Long-term Follow-up Observation Research Articles

Prognostic impact of renal function trajectories and temporal variability amongst anticoagulated atrial fibrillation patients: a subgroup analysis of the SPORTIF III and V trials

Abstract Background Renal function is a major determinant of major adverse outcomes in patients with atrial fibrillation (AF). Scarce data are available about the impact of renal function trajectories and creatinine clearance (CrCl) temporal variability, on prognosis. Aim To evaluate the progression and impact of renal function impairment and variability on outcomes over a long-term follow-up observation in a cohort of anticoagulated AF patients. Methods We included warfarin-treated AF patients in SPORTIF trials with available creatinine clearance (according to Cockroft-Gault) at baseline and at least 4 evaluations throughout their follow-up. Patients with a BMI ≥45 kg/m2 were excluded from the analysis. Average successive variability (ASV) was used as measure of variability. Results Among 3665 original patients, 3366 (91.8%) were included in this analysis. Median [IQR] CHA2DS2-VASc score was 3 [2–4] and HAS-BLED was 3 [2–4]. At baseline, 876 (26.0%) patients had CKD (CrCl <60 mL/min), with 14 (0.4%) patients having severe CKD (<30 mL/min), with a mean (SD) CrCl of 86.7 (47.4) mL/min. Over a mean (SD) 577.1 (122.1) days of follow-up, a total of 521 new CKD cases were found with an overall incidence of 13.1 per 100 patient-years, with 91 new severe CKD cases (1.71 per 100 patient-years). Across follow-up, prevalence of CKD and severe CKD increased progressively (both p<0.001) [Figure]. Mean (SD) AVS was −0.567 (±2.803) mL/min. According to AVS, patients were divided into quartiles: i) Q1: +34.012/+0.450; ii) Q2: +0.449/−0.443; iii) Q3: −0.443/−1.503; Q4: −1.505/−19.750. While no difference was found in stroke/systemic embolism, rate of major bleeding was higher in Q4 (4.5%) and Q1 (4.0%) than in other quartiles (Q2 2.5%, Q3 2.0%; p=0.009) as well as all-cause death (Q4: 6.7%; p=0.003 compared to other quartiles). A Cox multivariate adjusted model documented that AVS Q1 and Q4 were independently associated with a higher risk of major bleeding, while Q4 was associated with a higher risk of all-cause death (Table). Conclusion In a cohort of AF patients treated with warfarin, characterized by a progressive increase in the proportion with CKD and severe CKD, the largest reduction in CrCl throughout follow-up was associated to an increased risk of major bleeding and all-cause death. Renal Function Trajectories Funding Acknowledgement Type of funding source: None

MORPHOFUNCTIONAL OUTCOMES OF LAPAROSCOPIC PYELOPLASTY IN INFANTS OF THE FIRST THREE MONTHS OF LIFE

Introduction. This study describes authors’ experience in performing laparoscopic pyeloplasty in infants whose age does not exceed 3 months of life, and compares pre- and postoperative results of these surgeries in order to answer the question - does the laparoscopic technology for the treatment of hydronephrosis in newborns and infants provide acceptable results based on improving kidney morphology and function? Material and methods. 105 children, aged 3 months, were enrolled into this retrospective study who for 8 years, since 2012, have been laparoscopically operated on for congenital hydronephrosis. Because of bilateral renal damage, a total of 110 surgeries were performed, including simultaneous pyeloplasty in 5 patients. All patients had dismembered pyeloplasty with the Anderson-Hynes technique via transparietal laparoscopic access. Indications for surgery were: decreased renal function with obstruction signs of urine outflow from the pelvis confirmed by radioisotope renography; a combination of reduction of parenchyma thickness and increase of pelvis diameter at serial ultrasound studies; or a combination of these pathologies with urinary tract infection. During the trial, the following parameters were recorded: demographic data, findings of perioperative diagnostic examinations, surgical details, recovery process after surgery and long-term consequences. Results. The average age of patients was 50.24 days. Of 105 patients, 60 (57.14%) were less than 1 month old, and the remaining 45 (42.86%) were 1-3 months old. Gender distribution in groups was as follows: m / f = 73:32. Unilateral operations on the left kidney were in 61.82% patients, on the right kidney - in 33.64% patients. 4.54% patients had bilateral pyeloplasty. Average duration of surgery was 73.07 minutes (40-120 minutes). The average length of hospital stay was 4.19 days (2-9 days). At the early postoperative period, 4 (3.6%) patients developed postoperative complications - urinoma formation. A comparison of pre- and postoperative renal morphometry findings by ultrasound and Doppler ultrasound examination showed a significant decrease of renal pelvis dimensions and improved renal blood flow. The pelvis size decreased in average from 23.5 to 5.5 mm (p = 0.001), and RI from 0.72 to 0.64 (p = 0.001). Functioning of the operated kidney, as showed by the radioisotope renography, improved from 34 to 45.27 (p = 0.001). Long-term follow-up observation revealed one relapse of the disease (0.9%) - stenosis of pyeloureteral anastomosis which required a repeated laparoscopic pyeloplasty. One patient (0.9%)/ who was under follow-up observation for 36 months, had deterioration and loss of kidney function without signs of renal obstruction at the level of pyeloureteral segment which required laparoscopic nephrectomy. Thus, taking into account one relapse and loss of kidney function in one patient, we can state that the effectiveness of laparoscopic pyeloplasty in our study was 98.2%. Conclusion. Summarizing results of the applied laparoscopic pyeloplasty in the youngest group of patients whose age does not exceed 3 months of life, it can be stated that the minimally invasive approach contributes to normalizing morphological and functional parameters of kidney.

Prognosis evaluation of universal acute coronary syndrome: the interplay between SYNTAX score and ApoB/ApoA1

BackgroundAcute coronary syndrome (ACS) is a group of clinical syndromes associated with substantial morbidity and mortality rate. SYNTAX and SYNTAX II score used to be a reference for surgical selection of coronary revascularization and prognosis evaluation in patients with 3-vessel or left main artery disease. In addition, apoB/apoA1 is an important predictor of ACS risk. This study aims to assess the prognosis value of different kinds of SYNTAX score together with apoB/apoA1 in universal ACS patients (Regardless of ACS type, lesion location and vessel numbers).MethodThree hundred ninety-six patients with ACS undergoing percutaneous coronary intervention(PCI)and coronary stenting from 2013 to 2014 were chosen and recorded the major adverse cardiovascular and cerebrovascular events (MACCE) and quality of life during the next 5 years. According to SYNTAX and SYNTAX II score, the patients were divided into low-risk, medium-risk and high-risk groups, and the clinical features, MACCE incidence and EQ-5D score at each time points were compared. And the predictive factors of MACCE incidence were analyzed.Results① Compared with SYNTAX low-risk group, MACCE incidence in 1 year significantly increased in medium/high risk group (p = 0.011). Compared with SYNTAX II low-risk group, MACCE incidence in 5 years significantly increased in medium and high-risk group (p = 0.032). ② Compared with SYNTAX II low-risk group, cardiovascular mortality in 3 and 5 years significantly elevated in high-risk group (p = 0.001, p<0.001 respectively). ③ Compared with SYNTAX II low and medium-risk group, EQ-5D score in 5 years significantly decreased in high-risk group (p = 0.019, p = 0.023 respectively). ④ ApoB/ApoA1 was more likely to be classified as high risk in SYNTAX/SYNTAX II medium and high-risk group (p = 0.023, p = 0.044 respectively). ⑤ Logistic regression analysis showed that apoB/apoA1 was an independent predictor of MACCE events in hospital and 5 years (p = 0.038, p = 0.016 respectively), SYNTAX score was an independent predictor of MACCE events in 1 year (medium-risk group: p = 0.02; high-risk group: p = 0.015) SYNTAX II score was an independent predictor of MACCE events in 5 yeasrs (p = 0.003).Conclusions① SYNTAX score has a high predictive value for short-term prognosis while SYNTAX II score is more predictive of long-term prognosis. ② SYNTAX II score is superior to SYNTAX score in predicting cardiovascular death. ③ The combination of apoB/apoA1 high-risk and SYNTAX II medium and high-risk group is the focus of clinical treatment and long-term follow-up observation.

Clinical Characteristics of Anti-GABA-B Receptor Encephalitis.

Objective: Anti-GABA-B (gamma aminobutyric acid-B) receptor encephalitis is an autoimmune disease mediated by GABA-B-related antibodies. To fully understand the disease, we collected clinical data from patients with GABA-B receptor encephalitis and conducted an analysis to draw conclusions.Methods: All patients with GABA-B receptor encephalitis from the Neurology Department of Beijing Tiantan Hospital, affiliated with Capital Medical University, from August 2015 to September 2019 were accepted as study subjects. The clinical data of the patients were analyzed retrospectively and included the general demographic characteristics, clinical manifestations, and auxiliary examinations, including laboratory results, electroencephalograms (EEGs), brain magnetic resonance imaging (MRI), and positron emission tomography (PET-CT) results, as well as treatments.Results: From August 2015 to September 2019, 14 cases of anti-GABA-B receptor encephalitis were diagnosed. Among these patients, middle-aged and elderly men were the main demographic, with an average age of 52 years; moreover, the onset of the disease was relatively sudden, and the time from onset to diagnosis was ~1 month. The main clinical symptoms were frequent epileptic seizures, cognitive dysfunction, and mental behavioral disorders. In seven (50%) patients, the leukocyte in cerebrospinal fluid (CSF) were increased. Five (36%) patients had elevated cerebrospinal fluid protein. In most patients, the oligoclonal bands (83%) of CSF were positive, and 24 h IgG levels (92%) were increased. Anti-Hu or anti-Yo antibodies were positive in two (14%) patients. Tumor markers in 10 (71%) patients indicated that neuron-specific enolase, gastrin-releasing precursor, non-small cell lung cancer-related antigen, or carcinoembryonic antigen levels were increased. EEG results often indicated slow waves, sharp waves, or spike waves in temporal areas. Brain MRI always showed high T2 signals in the medial temporal lobe, hippocampus, and amygdala and swelling in the medial temporal lobe and hippocampus. PET-CT scans almost showed abnormal metabolism in the hippocampus and temporal lobe. Three (21%) patients who underwent systemic PET-CT showed hypermetabolism in pulmonary parenchymal nodules and enlargement of mediastinal lymph nodes. All patients underwent high-dose hormone therapy or immunoglobulin immunotherapy. After treatment, the symptoms of epilepsy, cognitive disorders, and mental behavioral disorders improved to varying degrees. However, one patient died of lung cancer.Conclusion: Anti-GABA-B receptor encephalitis mainly occurred in middle-aged and elderly men, and the disease onset was relatively sudden. Before disease onset, some patients experienced fever and non-specific respiratory symptoms, which mainly manifested as frequent epileptic seizures, cognitive dysfunction, and abnormal mental behavior. MRI and PET-CT revealed abnormal signals and local metabolism, respectively, in the temporal lobe. Moreover, the disease has a close relationship with lung cancer, which requires long-term follow-up observation.

A Field Investigation on a Group of Morning Runners

The background of this article comes from the marathon craze in China. The main purpose of this paper is to analyze the common people's morning exercise behavior, reveal the motivation and social background behind people's running phenomenon, and provide reasonable suggestions for national fitness. This paper makes a long-term follow-up observation on the morning exercise activities and competition behaviors of a group of runners, by using sociological and anthropological research methods such as field investigation and deep description. This paper deeply depicts the group image of mass runners, describes the different mentality of different runners when they run and participate in competitions, reveals the social background and deep-seated motivation of mass fitness in the new era, so as to improve public fitness behavior and cultivate public fitness, to provide reference and suggestions for further promoting the construction of healthy China. The conclusion of this paper shows that stable material living conditions are the main cause of the upsurge of running and the paired running behavior reflects the fact that people's purpose of running is not only to keep fit or exercise, but also to meet the needs of people's social interaction.

P5609Outcomes of chimney technique for aortic arch diseases: a single-center experience with 226 cases

Abstract Objective The aim of the present study is to report our single-center experience with chimney technique for aortic arch diseases and the early- and mid-term outcomes in these patients. Methods From August 2012 to October 2017, 226 patients (mean age 54±12 years; 197 men) with aortic arch diseases underwent thoracic endovascular aortic repair combined with chimney stents. Pathologies included type B aortic dissection (n=185), aortic arch aneurysm/descending thoracic aortic aneurysm (n=13), aortic arch pseudoaneurysm (n=10), penetrating aortic ulcer (n=7), intramural hematoma (n=7), and aortic rupture (n=4). Results The aortic stent-grafts were deployed in zone 0 (n=22), zone 1 (n=13), and zone 2 (n=191). A total of 230 chimney stents were deployed (innominate artery, n=21; right common carotid artery, n=1; left common carotid artery, n=13; left subclavian artery, n=195). The technical success rate was 84% (189/226) and immediate type Ia endoleak occurred in 37 (16%) patients. In the early-term, four patients died, of which from aortic rupture (n=1), ventricular fibrillation (n=1) or major stroke (n=2). Four major strokes occurred (two patients died and two recovered), but no reintervention was recorded. Spinal cord ischemia developed in three patients. The mean duration of follow-up was 22±16 months. Late type Ia endoleaks were recorded in two patients. Chimney stent occlusions were recorded in six patients. During follow-up, five patients died, of which from aortic rupture (n=3), cerebral hemorrhage (n=1) or rectal cancer (n=1). Two major strokes occurred (one patient died and one recovered) and reintervention performed in one case. Conclusion The chimney technique for aortic arch diseases is safe and feasible. And long-term follow-up observation is needed.

Clinical analysis of juxtapapillary retinal capillary hemangioma

Objective: To discuss the clinical features and treatment of juxtapapillary retinal capillary hemangioma (JRCH). Methods: Retrospective study of the clinical data of 6 patients (7 eyes) who were diagnosed with JRCH, among which 2 eyes were treated by laser therapy (thermotherapy TTT or photodynamic therapy PDT), 2 eyes were treated by intravitreal anti-VEGF injection, 2 eyes with vitreous hemorrhage were treated with vitrectomy (PPV)+ anti-VEGF, and 1 eye was untreated. Results: In the 6 cases, the gender ratio of male to female is 2∶1 with average age of 46 years. Four eyes were associated with macular edema(57.1%), vitreous hemorrhage(n=2, 28.6%), and epiretinal membrane(n=1, 14.2%) in the initial examination. Three patients were associated with von Hippel-Lindau(VHL). During the follow-up period, the visual acuity of the 2 patients treated by TTT decreased. Among the 2 eyes treated by anti-VEGF, the visual acuity of 1 eye associated with macular edema increased, and the visual acuity of 1 eye with macular epiretinal membrane did not change significantly, the visual acuity of both 2 eyes treated by PPV+anti-VEGF improved, the vision of the 1 eye untreated appeared to be stable. Conclusions: Juxtapapillary retinal capillary hemangioma is the orange or red vascular hamartomas that occur on or adjacent to the optic nerve head. It is often associated with macular edema, vitreous hemorrhage, and local subretinal effusion. Symptomatic treatment of complications can effectively improve the visual acuity of patients, while long-term follow-up observation should be organized for patients without complications, laser treatment appears to be ineffective. (Chin J Ophthalmol, 2019, 55:609-615).

Removal of an endometrioma passing through the left greater sciatic foramen using a concomitant laparoscopic and transgluteal approach: case report

BackgroundThe combination of intrapelvic and extrapelvic endometriosis is a very rare condition in gynecology. Patients with endometriosis involving the sciatic nerve are easily misdiagnosed because they usually present with atypical symptoms of endometriosis. Here, we present a rare case of an endometrioma passing through the left greater sciatic foramen. Removal of the endometriotic lesion was performed with a concomitant laparoscopic and transgluteal approach through the cooperation of gynecologists and orthopedic (neuro)surgeons.Case presentationA 20-year-old woman presented with complaints of severe dysmenorrhea lasting for more than 6 years and dysfunction of her left lower limb lasting for approximately 4 months. Both CT and MRI demonstrated a suspected intrapelvic and extrapelvic endometriotic cyst (7.3 cm × 8.1 cm × 6.5 cm) passing through the left greater sciatic foramen. Laparoscopic exploration showed a cyst full of dark fluid occupying the left obturator fossa and extending outside the pelvis. A novel combination of transgluteal laparoscopy was performed for complete resection of the cyst and decompression of the sciatic nerve. Postoperative pathology confirmed the diagnosis of endometriosis. Long-term follow-up observation showed persistent pain relief and lower limb function recovery in the patient.Discussion and conclusionsWhen a woman complains of unexplained unilateral sciatica, especially a woman suffering from dysmenorrhea, endometriosis of the sciatica nerve should be considered as a potential etiology. Complete excision of the endometriotic lesion and adequate neurolysis (or decompression) of the sciatic nerve through the multidisciplinary cooperation of experienced gynecologists with proper training in laparoscopic pelvic (neuro)surgery and orthopedic (neuro)surgeons is effective.

Abstract P2-14-08: Clinicopathological features and prognosis of nipple–areola and skin flap recurrence after nipple-sparing mastectomy for breast cancer over 20 years

Abstract Background: Nipple-sparing mastectomy (NSM) is an increasingly popular surgical procedure for treatment of breast cancer. However, NSM is controversial because of its association with locoregional recurrence. We started performing NSM in 1978. Methods: We investigated the surgical safety including nipple necrosis, and nipple–areola recurrence (NAR) and skin flap recurrence (SFR) after NSM for 1071 patients with breast cancer, including 31 with stage 0, 414 with stage 1, 479 with stage 2, 141 with stage 3 and 6 with stage 4, from 1985 to 2017. Our NSM method involved creating a thick skin flap to avoid surgical complications. No patients received radiotherapy. In 1034 patients with stage 1–3 breast cancer treated with NSM who developed NAR or SFR, we evaluated cancer stage, nuclear grade, lymph node metastasis, tumor–nipple–areola distance, and histological classification as tubule forming, solid and scirrhous type. In 748 patients with early stage 1 and 2A breast cancer treated with NSM, NAR and SFR were evaluated for estrogen receptor and HER2 expression. We evaluated disease-free interval and frequency of late NAR and SFR. Results: Median follow-up after NSM was 87 (3–397) months. There was only one case of total nipple necrosis among all 1071 patients. There were 96 patients (9.0%) with local recurrence, including 44 (4.0%) with NAR and 52 (4.8%) with SFR. NAR was seen in 1 (3.1%), 14 (3.4%), 17 (5.1%), 5 (3.4%), 7 (5.0%) and 0 patients with stage 0, 1, 2A, 2B, 3 and 4 cancer, respectively. SFR was seen in 0, 15 (3.6%), 8 (2.7%), 7 (4.8%), 22 (15.6%) and 0 patients with stage 0, 1, 2A, 2B, 3 and 4 cancer, respectively. Median disease-free interval of NAR and SFR was 3.4 (0.96–22.3) and 2.5 (0.21–21.2) years, respectively. Twenty-three (53%), 12 (27.9%) and 6 (14%) patients had NAR at more than 3, 5 and 10 years after NSM, respectively. Twenty (38%), 13 (25%) and 6 (11.5%) patients had SFR at more than 3, 5 and 10 years after NSM, respectively. Therefore, late NAR and SFR were observed. Patients with stage 1–3 cancer treated with NSM who had significantly more frequent NAR, were characterized by high nuclear grade and tubule-forming type cancer. Patients with significantly more frequent SFR were characterized by stage 3 cancer, positive lymph node metastasis and age ≤40 years. Patients with early stage breast cancer treated with NSM with significantly more frequent NAR had negative estrogen receptor expression, positive HER2 expression and shorter tumor–nipple–areola distance (≤2 cm). Overall survival was significantly better in patients with NAR (97% at 5 years and 80% at 10 years) than SFR (71% at 5 years and 50% at 10 years). Regarding SFR, overall survival was significantly worse for multiple (≥2) and diffuse (clinical inflammatory syndrome) recurrence than for single-nodule recurrence. There was no significant difference in prognosis between NAR and single-nodule SFR. Conclusions: Our data showed that clinicopathological features and prognosis differed between patients with NAR and SFR. There was no significant difference in prognosis between NAR and single-nodule SFR. Late NAR and SFR were seen, and careful long-term follow-up observation is necessary after NSM. Citation Format: Sakurai T, Suzuma T, Yoshimura G, Sasaki E, Umemura T, Sakurai T. Clinicopathological features and prognosis of nipple–areola and skin flap recurrence after nipple-sparing mastectomy for breast cancer over 20 years [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-14-08.

The net GHG flux assessment model of reservoir(G-res Tool) and its application in reservoirs in upper reaches of Yangtze River in China

目前准确量化温室气体排放量已成为气候变化研究和政策制定的关键.在IPCC水库温室气体净通量的概念性框架下，国际水电协会汇总分析了全球223座水库的CO₂和CH₄研究成果，构建了G-res Tool，其可以用于评估已建或待建水库在长时间尺度下的温室气体净通量.本文介绍了G-res Tool模型的基本原理与模型框架，利用模型内置数据库中所涉及的中国长江上游12座典型水库数据进行初步应用分析，12座水库温室气体净通量平均值为88.17 g CO₂e/（m²·a），在全球约7000座水库中所处水平为11.67%，处于低阈值范围.在水库温室气体净通量分析结果中，其他非相关人类活动产生的水库温室气体通量（UAS）在蓄水后总通量（Post）中所占比重远高于蓄水前温室气体通量（Pre）.长江上游水库蓄水后的CH₄和CO₂通量对于温室效应的贡献量相当.通过将G-res Tool模型蓄水后的温室气体通量评估结果和所涉及到的12座水库中已发表的数据对比分析发现，G-res Tool具有简便、适用面广等特点.但G-res Tool毕竟仍为经验性模型，其基本原理和模块设计上的内在缺陷在很大程度上限制了其应用范围并造成了一定的不确定性.对个案水库而言，长期跟踪观测与机理研究仍是未来减少水库温室气体净通量不确定性的关键.;The identification and accurate quantification of greenhouse gas (GHG) have become a key challenge for scientists and policymakers working on climate change. Under the conceptual framework of the IPCC for the net GHG flux of reservoir, the International Hydropower Association analyzed the 223 reservoirs with CO₂ and CH₄ emissions data from the actual and past scientific literature to develop the G-res Tool, whether for an existing reservoir or planned reservoir project can provide an estimate of the net GHG flux. This paper introduces the basic principle and model framework of the G-res Tool model. We conducted the preliminary analysis of 12 typical reservoirs in the upper reaches of the Yangtze River in China, which were involved in the model built-in database. The average net flux of greenhouse gas in the reservoirs was 88.17 g CO₂e/(m²·a), which ranked 11.67% and was in the low threshold range among about 7000 reservoirs globally. Comparing the evaluation results of each part in the model, the contribution of emissions from the reservoir due to Unrelated Anthropogenic Sources (UAS) in the post-impoundment GHG balance from the catchment (Post) was much higher than in the pre-impoundment GHG balance from the catchment after introduction of a reservoir (Pre). Based on the post-impoundment GHG balance from the reservoirs in the upper reaches of the Yangtze River in China, it was estimated that CH₄ and CO₂ fluxes contributed quite to the greenhouse effect. After analysis and comparison of the published GHG flux data of the 12 reservoirs involved, G-res Tool was easy to operate and showed a wider application range. However, G-res Tool, as an empirical model, still has few internal defects in its basic principles and model design parts, which may cause some uncertainties and limit its application range. For case reservoirs, long-term follow-up observation and mechanism study are still the main methods to reduce the uncertainty of the net GHG flux assessment in the future.

Construction of a risk model for the development of metachronous squamous cell carcinoma after endoscopic resection of esopahageal squamous cell carcinoma.

Previously, we identified that rs1229984 in ADH1B, rs671 in ALDH2, and smoking status were independently associated with the risk of developing metachronous squamous cell carcinoma (SCC) after endoscopic resection (ER) for esophageal SCC (ESCC). However, this analysis included cases with short-term follow-up. In the present study, we investigated the environmental and genetic factors associated with developing metachronous SCC using long-term follow-up observation after ER for ESCC. One hundred and thirty ESCC patients who underwent treatment with ER were followed up using endoscopy for ≥ 30months. We investigated the incidence of, and genetic/environmental factors associated with, metachronous SCC development after ER for ESCC. We also analyzed the potential risk factors for multiple metachronous SCC development using Cox's proportional hazards model. Moreover, we constructed a risk model for the development of metachronous SCC after ER for ESCC. Male, rs1229984, rs671, alcohol consumption (> 20g/day), smoking, and multiple Lugol-voiding lesions (LVLs) significantly affected the incidence of multiple metachronous SCCs. Multiple Cox proportional analysis revealed that rs1229984, rs671, alcohol consumption, smoking, and multiple LVLs were independently associated with the risk of developing metachronous SCC. Patients who had ≤ 2 risk factors did not develop metachronous SCC, and the risk of developing metachronous SCC in patients with ≥ 3 risk factors was significantly higher than in patients with ≤ 2 risk factors. The risk model using these 5 genetic and environmental factors is useful as an indication for multiple metachronous development in ESCC patients.

HTA Reports In Gene And Cell Therapy Products: A Scoping Review

The approval of Strimvelis from GlaxoSmithKline (GSK) for treatment of “bubble boy syndrome” raised questions in field of gene and cell therapy products (GCT), whether new models of modified HTA assessment methodologies are needed. The objective of our study is to overview HTA reports in GCTs in Europe and United States (US). A scoping review was performed on HTA reports in GCTs from exiting HTA agencies in Europe and US. The assessment reports planned to identify limited within 8 approved advanced therapy medicinal products (ATMPs) from European Medicines Agency (EMA) and 13 approved gene and cellular therapy products (GCTs) from US Food and Drug Administration (US FDA). The Language is limited in English and German. 12 HTA reports have been identified, five from NICE, three from IQWIG, three from HAS and one from LBI. Two reports based on systematic review of clinical studies, which assessed MACI from LBI and NICE. The other assessment reports used methods of experts or committee’s comments on the dossier submitted by the company. Compare to focusing points on safety and efficacy from regulatory bodies, HTA agencies focus on added value and actual benefit comparing to the comparator for current treatment. For example, for assessing a cancer treatment for melanoma called “Imlygic”, both IQWIG and NICE criticized on its comparator, IQWIG needed the company to submit additional three RCTs to prove their added value, NICE also needed one RCT to prove actual benefit, because they suggested the current comparator used in pivotal study is ineffective. The assessment process for GCTs is similar to other medical products but with more flexibility. For safety concerns, a long-term follow-up observation in a registry is recommended from different agencies. To assess cost-effectiveness, make appropriate health economic model, early involving payers and HTA in the development of GCTs is necessary.

Abstract P2-05-31: High-risk breast cancer is less likely to occur in the ductal hyperplasia lesions or low-grade DCIS ∼ Consideration of long-term follow-up observation after surgical biopsy

Abstract &amp;lt;Introduction&amp;gt; Even if many ductal hyperplasia lesions and low grade DCIS are detected by breast cancer screening using high-resolution imaging modalities, we have often experienced high-grade breast cancer as an interval cancer. We might consider whether the detection of ductal hyperplasia lesions and low grade DCIS in breast cancer screening really leads to a decrease in breast cancer death. Therefore, we examined the follow-up periods after the removal of lesions. And we would like to refer to the problem of over-diagnosis and over-treatment of LGDCIS. &amp;lt;Subjects and Methods&amp;gt; At our facility from 1997 to 2012, we examined 354 cases of ductal hyperplasia lesions which were treated with surgical biopsy and followed up with observations spanning at least three years. The ductal hyperplasia lesions shown here are the usual ductal hyperplasia, flat epithelial atypia, atypical ductal hyperplasia, and intraductal papilloma. The median of the follow-up observation period was 73 months. In addition, we had 153 cases of low-grade DCIS patients who underwent follow-up of more than three years without postoperative irradiation. The median of the follow-up period was 63 months. &amp;lt;Result&amp;gt; (1) In ductal hyperplasia lesions, 25 cancers occurred in both breasts. There were 13 cases of DCIS in the histopathological examination (52%) and 12 cases of invasive cancer (46%). In DCIS, low-grade DCIS of Van Nuys1 accounted for 86%. Luminal A was 75% in invasive cancer. Lymph node metastasis was observed in only two cases, with one case having one metastatic lymph node and the other having two. Her2 type and triple-negative type accounted for one case each. Her2 type was microinvasive carcinoma, and Ki67 was 22% in triple negative type. The potential for malignancy in both was not so high. In low-grade DCIS (non-irradiated), 11 cancers occurred in both breasts. There were 8 cases of DCIS (73%) and three cases of invasive cancer (27%). All of the DCIS cases were VanNuys1. All of the invasive cancer cases were luminal A. (2) We compared the cancer occurrence in benign lesions and low-grade DCIS (surgery side). The occurrence rate was 2.2% for benign lesions and 3.2% for low-grade DCIS over a five-year period. There was no significant difference found between the two groups. &amp;lt;Conclusion&amp;gt; High-risk breast cancer is less likely to occur in ductal hyperplasia lesions or low-grade DCIS. In other words, terminal duct lobular unit (TDLU) in both breast who had been affected with ductal hyperplasia or low grade DCIS lost a risk of the occurrence of high grade malignant cancer. Therefore, women with ductal hyperplasia and LGDCIS should be placed in the low-risk group of future breast cancer deaths. Small low grade DCIS might be regarded to be nearly as innocent as benign hyperplastic lesions. Citation Format: Takebe K, Arai T. High-risk breast cancer is less likely to occur in the ductal hyperplasia lesions or low-grade DCIS ∼ Consideration of long-term follow-up observation after surgical biopsy [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-05-31.

Implications from the Upper Limit of Radio Afterglow Emission of FRB 131104/Swift J0644.5-5111

Abstract A γ-ray transient, Swift J0644.5-5111, has been claimed to be associated with FRB 131104. However, a long-term radio imaging follow-up observation only placed an upper limit on the radio afterglow flux of Swift J0644.5-5111. Applying the external shock model, we perform a detailed constraint on the afterglow parameters for the FRB 131104/Swift J0644.5-5111 system. We find that for the commonly used microphysics shock parameters (e.g., , , and p = 2.3), if the fast radio burst (FRB) is indeed cosmological as inferred from its measured dispersion measure (DM), the ambient medium number density should be , which is the typical value for a compact binary merger environment but disfavors a massive star origin. Assuming a typical ISM density, one would require that the redshift of the FRB be much smaller than the value inferred from DM ( ), implying a non-cosmological origin of DM. The constraints are much looser if one adopts smaller and values, as observed in some gamma-ray burst afterglows. The FRB 131104/Swift J0644.5-5111 association remains plausible. We critically discuss possible progenitor models for the system.

Clinical safety and efficacy of conbercept intravitreal injection on high myopic choroidal neovascularization

Background choroidal neovascularization (CNV) is the common reason of visual acuity impairment in high myopia patients, which usually leads to irreversible central visual impairment. Objective This study was to evaluate the clinical efficacy and safety of conbercept intravitreal injection for CNV in high myopia. Methods Fifteen high myopia patients with macular CNV diagnosed by OCT and fluorescein fundus angiography (FFA) from July 2014 to July 2015 were retrospectively analyzed.All patients were performed with intravitreal injection of conbercept 0.5 mg (0.05 ml). The best corrected visual acuity (BCVA) and central macular thickness (CMT) were examined 1 day, l week, 4, 8 and 12 weeks after injection.The ocular and systemic complications relating to drug were also observed. Results Fifteen eyes of 15 patients totally received 45 times of conbercept intravitreal injection.Among the total, 1 eye only received 1 time of treatment, 2 eyes received 2 times of treatment, 12 eyes received 3 times of treatment and 1 eye received 4 times of treatments.After 12 weeks of treatment, FFA showed that fluorescein leakage disappeared in 10 eyes; fluorescein leakage area decreased in 4 eyes; fluorescein leakage was continued in 1 eye.The BCVA before treatment and at 4, 8 and 12 weeks after treatment were 0.61±0.46, 0.60±0.43, 0.41±0.53 and 0.41±0.51, with significant difference among them ( F=7.862, P<0.001). The CMT before treatment and at 4, 8 and 12 weeks after treatment were (280.33±14.40), (269.00±10.10), (261.93±7.80) and (259.53±6.30)μm respectively, with significant difference among them (F=32.520, P<0.001). None of the patients conducted anterior chamber puncture because of elevated intraocular pressure, and no intraocular inflammation, vitreous hemorrhage, retinal detachment and cardiovascular disease or other serious complications occurred. Conclusions Intravitreal injection of conbercept can relieve macular edema and improve the vision.It is an effective method for the treatment of CNV associated with high myopia, but long-term follow-up observation still need to perform. Key words: High myopia; Choroidal neovascularization; Conbercept; Central macular thickness; Best corrected visual acuity

Sequential therapy with cyclophosphamide and mycophenolic acid in patients with progressive immunoglobulin A nephropathy: a long-term follow-up.

In progressive immunoglobulin (Ig)A nephropathy (IgAN), cyclophosphamide pulse therapy (CyP), high-dose intravenous immunoglobulins (IVIg) and mycophenolic acid (MPA) have been used to stop progressive loss of renal function, but disease progression may occur after the end of the initial treatment. Here, we report the long-term follow-up of patients with progressive IgAN with MPA as maintenance therapy after CyP (CyP-MPA). In a median observation time of 6·2 years, we analysed the slopes of the loss of renal function of 47 patients with biopsy-proven IgAN and treated with CyP. Thirty-one patients with further progression were treated with MPA maintenance for a median time of 5·2 years. Follow-up was compared with symptomatic therapy and IVIg as historically matched control groups. Median loss of renal function was reduced significantly from 0·9 ml/min to 0·1 ml/min per month with CyP (P < 0·05), and with MPA in patients with a relapse from -0·4 ml/min to -0·1 ml/min per month (P < 0·05) until the end of the study. Proteinuria decreased significantly from 1·6 g/l to 1·0 g/l after CyP, and during MPA treatment to 0·6 g/l (P = 0·001 Friedman test). Median renal survival time was in patients with CyP 10·5 years (range = 3·2-17·8), with CyP-MPA 10·7 years (range = 8·3-13·1), with IVIg 4·7 years (range = 2·6-6·6), and in untreated patients 1·2 years (range = 0·8-1·6; log-rank test P < 0·01). In patients with progressive IgAN, our long-term follow-up observation indicates that sequential CyP-MPA therapy maintains renal survival significantly.

Diagnosis of 65 cases of ampullary renal pelvis after postnatal follow-up of 1,167 newborn infants with prenatally suspected hydronephrosis.

The aim of the present study was to assess the morbidity of ampullary renal pelvis (ARP) and document its natural history in post-natal life. A total of 1,167 newborn infants with prenatally suspected hydronephrosis were retrospectively analyzed. Of these, 65 patients were diagnosed with ARP by computed tomography urography (CTU) and/or magnetic resonance urography (MRU). All cases were followed up with ultrasonogrophy at 1, 3, 6 and 12 months after birth, and one case was followed up for 5 years. Changes in the separation of the renal pelvis collection system were recorded. Children with ARP accounted for 5.57% of the total cases (65/1,167) followed-up. No lack of connection between the renal calyces and the renal pelvis was detected. The long-term follow-up revealed that the separation of the renal pelvis collection system did not tend to increase over time. In addition to imaging examinations, long-term follow-up observation is recommended for the accurate diagnosis of pediatric ARP, particularly for differentiation from hydronephrosis.

A Long-Term Follow-Up and Comprehensive Observation of Risk and Prognosis Factors of Recurrence and Survival After Resection of Hepatocellular Carcinoma

Although HBV, liver function and tumor characteristics were proven as hepatocellular carcinoma (HCC) prognosis-related, no large-scale and long-term follow-up studies have ever given robust evidence about prognosis predictive effect and contribution to different stage of postoperation. In this study, we evaluated the influence of above index on overall survival (OS) and disease-free survival (DFS) and other clinical data in a rather large population and long-term follow-up. Our study consisted of 1,326 HCC patients who underwent radical resection from 1996 to 2010. Epidemiology, clinical and prognosis data were analyzed. Risk factors of OS and DFS were explored. Cumulative survival comparison between groups was performed with log-rank. Multivariate analysis for independent prognostic factors was determined by Cox proportional hazards model. HBsAg status was a universal factor of HCC recurrence, while preoperational albumin (ALB) and portal vein tumor thrombus (PVTT) affected survival during the whole lifetime. Early stage recurrence was associated with capsule intact [OR (95 %) = 1.54,1.12-2.12, p = 0.009], preoperational alpha-fetoprotein (AFP), TNM and BCLC stages were the most important prognosis factors of recurrence in the early 5 years and PVTT affected the rest time. Survival was mainly associated with tumor characteristic and ALB. Short-time survival was affected with age and AFP, while BCLC was related with the long-time survival. We confirmed that during different periods after resection, factors affecting prognosis did not remain unchanged. Liver function and tumor characteristic affected DFS and OS the whole time, especially the early recurrence. However, HBV infection situation was associated with later recurrence. PVTT showed an opposite effect between early and later recurrence.

Long-Term Follow-up Observation of the Safety, Immunogenicity, and Effectiveness of Gardasil™ in Adult Women

BackgroundPrevious analyses from a randomized trial in women aged 24–45 have shown the quadrivalent HPV vaccine to be efficacious in the prevention of infection, cervical intraepithelial neoplasia (CIN) and external genital lesions (EGL) related to HPV 6/11/16/18 through 4 years. In this report we present long term follow-up data on the efficacy, safety and immunogenicity of the quadrivalent HPV vaccine in adult women.Methods Follow-up data are from a study being conducted in 5 sites in Colombia designed to evaluate the long-term immunogenicity, effectiveness, and safety of the qHPV vaccine in women who were vaccinated at 24 to 45 years of age (in the original vaccine group during the base study [n = 684]) or 29 to 50 years of age (in the original placebo group during the base study [n = 651]). This analysis summarizes data collected as of the year 6 post-vaccination visit relative to day 1 of the base study (median follow-up of 6.26 years) from both the original base study and the Colombian follow-up.ResultsThere were no cases of HPV 6/11/16/18-related CIN or EGL during the extended follow-up phase in the per-protocol population. Immunogenicity persists against vaccine-related HPV types, and no evidence of HPV type replacement has been observed. No new serious adverse experiences have been reported.ConclusionsVaccination with qHPV vaccine provides generally safe and effective protection from HPV 6-, 11-, 16-, and 18-related genital warts and cervical dysplasia through 6 years following administration to 24–45 year-old women.Trial Registration Clinicaltrials.gov NCT00090220

Novel epidural baclofen infusion trial for intractable spasticity with long-term follow-up observation and a focused review of the literature

Background Intrathecal baclofen (ITB) infusion has been increasingly used in patients with intractable spasticity. Prior to the implantation of the permanent pump, a trial is usually conducted to document efficacy. Intrathecal bolus injection of baclofen, followed by serial evaluations to confirm the improvement of spasticity, has been most commonly used during such trials. However, for patients who refused to undergo ITB trial injection due to previous untoward complications such as intractable headache, there has been no other alternatives. Objective To report the first case of a successful epidural baclofen infusion trial, conducted as outpatient in a lady with severe spasticity due to multiple sclerosis; to report the long term follow-up observation (3 years) following the permanent intrathecal pump placement; and to conduct a focused review of the literature pertaining to epidural baclofen. Design Case report. Setting: Tertiary-care pain clinic. Case Report: A 62-year-old female with progressive spasticity of bilateral lower extremities and left upper extremity due to multiple sclerosis, not responding to multiple oral antispasticity drugs, was referred to clinic for ITB therapy. The patient adamantly declined ITB bolus trial due to previous episode of severe headache following lumbar puncture. Thus an outpatient epidural baclofen infusion was performed and was successful. Based on the positive response from the epidural infusion trial, a permanent IT pump was subsequently placed and the patient has had sustained reduction of her spasticity since pump implantation 3 years ago. Limitation: Single center case report. Conclusion In patients who are reluctant to the ITB bolus trial due to previous complication such as headache, an outpatient epidural baclofen infusion trial, when done properly, can serve as an alternative approach to the ITB trial and provides needed information