Radiotherapy plus cetuximab for locally advanced squamous cell head and neck cancer in patients with cisplatin-ineligible renal dysfunction: A retrospective study

Clinical trials have not fully demonstrated the efficacy and safety of radiotherapy plus cetuximab for locally advanced squamous cell head and neck cancer (LA-SCCHN) in patients with cisplatin-ineligible renal dysfunction. Patients who received radiotherapy plus cetuximab for LA-SCCHN at Chiba University Hospital (Chiba, Japan) between July 2013 and October 2018 were retrospectively reviewed. Background characteristics and locoregional control and overall survival rates were compared between patients with and without renal dysfunction. Survival was examined using Kaplan-Meier analysis and an adjusted Cox proportional hazards model. Kaplan-Meier analysis demonstrated that overall survival was shorter in patients with creatinine clearance of <45 ml/min (P=0.041; log-rank test). However, there was no difference in the locoregional control rate (P=0.477; log-rank test). Adjusted Cox analysis revealed that the risk of death was increased by 2.52-fold (hazard ratio, 2.52; 95% confidence interval, 1.01-6.30; P=0.048) if creatinine clearance was <45 ml/min. Moderate to severe renal dysfunction did not affect the locoregional control rate in patients with LA-SCCHN treated with radiotherapy plus cetuximab but was an adverse prognostic factor.     

Effects of hemodialysis and reduced estimated glomerular filtration rate in nonhemodialysis on clinical outcomes after fractional flow reserve-guided deferral of revascularization

The effect of renal dysfunction on clinical outcomes following fractional flow reserve (FFR)-guided deferral of revascularization remains unelucidated.We retrospectively analyzed 224 patients with atherosclerotic coronary lesions who underwent deferred revascularization based on an FFR of >0.80. The median follow-up interval was 28.1 months. Patients were divided into 2 groups: the hemodialysis (HD) and the non-HD group. The non-HD group was further classified into 2 subgroups according to their estimated glomerular filtration rate (eGFR) level: eGFR <45, equivalent to chronic kidney disease stage 3b-5 and eGFR ≥45. We evaluated major adverse cardiac events (MACE), defined as a composite of cardiac death, myocardial infarction, and any revascularization.MACE occurred in 36 patients (16.1%). The rate of HD was significantly higher in the MACE group (19% vs 6%, P < .01). In non-HD patients, the eGFR was significantly lower in the MACE group (51.2 vs 63.2 mL/min/1.73 m², P < .01). Overall, univariate Cox regression analysis revealed a significant relationship between HD and MACE (HR 2.91, P = .01), as did the multivariate model (HR 2.90, P = .01). Of the MACE, more deaths occurred in HD patients (15.8% vs 2.9%, P = .03). Among non-HD patients, eGFR <45 (HR 2.70, P = .02), FFR (per 0.01, HR 0.87, P < .01), and low-density lipoprotein cholesterol (per 10 mg/dL, HR 1.17, P = .02) were independent predictors of MACE. Any revascularization was more common in patients with eGFR<45 than in those with eGFR ≥45 (21.4% vs 7.3%, P = .02). Kaplan–Meier estimates revealed that the HD group showed a significantly lower MACE-free survival rate than the nonHD group (log-rank P < .01). In non-HD patients, the eGFR<45 group showed a lower MACE-free survival rate than the eGFR ≥45 group (log-rank P = .01).HD and reduced eGFR in non-HD patients were associated with adverse cardiac events after FFR-guided deferral of revascularization.     

Combination of C‐reactive protein,procalcitonin, IL‐6, IL‐8, and IL‐10 for early diagnosis of hyperinflammatory state and organ dysfunction in pediatric sepsis

BackgroundAlthough early diagnosis and management are critical for prognosis of pediatric sepsis, there are no specific diagnostic biomarkers for the hyperinflammatory state and organ dysfunction, important stages of sepsis.MethodsWe enrolled 129 children with infection into three groups: non‐sepsis infection (33), Sepsis 1.0 (hyperinflammatory state, 67), and Sepsis 3.0 (organ dysfunction, 29). Another 32 children with no infections were included as controls. Serum C‐reactive protein (CRP), procalcitonin (PCT), interleukin (IL)‐1β, IL‐2, IL‐4, IL‐5, IL‐6, IL‐8, IL‐10, IL‐12p70, IL‐17, tumor necrosis factor (TNF)‐α, interferon (IFN)‐α, and IFN‐γ were assessed to diagnose the two stages, and their diagnostic capacities were evaluated using receiver operating characteristic (ROC) curves. We also examined whether combining biomarkers improved diagnostic efficiency.ResultsSignificantly higher CRP, PCT, and IL‐6 levels were detected in the Sepsis 1.0 than the non‐sepsis infection group (p < 0.001). The areas under the curve (AUCs) for diagnosing Sepsis 1.0 were 0.974 (CRP), 0.913 (PCT) and 0.919 (IL‐6). A combination of any two biomarkers increased diagnostic sensitivity to ≥92.54% and specificity to 100.00%. Significantly higher PCT, IL‐8, and IL‐10 levels were found in the Sepsis 3.0 than the Sepsis 1.0 group (p ≤ 0.01), with AUCs for diagnosing Sepsis 3.0 0.807 (PCT), 0.711 (IL‐8), and 0.860 (IL‐10). Combining these three biomarkers increased diagnostic sensitivity to 96.55% and specificity to 94.03%.ConclusionIn pediatric sepsis, combining any two of CRP, PCT, and IL‐6 can accurately diagnose the hyperinflammatory state and increase diagnostic specificity. Early diagnosis of organ dysfunction requires a combination of PCT, IL‐8, and IL‐10.     

Serum Osteoprotegerin Is an Independent Marker of Left Ventricular Hypertrophy,Systolic and Diastolic Dysfunction of the Left Ventricle and the Presence of Pericardial Fluid in Chronic Kidney Disease Patients

Background: Osteoprotegerin (OPG) is a molecule which belongs to the tumor necrosis factor receptor superfamily. OPG concentration is elevated in patients with left ventricle hypertrophy, heart failure and acute myocardial infarction. OPG concentrations rise in chronic kidney disease (CKD). The aim of this study was to investigate the association between OPG concentrations and cardiovascular complications, such as left ventricle hypertrophy, systolic and diastolic dysfunction of left ventricle and dysfunction of right ventricle in chronic kidney disease patients not treated with dialysis. The relation between OPG and the amount of pericardial fluid was also examined. Methods: One hundred and one men with CKD stage 3–5 not treated with dialysis were included in the study. Overhydration, body fat mass and lean body mass were measured using bioimpedance spectroscopy (BIS). Echocardiography was performed to evaluate the amount of pericardial fluid and to measure the thickness of the interventricular septum (IVS), systolic and diastolic function of left ventricle, as well as systolic function of right ventricle. Results: We observed a significant positive association between OPG and the thickness of the interventricular septum, the size of the left atrium (LA) and the presence of pericardial fluid. A negative relationship was observed between OPG and ejection fraction (EF). Conclusions: Our results suggest that OPG can be an independent marker of left ventricular hypertrophy, systolic and diastolic dysfunction of left ventricle and the presence of pericardial fluid in chronic kidney disease patients.     

体外循环围手术期血糖与术后临床预后的关系

目的：分析体外循环围手术期血糖的变化与临床预后的关系,探究体外循环术预后的预测指标。方法选取我院2008年2月至2013年2月成人体外循环手术患者300例,分为死亡组（15例）和存活组（285例）,比较两组静脉血糖转流时间、住ICU时间及pH值,并进行Logistic回归分析。结果（1）死亡组的静脉血糖及峰值、器官衰竭数转流时间、住 ICU 时间明显高于存活组,pH值则明显低于后者（P＜0．05）;（2）Logistic多因素回归分析结果仅术中血糖峰值及术后2 h血糖峰值是器官衰竭的独立危险因素。结论术中血糖与体外循环术患者的临床预后密切相关。     

Corosolic acid analogue,a natural triterpenoid saponin,induces apoptosis on human hepatocarcinoma cells through mitochondrial pathway in vitro

Context 2a,-3a,-24-Trihydroxyurs-12-en-28-oic acid (TEO, a corosolic acid analogue) is a triterpenoid saponin isolated from Actinidia valvata Dunn (Actinidiaceae), a well-known traditional Chinese medicine.

Objective This study investigated the anti-proliferation and inducing apoptosis effects of TEO in three human hepatocellular carcinoma (HCC) cell lines.

Materials and methods Cytotoxic activity of TEO was determined by the MTT assay at various concentrations from 2.5 to 40?μg/mL in BEL-7402, BEL-7404 and SMMC-7721 cell lines. Cell morphology was assessed by acridine orange/ethidium bromide and 4′-6-diamidino-2-phenylindole dihydrochloride staining and fluorescence microscopy. Cell-cycle distribution and DNA damage were determined by flow cytometry and comet assay. Mitochondrial dysfunction was assessed by JC-1 staining and transmission electron microscopy. Apoptosis changes were explored by Western blot, TNF-α and caspase-3, -8, -9 assays.

Results TEO exhibited inhibition effects on BEL-7402, BEL-7404 and SMMC-7721 cells treated for 24?h, the IC₅₀ values were 34.6, 30.8 and 30.5?μg/mL, respectively. TEO (40?μg/mL)-treated three cell lines increased by more than 21% in the G1 phase and presented the morphological change and DNA damage. TEO also declined the mitochondrial membrane potential and altered mitochondrial ultra-structure. Furthermore, caspase-3, caspase-8, caspase-9 and TNF-α were also activated. Mechanism investigation showed that TEO could decrease anti-apoptotic Bcl-2 protein expression, increase proapoptotic Bax and Bid proteins expressions and increase Bax/Bcl-2 ratio.

Conclusion Our results demonstrate for the first time that TEO inhibited growth of HCC cell lines and induced G1 phase arrest. Moreover, proapoptotic effects of TEO were mediated through the activation of TNF-α, caspases and mitochondrial pathway.     

老年睑板腺功能障碍蠕形螨感染率及茶树精油联合氟米龙的疗效

目的：研究老年睑板腺功能障碍(MGD)蠕形螨感染率及茶树精油联合氟米龙的疗效。

方法：回顾性病例对照研究。选择2017-09/2018-03在宁波市眼科医院门诊就诊的老年MGD患者59例118眼。将睫毛蠕形螨镜检为阳性的38例患者76眼进行症状评分、蠕形螨数量、泪膜破裂时间(BUT)、角膜荧光素染色(FL)、Schirmer I试验(SIaT)等检查,并按不同治疗方法分成3组,A组使用0.02%氟米龙滴眼液滴眼24眼; B组使用茶树精油(TTO)湿巾敷眼26眼; C组用0.02%氟米龙滴眼液滴眼联合TTO湿巾敷眼26眼,随访4wk。

结果：118眼中76眼(64.4%)睫毛蠕形螨镜检为阳性。睫毛蠕形螨阳性的三组患者治疗后的主观症状评分均较治疗前有改善(P<0.05)。治疗后A组蠕形螨数量较治疗前无显著差异(P=0.11); B、C组较治疗前明显减少(均P<0.01)。三组患者BUT治疗前后比较,A组BUT无显著差异(P=0.22); B、C组BUT明显延长(均P<0.05)。治疗后C组的BUT较A、B组明显延长(均P<0.05)。三组患者治疗前后的FL评分均较治疗前明显改善(P<0.05)。

结论：老年MGD患者睫毛蠕形螨感染率较高,睑板腺热疏通后TTO湿巾联合0.02%氟米龙滴眼液能有效驱螨、缓解MGD患者局部症状。     

Fetal stroke and cerebrovascular disease: Advances in understanding from lenticulostriate and venous imaging,alloimmune thrombocytopaenia and monochorionic twins

Fetal stroke is an important cause of cerebral palsy but is difficult to diagnose unless imaging is undertaken in pregnancies at risk because of known maternal or fetal disorders. Fetal ultrasound or magnetic resonance imaging may show haemorrhage or ischaemic lesions including multicystic encephalomalacia and focal porencephaly. Serial imaging has shown the development of malformations including schizencephaly and polymicrogyra after ischaemic and haemorrhagic stroke. Recognised causes of haemorrhagic fetal stroke include alloimmune and autoimmune thrombocytopaenia, maternal and fetal clotting disorders and trauma but these are relatively rare. It is likely that a significant proportion of periventricular and intraventricular haemorrhages are of venous origin. Recent evidence highlights the importance of arterial endothelial dysfunction, rather than thrombocytopaenia, in the intraparenchymal haemorrhage of alloimmune thrombocytopaenia. In the context of placental anastomoses, monochorionic diamniotic twins are at risk of twin twin transfusion syndrome (TTTS), or partial forms including Twin Oligohydramnios Polyhydramnios Sequence (TOPS), differences in estimated weight (selective Intrauterine growth Retardation; sIUGR), or in fetal haemoglobin (Twin Anaemia Polycythaemia Sequence; TAPS). There is a very wide range of ischaemic and haemorrhagic injury in a focal as well as a global distribution. Acute twin twin transfusion may account for intraventricular haemorrhage in recipients and periventricular leukomalacia in donors but there are additional risk factors for focal embolism and cerebrovascular disease. The recipient has circulatory overload, with effects on systemic and pulmonary circulations which probably lead to systemic and pulmonary hypertension and even right ventricular outflow tract obstruction as well as the polycythaemia which is a risk factor for thrombosis and vasculopathy. The donor is hypovolaemic and has a reticulocytosis in response to the anaemia while maternal hypertension and diabetes may influence stroke risk. Understanding of the mechanisms, including the role of vasculopathy, in well studied conditions such as alloimmune thrombocytopaenia and monochorionic diamniotic twinning may lead to reduction of the burden of antenatally sustained cerebral palsy.     

Colorectal Cancer Screening Program in Songjiang district,Shanghai between 2015 and 2017: Evaluation of participation rate and the associated factor

Little is known about the participation rate of newly implemented colorectal cancer (CRC) screening programs in China. Our goals were to identify factors associated with nonparticipation for CRC screening in Songjiang District, Shanghai.We analyzed individuals included in an observational cohort study from 4 towns (Xin Qiao, She Shan, Mao Gang, and Zhong Shan) in Songjiang District. The participation rate was calculated for the CRC screening program based on a fecal immunochemical test and a risk assessment questionnaire between 2015 and 2017 inclusive.Of the 27,130 individuals eligible for inclusion in this study, 20,863 (76.9%) participated in CRC screening at least once during 2015 and 2017. The factors linked with nonparticipation were; being male (odds ratio [OR] 0.87, 95% confidence interval [CI] 0.82–0.93, P < .01), unmarried (OR 0.71, 95% CI 0.64–0.80, P < .01), having a high education level (middle school, OR 0.82, 95% CI 0.74–0.90, P < .01, high school or above, OR 0.64, 95% CI 0.57–0.73, P < .01), absence of chronic disease (OR 0.90, 95% CI 0.85–0.96, P < .01), and living in 2 out of the 4 towns covered (Xin Qiao, OR 0.72, 95% CI 0.66–0.78, P < .01, Zhong Shan, OR 0.29, 95% CI 0.26–0.31, P < .01).The current study revealed several associated factors with nonparticipation for the CRC screening in Songjiang district. These findings will help identify target populations that require an individualized approach to increase the participation rate.