curve analysis showed positive net benefits at all thresholds. Conclusions:Currently, EPIs have a high incidence of longitudinal EUGR. The prediction model is helpful for early identification and intervention for EPIs with higher risks of longitudinal EUGR. It is necessary to expand the sample size and conduct prospective studies to optimize and validate the prediction model in the future.

Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia(ALSP)is a clinically rare autosomal dominant genetic disease,and its specific pathogenesis is not yet clear.The colony-stimulating factor 1 receptor(CSF1R)is a transmembrane tyrosine kinase receptor on the cell surface and mutations in the gene encoding it have been identified as potential pathogenic factors for ALSP.However,the specific mechanisms by which CSF1R gene mutations lead to the onset of ALSP are still unclear.After reviewing the mutation sites and pathogenic mechanisms of CSF1R in the pathogenesis of ALSP,CSF1R mutations have been shown to cause microglial dysfunction through mechanisms such as dominant-negative effects,loss of function,haploinsufficiency,and gain of function,thereby leading to the onset of ALSP.A deeper understanding of the causes of ALSP will help in exploring potential treatment methods.

Objective:To explore the level of physical activity of Chinese adults with haemophilia and its related factors so as to provide a reference for their comprehensive management.Methods:The daily physical activity of adults with haemophilia was surveyed using the International Physical Activity Questionnaire (IPAQ). A total of 110 questionnaires were eligible for analysis at last. The results were compared with published data from other societies using independent sample t-tests and chi squared tests. Spearman correlation analysis and multivariate logistic regression analysis were applied to explore factors related to the subjects′ physical activity levels.Results:Fully 30.9% of the subjects claimed to maintain a high level of physical activity. This was significantly different from the distribution of physical activity observed in Japan (12.4%), Ireland (50.9%) and the United Kingdom (43.1%). According to the Spearman correlation analysis, the number of joints affected, anxiety, and depression are all significantly related to the level of physical activity among such adults. Multivariate logistic regression analysis showed that depression was an independent factor affecting the patients′ level of physical activities.Conclusion:Chinese and Japanese adults with hemophilia have relatively low levels of physical activity, possibly influenced by depression.

A young male diagnosed with severe hemophilia A since childhood, was presented with recurrent joint and urinary bleeding. Annualized bleed rates dropped below five with low dose prophylactic medication.Bleeding in the right knee joint recently aggravated. Due to coexisting HIV infection and advanced hemophilic arthritis, the patient was managed by a multi-disciplinary team(MDT).Total knee arthroplasty was performed by an experienced surgeon using modern prosthesis design and intraoperative navigation technologies.Physical and rehabilitation therapy was provided during the postoperative period, and joint function improved. The MDT managed the young patient with HIV infection and advanced hemophilic arthritis. The patient was diagnosed with osteoporosis thought to have been caused by hemophilia, HIV infection and antiviral drugs; and he received treatment. The treatment of this patient reflects the importance of multidisciplinary cooperation in the management of difficult and rare diseases.

Objective:To determine the minimum clinically-important difference (MCID) in the rehabilitation effect among children with haemophilic knee joint contracture.Methods:The data describing 28 children with an average age of 13.89±3.00 years and haemophilic knee joint contracture who received no less than 10 sessions of physiotherapy in the Department of Rehabilitation Medicine at the Peking Union Medical College Hospital were analyzed. The therapeutic effect of the treatement was quantified in terms of Haemophilia Joint Health Scores (HJHSs) for their knees. The MCID after the therapy was evaluated using the mean change method, multivariate linear regression, receiver operating characteristics, and the distribution-based method.Results:The MCID for the improvement of knee HJHS was 5.13 by the mean change method, 4.31 by multivariate linear regression, 3.50 according to the ROC curve and 1.64 by the distribution-based method. Taking all of them into consideration, 4.31 was found to be an appropriate value.Conclusions:The MCID after physical therapy for the improvement in knee HJHS for a child with haemophilic knee contracture is 4.31. Improvements greater than 4.31 can be considered clinically significant.

Objective:To evaluate the efficacy and safety of limited pars plana vitrectomy(LPPV), pressure-controlled phacoemulsification(PCP), intraocular lens implantation(IOL), and posterior capsulotomy (PC) in treatment of nanophthalmic glaucoma eyes which intraocular pressure(IOP) were still out of control after peripheral iridectomy.Methods:All 24 patients(29 eyes) with nanophthalmic glaucoma whose IOP failed to be reduced after peripheral iridectomy and needed LPPV plus PCP plus IOL plus PC were recruited from July 2017 to April 2021. The age of these patients was(44.6±11.0) years old. Preoperative and postoperative IOP, best corrected visual acuity(BCVA), anterior chamber depth(ACD) and number of glaucoma medications were recorded by chart review and compared by using paired t-test or Wilcoxon signed rank-sum test. P<0.05 was considered as statistical significant. IOP could be controlled in normal range(≥5 mmHg and≤21 mmHg), without both of disease progression and serious complications were regarded as the success criteria of the operation. Surgical success rate was evaluated. Surgery-associated complications were recorded. Results:The average follow-up time was(11.52±12.44) months. After the microsurgery, IOP decreased from(33.12±9.25) mmHg to(14.23±3.44) mmHg( P<0.01); The ACD increased from(1.23±0.46) mm to(2.86±0.62) mm, and the median number of glaucoma medications dropped from 3(3,4) to 3(0,3) at final follow-up visit( P<0.05). There were no significant differences in BCVA( P=0.196) and the degrees of angle closure(AC) ( P=0.478) before and after operation. The total surgical success rate was 86.2%(25/29) at the final follow-up visit. Two eyes suffered from local choroidal detachment which recovered within 2 weeks with medical treatment. Conclusion:LPPV plus PCP plus IOL plus PC is a safe and effective novel surgical procedure in the treatment of nanophthalmic glaucoma patients with uncontrolled IOP after peripheral iridectomy. It could significantly decrease IOP, increase the depth of ACD, reduce the number of glaucoma medications and maintain BCVA. It can be considered as a first choice for the surgical management for patients with a such condition.