The efficacy and toxicity of immune checkpoint inhibitors in a real-world older patient population

ImportanceImmunotherapy has emerged as an effective treatment option for the management of advanced cancers. The effects of these immune checkpoint inhibitors in the older patient population has not been adequately assessed.ObjectiveTo understand the impact of aging on CTLA-4 and PDL-1 inhibitors efficacy and immune-related adverse events (irAE) in the context of real-world management of advanced solid cancers.Design, Setting, and ParticipantsThis retrospective study involved all non-study patients with histologically-confirmed metastatic or inoperable solid cancers receiving immunotherapy at Kingston Health Sciences Centre. We defined ‘older patient’ as age ≥ 75. All statistical analyses were conducted under SPSS IBM for Windows version 24.0.Main Outcomes and MeasuresStudy outcomes included immunotherapy treatment response, survival, as well as number, type, and severity of irAEs.ResultsOur study (N = 78) had 29 (37%) patients age <65, 26 (33%) patients age 65–74, and 23 (30%) patients age ≥75. Melanoma, non-small cell lung cancer, and renal cell carcinoma accounted for 70%, 22%, and 8% of the study population, respectively. Distributions of ipilimumab (32%), nivolumab (33%), and pembrolizumab (35%) were similar in the study. The response rates were 28%, 27%, and 39% in the age <65, age 64–74, age ≥75 groups, respectively (P = 0.585). Kaplan-Meier curve showed a median survival of 28 months (12.28–43.9, 95% CI) and 17 months (0–36.9, 95% CI) in the age <65 and age 64–74 groups, respectively; the estimated survival probability did not reach 50% in the age ≥75 group (P = 0.319). There were no statistically significant differences found in terms of irAEs, multiple irAEs, severity of grade 3 or higher, types of irAEs, and irAEs resolution status when comparing between different age groups.Conclusion and RelevanceOur results suggest that patients age ≥75 are able to gain as much benefit from immunotherapy as younger patients, without excess toxicity. Our findings suggest that single agent immunotherapy is generally well-tolerated across different age groups with no significant difference in the type, frequency or severity of irAEs. Future studies evaluating aging and combination immunotherapy are warranted.     

Long-term skeletal stability in the treatment of mandibular prognathism with a physiological positioning strategy

Our aim was to evaluate the long-term skeletal stability of the mandible in 21 patients after orthognathic surgery with physiological positioning. The measurement points SNB, B point (X, Y), Pog (X, Y), and the angle of the ramus were measured on cephalometric photographs to assess skeletal stability preoperatively, immediately after operation, and one and two years postoperatively. In addition, we evaluated the clinical symptoms of disorders of the temporomandibular joint (TMJ). The analysis of the cephalometric photographs showed that SNB, B point X, and Pog X showed no significant differences among the postoperative time points. On the other hand, B point Y and Pog Y showed no significant differences throughout the study period. We compared the angle of the ramus before operation and two years postoperatively, and no significant difference was found. In addition, no cases showed any pathological symptoms of disorders of the TMJ two years postoperatively. The long-term stability after orthognathic surgery with physiological positioning was confirmed, and it seems to be a reliable orthognathic treatment in patients with mandibular prognathism.     

Tanzania IR Initiative: Training the First Generation of Interventional Radiologists

Despite a population of nearly 60 million, there is currently not a single interventional radiologist in Tanzania. Based on an Interventional Radiology (IR) Readiness Assessment, the key obstacles to establishing IR in Tanzania are the lack of training opportunities and limited availability of disposable equipment. An IR training program was designed and initiated, which relies on US-based volunteer teams of IR physicians, nurses, and technologists to locally train radiology residents, nurses, and technologists. Preliminary results support this strategy for addressing the lack of training opportunities and provide a model for introducing IR to other resource-limited settings.     

农村青少年不同时期家庭逆境与精神病理症状的关联

目的探讨家庭逆境致精神病理症状结局的累积性与关键期效应,为预防与干预逆境伤害提供依据。方法2017年12月,采用方便抽样的方法选取安徽省阜阳地区2所农村学校的710名青少年。采用《童年期不良经历问卷》评估家庭逆境,《MacArthur健康与行为问卷》评价内化症状和外化症状。采用多元线性回归分析家庭逆境发生时间与数量和精神病理症状的关联。结果持续家庭逆境组与内化症状、外化症状增加均有相关性[β值(95%CI)分别为0.35(0.15~0.54),0.16(0.01~0.32)]。家庭逆境数量为2和≥3与内化症状[β值(95%CI)分别为0.20(0.04~0.36),0.42(0.24~0.60)]、外化症状[β值(95%CI)分别为0.14(0.01~0.26),0.23(0.09~0.37)]增加有关。在仅童年期家庭逆境中,家庭逆境数量为2和≥3的内化症状[β值(95%CI)分别为0.23(0.06~0.41),0.34(0.11~0.58)]、外化症状[β值(95%CI)分别为0.17(0.02~0.31),0.21(0.02~0.39)]的风险增高。在持续家庭逆境组中,逆境数量≥3与内化症状、外化症状相关[(β值(95%CI)分别为0.56(0.31~0.82),0.24(0.02~0.45)]。仅青春期家庭逆境与精神病理症状无关。结论家庭逆境的多次发生可增加精神病理症状风险,童年期可能是家庭逆境致精神病理症状的关键期。     

Comparison of gas-liquid chromatography and EMIT assay for serum valproic acid

We describe a simple direct extraction method for the gas-liquid chromatography determination of serum valproic acid. The working range for the assay is 2-180 mg/L and our within-run precision was 5.8 and 4.3% at the 40 and 90 mg/L concentrations respectively. Hemolyzed and lipemic sera as well as samples from patients with hyperbilirubinemia and from patients with decreased renal function were put through the assay and no interfering peaks were noted. Interference occurred when teflon-lined screw caps were used during the extraction step. The method was proven to be accurate by linear regression analysis of samples containing weighed-in amounts of valproic acid. The above assay was compared to an enzyme immunoassay technique (EMIT). The working range for the latter is 10-150 mg/L and the with-run precision was 10.8 and 5.9% and 90 mg/L concentration respectively. Samples were run by both the gas-liquid chromatograph and enzyme immunoassay methods and gave very similar results over the range 16-139 mg/L.