Evaluation of the efficacy and safety of home treatment with the recombinant human C1-inhibitor in hereditary angioedema resulting from C1-inhibitor deficiency

ObjectiveConestat alpha, a C1-inhibitor produced by recombinant technology (rhC1-INH) is an acute treatment for edematous attacks occurring in hereditary angioedema (HAE) with C1-inhibitor deficiency (C1-INH-HAE). Our study evaluated the efficacy and safety of rhC1-INH administered during HAE attacks, and for short-term prophylaxis (STP).Materials & methodOur prospective study analyzed the course of 544 HAE attacks experienced by the 21 C1-INH-HAE patients treated, as well as the outcome of 97 instances of STP implemented with rhC1-INH. Using a purpose-designed questionnaire, the patients recorded relevant, treatment-related information.ResultsTime to the administration of rhC1-INH was 90.0 min (median) after the onset of HAE attacks. The symptoms started to improve as early as 60 min after the injection of rhC1-INH, and the attack resolved 730.0 min after treatment. The interval between the onset of the HAE attack and the administration of rhC1-INH correlated with time until the onset of improvement (R = 0.2053 p < 0.0001), and with time to the complete resolution of symptoms (R = 0.2805, p < 0.0001). Nine patients received STP with rhC1-INH in 97 instances. STP successfully prevented the HAE attack within 72 h of the event on 93/97 occasions. No local and serious systemic adverse events/effects were observed.ConclusionsTreatment with rhC1-INH is effective and safe both for acute management, and for STP. Following the onset of an HAE attack, early administration of rhC1-INH may reduce time to the improvement and to the complete resolution of symptoms. Repeated administration of rhC1-INH does not impair its efficacy.     

Stratification of HPV-associated and HPV-negative oropharyngeal squamous cell carcinomas based on DNA methylation epigenotypes

While the incidence of oropharyngeal squamous cell carcinoma (OPSCC) has been increasing in these two decades, primarily due to human papillomavirus (HPV), stratification of OPSCC into molecular subgroups showing different clinicopathological features has not been fully investigated. We performed DNA methylome analysis using Infinium 450k for 170 OPSCC cases, including 89 cases in our cohort and 81 cases reported by The Cancer Genome Atlas, together with targeted exon sequencing analysis. We stratified OPSCC by hierarchical clustering analysis using methylome data. Methylation levels of classifier markers were validated quantitatively using pyrosequencing, and area under the curve (AUC) values of receiver operating characteristics (ROC) curves were calculated. OPSCC was stratified into four epigenotypes: HPV(+) high-methylation (OP1), HPV(+) intermediate-methylation (OP2), HPV(−) intermediate-methylation (OP3) and HPV(−) low-methylation (OP4). Ten methylation marker genes were generated: five to classify HPV(+) cases into OP1 and OP2, and five to classify HPV(−) cases into OP3 and OP4. AUC values of ROC curves were 0.969 and 0.952 for the two marker panels, respectively. While significantly higher TP53 mutation and CCND1 copy number gains were observed in HPV(−) than in HPV(+) groups (p < 0.01), no significant difference of genomic aberrations was observed between OP1 and OP2, or OP3 and OP4. The four epigenotypes showed significantly different prognosis (p = 0.0006), distinguishing the most favorable OPSCC subgroup (OP1) among generally favorable HPV(+) cases, and the most unfavorable OPSCC subgroup (OP3) among generally unfavorable HPV(−) cases. HPV(+) and HPV(−) OPSCC are further divided into distinct DNA methylation epigenotypes, showing significantly different prognosis.     

Human papillomavirus genotype contribution to cervical cancer and precancer: Implications for screening and vaccination in Japan

To obtain baseline data for cervical cancer prevention in Japan, we analyzed human papillomavirus (HPV) data from 5045 Japanese women aged less than 40 years and diagnosed with cervical abnormalities at 21 hospitals during 2012‐2017. These included cervical intraepithelial neoplasia grade 1 (CIN1, n = 573), CIN2‐3 (n = 3219), adenocarcinoma in situ (AIS, n = 123), and invasive cervical cancer (ICC, n = 1130). The Roche Linear Array was used for HPV genotyping. The HPV type‐specific relative contributions (RCs) were estimated by adding multiple infections to single types in accordance with proportional weighting attributions. Based on the comparison of type‐specific RCs between CIN1 and CIN2‐3/AIS/ICC (CIN2+), RC ratios were calculated to estimate type‐specific risks for progression to CIN2+. Human papillomavirus DNA was detected in 85.5% of CIN1, 95.7% of CIN2‐3/AIS, and 91.2% of ICC. Multiple infections decreased with disease severity: 42.9% in CIN1, 40.4% in CIN2‐3/AIS, and 23.7% in ICC (P < .0001). The relative risk for progression to CIN2+ was highest for HPV16 (RC ratio 3.78, 95% confidence interval [CI] 3.01‐4.98), followed by HPV31 (2.51, 1.54‐5.24), HPV18 (2.43, 1.59‐4.32), HPV35 (1.56, 0.43‐8.36), HPV33 (1.01, 0.49‐3.31), HPV52 (0.99, 0.76‐1.33), and HPV58 (0.97, 0.75‐1.32). The relative risk of disease progression was 1.87 (95% CI, 1.71‐2.05) for HPV16/18/31/33/35/45/52/58, but only 0.17 (95% CI, 0.14‐0.22) for HPV39/51/56/59/66/68. Human papillomavirus 16/18/31/33/45/52/58/6/11 included in a 9‐valent vaccine contributed to 89.7% (95% CI, 88.7‐90.7) of CIN2‐3/AIS and 93.8% (95% CI, 92.4‐95.3) of ICC. In conclusion, our data support the Japanese guidelines that recommend discriminating HPV16/18/31/33/35/45/52/58 genotypes for CIN management. The 9‐valent vaccine is estimated to provide over 90% protection against ICC in young Japanese women.     

新冠肺炎危重症患者收治医院护理人力资源应急管理策略

面对新型冠状病毒肺炎疫情,积极与各医疗队进行沟通协调,护理部积极统筹部署,采取系列应急管理策略:梯队调配、建立规章制度、严格岗前培训、提供心理支持和后勤保障等,从而科学合理地进行人力资源管理,对新型冠状病毒肺炎防治工作顺利进行起到积极作用。     

Ebola Virus RNA Stability in Human Blood and Urine in West Africa’s Environmental Conditions

We evaluated RNA stability of Ebola virus in EDTA blood and urine samples collected from infected patients and stored in West Africa’s environmental conditions. In blood, RNA was stable for at least 18 days when initial cycle threshold values were <30, but in urine, RNA degradation occurred more quickly.