Surgical resection after neoadjuvant durvalumab and radiation is feasible and safe in non–small cell lung cancer: Results from a randomized trial

ObjectiveSeveral trials have recently reported the safety of pulmonary resection after neoadjuvant immunotherapy with encouraging major pathological response rates. We report the detailed adverse events profile from a recently conducted randomized phase II trial in patients with resectable non–small cell lung cancer treated with neoadjuvant durvalumab alone or with sub-ablative radiation.MethodsWe conducted a randomized phase II trial in patients with non–small cell lung cancer clinical stages I to IIIA who were randomly assigned to receive neoadjuvant durvalumab alone or with sub-ablative radiation (8Gyx3). Secondary end points included the safety of 2 cycles of preoperative durvalumab with and without radiation followed by pulmonary resection. Postoperative adverse events within 30 days were recorded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.0).ResultsSixty patients were enrolled and randomly assigned, with planned resection performed in 26 patients in each arm. Baseline demographics and clinical variables were balanced between groups. The median operative time was similar between arms: 128 minutes (97-201) versus 146 minutes (109-214) (P = .314). There was no 30- or 90-day mortality. Grade 3/4 adverse events occurred in 10 of 26 patients (38%) after monotherapy and in 10 of 26 patients (38%) after dual therapy. Anemia requiring transfusion and hypotension were the 2 most common adverse events. The median length of stay was similar between arms (5 days vs 4 days, P = .172).ConclusionsIn this randomized trial, the addition of sub-ablative focal radiation to durvalumab in the neoadjuvant setting was not associated with increased mortality or morbidity compared with neoadjuvant durvalumab alone.     

圆锥型套筒冠修复体修复治疗对牙周病患者牙龈指数、龈乳头探诊出血指数、牙周探诊深度的影响

目的 探讨圆锥型套筒冠修复体修复治疗对牙周病患者牙龈指数、龈乳头探诊出血指数、牙周探诊深度的影响。方法 选取2017年3月～2019年3月我院收治的牙周病患者60例,随机分为对照组和研究组两组。对照组进行常规治疗,研究组进行圆锥型套筒冠修复体修复治疗。比较两组患者疗效、牙齿松动度(TM)、牙龈指数(GI)、龈乳头探诊出血指数(PBI)、牙周探诊深度(PD)、改良菌斑指数(mPLI)、改良龈沟出血指数(MSBI)、牙龈乳头指数(PIS)、白细胞介素-8(IL-8)、白细胞介素-2(IL-2)水平、口腔健康影响程度评分(OHIP-14)、咀嚼功能、满意率。结果 研究组有效率高于对照组(P0.05);研究组TM、GI、PBI、PD低于对照组(P0.05);研究组mPLI、MSBI、PIS低于对照组(P0.05);研究组IL-8、IL-2水平低于对照组(P0.05);研究组OHIP-14评分低于对照组(P0.05);研究组咀嚼功能高于对照组(P0.05);研究组修复满意率高于对照组(P0.05)。结论 牙周病治疗中,圆锥型套筒冠修复体修复疗效显著,应在临床上广泛推广与应用。     

Accurate expression of PD‐L1/L2 in lung adenocarcinoma cells: A retrospective study by double immunohistochemistry

The percentage of programmed death ligand 1 (PD‐L1) positivity in cancer cells, named as the tumor proportion score, is considered to be a predictive biomarker for anti‐PD‐1/PD‐L1 therapy in lung cancer. PD‐L1 is expressed on not only cancer cells but also on immune cells, including macrophages. Although previous studies related to PD‐L1/2 expression in cancer tissues have been generally based on single immunohistochemistry (IHC), in the present study, we attempted to evaluate accurate PD‐L1/2 expression in cancer cells in lung adenocarcinoma cells using double IHC to also evaluate macrophages. Of the 231 patients, PD‐L1 expression was negative in 169 patients (73.2%), 1%‐49% positive in 47 patients (20.3%), and ≥50% positive in 15 patients (6.5%). Interestingly, PD‐L1 positivity was decreased when using double IHC compared with the estimation by single IHC. High PD‐L1 expression was associated with high‐grade cancer cells and in higher stage cancer. PD‐L2 was negative in 109 patients (47.2%), 1%‐49% positive in 50 patients (21.6%), and ≥50% positive in 72 patients (31.2%). The number of PD‐L2‐positive patients was increased in cases that had an epidermal growth factor receptor (EGFR) mutation and in lower stage cancer. Thirty‐five patients (15.2%) were positive for both PD‐L1 and PD‐L2, whereas 81 patients (35.1%) were negative for both PD‐L1 and PD‐L2. Log‐rank analysis showed that progression‐free survival and overall survival were significantly the longest in the PD‐L1‐negative and PD‐L2‐positive groups (P < .0001 and P = .0120). We observed lower PD‐L1 or PD‐L2 expression in lung adenocarcinoma than previously reported. Double IHC for macrophages may help clinicians to evaluate PD‐L1 or PD‐L2 expression specifically in cancer cells.     

Perceptions of Home Dialysis Training and Experience Among US Nephrology Fellows

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Intralesional interleukin‐2: A novel option to maximize response to systemic immune checkpoint therapy in loco‐regional metastatic melanoma

The management of metastatic melanoma has been transformed by the development of immune checkpoint inhibitors. However, disease control in patients with extensive locoregional metastases remains a significant challenge. In this context, intralesional interleukin 2 (IL‐2) presents a useful therapeutic option to maximize intratumoural drug concentration and minimize systemic toxicity. The utility of combined intralesional IL‐2 and systemic immune checkpoint therapy, particularly in loco‐regional disease, is unknown. We report the clinical and cellular effects of combined anti‐programmed death‐1 blockade and intralesional IL‐2 therapy in two patients with loco‐regional metastatic melanoma. Combined intralesional and systemic therapy induced a lasting resolution of the injected skin tumors; maintained for up to 2 years. This impressive response was associated with increased PD‐L1 expression and CD8 T cell infiltration. To our knowledge, this is the first report that raises the possibility of a synergistic effect between intralesional IL‐2 and systemic checkpoint inhibition. The lasting remission of injected metastases may be in part due to an altered tumor microenvironment; characterized by increased PD‐L1 expression and increased CD8 T cell infiltration. If this interesting and novel preliminary observation is confirmed in larger studies, combined local and systemic immunotherapy could highlight a novel treatment strategy for extensive loco‐regional disease.     

Fungal infections in solid organ transplantation: An update on diagnosis and treatment

Invasive fungal infections constitute an important cause of morbidity and mortality in solid organ transplantation recipients. Since solid organ transplantation is an effective therapy for many patients with end-stage organ failure, prevention and treatment of fungal infections are of vital importance. Diagnosis and management of these infections, however, remain difficult due to the variety of clinical symptoms in addition to the lack of accurate diagnostic methods. The use of fungal biomarkers can lead to an increased diagnostic accuracy, resulting in improved clinical outcomes. The evidence for optimal prophylactic approaches remains inconclusive, which results in considerable variation in the administration of prophylaxis. The implementation of a standard protocol for prophylaxis remains difficult as previous treatment regimens, which can alter the distribution of different pathogens, affect the outcome of antifungal susceptibility testing. Furthermore, the increasing use of antifungals also contributes to incremental costs and the risk of development of drug resistance. This review will highlight risk factors, clinical manifestations and timing of fungal infections and will focus predominately on the current evidence for diagnosis and management of fungal infections.     

Effects of dance therapy on cognitive and mood symptoms in people with Parkinson's disease: A systematic review and meta-analysis

ObjectiveTo investigate whether the dance therapy was more beneficial than non-dance therapy on cognitive and mood symptoms in patients with Parkinson's disease (PD).MethodsMEDLINE, CINAHL, Embase and the Cochrane Central Register of Controlled Trials were searched from inception to December 11, 2018. Risk of bias for the included trials was assessed using criteria in the Cochrane Handbook for Systematic Reviews of Interventions.ResultsSeven randomized controlled trials were identified on cognitive and mood symptoms in patients with PD. There were significant differences in favor of dance in executive function (WMD = 1.17, 95% CI:0.39 to 1.95, P = 0.003; I² = 0%, P = 0.45), but not in outcomes of global cognitive function, depression and apathy.ConclusionsDance therapy is beneficial in improving executive function for adults with PD. However, there are no positive effects were founded on global cognitive function, depression and apathy for PD.