Three-Dimensional Computer-Aided Design Modeling and Printing for Accurate Toe-to-Hand Transplantation.

PURPOSE: To introduce toe-to-hand transplantation performed with the assistance of both bone and soft tissue modeling using 3-dimensional printing technology. METHODS: From May 2015 to October 2018, 31 patients (group A, 24 thumbs and 7 fingers) were included. Computed tomography scans were acquired using a spiral computed tomography scanner, and the data were processed with software. Bone, skin, and nail models were created for tailoring the flap taken from the great toe. The impact of foot pathology in terms of pain, disability, and activity restriction was assessed using the Foot Function Index. For comparison, we included 35 patients (group B) who underwent toe-to-hand transplantation without the assistance of 3-dimensional computer-aided modeling. RESULTS: The mean duration of follow-up of groups A and B was 26 months (range, 24-31 months) and 27 months (range, 24-33 months), respectively. The mean Foot Function Index of groups A and B was 5 (range: 0-15) and 17 (range, 0-39), respectively. CONCLUSIONS: Three-dimensional computer-aided modeling and printing provide geometric accuracy in toe-to-hand transplantation. It also may reduce the donor foot morbidity by accurate flap designing and harvesting. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

miR-1184 regulates inflammatory responses and cell apoptosis by targeting TRADD in an LPS-induced cell model of sepsis.

MicroRNAs (miRs) have been reported to be potential clinical biomarkers for sepsis. miR-1184 is a multifunctional microRNA that exerts roles in the development of various diseases. However, the role of miR-1184 in children with sepsis remain unknown. In the present study, THP-1 cells were stimulated with 1 µg/ml lipopolysaccharide (LPS) for 24 h to establish an in vitro sepsis model. Reverse transcription-quantitative PCR was used to evaluate the expression of miR-1184 in clinical specimens, and of IL-6, TNF-α, IL-1ß, miR-1184 and TNF receptor type 1-associated DEATH domain protein (TRADD) in cells with and without LPS treatment. Cell apoptosis was assessed using flow cytometry. Binding between miR-1184 and TRADD was predicted using bioinformatics software, and a luciferase reporter assay was performed to verify the interaction between miR-1184 and TRADD in LPS-induced THP-1 cells. In addition, western blot analysis was performed to detect TRADD and proteins associated with the NF-κB pathway. The results showed that miR-1184 was downregulated in the blood of children with sepsis and LPS-induced THP-1 cells. Overexpression of miR-1184 alleviated the LPS-induced production of inflammatory cytokines and cell apoptosis. Moreover, TRADD was verified to be a direct target of miR-1184. Upregulation of TRADD reversed the effects of miR-1184 on the LPS-induced inflammatory response and apoptosis of THP-1 cells. Furthermore, the NF-κB pathway was shown to be associated with the regulatory role of miR-1184 in sepsis. The present study provides evidence that miR-1184 exerts inhibitory effects on inflammatory responses and apoptosis in sepsis by targeting TRADD, which suggests that miR-1184 may be a novel potential target for the therapy of children with sepsis.

Epidemiology of Pediatric Severe Sepsis in Main PICU Centers in Southwest China.

OBJECTIVES: To estimate the prevalence, management, and outcomes of pediatric severe sepsis in the main PICUs in Southwest China. DESIGN: A prospective, observational, and multicenter study. SETTING: Eight PICUs in Southwest China with 19 (13-24) beds and 1,322 (1,066-1,452) annual admissions each. PATIENTS: A total of 10,598 patients (29 d to 18 yr old) were consecutively admitted between September 1, 2016, and August 31, 2017. All patients were screened and evaluated for severe sepsis or septic shock. Of them, 10,353 patients were excluded due to incomplete data or not meeting the consensus criteria for severe sepsis or septic shock; 245 patients were included with complete data. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Finally, 245 patients who were diagnosed with severe sepsis or septic shock were included in the study, with an incidence rate of 2.3%. Of them, 64.0% of the enrolled patients were male with 80.8% being less than 5 years old and 60.8% being from rural areas. The respiratory system was the most common organ system in which dysfunction was observed (76.7%) as well as the most frequently infected site (37.6%). The primary therapies were antibiotics (99.0%), immunoglobulin (88.3%), mechanical ventilation (78.4%), vasoactive infusions (59.6%), and corticosteroids (46.1%). Among the 188 patients who had respiratory dysfunction, 173(92%) required mechanical ventilation and 39 (20.7%) met the criteria for pediatric acute respiratory distress syndrome. Seven of the patients with pediatric acute respiratory distress syndrome died (7/39, 17.9%). The median durations for mechanical ventilation and vasoactive medications were 123.5 hours (35.25-226.00 hr) and 2 days (1-5 d), respectively. Eighty-six percent of patients had multiple organ dysfunction syndrome at the point at which severe sepsis was recognized, and 31% had underlying conditions. The hospital mortality rate was 18.8%. CONCLUSIONS: This report is the first to present the prevalence, treatment, and outcomes of pediatric severe sepsis in the main PICU centers in Southwest China. The mortality rate remains high; therefore, improved clinical management and implementation of large-scale clinical trials are necessary to improve early diagnoses and treatment.

A novel dynamic distraction external fixator for proximal interphalangeal joint fracture dislocation.

OBJECTIVE: To evaluate the efficacy of a novel dynamic distraction external fixator for proximal interphalangeal joint (PIPJ) fracture-dislocation. METHODS: From March 2005 to March 2014, 20 patients with PIPJ fracture-dislocation were treated with our technique. Function scores according to the Michigan Hand Outcome Questionnaire (MHQ) score, union time, grip strength, and range of motion (ROM) were recorded before and after treatment. RESULTS: All patients completed a mean follow-up of 22 months (range, 12-60 months). All patients achieved fracture union and joint reduction. The mean union time was 3 months (range, 2-6 months). The mean postoperative MHQ score was 88.00 ± 3.42 (range, 84.00-92.00). Postoperative grip strength of the affected sides was 92% of the contralateral sides. X-rays showed that the fracture line disappeared completely with a good joint contour. The range of extension in the PIPJ was -5° (range, -10°-0°). The range of flexion in the PIPJ was 89.40° ± 9.79° (range, 75°-100°). Postoperatively, four patients had slight narrowing of the joint space and two had an uneven articular surface. Pin breakage, loosening, and tract infection were not observed. CONCLUSIONS: The novel dynamic distraction external fixator is a promising option for PIPJ fracture-dislocation.

[First-line chemotherapy and its survival analysis of 394 patients with extensive-stage small cell lung cancer in a single institute].

BACKGROUND AND OBJECTIVE: Small cell lung cancer (SCLC) is the most malignant neuroendocrine tumor but highly sensitive to chemotherapy and radiotherapy. At present, the standard first-line chemotherapy regimen of extensive-stage SCLC is platinum combined etoposide regimen. However, most patients who receive first-line chemotherapy will relapse within one to two years. Once recurrent, it indicates poor prognosis. In this study, we analyzed the survival among all extensive-stage SCLC and patients who received first-line chemotherapy and determined prognostic factors. METHODS: Total of 394 patients who were diagnosed as extensive-stage small cell lung cancer from February 2001 to December 2011 hospitalized in Peking Union Medical College Hospital were collected. Kaplan-Meier method was used to calculate the overall survival (OS) and progression-free survival (PFS). Univariate analysis and Cox regression analysis were used to detect the influence factors of survival. RESULTS: The median OS of all extensive-stage small cell lung cancer was 14.8 months; 1-year, 2-year and 5-year survival rates were 58.9%, 27.2% and 7.8%, respectively. According to the results of univariate and Cox multivariate analysis, OS of extensive-stage SCLC was closely associated with age (P=0.006), ECOG PS (P=0.021), liver metastasis (P<0.001), bone metastasis (P<0.001) and chemotherapy (P<0.001). The mortality risk of patients who didn't receive chemotherapy was 4.919 times higher than that who received; the mortality risk of patients without liver, bone metastasis was reduced by approximately 50 percent. The first-line chemotherapy was mainly EP (DDP+VP-16) or CE (CBP+VP-16) regimens (accounting for 82.8%) with 4-6 cycles. The median OS and PFS in first-line chemotherapy were 15.1 months and 7.5 months, respectively. The result of Cox regression analysis indicated that OS in first-line chemotherapy was remarkably related to smoking history (P=0.041), liver metastasis (P<0.001), bone metastasis (P<0.001), chemotherapy cycle number (P<0.001); PFS was relevant with smoking history (P=0.003), liver metastasis (P=0.001), bone metastasis (P<0.001), chemotherapy cycle number (P<0.001). Thoracic radiotherapy was not an independent influence factor of OS and PFS in extensive-stage small cell lung cancer. CONCLUSIONS: The patients who were younger than 60-year old, with good KPS, absence of liver and bone metastasis had better prognosis. Patients should receive chemotherapy with first-line standard regimen (CE/EP regimen). It was beneficial to survival if the effect of first-line chemotherapy was SD or PR-CR and the proper chemotherapy cycle number was 4-6 cycles. The role of thoracic radiotherapy in extensive-stage small cell lung cancer needed to be investigated further.

[Value of surgery for stage IIIa non-small cell lung cancer].

BACKGROUND AND OBJECTIVE: Nowadays, comprehensive treatment, including surgery, chemotherapy and radiotherapy is advocated for stage III non-small cell lung cancer (NSCLC). However, many researchers have questioned the effectiveness of surgery. The aim of this study is to evaluate the effect of surgery for stage III NSCLC. METHODS: Between March 2002 and October 2012, 310 cases that have completed followed-up data with stage III NSCLC were received in the Peking Union Medical College Hospital. They were divided into surgical and non-surgical groups according to whether received surgery when diagnosed. In TNM staging, stage III NSCLC includes stage IIIa and IIIb, and stage IIIa NSCLC can be grouped into stage T4N0/T3-4N1M0 and T1-3N2M0 according to different N stages. Analyzed the enumeration data by Chi-Square test. Kaplan-Meier survival method was used to calculate the overall survival (OS) and progression-free survival (PFS), and to draw the survival curves. A P value less than 0.05 was evaluated as statistically significant. RESULTS: Three hundred and ten stage III NSCLC patients include surgical group 189 cases and non-surgical group 121 cases. One hundred and eighty-eight stage IIIa NSCLC patients include surgical group 152 cases and non-surgical group 36 cases. In stage IIIa, stage T4N0/T3-4N1M0 had 57 patients with 44 surgical and 13 non-surgical patients, and stage T1-3N2M0 had 131 patients with 108 surgical and 23 non-surgical patients. Thirty-seven out of 121 stage IIIb NSCLC patients received surgery. They had 22 stage T4N2M0 cases and 15 stage T1-4N3M0 cases. The patient whose performance status was 0 and staging was stage IIIa was more inclined to undergo surgery. For stage IIIa NSCLC patients, the median OS of surgical and non-surgical groups were 38.9 and 21.8 months, and the median PFS of them were 19.2 and 11.9 months respectively. The difference of OS between the two groups was significant (P=0.041), but the PFS of them had no significant difference (P=0.209). For stage T4N0/T3-4N1M0 which belongs to stage IIIa, the median OS of surgical and non-surgical groups were 48.7 and 20.1 months, and the median PFS of them were 14.6 and 10.5 months respectively. There were no significant differences of OS and PFS between the two groups (P>0.05). For stage T1-3N2M0 which also belongs to stage IIIa, the median OS of surgical and non-surgical groups were 38.9 and 30.8 months, and the median PFS of them were 19.8 and 12.7 months respectively. There were also no significant differences of OS and PFS between the two groups (P>0.05). The maximum diameter of tumor and auxillary chemotherapy had significant influences on OS and PFS of stage IIIa-N2 NSCLC patients, while the histology of tumor only influenced the OS of them (P<0.05). CONCLUSIONS: The patient whose performance status is 0 and staging is stage IIIa is more inclined to undergo surgery. Surgery can prolong OS of patients with stage IIIa, especially for stage T4N0/T3-4N1M0. However, it has no benefit on PFS. The maximum diameter of tumor and auxillary chemotherapy have significant influences on OS and PFS of stage IIIa-N2 NSCLC patients, while the histology of tumor only influence the OS of them.

[Second-line chemotherapy and its survival analysis of 181 patients with extensive-stage small cell lung cancer in a single institute].

BACKGROUND AND OBJECTIVE: Small cell lung cancer (SCLC) is the most malignant neuroendocrine tumor and sensitive to chemotherapy and radiotherapy. However, most patients who receive first-line chemotherapy will relapse within one to two years. Once recurrent, it indicates poor prognosis. Currently, the standard first-line chemotherapy regimen of extensive-stage SCLC is platinum combined etoposide regimen while the standard second-line chemotherapy regimen is open to debate. The aim of this study is to analysis the prognostic factors of second-line chemotherapy in extensive-stage SCLC and to compare the differences of objective response rate, side effects and survival among different second-line chemotherapy regimens. METHODS: 181 patients who were diagnosed as extensive-stage SCLC and received second-line chemotherapy were collected. χ(2) test was used to analysis the differences of enumeration data and between different groups. Kaplan-Meier method was used to calculate the overall survival (OS) and progression-free survival (PFS). Univariate analysis and Cox regression analysis were used to detect the prognostic factors. Objective response rate was evaluated by RECIST criteria and side effects were evaluated by WHO criteria. RESULTS: The patients who received second-line chemotherapy can be divided into 6 groups, namly group A (CE/EP regimen) 27 cases, group B (regimens containing TPT) 44 cases, group C (regimens containing CPT-11) 33 cases, group D (regimens containing TAX/DXL) 20 cases, group E (regimens containing IFO) 28 cases and group F (other regimens) 29 cases. The median OS in second-line chemotherapy as 7.0 months and was relevant with smoking history (P=0.004), ECOG PS (P<0.001), liver metastasis (P=0.019) and bone metastasis (P=0.028) independently. The median PFS in second-line chemotherapy as 3.0 months and was relevant with smoking history (P=0.034), ECOG PS (P=0.011) and bone metastasis (P=0.005). The response rate among six regimens was significantly different (P=0.017); There was not statistical significance between each group. As to side effects, the incidence of gastrointestinal reaction in group C was higher than any other group. The differences of OS and PFS between six regimens in second-line therapy were not statistically different (P=0.914, P=0.293). CONCLUSIONS: The most significant prognostic factor of extensive-stage small cell lung cancer patients who received second-line chemotherapy was ECOG PS. The most optimal second-line chemotherapy regimen with definite curatice effect was controversial.

[Postoperative survival of patients with stage IIIa non-small cell lung cancer].

BACKGROUND AND OBJECTIVE: At present, surgery is advocated for stage IIIa non-small cell lung cancer (NSCLC), and the survival of them is determined by many factors. The aim of this study is to analyze the influencing factors of prognosis for stage IIIa surgical patients. METHODS: Between March 2002 and October 2012, 151 surgical cases that have postoperative pathological finding of stage IIIa NSCLC with completed followed-up data were received in the Peking Union Medical College Hospital. According to different N stages, 151 patients were divided into T4N0/T3-4N1M0 and T1-3N2M0 stages. Kaplan-Meier survival method was used to calculate the overall survival (OS) and progression-free survival (PFS), and to proceed univariate analysis of survival. Cox regression analysis was used to conduct multivariate analysis. A p-value less than 0.05 was evaluated as statistically significant. RESULTS: 151 stage IIIa NSCLC patients had 43 stage T4N0/T3-4N1M0 cases and 108 stage T1-3N2M0 cases. The median OS and PFS of the whole group were 38.9 and 12.9 months respectively. The median OS of stage T4N0/T3-4N1M0 and T1-3N2M0 were 48.7 and 38.9 months. The median PFS of them were 14.9 and 19.8 months respectively. There were no significant differences of OS and PFS between two groups. Univariate and multivariate analysis indicated that postoperative chemotherapy had a significant influence on OS of the surgical patients with stage IIIa NSCLC (P=0.001), and family history of tumor had a significant influence on PFS (P<0.05). The maximum diameter of tumor had a significant influence on PFS only in univariate analysis. CONCLUSIONS: For stage IIIa NSCLC, postoperative chemotherapy can increase OS and PFS, but postoperative radiotherapy have no benefit on them.

[Research progress of the resistance mechanism of non-small cell lung cancer to EGFR-TKIs].

Nowadays, lung cancer is the malignant tumor of the highest morbidity and mortality over the world, and non-small cell lung cancer (NSCLC) makes up about 80%. There is a great many NSCLC patients have been in advanced stage when diagnosed. As a result, people pay more attention to curing advanced NSCLC. The standard treatment to advanced NSCLC is platinum-based combined chemotherapy. However, chemotherapy drugs usually have limited effects on improving the survival of the patients. Then exploring new therapies is extremely urgent to us. Now, molecular targeted therapy has been the most promising research area for the treatment of NSCLC with researches going deep into pathogenesis and biological behavior of lung cancer. Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have achieved a great success in the treatment of advanced NSCLC. Their representatives are erlotinib and gefitinib. The two drugs have been widely used to treat advanced NSCLCs worldwide, especially for the patients with EGFR activating mutations. However, after a period of treatment (median time is 6 to 12 months), most patients will develop drug resistance to EGFR-TKIs. Intense research in these NSCLCs has identified two major mechanisms of resistance to TKIs: primary and acquired resistances. The research about resistance mechanism of NSCLC to EGFR-TKIs is a hot one because of their excellent effects on improving overall and progression-free survival. The aim of this article was to summarize the development of the resistance mechanisms.

[Abdominal random single pedicled flap of three leaves for the treatment of multiple finger skin defects].

OBJECTIVE: To discuss the effect of abdominal random single pedicled flap of three leaves for skin defects construction of the ends of several fingers. METHODS: From March 2005 to October 2010, 30 patients (90 fingers) with skin defects of the ends of several fingers were treated by abdominal random single pedicled flap of three leaves, including 20 males (60 fingers) and 10 females (30 fingers) with an average age of 36 years old ranging from 15 to 56 years. The degloving injury or transverse defect of distal phalanx were treated with abdominal random single pedicled flap of three leaves. Postoperative survival of skin flap, flap shape, complications were observed, and the static two-point discrimination of flap were determined. RESULTS: All patients were followed up for 12.6 mouths in average. All the flaps survived. The color, texture and shape of the flaps were good. The static two-point discrimination was 5 to 10 mm. The function of the hands recovered satisfactory. CONCLUSION: The method of abdominal random single pedicled flap of three leaves has the advantages of simple, safe and less trauma for the donor site. The effect is satisfatory for skin defects construction of the ends of several fingers.

[Gefitinib in the treatment of advanced non-small cell lung cancer with brain metastasis].

OBJECTIVE: Brain metastasis is frequently found in patient with advanced non-small cell lung cancer. Gefitinib is a inhibitor of epidermal growth factor receptor and can be used for the treatment of advanced non-small cell lung cancer (NSCLC). The aim of this study was to evaluate the antitumor efficacy of Gefitinib in advanced NSCLC patients with brain metastasis. METHODS: Forty-four consecutive NSCLC patients with brain metastases were treated with gefitinib, which was administered orally at daily dose of 250 mg. Of these patients, 30 had been treated with WBRT and 42 received chemotherapy one month before enrolled into the study. RESULTS: Partial response (PR) was observed in 14 patients (31.8%), stable disease (SD) in 21 (47.7%) with an overall disease control rate of 79.5%. Median progression-free survival (PFS) was 9 months and median overall survival (OS) was 13.0 months. The difference in disease control rate between the patients who had previous WBRT and those without was not significant (P = 0.566). The toxicity is mild and tolerable. CONCLUSION: Our data shows that Gefitinib is safe and may be effective on brain metastasis, which may become an alternative treatment option for the patient with advanced NSCLC.