Multicenter Retrospective Clinical Study Research Articles

A Novel Parallel-Walled Dental Implant with a Self-Tapping Apex, Conical Connection, and Platform Shifting: Short-Term Results from a Retrospective Multicenter Clinical Study.

This multicenter retrospective study assessed clinical and radiographic outcomes of 686 parallel-walled conical-connection implants consecutively placed in 281 partially and fully edentulous patients. Implants were placed in healed and postextraction sites and subjected to immediate, early, or delayed loading. With a mean follow-up of 10 ± 6.7 months, the implant survival rate was 97.7%, while mean marginal bone loss was 0.7 ± 1.5 mm between implant placement and 1 year (n = 290 implants) and 0.1 ± 0.6 mm between 1 and 2 years (n = 72 implants). Advanced patient age and longer implants were associated with fewer implant failures, while different crestal positions at implant placement were not associated with differences in implant survival or changes in marginal bone level over time.

Effects of hydroxyethyl starch and gelatin on the risk of acute kidney injury following orthotopic liver transplantation: A multicenter retrospective comparative clinical study.

ObjectivesThis multicenter retrospective study aimed to compare the effects of HES and gelatin (GEL) on the risk of post-OLT AKI.MethodA total of 1,672 patients undergoing OLT were enrolled from major transplant centers in China between 2005 and 2013. These patients were divided into three groups: GEL, hydroxyethyl starch (HES), and GEL + HES group.ResultsThere was no significant difference in the incidence of post-OLT AKI among the GEL, HES, and GEL + HES groups. The GEL + HES group had a lower incidence of stage II post-OLT AKI than the other two groups. Compared with patients receiving GEL, patients receiving HES did not harbor an increased risk of AKI. Our results showed that MELD score (adjusted odds ratio [OR], 1.579; 95% confidence interval [CI], 1.123–2.219; P = 0.009) and preoperative anemia (adjusted OR, 1.533; 95% CI, 1.212–1.939; P < 0.001) were independent risk factors for post-OLT AKI, and normal preoperative Scr level (vs abnormal; adjusted OR, 0.402; 95% CI, 0.222–0.729; P = 0.003) was independent protective factors for post-OLT AKI.ConclusionThis large-scale multicenter retrospective study found that the intraoperative use of HES did not increase the overall incidence of post-OLT AKI in patients when compared with GEL, and whether to increase the risk of post-OLT AKI needs to be further explored.

Endocrine Therapy for Hormone Receptor-Positive Advanced Breast Cancer: A Nation-Wide Multicenter Epidemiological Study in China.

BackgroundClinical guidelines generally recommend endocrine therapy (ET) as first-line treatment of hormone receptor-positive advanced breast cancer (HR+ ABC) whereas chemotherapy (CT) should be considered in the presence of life-threatening disease or limited clinical benefit after three sequential ET regimens. However, it is unclear if real-world clinical practice is in accordance with the current guidelines. This study was to present the real-world treatment patterns and ET regimens among HR+ ABC patients in China.MethodsUsing data from the Nation-wide Multicenter Retrospective Clinical Epidemiology Study of Female Advanced Breast Cancer in China (ClinicalTrials.gov identifier: NCT03047889), we investigated the clinicopathological characteristics, clinical profiles, and treatment patterns of HR+ ABC patients from January 2012 to December 2014.ResultsA total of 2,342 patients with HR+ ABC were included in this study. Our findings revealed that, in comparisons with those receiving initial CT (n = 1445), patients initiated ET (n =402) were significantly older, later recurrent after adjuvant treatment, with a lower rate of visceral involvement and a decreasing quantity of metastatic sites. A total of 1,308 patients received palliative ET while only 18.9% patients (n = 247) reached three lines of ET. Among patients completing more than one line of ET, the median treatment duration was 8 months for the first line, 6 months for the second line, and 3 months for the third line for patients receiving ET. In the advanced setting, the choices of palliative ET regimens were diverse, yet aromatase inhibitor (AI) monotherapy was still the overall mainstay of ET; in contrast, patients were less accessible to everolimus plus AI regimen in this population.ConclusionsLess than one quarter of patients initiated palliative ET for HR+ ABC in routine clinical practice. Patients who received multi-lines of ET experienced successive shorter durations following each line of therapy. This real-life data provides a solid overview of ET for HR+ ABC from China, indicating unmet need for treatment options that improve the effectiveness of endocrine therapy.

Obstructive Sleep Apnea and Incident Cancer: A Large Retrospective Multicenter Clinical Cohort Study.

To examine the association between the severity of obstructive sleep apnea (OSA) and nocturnal hypoxemia with incident cancer. This was a multicenter retrospective clinical cohort study using linked clinical and provincial health administrative data on consecutive adults who underwent a diagnostic sleep study between 1994 and 2017 in four academic hospitals (Canada) who were free of cancer at baseline. Cancer status was derived from the Ontario Cancer Registry. Cox cause-specific regressions were utilized to address the objective and to calculate the 10-year absolute risk difference (ARD) in the marginal probability of incident cancer and the number needed to harm (NNH). Of 33,997 individuals considered, 33,711 with no missing OSA severity were included: median age, 50 years; 58% male; and 23% with severe OSA (apnea-hypopnea index >30). Of the 18,458 individuals with information on sleep time spent with oxygen saturation (SaO2) <90%, 5% spent >30% of sleep with SaO2 <90% (severe nocturnal hypoxemia). Over a median of 7 years, 2,498 of 33,711 (7%) individuals developed cancer, with an incidence rate of 10.3 (10.0-10.8) per 1,000 person-years. Controlling for confounders, severe OSA was associated with a 15% increased hazard of developing cancer compared with no OSA (HR = 1.15, 1.02-1.30; ARD = 1.28%, 0.20-2.37; and NNH = 78). Severe hypoxemia was associated with about 30% increased hazard (HR = 1.32, 1.08-1.61; ARD = 2.38%, 0.47-4.31; and NNH = 42). In a large cohort of individuals with suspected OSA free of cancer at baseline, the severity of OSA and nocturnal hypoxemia was independently associated with incident cancer. These findings suggest the need for more targeted cancer risk awareness in individuals with OSA.

Effectiveness and safety of nivolumab in patients with head and neck cancer in Japanese real-world clinical practice: a multicenter retrospective clinical study

BackgroundTo fill the data gap between clinical trials and real-world settings, this study assessed the overall effectiveness and safety of nivolumab in patients with head and neck cancer (HNC) during Japanese real-world clinical practice.MethodsThis was a multicenter, retrospective study in Japanese patients with recurrent or metastatic HNC who received nivolumab for the first time between July and December 2017. Data on the clinical use, effectiveness, and safety of nivolumab were extracted from patient medical records.ResultsOverall, 256 patients were enrolled in this study. The median duration of nivolumab treatment was 72.5 days, with patients receiving a median of 6.0 (range 1–27) doses. Median overall survival (OS) was 9.5 (95% confidence interval [CI] 8.2–12.0) months and the estimated 12-month OS rate was 43.2%. The objective response rate (ORR) was 15.7% overall and 21.1%, 7.1%, and 13.6% in patients with primary nasopharynx, maxillary sinus, and salivary gland tumors, respectively, who had been excluded from CheckMate 141. Grade ≥ 3 immune-related adverse events occurred in 5.9% of patients. No new safety signals were identified compared with adverse events noted in CheckMate 141.ConclusionsThe effectiveness and safety of nivolumab in real-world clinical practice are consistent with data from the CheckMate 141 clinical trial. Therapeutic response was also observed in the groups of patients excluded from CheckMate 141.Trial registration numberUMIN-CTR (UMIN000032600), Clinicaltrials.gov (NCT03569436)

Adjuvant intravesical chemotherapy with titanium glycerosolvate aquacomplex versus BCG therapy in patients with high risk nonmuscle-invasive bladder cancer

Objective: to compare recurrence rate, progression rate and recurrence-free survival in patients with high-risk non-muscle-invasive bladder cancer (NMIBC) after adjuvant intravesical chemotherapy (IVCT) with titanium glycerosolvate aquacomplex (TGA) versus intravesical BCG therapy.Material and methods. In a retrospective multicenter clinical study initially were included 126 patients with NMIBC. Of all 126 patients, 94 patients with high-risk NMIBC were selected and divided into 2 groups using a pseudo randomization with propensity score matching to minimize systematic differences in the process of forming groups. The treatment group (n = 55) consisted of patients with high-risk NMIBC who received a 6-week course of adjuvant IVCT with TGA. In the control group (n = 39) patients received an induction 6-week course of adjuvant intravesical BCG therapy, 19 (49 %) of 39 patients received maintenance therapy. Both methods were compared according to recurrence rate, progression rate and recurrence-free survival. Significance of difference was set at p &lt;0.05.Results. The compared groups of patients were well balanced in terms of clinical and morphological characteristics and the main risk factors for recurrence and progression of non-muscle-invasive bladder cancer, no significant differences were found between the groups (p &gt;0.5). The recurrence rate in treatment and control groups was 33 % and 23 %, respectively (p = 0.31). The disease progression was observed in 1 (2 %) patient in the treatment group and in 4 (13 %) patients in the control group (p = 0.08). The median disease-free survival in both groups of patients was not reached at the time of analysis. Three- and five-year recurrence-free survival in the treatment group of patients were 71 % and 62 %, respectively; in the control group — 76 % and 72 %, respectively. There were no significant differences between recurrence-free-survival curves of the treatment and control groups (p = 0.58).Conclusion. Adjuvant IVCT with TGA has demonstrated a clinical effectiveness comparable to intravesical BCG therapy and it can be used as an alternative method of treatment in patients with high-risk NMIBC.

Dual-Plane Retro-pectoral Versus Pre-pectoral DTI Breast Reconstruction: An Italian Multicenter Experience

BackgroundThe use of conservative mastectomies has risen significantly during the last few years. The reconstructive choice of direct-to-implant reconstruction has become more practicable with modern mastectomy techniques. The initial trend in Italian centers was to use dual-plane hybrid reconstruction. However, a high level of complications has been registered. From 2015 onward, in our centers, a pre-pectoral approach has been adopted. The authors sought to describe the Italian trend to gradually discard the sub-pectoral technique with lower lateral pole coverage of the prosthesis using ADMs comparing it with the pre-pectoral approach with ADMs, without any muscle dissection, in terms of complication rates.Materials and MethodsA multicenter retrospective clinical study was performed from January 2010 to June 2018. The enrolled patients were divided into two groups: Cases with an ADM-only coverage pre-pectoral reconstruction made up the first group (Group 1). Those with the retro-pectoral muscular position + ADM implant coverage comprised the second one (Group 2). Complications such as seroma, hematoma, wound dehiscence, surgical site infection, reconstruction failure, animation deformity and capsular contracture were recorded.ResultsWe performed 716 direct-to-implant reconstructions: 509 were partially sub-pectoral and 207 were pre-pectoral. Minimum follow-up was 1 year. Incidence of complications was higher in dual-plane reconstructions. There were statistical significant differences in the rates of seroma and hematoma.ConclusionUsing the pre-pectoral approach, the authors have experienced favorable aesthetics and superior clinical and functional outcomes. Retro-pectoral muscular ADM implant coverage has to be considered only in specific complicated second-stage surgeries.Level of Evidence VThis journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Association between obesity and clinical prognosis in patients infected with SARS-CoV-2

BackgroundIt is well established that obesity is a disease of sustained low-grade inflammation. However, it is currently unknown if obesity plays a role in the clinical manifestations and prognosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients. In this study, we aimed to investigate whether obesity played a role in clinical manifestations and prognosis in patients infected with SARS-CoV-2.MethodsThis is a retrospective multicenter clinical study. A total of 96 patients hospitalized with SARS-CoV-2 infection were enrolled from Dongguan People’s Hospital, Nanfang hospital and the First Affiliated Hospital of Xiamen University between 23 January and 14 February 2020. Demographic and clinical data were extracted from medical records. Acute respiratory distress syndrome (ARDS) was defined as oxygenation index (PaO2/FiO2) ≤ 300 mmHg. We grouped patients through the body mass index (BMI). Associations were examined using the t test, χ2 test and multivariate logistic forward regression test.ResultsPatients with BMI < 24 were significantly younger (P = 0.025) with lower creatine kinase (P = 0.013), lower diastolic pressure blood (P = 0.035), lower serum creatinine (P = 0.012), lower lactate dehydrogenase (P = 0.001) and higher platelet count (P = 0.002). The BMI level was 20.78 ± 3.15 in patients without pneumonia compared with the patients with pneumonia (23.81 ± 3.49, P = 0.001). For patients without ARDS, an average BMI level of 22.65 ± 3.53 was observed, significantly lower than patients with ARDS (24.57 ± 3.59, P = 0.022). The mean BMI was 22.35 ± 3.56 in patients experienced with relieving the clinical symptoms or stable condition by radiographic tests, lower than patients with disease exacerbation with 24.89 ± 3.17 (P = 0.001). In addition, lymphocyte count (r = − 0.23, P = 0.027) and platelet count (r = − 0.44, P < 0.001) were negatively correlated with BMI. While hemoglobin (r = 0.267, P = 0.008), creatine kinase (r = 0.331, P = 0.001), serum creatinine (r = 0.424, P < 0.001) and lactate dehydrogenase (r = 0.343, P = 0.001) were significantly positive correlated with BMI. Multivariate analysis showed that older age (OR = 1.046, P = 0.009) and BMI ≥ 24 (OR = 1.258, P = 0.005) were independent risk factors associated ICU admission while BMI ≥ 24 (OR = 4.219, P = 0.007) was independent risk factor associated with radiographic disease exacerbation.ConclusionsOur study found BMI was significantly associated with clinical manifestations and prognosis of patients with SARS-CoV-2 infection. For patients with increased risk, clinicians should intervene promptly to avoid disease progression.

Clinical analysis of 67 cases of pure red cell aplastic anemia

目的总结纯红细胞再生障碍（PRCA）的继发因素、实验室特点、治疗方案及预后。方法本研究为多中心回顾性临床研究，纳入2010年6月1日至2019年6月1日初诊的18岁以上PRCA患者进行随访，并根据不同治疗方案与药物减量速度等进行疗效、生存的比较分析。结果共纳入67例PRCA患者，其中继发性PRCA占44.8%（30/67），最常见的基础疾病为胸腺瘤（10例）和T细胞大颗粒淋巴细胞白血病（6例）。PRCA患者总缓解率（ORR）为85.7%，3年总体生存（OS）率为（74.3±7.5）%。单用环孢素A治疗缓解率稍高于单用激素或环孢素A联合糖皮质激素[90.0%（36/40）对75.0%（12/16），P=0.147]。环孢素A治疗达完全缓解或部分缓解3~6个月后，每次减量25 mg/d，减量间隔≥1个月组中位无病生存时间长于减量间隔<1个月组[未达到对15（95% CI 7~23）个月，P<0.001]。有62.5%（10/16）患者复发后按初始治疗方案或增加剂量再次治疗仍有效。结论PRCA可发生于多种疾病，缓解率与生存率高，单用环孢素A治疗效果好，起效且稳定后需缓慢减量以降低复发率。

Macrophage activation syndrome associated with adult-onset Still's disease: a multicenter retrospective analysis.

To explore the clinical features, treatments, and prognostic factors of adult-onset Still's disease (AOSD)-associated macrophage activation syndrome (MAS), we conducted a multicenter retrospective clinical study of AOSD-associated MAS patients. AOSD patients were collected from six tertiary hospitals in China. Medical charts were reviewed and clinical information was recorded and analyzed. There were 447 AOSD patients enrolled into this retrospective clinical study. Among them, 55 were diagnosed with MAS. Liver dysfunction was the most reliable predictive factor for the screening of MAS in AOSD patients (OR = 75.744, 95%CI = 23.015-249.284, p < 0.0001). In multivariate analysis, clinical features including platelets < 100 × 109/L (OR = 9.546, p = 0.005), aspartate transaminase (AST) > 120U/L (OR = 25.853, p < 0.0001), triglycerides > 3mmol/L (OR = 12.9833, p = 0.011)), ferritin > 1500ng/mL (OR = 5.513, p = 0.050), as well as hemophagocytosis in bone puncture (OR = 18.132, p = 0.001) were highly associated with the occurrence of MAS. The mortality rate of total AOSD patients was 4.47%, MAS was the main cause of death in AOSD patients (OR = 11.705, 95%CI = 4.783-28.647, p < 0.0001). PLT ≤ 100 × 109/L (p = 0.0001), fibrinogen < 1.5g/L (p = 0.0286), splenomegaly (p = 0.0002), and liver dysfunction (p = 0.0008) highly suggested poor prognosis. MAS occurrence is the major cause of death in AOSD patients. Notable liver dysfunction, as well as splenomegaly, low number of platelets or neutrophils, high levels of serum ferritin, and reduced level of fibrinogen are risk factors for poor outcome. Key Points • This is a multicenter retrospective study of AOSD-associated MAS with large number of cases.

Prevalence and Diagnosis of Diabetic Cardiovascular Autonomic Neuropathy in Beijing, China: A Retrospective Multicenter Clinical Study.

Cardiovascular autonomic neuropathy (CAN) is a debilitating condition occurring among diabetic patients especially those with long duration of disease. Whereas incidences and treatment of CAN has been well described for Western populations, fewer studies have been conducted among the Chinese. This study, therefore, aimed to assess the prevalence of CAN among sampled Chinese diabetic patients. Accordingly, 2,048 participants with a history of type 1 diabetes mellitus (T1DM, 73) and type 2 diabetes mellitus (T2DM, 1975) were randomly sampled from 13 hospitals. Patients’ biodata were recorded, and autonomic nervous system function tests performed to aid in the preliminary diagnosis of CAN. The final CAN diagnosis was based on the Ewing’s test in which heart rate variation (HRV) values were evaluated through deep-breathing (DB), lying-to-standing (LS), and Valsalva (V) tests. Systolic blood pressure (SBP) variation values were also evaluated through LS. In the T1DM group, 61.6% patients were diagnosed with CAN and no differences were observed in the baseline and clinical data between this group and those without CAN (P > 0.05). In the T2DM group, 62.6% patients were diagnosed with CAN and statistically significant differences were found between the CAN and non- CAN group with regards to age, duration of diabetes, metformin treatment, retinopathy, and hypertension history (P < 0.05). The most common manifestations of CAN included weakness (28.6%), dizziness (23.4%), frequent urination (19.6%), upper body sweating (18.3%), and nocturia (15.9%). Additionally, duration of disease and age were independent risk factors for CAN in T1DM and T2DM, respectively. On diagnosis, a combination of the V test + LS test provided the highest sensitivity of detecting CAN among T1DM group (sensitivity = 97.6%, AUC = 0.887) while for T2DM category, DB test had the highest sensitivity (83.6%), and maximal AUC (0.856) was found with V test + DB test. The overall prevalence of diabetes with CAN in the study was up to 63%.

What are the clinical symptoms and physical signs for non-small cell lung cancer before diagnosis is made? A nation-wide multicenter 10-year retrospective study in China.

BackgroundMost lung cancer patients are diagnosed after the onset of symptoms. However, whether the symptoms of lung cancer were independently associated with the diagnosis of lung cancer is unknown, especially in the Chinese population.MethodsWe conducted a 10 years (2005‐2014) nationwide multicenter retrospective clinical epidemiology study of lung cancer patients diagnosed in China. As such, this study focused on nonsmall cell lung cancer (NSCLC). We calculated the odds ratios (ORs) for variables associated with the symptoms and physical signs using multivariate unconditional logistic regressions.ResultsA total of 7184 lung cancer patients were surveyed; finally, 6398 NSCLC patients with available information about their symptoms and physical signs were included in this analysis. The most common initial symptom and physical sign was chronic cough (4156, 65.0%), followed by sputum with blood (2110, 33.0%), chest pain (1146, 17.9%), shortness of breath (1090, 17.0%), neck and supraclavicular lymphadenectasis (629, 9.8%), weight loss (529, 8.3%), metastases pain (378, 5.9%), fatigue (307, 4.8%), fever (272, 4.3%), and dyspnea (270, 4.2%). Patients with squamous carcinoma and stage III disease were more likely to present with chronic cough (P < 0.0001) and sputum with blood (P < 0.0001) than patients with other pathological types and clinical stages, respectively. Metastases pain (P < 0.0001) and neck and supraclavicular lymphadenectasis (P = 0.0006) were more likely to occur in patients with nonsquamous carcinoma than in patients with other carcinomas. Additionally, patients with stage IV disease had a higher percentage of chest pain, shortness of breath, dyspnea, weight loss, and fatigue than patients with other stages of disease. In multivariable logistic analyses, compared with patients with adenocarcinoma, patients with squamous carcinoma were more likely to experience symptoms (OR = 2.885, 95% confidence interval [CI] 2.477‐3.359) but were less likely to present physical signs (OR = 0.844, 95% CI 0.721‐0.989). The odds of having both symptoms and physical signs were higher in patients with late‐stage disease than in those with early‐stage disease (P < 0.0001).ConclusionsThe symptoms and physical signs of lung cancer were associated with the stage and pathological diagnosis of NSCLC. Patients with squamous carcinoma were more likely to develop symptoms, but not signs, than patients with adenocarcinoma. The more advanced the stage at diagnosis, the more likely that symptoms or physical signs are to develop. Further prospective cohort studies are needed to explore these results.

A nomogram for predicting the HER2 status in female patients with breast cancer in China: a nationwide, multicenter, 10-year epidemiological study

BackgroundThe concordance rate of human epidermal growth factor receptor 2 (HER2) status between core needle biopsy (CNB) and subsequent excisional biopsies of the same tumor varies from 81 to 96%, which may cause inappropriate neoadjuvant therapy that impair the potential benefit from HER2 targeted therapy for patients. This study aimed to establish a nomogram to predict the HER2 status pre-operatively as an auxiliary diagnosis to CNB assessment.MethodsAmong 4211 breast cancer patients cataloged in the Nation-wide Multicenter 10-year Retrospective Clinical Epidemiological Study of Breast Cancer in China, 2291 patients with complete relevant information were included in this study, which were further randomized 3:1 and divided into a training set and a validation set. The nomogram was established based on independent predictors of HER2 positivity recognized by logistic regression analysis and further validated internally and externally.ResultsThe multivariate logistic regression analysis showed that T-stage, N-stage, estrogen receptor (ER) status, progesterone receptor (PR) status were independent predictors for HER2 status. The nomogram was thereby constructed by those independent predictors as well as histology type. The areas under the receiver operating characteristic curve (AUC) of the training set and the validation set were 0.636 and 0.681, respectively. The calibration plots demonstrated good fitness of the nomogram for HER2 status prediction. With the optimal cutoff value, the nomogram yielded 80.0% sensitivity, 43.1% specificity in the training set and 81.1% sensitivity, 49.8% specificity in the validation set.ConclusionsThe present nomogram can provide valuable information on HER2 status and combined with standard CNB assessment, clinicians could make more appropriate decision on neoadjuvant therapy of breast cancer.

Pilot study of the relationship between clinical classification of gallbladder cancer and prognosis: a retrospective multicenter clinical study

Objectives: To propose a novel clinical classification system of gallbladder cancer, and to investigate the differences of clinicopathological characteristics and prognosis based on patients who underwent radical resection with different types of gallbladder cancer. Methods: The clinical data of 1 059 patients with gallbladder cancer underwent radical resection in 12 institutions in China from January 2013 to December 2017 were retrospectively collected and analyzed.There were 389 males and 670 females, aged (62.0±10.5)years(range:22-88 years).According to the location of tumor and the mode of invasion,the tumors were divided into peritoneal type, hepatic type, hepatic hilum type and mixed type, the surgical procedures were divided into regional radical resection and extended radical resection.The correlation between different types and T stage, N stage, vascular invasion, neural invasion, median survival time and surgical procedures were analyzed.Rates were compared by χ(2) test, survival analysis was carried by Kaplan-Meier and Log-rank test. Results: Regional radical resection was performed in 940 cases,including 81 cases in T1 stage,859 cases in T2-T4 stage,119 cases underwent extended radical resection;R0 resection was achieved in 990 cases(93.5%).The overall median survival time was 28 months.There were 81 patients in Tis-T1 stage and 978 patients in T2-T4 stage.The classification of gallbladder cancer in patients with T2-T4 stage: 345 cases(35.3%)of peritoneal type, 331 cases(33.8%) of hepatic type, 122 cases(12.5%) of hepatic hilum type and 180 cases(18.4%) of mixed type.T stage(χ(2)=288.60,P<0.01),N stage(χ(2)=68.10, P<0.01), vascular invasion(χ(2)=128.70, P<0.01)and neural invasion(χ(2)=54.30, P<0.01)were significantly correlated with the classification.The median survival time of peritoneal type,hepatic type,hepatic hilum type and mixed type was 48 months,21 months,16 months and 11 months,respectively(χ(2)=80.60,P<0.01).There was no significant difference in median survival time between regional radical resection and extended radical resection in the peritoneal type,hepatic type,hepatic hilum type and mixed type(all P>0.05). Conclusion: With application of new clinical classification, different types of gallbladder cancer are proved to be correlated with TNM stage, malignant biological behavior and prognosis, which will facilitate us in preoperative evaluation,surgical planning and prognosis evaluation.

Survival outcomes of appendiceal mucinous neoplasms by histological type and stage: Analysis of 266 cases in a multicenter collaborative retrospective clinical study.

AimAppendiceal mucinous neoplasms are rare, and thus the literature is sparse with regard to histological types, staging, and prognosis. In particular, it is unclear how long‐term outcome may differ between mucinous adenocarcinomas and other adenocarcinomas. In the present study, we aimed to investigate the histological types and stages of appendiceal neoplasms, and to evaluate the prognostic impacts of these factors in patients with mucinous adenocarcinomas and non‐mucinous adenocarcinomas.MethodsPatients with appendiceal tumors diagnosed between 2007 and 2016 were retrospectively identified from the databases of 19 institutions in the Clinical Study Group of Osaka University, Colorectal Group.ResultsA total of 266 patients with appendiceal tumors were identified, of whom 130 had pathologically diagnosed adenocarcinomas, including 57 with mucinous adenocarcinomas and 73 with non‐mucinous adenocarcinomas. Five‐year overall survival (OS) rates were 64.5% for mucinous adenocarcinomas, and 49.0% for non‐mucinous adenocarcinomas. OS was significantly shorter among patients with non‐mucinous adenocarcinomas compared to mucinous adenocarcinomas. Among patients with mucinous adenocarcinomas, 5‐year OS rates were 53.6% for stage 0/I, 82.6% for II/III, and 48.4% for IV. Among patients with non‐mucinous adenocarcinomas, 5‐year OS rates were 90.9% for stage 0/I, 68.8% for II/III, and 7.1% for IV. Analysis of patients with stage IV disease revealed significantly shorter OS among patients with non‐mucinous adenocarcinomas compared to mucinous adenocarcinomas.ConclusionOur present findings showed a better prognosis in patients with mucinous adenocarcinomas compared to non‐mucinous adenocarcinomas. In this setting, Union for International Cancer Control staging was associated with prognosis for non‐mucinous adenocarcinomas, but not for mucinous adenocarcinomas.

A multicenter retrospective clinical study on "symptomatic facet of residual bone mass", a rare complication of percutaneous trasforaminal endoscopic discectomy

Objective Retrospective study and report on cases of symptomatic facet of residual bone caused by percutaneous transforaminal endoscopic discectomy (PTED), to analysis of its causes and revision strategies. Methods Seven cases of symptomatic facet of residual bone after PTED were found in six medical centers from July 2015 to November 2017.Weintroduced the course of diagnosis and treatment, to analysis of the causes, clinical features and revision strategies of the rare complication. Results Seven patients came from different medical centers (2 cases in Ningbo No.6 Hospital and 1 case in each of the other medical centers). The average age of the subject is 67.29±9.64 years (range from 57-83 years). Among them there were 1 male and 6 female. PTED was performed for all cases with lumbar disc herniation or stenosis. The operative segments were 1 of L2,3, 2 of L3,4, 3 of L4,5, 1 of L5S1. Symptoms occurred immediately after surgery in all cases except one after a week of operation and another one month later. Two cases were appeared symptom of contralateral irritation, and the rest were aggravated by the original symptoms. Two cerebrospinal fluid leakage caused by bone mass piercing the dural sac. The bone mass compressed the nerve root and caused 1 case of lower limb muscle weakness. Foraminoplasty was performed during PTED in all patients. After CT scan, 5 cases of bone mass were found on the same side of operation, and 2 cases were in the contralateral side. The shortest time for revision was 2 days and the longest 3 months. After conservative treatment, the symptoms were relieved in only one case. Revision surgeries were performed for all the other 6 cases, 2 with microendoscopic discectomy (MED), 1 mobile microendoscopic discectomy (MMED), 1 small incision operation, 1 PTED and 1 with minimal invasive surgery of transforaminal lumbar intervertebral fusion (MIS-TLIF). The VAS scores of low back pain and leg pain was significantly relieved from 8.67±0.52 to 1.50±0.55. Conclusion PTED may lead to residual bone mass in lumbar foraminoplasty. The penetration of the bone mass block into the spinal canal can cause the compression symptoms of the corresponding segment. The patients showed the corresponding spinal canal stenosis and nerve root irritation symptoms. A revision operation is required to remove the oppressed bone mass to relieve the symptoms as soon as possible if the conservative treatment not effective. Key words: Zygapophyseal joint; Multicenter study; Treatment outcome

Is focused magnetic resonance imaging adequate for treatment decision making in acute traumatic thoracic and lumbar spine fractures seen on whole spine computed tomography?

PURPOSETo assess whether a focused magnetic resonance imaging (MRI) limited to the region of known acute traumatic thoracic or lumbar fracture(s) would miss any clinically significant injuries that would change patient management. STUDY DESIGN/SETTINGA multicenter retrospective clinical study. PATIENT SAMPLEAdult patients with acute traumatic thoracic and/or lumbar spine fracture(s). OUTCOME MEASURESPathology identified on MRI (ligamentous disruption, epidural hematoma, and cord contusion), outside of the focused zone, an alteration in patient management, including surgical and nonsurgical, as a result of the identified pathology outside the focused zone. METHODSRecords were reviewed for all adult trauma patients who presented to the emergency department between 2008 and 2016 with one or more fracture(s) of the thoracic and/or lumbar spine identified on computed tomography (CT) and who underwent MRI of the entire thoracic and lumbar spine within 10 days. Exclusion criteria were patients with >4 fractured levels, pathologic fractures, isolated transverse, and/or spinous process fractures, prior vertebral augmentation, and prior thoracic or lumbar spine instrumentation. Patients with neurologic deficits or cervical spine fractures were also included. MRIs were reviewed independently by one spine surgeon and one musculoskeletal fellowship-trained emergency radiologist for posterior ligamentous complex (PLC) integrity, vertebral injury, epidural hematoma, and cord contusion. The surgeon also commented on the clinical significance of the pathology identified outside the focused zone. All cases in which pathology was identified outside of the focused zone (three levels above and below the fractures) were independently reviewed by a second spine surgeon to determine whether the pathology was clinically significant and would alter the treatment plan. RESULTSIn total, 126 patients with 216 fractures identified on CT were included, with a median age of 49 years. There were 81 males (64%). Sixty-two (49%) patients had isolated thoracolumbar junction injuries and 36 (29%) had injuries limited to a single fractured level. Forty-seven (37%) patients were managed operatively. PLC injury was identified by both readers in 36 (29%) patients with a percent agreement of 96% and κ coefficient of 0.91 (95% CI 0.87–0.95). Both readers independently agreed that there was no pathology identified on the complete thoracic and lumbar spine MRIs outside the focused zone in 107 (85%) patients. Injury outside the focused zone was identified by at least one reader in 19 (15%) patients. None of the readers identified PLC injury, cord edema, or noncontiguous epidural hematoma outside the focused zone. Percent agreement for outside pathology between the two readers was 92% with a κ coefficient of 0.60 (95% CI 0.48–0.72). The two spine surgeons independently agreed that none of the identified pathology outside of the focused zone altered management. CONCLUSIONSA focused MRI protocol of three levels above and below known thoracolumbar spine fractures would have missed radiological abnormality in 15% of patients. However, the pathology, such as vertebral body edema not appreciated on CT, was not clinically significant and did not alter patient care. Based on these findings, the investigators conclude that a focused protocol would decrease the imaging time while providing the information of the injured segment with minimal risk of missing any clinically significant injuries.

Development and validation of a risk score to predict 30-day mortality in patients with atrial fibrillation-related stroke: GPS-GF score

ABSTRACTObjective Stroke due to atrial fibrillation (AF) is common and frequently devastating. However, there is no specific tool to accurately estimate the risk of mortality. This study aims to develop and validate a comprehensive risk score for predicting 30-day mortality in the patients with AF-related stroke.Methods A retrospective multi-center clinical study was performed based on the data from the project of secondary prevention of stroke in patients with nonvalvular AF in Shaanxi province, China. A total of 1077 consecutive patients were randomly classified into derivation (66.7%, n = 718) and internal validation cohort (33.3%, n = 359). Independent predictors of 30-day mortality were obtained using univariate and multivariable analyses. The area under the receiver operating characteristic curve (AUROC) and the Hosmer–Lemeshow test were used to assess model discrimination and calibration, respectively.Results Two hundred patients (18.6%) of 1077 participants died within 30 days. An 8-point score was generated from the five independent predictors for 30-day mortality including Glasgow Coma Scale, pneumonia, midline shift on brain images, blood glucose, and female sex, which was named GPS-GF. The resulting score showed good discrimination (AUROC) and well calibrated (Hosmer–Lemeshow test) in the derivation (0.909; p = 0.102) and internal validation cohort (0.922; p = 0.153). Compared with iScore, the GPS-GF score exhibited remarkably better discriminative power and predictive accuracy regarding the 30-day mortality in patients with AF-related stroke.Conclusion The GPS-GF score is a simple and valid tool for predicting 30-day mortality in patients with AF-related stroke.

PSORS1C1 Hypomethylation Is Associated with Allopurinol-Induced Severe Cutaneous Adverse Reactions during Disease Onset Period: A Multicenter Retrospective Case-Control Clinical Study in Han Chinese.

Background: Allopurinol-induced severe cutaneous adverse reactions (SCARs), including drug rash with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS) and toxic epidermal necrosis (TEN), are life-threatening autoimmune reactions. Evidence is growing that epigenetic variation, particularly DNA methylation, is associated with autoimmune diseases. However, the potential role of aberrant DNA methylation in allopurinol-SCARs is largely unknown.Objective: To address the knowledge gap between allopurinol-SCARs and DNA methylation, we studied the DNA methylation profiles in peripheral blood cells from allopurinol-SCARs and allopurinol-tolerant subjects.Methods: A genome-scale DNA methylation profiling was conducted using the Illumina Infinium HumanMethylation450 (HM450) platform on 15 patients with allopurinol-SCARs (3 TEN, 2 SJS/TEN overlap and 10 SJS) and 20 age- and gender-matched allopurinol-tolerant controls at disease onset. Pyrosequencing was used to validate the candidate CpG (cytosine-guanine dinucleotide) sites in an independent cohort of 40 allopurinol-SCARs and 48 allopurinol-tolerants.Results: After bioinformatics analysis of methylation data obtained from HM450 BeadChip, we identified 41 differentially methylated CpG loci (P < 0.05) annotated to 26 genes showing altered DNA methylation between allopurinol-SCARs and allopurinol-tolerants. Among these genes, significant hypomethylation of PSORS1C1 (cg24926791) was further validated in a larger sample cohort, showing significant difference between DRESS and controls (P = 0.00127), ST (SJS and TEN) and controls (P = 3.75 × 10−13), and SCARs and controls (P = 5.93 × 10−15).Conclusions: Our data identified differentially methylated genes between allopurinol-SCARs and allopurinol-tolerant controls and showed that PSORS1C1 hypomethylation was associated with allopurinol-SCARs (OR = 30.22, 95%CI = 4.73–192.96) during disease onset, suggesting that aberrant DNA methylation may be a mechanism of allopurinol-SCARs.Limitations: Firstly, the data come from whole blood samples known to possess epigenetic heterogeneity, i. e., blood samples comprise a heterogeneous cell population with varying proportions of distinct cell-types with different DNA methylation patterns. Consequently, the interpretation of DNA methylation results should be performed with great caution due to the heterogeneous nature of the sample. Secondly, whether the identified disease-associated changes of epigenome precede disease onset, or result from the disease progression, needs further investigation. Comparing the methylation status before patients develop allopurinol-SCARs and after may help examine methylation levels from disease onset to disease progression.

Three-Year Outcomes of Cross-Linking PLUS (Combined Cross-Linking with Femtosecond Laser Intracorneal Ring Segments Implantation) for Management of Keratoconus.

Purpose To analyze the results of three-year outcomes of combined epithelium-on cross-linking with femtosecond laser ICRS (cross-linking PLUS) for keratoconus management. Design A retrospective multicenter clinical study. Methods 43 eyes of 38 patients were subjected to preoperative and postoperative UCVA, BCVA, refraction, Pentacam pachymetry, and keratometry examinations at 3-, 6-, 12-, 24-, and 36-month follow-up period. Results The preoperative and postoperative mean UCVA was 1.30 ± 0.48 (logMAR ± SD) and 0.82 ± 0.22 respectively. The preoperative and postoperative mean BCVA was 0.90 ± 0.40 and 0.60 ± 0.30, respectively. The preoperative and postoperative mean K average was 50.63 ± 0.87 (D ± SD) and 45.56 ± 0.98, respectively. The preoperative and postoperative mean pachymetry was 471 ± 92.36 (μm ± SD) and 423 ± 39.58, respectively. The preoperative and postoperative mean astigmatism was 7.55 ± 1.75 and 3.39 ± 1.26, respectively. One eye showed ICRS edge exposure while 6 eyes showed progression of keratoconus. Conclusion CXL PLUS was proved to be a successful procedure to halt progression (mainly by CXL) and to correct the refractive status of the keratoconic eye (mainly by ICRS). CXL PLUS performed a synergistic action correcting and maintaining the correction of both myopic and astigmatic components of keratoconus.