Management of immune-related adverse events resulting from immune checkpoint blockade

Introduction: Immune checkpoint inhibitors (ICI) are now a standard of care in the treatment of many cancers leading to durable responses in patients with metastatic disease. These agents are generally well tolerated but may lead to the occurrence of immune-related adverse events (irAEs). As any organ may be affected, clinicians should be aware of the broad range of clinical manifestations and symptoms and keep in mind that toxicities may occur late, at any point along a patient’s treatment course. Although the most common irAEs are rarely severe, some of them may be associated with great morbidity and even become life-threatening. The rate of occurrence, type and severity of irAEs may vary with the type of ICI; thus, grade 3 and 4 irAEs are reported in more than 55% of patients treated with the combination of ipilimumab 3 mg/kg and nivolumab 1 mg/kg.

Area covered: This review presents the management of irAEs resulting from checkpoint blockade, with a focus on rare irAEs.

Expert commentary: With the development of immuno-oncology and the expanding role of ICI, physicians have learnt to diagnose and treat most of the irAEs that can occur. This review provides an overview of current guidelines, previously published studies and our multidisciplinary team based practices.     

Clinical analysis of peritoneal dialysis in the treatment of rapidly progressive glomerulonephritis

Objective To observe the clinical characteristics and prognosis of patients with rapidly progressive glomerulonephritis (RPGN) caused by lupus nephritis, antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis, or primary glomerulonephritis who were treated with peritoneal dialysis (PD) and then withdrew PD because of renal recovery. Methods Data of the above patients were retrospectively analyzed. The patients were diagnosed as RPGN and received PD therapy in Kidney Disease Center, the First Affiliated Hospital, College of Medicine, Zhejiang University from February 2009 to August 2018. The patients were divided into early withdrawal group (PD time≤183 days, n=24) and late withdrawal group (PD time＞183 day, n=24). The differences of clinical characteristics between the two groups were compared. The cumulative incidence of adverse events in both groups was analyzed using Kaplan-Meier curves. Cox proportional hazards model was used to analyze the risk factors influencing the prognosis of patients. Results Forty-eight RPGN patients were included. The median time of maintaining PD was 178(76, 378) days. Compared with the late withdrawal group, the patients in early withdrawal group had lower levels of urine volume, serum albumin and parathyroid hormone, and lower rates of gross hematuria and hypertension at the beginning of PD, and received higher rates of methylprednisolone impulse, combined immunosuppressive agents, and hemodialysis or continuous renal replacement therapy (all P＜0.05). At the time of PD withdrawal, the levels of serum creatinine, serum calcium, serum albumin and parathyroid hormone in the early withdrawal group were significantly lower than those in the late withdrawal group (all P＜0.05). The Kaplan-Meier curves showed that there was no significant difference in the cumulative survival of patients in both groups (log-rank test χ2=3.485, P=0.062). Cox regression analysis revealed serum creatinine≥209 μmol/L at the time of PD withdrawal was an independent risk factor for poor prognosis (HR=5.253，95%CI 1.757-15.702, P=0.003). Conclusions PD can be used for RPGN patients caused by lupus nephritis, ANCA-associated vasculitis and primary nephritis. Serum creatinine≥209 μmol/L at the time of PD withdrawal is an independent risk factor for poor prognosis.     

Analysis of early mortality and related risk factors in maintenance hemodialysis patients

Objective To analyze the early mortality and related risk factors of new hemodialysis patients in Zhejiang province, and provide basis for reducing the death risk of hemodialysis patients. Methods The early mortality and related factors of new hemodialysis patients from January 1, 2010 to June 30, 2018 were retrospectively analyzed using the database of Zhejiang province hemodialysis registration. The early mortality was defined as death within 90 days of dialysis. Cox regression model was used to analyze the related risk factors of the early mortality in hemodialysis patients. Results The mortality was the highest in the first month after dialysis (46.40/100 person year), and gradually stabilized after three months. The early mortality was 25.33/100 person year. The mortality within 120 days and 360 days were 21.40/100 person year and 11.37/100 person year, respectively. The elderly (≥65 years old, HR=1.981, 95%CI 1.319-2.977, P＜0.001), primary tumor (HR=3.308, 95%CI 1.137-5.624, P=0.028), combined with tumors (not including the primary tumor, HR=2.327, 95%CI 1.200-4.513, P=0.012), temporary catheter (the initial dialysis pathway, HR=3.632, 95%CI 1.806-7.307, P＜0.001), lower albumin (＜30 g/L, HR=2.181, 95%CI 1.459-3.260, P＜0.001), lower hemoglobin (every 0.01 g/L increase, HR=0.861, 95%CI 0.793-0.935, P=0.001), lower high density lipoprotein (＜0.7 mmol/L, HR=1.796, 95%CI 1.068-3.019, P=0.027) and higher C reactive protein (≥40 mg/L, HR=1.889, 95%CI 1.185-3.012, P=0.008) were the risk factors of early death for hemodialysis patients. Conclusions The early mortality of hemodialysis patients is high after dialysis, and gradually stable after 3 months. The elderly, primary tumor, combined with tumors, the initial dialysis pathway, lower albumin, lower hemoglobin, lower high density lipoprotein and higher C reactive protein are the risk factors of early death for hemodialysis patients.     

Bilateral Implantation of Centromedian‐Parafascicularis Complex and GPi: A New Combination of Unconventional Targets for Deep Brain Stimulation in Severe Parkinson Disease

Objectives. Traditional deep brain stimulation (DBS) at the subthalamic nucleus (STN) has proved to be efficacious on core Parkinsonian symptoms. However, very disabling l ‐dopa–induced abnormal involuntary movements (AIMs) and axial signs are slightly affected, suggesting that we target less conventional targets. Our candidates for DBS were the globus pallidus internus (GPi) plus the intralaminar thalamic complex (Pf or CM), given its extensive functional links with basal ganglia nuclei. Materials and Methods. The routine utilization of our innovative stereotactic apparatus allows us to implant, at the same time, both the CM‐Pf complex together with the GPi in six Parkinson disease patients. Both intraoperative and postoperative neurophysiologic assessments helped us recognize functional subregions while optimizing implantation of electrodes. Unified Parkinson disease rating scale (UPDRS) motor scores, AIMs, and freezing were carefully blindly evaluated for each condition. Results. A significant amelioration of UPDRS scores was achieved by simultaneous activation of both targets. CM‐Pf activation was only slightly effective in reducing rigidity and akinesia, but more efficacious on freezing. Not surprisingly, AIMs were peculiarly decreased by the activation of the permanent electro‐catheter in the posteroventral GPi. Conclusions. These findings confirm that, in selected patients, it is conceivable to target structures other than the conventional STN in order to maximize clinical benefit.     

Shortening peel-away sheaths prior to dialysis line insertion--potential decrease of patient risk.

Placement of tunnelled dialysis lines is effective using ultrasoundand fluoroscopic guidance [1] and has a higher success ratethan ‘blind’ insertion [2]. After the ultrasound guided access into a neck vein, wires andcatheters are guided in to a suitable position in the