PARP7 negatively regulates the type I interferon response in cancer cells and its inhibition triggers antitumor immunity

1. Download : Download high-res image (204KB)
2. Download : Download full-size image

     

Imaging Features of Pulmonary Immune-related Adverse Events

Pulmonary immune-related adverse events represent rare but potentially severe side effects of immunotherapies. Diagnosis is often challenging, as symptoms and imaging features are not specific and may mimic other lung diseases, thus potentially delaying appropriate patient management. In this setting, an accurate imaging evaluation is essential for a prompt detection and correct management of these drug-induced lung diseases. The purpose of this article is to review the different types of pulmonary immune-related adverse events, describe their imaging characteristics on both high-resolution computed tomography and positron emission tomography/computed tomography and stress their underlying diagnostic challenge by presenting the mimickers.     

脾脏血管性病变与淋巴瘤CT鉴别诊断

目的 运用CT区分脾脏血管性病变与淋巴瘤。方法 回顾性分析20例经手术、穿刺病理学检查证实的脾脏病变的发病年龄、性别、脾脏指数、病变大小、数目、有无液化、钙化、强化幅度、强化方式等特征,并进行统计学分析。结果 20例脾脏病变中,11例血管性病变(6例海绵状血管瘤,3例窦岸细胞血管瘤,2例硬化性血管瘤样结节性转化),9例淋巴瘤;两组间发病年龄、病变大小、数目、有无液化、钙化等差异无统计学意义;两组间脾脏指数、动脉期强化幅度差异具有统计学意义(P＜0.05)。5例海绵状血管瘤呈不均匀性强化,1例呈渐进性填充式强化,2例窦岸细胞血管瘤呈“雀斑征”,1例硬化性血管瘤样结节性转化呈“辐轮征”;9例淋巴瘤实质部分均呈均匀、轻中度强化。结论 脾脏血管性病变与淋巴瘤CT表现不同,CT有助于明确诊断。     

Perioperative,short-, and long-term outcomes of gastric cancer surgery: Propensity score-matched analysis of patients with or without prior solid organ transplantation

BackgroundDetails of perioperative outcomes and survival after gastric cancer surgery in prior transplant recipients have received minimal research attention.MethodsWe performed an observational cohort study using the database of 20,147 gastric cancer patients who underwent gastrectomy at a single gastric cancer center in Korea. Forty-one solid organ recipients [kidney (n = 35), liver (n = 5), or heart (n = 1)] were matched with 205 controls using propensity score matching.ResultsOperation time, blood loss, and postoperative pain were similar between groups. Short-term complication rates were similar between transplantation and control groups (22.0% vs. 20.1%, P = 0.777). Transplantation group patients with stage 1 gastric cancer experienced no recurrence, while those with stage 2/3 cancer had significantly higher recurrence risk compared to the controls (P = 0.049). For patients with stage 1 cancer, the transplantation group had a significantly higher rate of non-gastric cancer-related deaths compared to the controls (19.2% vs. 1.4%, P = 0.001). For those with stage 2/3 cancer, significantly lower proportion of the transplantation group received adjuvant chemotherapy compared to the control group (26.7% vs. 80.3%, P < 0.001). The transplantation group had a higher (albeit not statistically significant) rate of gastric cancer-related deaths compared to the controls (40.0% vs. 18.0%, P = 0.087).ConclusionTransplant recipients and non-transplant recipients exhibited similar perioperative and short-term outcomes after gastric cancer surgery. From long-term outcome analyses, we suggest active surveillance for non-gastric cancer-related deaths in patients with early gastric cancer, as well as strict oncologic care in patients with advanced cancer, as effective strategies for transplant recipients.     

Memory specificity is linked to repetition effects in event-related potentials across the lifespan

The specificity with which past experiences can be remembered varies across the lifespan, possibly due to differences in how precisely information is encoded. Memory formation can be investigated through repetition effects, the common finding that neural activity is altered when stimuli are repeated. However, whether differences in this indirect measure of memory formation relate to lifespan differences in memory specificity has not yet been established. In the present study, we examined repetition effects in event-related potentials and their relation to recognition. During incidental encoding, children (aged 7–9 years), young adults (18–30 years), and older adults (65–76 years) viewed repeated object images from different categories. During subsequent recognition, we distinguished memory for the specific items versus the general categories. We identified repetition suppression in all age groups, and repetition enhancement for adults. Furthermore, individual item recognition performance comprising lure discrimination was positively associated with the magnitude of the neural repetition effects, which did not differ between groups, indicating common neural mechanisms of memory formation. Our findings demonstrate that neural repetition effects reflect the formation of highly specific memory representations and highlight their significance as a neural indicator of individual differences in episodic memory encoding across the lifespan.     

Factors Associated with Hepatitis B Surface Antigen Kinetics and Responses in Pegylated Interferon Alpha-2a Monotherapy for Patients with Chronic Hepatitis B

Objective Pegylated-interferon monotherapy is the standard treatment for patients with chronic hepatitis B; however, the factors associated with its therapeutic effects remain unclear. Methods Patients with chronic hepatitis B were treated with pegylated interferon α-2a for 48 weeks. We evaluated the kinetics of hepatitis B surface antigen (HBsAg) during treatment and follow-up periods and the factors associated with an HBsAg response (defined as a change in HBsAg of ≥-1 log IU/mL from baseline). Results The study population comprised 50 patients. The median baseline levels of hepatitis B virus DNA and HBsAg were 5.00 and 3.40 log IU/mL. The median values of HBsAg reduction from baseline were -0.44 (n=48), -0.41 (n=40), and -0.68 (n=11) log IU/mL at the end of treatment and at 48 and 144 weeks post-treatment, respectively. The rates of HBsAg response were 24.0% and 22.5% at the end of treatment and at 48 weeks post-treatment, respectively. A multivariate analysis identified HBsAg <3.00 log IU/mL as an independent baseline factor contributing to the HBsAg response at the end of treatment and 48 weeks post-treatment (p=1.07×10^-2 and 4.42×10^-2, respectively). There were significant differences in the reduction of the HBsAg levels at 12 weeks of treatment and in the incidence of serum ALT increase during treatment between patients with and without an HBsAg response. Conclusion These findings suggest that the baseline HBsAg level, HBsAg kinetics at 12 weeks of treatment, and ALT increase during treatment are important factors contributing to the HBsAg response in pegylated interferon α-2a monotherapy for patients with chronic hepatitis B.     

Extracellular vesicles: Their emerging roles in the pathogenesis of respiratory diseases

Alveoli are the basic structure of the lungs, consisting of various types of parenchymal and bone marrow-derived cells including alveolar macrophages. These various types of cells have several important functions; thus, communication between these cells plays an important role in homeostasis as well as in the pathophysiology of diseases in the lungs. For a better understanding of the pathophysiology of lung diseases, researchers have isolated each type of lung cell to investigate the changes in their gene expressions, including their humoral factor or adhesion molecules, to reveal the intercellular communication among these cells. In particular, investigations during the past decade have focused on extracellular vesicles, which are lipid bilayer delimited vesicles released from a cell that can move among various cells and transfer substances, including microRNAs, mRNAs and proteins, thus, functioning as intercellular messengers. Extracellular vesicles can be classified into three general groups: apoptotic bodies, exosomes, and microparticles. Extracellular vesicles, especially exosomes and microparticles, are attracting increasing attention from pulmonologists as tools for understanding pathogenesis and disease diagnosis. Here, we review studies, including our own, on exosomes and microparticles and their roles in both lung homeostasis and the pathogenesis of lung diseases such as idiopathic pulmonary fibrosis, chronic obstructive lung diseases, and acute respiratory distress syndrome. This review also addresses the roles of extracellular vesicles in COVID-19, the current global public health crisis.     

Synthetic MRI is not yet ready for morphologic and functional assessment of patellar cartilage at 1.5 Tesla

PurposeThe purpose of this study was to compare morphologic assessment and relaxometry of patellar hyaline cartilage between conventional sequences (fast spin-echo [FSE] T2-weighted fat-saturated and T2-mapping) and synthetic T2 short-TI inversion recovery (STIR) and T2 maps at 1.5 T magnetic resonance imaging (MRI).MethodThe MRI examinations of the knee obtained at 1.5 T in 49 consecutive patients were retrospectively studied. There were 21 men and 28 women with a mean age of 45 ± 17.7 (SD) years (range: 18–88 years). Conventional and synthetic acquisitions were performed, including T2-weighted fat-saturated and T2-mapping sequences. Two radiologists independently compared patellar cartilage T2-relaxation time on conventional T2-mapping and synthetic T2-mapping images. A third radiologist evaluated the patellar cartilage morphology on conventional and synthetic T2-weighted images. The presence of artifacts was also assessed. Interobserver agreement for quantitative variables was assessed using intraclass correlation coefficient (ICC).ResultsIn vitro, conventional and synthetic T2 maps yielded similar mean T2 values 58.5 ± 2.3 (SD) ms and 58.8 ± 2.6 (SD) ms, respectively (P = 0.414) and 6% lower than the expected experimental values (P = 0.038). Synthetic images allowed for a 15% reduction in examination time compared to conventional images. On conventional sequences, patellar chondropathy was identified in 35 patients (35/49; 71%) with a mean chondropathy grade of 4.8 ± 4.8 (SD). On synthetic images, 28 patients (28/49; 57%) were diagnosed with patellar chondropathy, with a significant 14% difference (P = 0.009) and lower chondropathy scores (3.7 ± 4.9 [SD]) compared to conventional images. Motion artifacts were more frequently observed on synthetic images (18%) than on conventional ones (6%). The interobserver agreement was excellent for both conventional and synthetic T2 maps (ICC > 0.83). Mean cartilage T2 values were significantly greater on synthetic images (36.2 ± 3.8 [SD] ms; range: 29-46 ms) relative to conventional T2 maps (31.8 ± 4.1 [SD] ms; range: 26-49 ms) (P < 0.0001).ConclusionDespite a decrease in examination duration, synthetic images convey lower diagnostic performance for chondropathy, greater prevalence of motion artifacts, and an overestimation of T2 values compared to conventional MRI sequences.     

Myocardial deformation assessment in patients with precapillary pulmonary hypertension: A cardiac magnetic resonance study

PurposeThe purpose of this study was to investigate right atrial and ventricular strain parameters on cardiac magnetic resonance (CMR) in patients with precapillary pulmonary hypertension (PPH) and whether they can aid in the assessment of PPH prognosis.Materials and methodsAdult patients with groups 1 and 4 PPH were invited to participate in the study. Age- and sex-matched healthy volunteers were also recruited as controls. At baseline, patients underwent clinical examination, N-terminal pro-B-type natriuretic peptide measurement and CMR with feature tracking post-processing (CMR-FT). Healthy controls underwent only CMR-FT. The study's primary endpoint was clinical failure, defined as death, hospitalization or demonstrable clinical deterioration during follow-up. Patients who were unable to perform 6-minute walking test due to musculoskeletal disorders were excluded from the study.ResultsThirty-six patients (8 men, 28 women; mean age, 50.6 ± 13.8 [SD] years [range: 18.6–78.5 years]) and 12 healthy control subjects (5 mean, 7 women; mean age, 40.6 ± 13.5 [SD] years [range: 23.1–64.4 years]) were recruited. Right ventricular global longitudinal strain (GLS) was significantly impaired in PPH patients (?20.2 ± 5.3 [SD] % [range: ?28.8 to ?9.1%] vs. ?28.4 ± 3.1% [?33.7 to ?22.7%] respectively, P < 0.001). The right atrial GLS was significantly impaired in PPH compared to healthy controls (?19.9 ± 4.5% [range: ?28.6 to ?3.6%] vs. ?26.5 ± 4.2% [range: ?32.8 to ?15.8%] respectively) (P < 0.001). Clinical failure occurred in 19 (19/36, 53%) of patients. Right ventricular GLS predicted clinical failure most reliably among CMR parameters (?22.6 ± 3.8 [SD] % [range: ?27.6 to ?12.7%] for patients without clinical failure vs. ?18 ± 5.6 [SD] % [range: ?28.8 to ?9.1%] for patients with clinical failure; hazard ratio [HR] = 1.85; P = 0.007; area under the AUC curve = 0.75). Lower absolute right atrial GLS was significantly associated with clinical failure (?22.7 ± 3.0 [SD] % [range: ?28.6 to ?17.7%] for patients without clinical failure vs. ?16.9 ± 5.8 [SD] % [range: ?24.2 to ?3.6%] for patients with clinical failure) (HR = 1.53; P = 0.035).ConclusionCMR feature tracking-derived myocardial strain parameters of both the right atrium and ventricle can assist clinicians in the prognosis of PPH.