Immune Checkpoint Inhibitor Toxicities

Immune checkpoint inhibitors are molecules that increase the endogenous immune response against tumors. They have revolutionized the field of oncology. Since their initial approval for the treatment of advanced melanoma, their use has expanded to the treatment of several other advanced cancers. Unfortunately, immune checkpoint inhibitors have also been associated with the emergence of a new subset of autoimmune-like toxicities, known as immune-related adverse events. These toxicities differ depending on the agent, malignancy, and individual susceptibilities. Although the skin and colon are most commonly involved, any organ may be affected, including the liver, lungs, kidneys, and heart. Most of these toxicities are diagnosed by excluding other secondary infectious or inflammatory causes. Corticosteroids are commonly used for treatment of moderate and severe immune-related adverse events, although additional immunosuppressive therapy may occasionally be required. The occurrence of immune-related toxicities may require discontinuation of immunotherapy, depending on the specific toxicity and its severity. In this article, we provide a focused review to familiarize practicing clinicians with this important topic given that the use of immune checkpoint inhibitors continues to increase.     

Enhanced surveillance of tetanus toxoid,reduced diphtheria toxoid,and acellular pertussis (Tdap) vaccines in pregnancy in the Vaccine Adverse Event Reporting System (VAERS), 2011–2015

BackgroundIn October 2011, the Advisory Committee on Immunization Practices (ACIP) issued updated recommendations that all pregnant women routinely receive a dose of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine.ObjectivesWe characterized reports to the Vaccine Adverse Event Reporting System (VAERS) in pregnant women who received Tdap after this updated recommendation (2011–2015) and compared the pattern of adverse events (AEs) with the period before the updated recommendation (2005–2010).MethodsWe searched the VAERS database for reports of AEs in pregnant women who received Tdap vaccine after the routine recommendation (11/01/2011–6/30/2015) and compared it to published data before the routine Tdap recommendation (01/01/2005–06/30/2010). We conducted clinical review of reports and available medical records. The clinical pattern of reports in the post-recommendation period was compared with the pattern before the routine Tdap recommendation.ResultsWe found 392 reports of Tdap vaccination after the routine recommendation. One neonatal death but no maternal deaths were reported. No maternal or neonatal deaths were reported before the recommendation. We observed an increase in proportion of reports for stillbirths (1.5–2.8%) and injection site reactions/arm pain (4.5–11.9%) after the recommendation compared to the period before the routine recommendation for Tdap during pregnancy. We noted a decrease in reports of spontaneous abortion (16.7–1%). After the 2011 Tdap recommendation, in most reports, vaccination (79%) occurred during the third trimester compared to 4% before the 2011 Tdap recommendation. Twenty-six reports of repeat Tdap were received in VAERS; 13 did not report an AE. One medical facility accounted for 27% of all submitted reports.ConclusionsNo new or unexpected vaccine AEs were noted among pregnant women who received Tdap after routine recommendations for maternal Tdap vaccination. Changes in reporting patterns would be expected, given the broader use of Tdap in pregnant women in the third trimester.     

Circumstances of substance use by street youth in Egypt support the case for intervening to prevent adverse childhood experiences

Background: Egyptian street youth use substances including tobacco, illicit drugs, and pharmaceutical drugs. To understand the circumstances, including adverse childhood experiences, that place adolescents at risk for engaging in substance use, we conducted in-depth interviews among a sample of Egyptian street children. Methods: From youth residing at or attending Caritas, a non-profit organization, which provides shelter and education to street youth, seven girls and twelve boys, aged 12–18 years, participated in open-ended, in-depth interviews. Results: Eight out of the 19 participants reported family history (early exposure) to substance use; and seven of them were initiated by either a family member (sibling), friend or coworker. Most of the participants reported a history of conflict with or abuse (verbal or physical) by their parents or siblings, or stressful situations at home; they used substance(s) to alleviate their stress. Few attended school, and some were forced to work and help their family. Conclusions: Among Egyptian youth, adverse childhood experiences, such as poverty, child abuse, and family substance use, challenge somewhat susceptible youths and lead them to the path of substance use and addiction. Prevention intervention should be multifaceted, culturally adaptable, and primarily targeting the social environment during childhood.     

Buried Bumper Syndrome: A common complication of levodopa intestinal infusion for Parkinson disease

BackgroundPercutaneous endoscopic gastrostomy (PEG) is required for Levodopa/Carbidopa Intestinal Gel (LCIG) delivery in patients with advanced Parkinson's disease (PD) as well as for enteral feeding in a variety of neurological disorders. Buried Bumper Syndrome (BBS) is a serious complication of PEG. The frequency of BBS in patients receiving LCIG treatment has never been reported.ObjectivesTo compare the frequency of BBS in patients on LCIG treatment or on enteral feeding over the past 12 years and identify possible risk factors.MethodsWe reviewed prospectively recorded data from 2009 to 2020 on two case-series: LCIG-treated PD patients and non-PD patients on enteral nutrition. We identified all BBS incidences. Patients’ characteristics, clinical manifestations, BBS management, possible risk factors and outcomes were analyzed.ResultsDuring the 12 years, 35 PD patients underwent PEG insertion for LCIG infusion, and 123 non-PD patients for nutritional support. There were eight cases of BBS in six PD patients (17.1%). Six of them were effectively managed without treatment discontinuation. Of the enteral feeding patients, only one developed BBS (0.8%) (p < 0.001). We identified inappropriate PEG site aftercare, weight gain, early onset PD, longer survival, treatment duration, dementia and PEG system design as potential risk factors for BBS development.ConclusionsBBS occurs more frequently in LCIG patients than in patients receiving enteral feeding. If detected early, it can be successfully managed, and serious sequalae or treatment discontinuation can be avoided. Regular endoscopic follow-up visits of LCIG-treated patients and increased awareness in patients and clinicians are recommended.     

Safety profile of the adjuvanted recombinant zoster vaccine: Pooled analysis of two large randomised phase 3 trials

Background

The ZOE-50 (NCT01165177) and ZOE-70 (NCT01165229) phase 3 clinical trials showed that the adjuvanted recombinant zoster vaccine (RZV) was ≥90% efficacious in preventing herpes zoster in adults. Here we present a comprehensive overview of the safety data from these studies.

丙泊酚复合瑞芬太尼喉罩全麻的效果分析与研究

目的 探讨丙泊酚复合瑞芬太尼喉罩全身麻醉(全麻)的效果。方法 62例腹腔镜、泌尿科、骨科、肛肠科、妇科等手术治疗的患者,随机分为实验组和对照组,每组31例。对照组采用常规气管插管静脉复合全麻,实验组给予靶控输注丙泊酚复合瑞芬太尼喉罩全麻。比较两组患者插入喉罩(插管)、插管1 min、插管3 min、拔出喉罩(拔管)1 min、拔管3 min时心率(HR)和平均动脉压(MAP)水平;不良反应发生情况、麻醉效果;全麻起效时间、维持全麻时间、术后苏醒时间。结果 实验组插管时、插管1 min、插管3 min、拔管1 min、拔管3 min的HR水平分别为(77.52±6.36)、(73.26±5.56)、(72.01±4.69)、(75.35±7.63)、(72.34±6.79)次/min,均低于对照组的(92.34±7.85)、(87.97±5.25)、(78.85±5.20)、(95.69±9.21)、(85.63±7.43)次/min,差异均具有统计学意义(P<0.05)。实验组插管时、插管1 min、插管3 min、拔管1 min、拔管3 min的MAP水平分别为(90.25±6.73)、(87.65±7.98)、(88.79±7.65)、(88.09±5.61)、(88.52±5.16)mm Hg(1 mm Hg=0.133 kPa),均低于对照组的(109.51±7.85)、(103.27±12.43)、(102.52±8.21)、(106.74±7.68)、(104.62±7.71)mm Hg,差异均具有统计学意义(P<0.05)。实验组不良反应发生率3.23%低于对照组的19.35%,差异具有统计学意义(P<0.05)。实验组麻醉总有效率96.77%均高于对照组的80.65%,差异均具有统计学意义(P<0.05)。实验组全麻起效、维持全麻、术后苏醒时间分别为(1.61±0.23)、(100.59±6.72)、(17.99±3.52)min,均短于对照组的(2.93±0.41)、(123.61±7.85)、(36.87±4.16)min,差异均具有统计学意义(P<0.05)。结论 针对腹腔镜等手术患者应用丙泊酚复合瑞芬太尼喉罩全麻对血液动力学影响小,不良反应发生率低,麻醉效果良好,降低对机体损伤,值得推广应用。     

A Noninterventional,Observational, European Post-Authorization Safety Study of Patients With Relapsed/Refractory Multiple Myeloma Treated With Lenalidomide

IntroductionLenalidomide plus dexamethasone is effective and well tolerated in relapsed/refractory multiple myeloma (RRMM). In this observational, noninterventional European post-authorization safety study, the safety profile of lenalidomide plus dexamethasone was investigated and compared with that of other agents in the treatment of RRMM in a real-world setting.Patients and MethodsPatients had received ≥ 1 prior antimyeloma therapy; prior lenalidomide was excluded. Treatment was per investigator’s routine practice. Adverse events were analyzed by incidence rates per 100 person-years to account for differences in observation length and treatment duration.ResultsIn total, 2150 patients initiated lenalidomide, and 1479 initiated any other antimyeloma therapy, predominately bortezomib (80.3%), which was primarily administered intravenously (74.3%). The incidence rate of neuropathy was lower with lenalidomide (10.5) than with bortezomib (78.9) or thalidomide (38.7). Lenalidomide also had a lower incidence rate of infections (68.7) versus bortezomib (95.9) and thalidomide (76.0). Conversely, the incidence rate of neutropenia was higher with lenalidomide (38.0) than with bortezomib (18.2) or thalidomide (25.7). The incidence rates of thrombocytopenia were 24.4, 40.4, and 14.4 with lenalidomide, bortezomib, and thalidomide, respectively.ConclusionNo new safety signals for lenalidomide were identified in this study, which is the largest prospective real-world European study of lenalidomide in patients with RRMM to date. These results confirm that the safety profile of lenalidomide plus dexamethasone in RRMM in a real-world setting is comparable to that reported in clinical trials.     

优化温针灸流程对不良事件发生及患者舒适度的影响

目的:观察优化温针灸流程对患者温针灸过程中不良事件发生及舒适度的影响。方法:选取行温针灸治疗的140例患者为研究对象,按随机数字表法分为观察组和对照组各70例。对照组采用传统纸片承接散灰,观察组使用锡纸圆杯代替传统纸片。结果:观察组无不良事件发生。对照组出现不良事件频率较高,其中灰烬跌落床单和灰烬跌落皮肤发生率与观察组比较,差异均有统计学意义(P<0.05)。观察组舒适度优于对照组,差异有统计学意义(P<0.05)。结论:优化温针灸流程在温针灸过程中能减少不良事件发生,提高患者的舒适度。