Purpose: To evaluate the outcome of small volume injection of perfluoropropane (C3F8) gas for symptomatic vitreomacular traction (VMT).
Methods: A retrospective review of eyes with VMT treated with a ...limited volume of 0.2 ml of C3F8 gas was performed with limited face‐down position. Main outcome measures were release of VMT, best‐corrected visual acuity (BCVA), central macular thickness (CMT) and adverse events.
Results: Ten consecutive patients with symptomatic VMT underwent pneumatic vitreolysis. Overall success was of 90% in VMT release. The CMT decreased from 397,8 μm ±) 81.87) preoperatively to 309,8 μm ±) 51.76) postoperatively (p < 0.001). Mean BCVA improved from 0.42 ±) 0.24) to 0.24±) 0.23) logMAR at 6 months (p < 0.001). One patient with a large VMT had no change in the optical coherence tomography aspect. Another patient with large VMT associated to large retrofoveal cyst has VMT release but formed a macular hole after gas injection. No other adverse events were seen.
Conclusions: Pneumatic vitreolysis with small volume of C3F8 and limited face‐down position is a viable option for treating VMT with few adverse events. Macular hole formation can occur in cases of large retrofoveal cysts.
A review of cancer immunotherapy toxicity Kennedy, Lucy Boyce; Salama, April K. S.
CA: a cancer journal for clinicians,
March/April 2020, Letnik:
70, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Cancer immunotherapies, including checkpoint inhibitors and adoptive cell therapy, manipulate the immune system to recognize and attack cancer cells. These therapies have the potential to induce ...durable responses in multiple solid and hematologic malignancies and thus have transformed treatment algorithms for numerous tumor types. Cancer immunotherapies lead to unique toxicity profiles distinct from the toxicities of other cancer therapies, depending on their mechanism of action. These toxicities often require specific management, which can include steroids and immune‐modulating therapy and for which consensus guidelines have been published. This review will focus on the toxicities of checkpoint inhibitors and chimeric antigen receptor T cells, including pathophysiology, diagnosis, and management.
Background
Immune‐checkpoint inhibitors (ICIs) are now standard of care for advanced non‐small cell lung cancer (NSCLC). Unfortunately, many patients experience immune‐related adverse events (irAEs), ...which are usually mild and reversible, but they require timely management and may be life threatening. No predictive markers of irAEs are available.
Materials and Methods
The neutrophil‐to‐lymphocyte ratio (NLR) and platelet‐to‐lymphocyte ratio (PLR) were evaluated in patients with NSCLC consecutively treated with ICIs. Prespecified cutoff values of NLR and PLR were used and related to outcome and onset of irAEs. A control group of patients with advanced NSCLC not receiving ICIs was included.
Results
The study included 184 patients: 26 (14.1%) received pembrolizumab upfront, and 142 (77%) received ICIs (pembrolizumab, nivolumab or atezolizumab) after one or more lines of chemotherapy. The median number of ICIs cycles was six (range, 1–61). The median progression‐free survival and overall survival were 4.8 (95% CI, 3.4–6.3) and 20.6 (95% CI, 14.7–26.5) months, respectively. Sixty patients (32.6%) developed irAEs, mainly grade 1–2 (65.0%), causing ICI interruption in 46 cases (25.0%). Low NLR and low PLR at baseline were significantly associated with the development of irAEs (odds ratio OR, 2.2; p = .018 and OR, 2.8; p = .003, respectively). Multivariate analyses confirmed PLR as independent predictive marker of irAEs (OR, 2.3; p = .020).
Conclusion
NLR and PLR may predict the appearance of irAEs in non‐oncogene‐addicted aNSCLC, although this conclusion warrants prospective validation.
Implications for Practice
This study was designed to investigate the role of blood biomarkers in predicting the occurrence of immune‐related adverse events (irAEs) in patients with advanced non‐small cell lung cancer receiving immunotherapy. The results of the study suggest a potential predictive role of neutrophil‐to‐lymphocyte ratio and platelet‐to‐lymphocyte ratio as markers for irAE development in this category of patients. These data provide rationale for an easy and feasible application to be validated in clinical practice.
摘要
背景。免疫检查点抑制剂 (ICI) 药物目前是治疗晚期非小细胞肺癌 (NSCLC) 的标准药物。不幸的是，许多患者会出现免疫相关不良事件 (irAE)，虽然此类事件通常并不严重而且可逆，但需要及时治疗而且可能会危及生命。目前还没有 irAE 的预测标志物。
材料和方法。评估连续接受 ICI 治疗的 NSCLC 患者的中性粒细胞淋巴细胞比 (NLR) 和血小板淋巴细胞比 (PLR)。使用预先指定的 NLR 和 PLR 临界值，该值与 irAE 结局和发病相关。对照组选择未接受 ICI 治疗的晚期 NSCLC 患者。
结果。研究包括 184 名患者:26 例 (14.1%) 预先接受帕博利珠单抗 (Pembrolizumab) 治疗，142 例 (77%) 在经过一线或多线化疗之后接受 ICI(帕博利珠单抗、纳武单抗或阿特朱单抗)治疗。中位ICI 周期为 6(范围:1‐61)。中位无进展生存期和总生存期分别为 4.8 个月(95% CI, 3.4‐6.3) 和 20.6 个月 (95% CI, 14.7‐26.5)。60 例 (32.6%) 患者发生 irAE，以 1‐2 级为主 (65.0%)，其中 46 例 (25.0%) 中断 ICI 治疗。基线 NLR 低和 PLR 低与 irAE 的发生显著相关 分别为:比值比 (OR)， 2.2；p = 0.018, OR, 2.8; p = 0.003。多变量分析证实 PLR 是 irAE 的独立预测标志物 (OR, 2.3; p = 0.020)。
结论。NLR 和 PLR 可能预测非嗜癌性 aNSCLC 中是否会出现 irAE，但这一结论仍需接受前瞻性验证。
实践意义:本研究旨在探讨血液生物标志物在预测晚期非小细胞肺癌患者免疫相关不良事件 (irAE) 发生中的作用。研究结果表明，中性粒细胞淋巴细胞比和血小板淋巴细胞比是预测此类患者是否发生 irAE 的潜在预测标志物。这些数据为简单可行的应用提供了理论依据，有待临床实践验证。
Predictive markers for immune‐related adverse events (irAEs) are not available. This article evaluates the association of peripheral blood markers with the onset of irAEs in patients with non‐oncogene addicted advanced non‐small cell lung cancer treated with immune‐checkpoint inhibitors.
Since the outbreak of coronavirus disease 2019 (Covid‐19) in December 2019, caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), the number of confirmed infections has risen to ...more than 242 million worldwide, with nearly 5 million deaths. Currently, nine Covid‐19 vaccine candidates based on the original Wuhan‐Hu‐1 strain are at the forefront of vaccine research. All nine had an efficacy over 50% against symptomatic Covid‐19 disease: NVX‐CoV2373 (∼96%), BNT162b2 (∼95%), mRNA‐1273 (∼94%), Sputnik V (∼92%), AZD1222 (∼81%), BBIBP‐CorV (∼79%), Covaxin (∼78%), Ad26.CoV.S (∼66%) and CoronaVac (∼51%). However, vaccine efficacy (VE) can be jeopardised by the rapid emergence and spread of SARS‐CoV‐2 variants of concern (VOCs) that could escape from neutralising antibodies and/or cell‐mediated immunity. Rare adverse events have also been reported soon after administration of viral vector and mRNA vaccines. Although many Covid‐19 vaccines have been developed, additional effective vaccines are still needed to meet the global demand. Promising Covid‐19 vaccines such as WIBP‐CorV, AD5‐nCOV, ZyCoV‐D, CVnCoV, EpiVacCorona and ZF2001 have advanced to clinical studies. This review describes the most relevant mutations in the SARS‐CoV‐2 spike protein, discusses VE against VOCs, presents rare adverse events after Covid‐19 vaccination and introduces some promising Covid‐19 vaccine candidates.
Management of Pediatric Postendoscopy Fever Boster, Julia M.; Iwanowski, Melissa; Kramer, Robert E.
Journal of pediatric gastroenterology and nutrition,
February 2021, Letnik:
72, Številka:
2
Journal Article
Recenzirano
Odprti dostop
ABSTRACT
Objectives:
The aim of the study was to validate rates of fever after pediatric gastrointestinal endoscopy, to describe clinical outcomes of postendoscopy fever (PEF) cases, and to assess ...the effect of a PEF clinical care guideline (CCG) on hospital use.
Patients and Methods:
Episodes of PEF were reviewed from a large prospective database of all adverse events following pediatric gastrointestinal endoscopy at an academic children's hospital. A CCG was implemented to standardize care of children with reported fever after endoscopy and reduce unnecessary resource use. Chi‐squared analysis was performed to compare rates of hospital use for evaluation of PEF before and after implementation of the CCG.
Results:
PEF occurred in 0.55% of the 27,100 endoscopies performed during the present study period. In the 150 cases of reported fever, the rate of identified endoscopy‐related infection was low (4.0%). The rate of PEF was significantly higher in patients who underwent interventional procedures (0.81%) than those who underwent diagnostic endoscopy (0.51%, P = 0.02). In patients who experienced PEF, the CCG significantly reduced hospital use, decreasing emergency department visits and hospital admissions by 52.1% (P < 0.0001) without leading to negative patient outcomes.
Conclusion:
PEF in children rarely represents clinically significant infection and may be due in part to inflammation from tissue damage and/or physiologic stress. The present study shows that implementation of a PEF CCG may reduce unnecessary care while maintaining patient safety. Furthermore, multicenter studies are required to confirm the overall safety of similar clinical algorithms.
Immunotherapy approaches boosting spontaneous and durable antitumor immune responses through immune checkpoint blockade are revolutionizing treatment and patient outcomes in solid tumors and ...hematological malignancies. Among the various inhibitory molecules employed by the immune system to regulate the adaptive immune responses, cytotoxic T lymphocyte antigen‐4 (CTLA‐4) is the first successfully targeted immune checkpoint molecule in the clinic, giving rise to significant but selective benefit either when targeted alone or in combination with anti‐programmed cell death protein‐1 (PD‐1) antibodies (Abs). However, the use of anti‐CTLA‐4 Abs was associated with the incidence of autoimmune‐like adverse events (AEs), which were particularly frequent and severe with the use of combinational strategies. Nevertheless, the higher incidence of AEs is associated with an improved clinical benefit indicating treatment response. A prompt recognition of AEs followed by early and adequate treatment with immunosuppressive agents allows the management of these potentially serious AEs. This narrative review aims to summarize CTLA‐4 biology, the rationale for the use as a companion for anti‐PD‐1 Abs in humans with results from the most relevant Phase III clinical trials including anti‐CTLA‐4 Abs in combination with anti‐PD‐1 Abs in solid tumors.
Background and Aim
Immune checkpoint inhibitors pose the risk of immune‐related adverse events (irAEs). Recent data suggest that irAEs may be associated with a favorable prognosis. This study aimed ...to investigate and analyze the association between these adverse events and the clinical benefits in patients with unresectable hepatocellular carcinoma.
Methods
The study enrolled 130 patients with advanced hepatocellular carcinoma treated with atezolizumab plus bevacizumab between November 2020 and January 2023 at a single center. The relationship between irAEs and both response rate and post‐treatment outcomes was investigated.
Results
Out of the 130 patients, irAEs developed in 36 (27.7%) patients. The irAE group exhibited a significantly longer progression‐free survival (PFS) than the non‐irAE group, with a median PFS of 8.9 compared with 4.6 months (P < 0.01). No difference was found in the overall survival between the irAE and non‐irAE groups. The irAE group demonstrated significantly higher disease control rate (DCR) than the non‐irAE group (97.0% vs 65.5%, P < 0.01). The analysis by irAE severity revealed that the grade 1/2 group exhibited significantly longer PFS (7.9 vs 4.6 months, P = 0.007) and higher DCR (100% vs 65.5%, P < 0.01) than the non‐irAE group. Furthermore, hypothyroidism correlated with a favorable PFS (8.9 vs 5.4 months, P = 0.02), DCR (100% vs 71.3%, P = 0.03), and overall response rate (58.3% vs 18.5%, P = 0.005).
Conclusion
The presence of irAEs is associated with prolonged PFS and higher DCR. Specifically, mild irAEs (grade 1/2) and hypothyroidism displayed prolonged PFS and higher DCR.
The Global COVID Vaccine Safety (GCoVS) Project, established in 2021 under the multinational Global Vaccine Data Network™ (GVDN®), facilitates comprehensive assessment of vaccine safety. This study ...aimed to evaluate the risk of adverse events of special interest (AESI) following COVID-19 vaccination from 10 sites across eight countries.
Using a common protocol, this observational cohort study compared observed with expected rates of 13 selected AESI across neurological, haematological, and cardiac outcomes. Expected rates were obtained by participating sites using pre-COVID-19 vaccination healthcare data stratified by age and sex. Observed rates were reported from the same healthcare datasets since COVID-19 vaccination program rollout. AESI occurring up to 42 days following vaccination with mRNA (BNT162b2 and mRNA-1273) and adenovirus-vector (ChAdOx1) vaccines were included in the primary analysis. Risks were assessed using observed versus expected (OE) ratios with 95 % confidence intervals. Prioritised potential safety signals were those with lower bound of the 95 % confidence interval (LBCI) greater than 1.5.
Participants included 99,068,901 vaccinated individuals. In total, 183,559,462 doses of BNT162b2, 36,178,442 doses of mRNA-1273, and 23,093,399 doses of ChAdOx1 were administered across participating sites in the study period. Risk periods following homologous vaccination schedules contributed 23,168,335 person-years of follow-up. OE ratios with LBCI > 1.5 were observed for Guillain-Barré syndrome (2.49, 95 % CI: 2.15, 2.87) and cerebral venous sinus thrombosis (3.23, 95 % CI: 2.51, 4.09) following the first dose of ChAdOx1 vaccine. Acute disseminated encephalomyelitis showed an OE ratio of 3.78 (95 % CI: 1.52, 7.78) following the first dose of mRNA-1273 vaccine. The OE ratios for myocarditis and pericarditis following BNT162b2, mRNA-1273, and ChAdOx1 were significantly increased with LBCIs > 1.5.
This multi-country analysis confirmed pre-established safety signals for myocarditis, pericarditis, Guillain-Barré syndrome, and cerebral venous sinus thrombosis. Other potential safety signals that require further investigation were identified.
Vaccinees experience no adverse events, mild adverse events, multiple adverse events, or serious adverse events post vaccination. Many of these vaccine adverse events occur with different vaccines ...with different occurrence frequencies. Many of these adverse events are generally considered as associated with immune responses to the active vaccine components (antigens) and/or to possibly one or more of the vaccine excipients. Most of these vaccine adverse events are self-limiting and resolve within days. Many of these adverse events symptoms overlap symptoms associated with elevated histamine levels. Based on these observations, the hypothesis that the majority of vaccine associated reactogenicity adverse events are caused by temporal histamine intolerance in vaccinees is proposed. This hypothesis is based on a model of innate immune responses releasing a surge of inflammatory molecules including histamine; this surge is hypothesized to exceed the normal histamine tolerance level for vaccinees with reactogenicity adverse events. Further, these symptoms resolve as histamine levels fall below the vaccinee's tolerance threshold. This model can be evaluated by the detection of elevated histamine levels in vaccinees corresponding to timing of symptoms onset. If confirmed, a direct consequence of this model predicts that some antihistamine treatments, mast cell stabilizers, and possibly diamine oxidase enzyme may reduce the incidence or severity of adverse events experienced by vaccinees post vaccinations for most or all high reactogenicity vaccines including coronavirus disease 2019 (COVID-19) Spike vaccines.
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