Longstanding humeral shaft nonunion is uncommon because humeral shaft fractures often respond well to conservative and surgical treatments. However, when it occurs, the treatment of longstanding humeral shaft nonunion is challenging. This study is a retrospective analysis of the clinical and radiographic findings in a consecutive series of patients with longstanding humeral shaft nonunions who underwent locking compression plate (LCP) fixation and autogenous iliac crest bone grafting.Six patients were surgically treated at Xi'an Hong Hui Hospital for longstanding humeral shaft nonunions between February 2011 and June 2015. Four patients were of synovial pseudarthrosis, 1 was atrophic, and 1 was hypertrophic. Follow-up was for at least 12 months after intervention. Standardized treatment included a thorough debridement, LCP and screw fixation, and autogenous iliac crest bone grafting. In 3 patients, a single plate was applied, and in the other 3 patients, double plates were used. The main outcome measurements were shoulder and elbow function (Constant and Murley scale, and Mayo elbow performance index [MEPI]) and the visual analog scale (VAS) for pain. In addition, all complications were documented.Our series included 6 male patients with an average age of 56.3 years and an average nonunion duration of 19.5 years. All patients had previously undergone at least 1 operation. At a mean of 26 months follow-up, all fractures had achieved solid union and none of the implants had evidence of loosening or breakage. Postoperative alignment was within 10° of anatomic in 4 patients, 1 patient had 23° of valgus angulation, and 1 patient had a posterior angulation of 12°. Mean humeral shortening was 2.8 cm. The mean Constant and Murley joint function score was 88.3 points, the mean MEPI was 96.7 points, and the mean VAS was 0.7. All patients reported significant improvement in shoulder and elbow function, and each patient was able to resume work and was satisfied with the treatment.Plate fixation combined with autogenous iliac crest bone grafting is an excellent option for the treatment of longstanding humeral shaft nonunion.
Leptomeningeal metastasis (LM) refers to the dissemination of malignant cells in the subarachnoid space, pia, and arachnoid mater and is a severe condition associated with metastatic solid tumors. The most common solid tumor that develops into LM is lung cancer and the incidence increased in patients with advanced non‐small‐cell lung cancer (NSCLC) with targetable mutations. However, tissue biopsy of LM is inaccessible, leading to the paucity of genomic profiles of LM to guide targeted treatments and explore biological mechanisms. In recent years, liquid biopsy is considered a minimally invasive and dynamic method to trace the genomic alterations of cancer cells and some studies started to perform sequencing of cerebrospinal fluid (CSF) in patients with LM to reveal the targeted mutations and genomic profiles. In this review, we focused on studies performed sequencing of CSF in NSCLC patients with LM and summarized the sequencing results and their commonality. As the only way to reveal the genomic landscapes of LM, our review provided evidence that sequencing of CSF is a promising management method in LM patients to dynamically guide target therapy and monitor intracranial tumor response. Furthermore, it reveals a unique genomic profile of LM including driver genes, drug‐resistant mutations, and a number of copy number variations. Sequencing of CSF in LM patients seems to provide more comprehensive genomic information than we expected and the biological significance behind the genomic alternations needs further study.
ObjectivesFor accurate diagnosis of leptomeningeal metastasis (LM) and to avoid unnecessary examinations or lumber puncture (LP), we develop two diagnostic prediction models for patients with solid tumors.Study Design, Setting, and ParticipantsThis is a retrospective cohort study launched at the Second Affiliated Hospital of Dalian Medical University. In total, 206 patients who had been admitted between January 2005 and December 2021 with a solid tumor and clinical suspicion of LM were enrolled to develop model A. In total, 152 patients of them who underwent LPs for cytology and biochemistry were enrolled to develop model B.Model DevelopmentDiagnostic factors included skull metastasis, active brain metastasis, progressed extracranial disease, number of extracranial organs involved, number of symptoms, cerebrospinal fluid (CSF) protein, and CSF glucose. The outcome predictor was defined as the clinical diagnosis of LM. Logistic least absolute shrinkage and selection operator (LASSO) regression was used to identify relevant variables and fit the prediction model. A calibration curve and the concordance index (c-index) were used to evaluate calibration and discrimination ability. The n-fold cross-validation method was used to internally validate the models. The decision curve analysis (DCA) and the interventions avoided analysis (IAA) were used to evaluate the clinical application.ResultsThe area under the curve (AUC) values of models A and B were 0.812 (95% CI: 0.751–0.874) and 0.901 (95% CI: 0.852–0.949). Respectively, compared to the first magnetic resonance imaging (MRI) and first LP, models A and B showed a higher AUC (model A vs. first MRI: 0.812 vs. 0.743, p = 0.087; model B vs. first LP: 0.901 vs. 0.800, p = 0.010). The validated c-indexes were 0.810 (95% CI: 0.670–0.952) and 0.899 (95% CI: 0.823–0.977). The calibration curves show a good calibrated ability. The evaluation of clinical application revealed a net clinical benefit and a reduction of unnecessary interventions using the models.ConclusionsThe models can help improve diagnostic accuracy when used alone or in combination with conventional work-up. They also exhibit a net clinical benefit in medical decisions and in avoiding unnecessary interventions for patients with LM. Studies focused on external validation of our models are necessary in the future.
Purpose: Pyrotinib, a novel human epidermal growth factor receptor 2 (HER2)-targeted tyrosine kinase inhibitor (TKI), has led to remarkable survival outcomes in HER2-positive advanced breast cancer (ABC) in clinical trials and was approved for second-line standards of treatment for HER2+ ABC in China. However, the clinical trials could not fully reflect reality of clinical practice, and predictive factors were still lacking. This study aimed to assess the actual efficacy and safety of pyrotinib in HER2+ ABC in real-world setting. Patients and Methods: In this multicenter, retrospective, observational real-world study, we analyzed 171 patients with HER2+ ABC, who received pyrotinib-based treatment from November 2017 to November 2020. The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR) and safety. Results: Up to November 30, 2021, the median PFS (mPFS) was 12.0 months for all patients. One hundred and sixty-two patients (94.7%) with measurable lesions had been included in efficacy assessment. The ORR and CBR were 45.1% and 81.5%, respectively. A significantly longer PFS was reported in patients who received pyrotinib as first-line treatment, had the ECOG-PS of 0-1, as well as those who were lapatinib-naive. In addition, multivariable analysis indicated that ECOG-PS of 2-4, positive hormone receptor (HR) status, and presence of visceral metastasis were independent negative predictors of PFS. As far as we know, this study first reported the survival outcome of pyrotinib cross-line treatment, with a mPFS of 5.0 months. All grades of adverse events (AEs) occurred in 171 patients (100%), and the most common AE was diarrhea (86.5%). Conclusion:This study further demonstrated the outstanding efficacy and safety of pyrotinib and reported the potential predictors of survival in HER2+ ABC.
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