Short-term outcomes of three- and two-field lymphadenectomy with minimally invasive esophagectomy for esophageal cancer: a propensity score-matching analysis.

Background: Whether patients can benefit from three-field lymphadenectomy (3-FL) in minimally invasive esophagectomy (MIE) remains unclear. This study retrospectively compared short-term outcomes between 3-FL and two-field lymphadenectomy (2-FL) in MIE for patients with esophageal cancer (EC) and aimed to evaluate the clinical significance of 3-FL. Methods: There were 284 patients enrolled in the study (124 patients with 3-FL and 160 patients with 2-FL). The cases were matched based on their propensity scores using a matching ratio of 1:1, the nearest neighbor matching protocol, and a caliper of 0.02. Patients were propensity-score matched for sex, cancer location, Age-adjusted Charlson Comorbidity Index (ACCI), and neoadjuvant treatment. The short-term outcomes were postoperative complications, operation characteristics, pathology results and postoperative hospital stay. Results: There were no significant differences in intraoperative hemorrhage, postoperative hospital stay, or postoperative complications between the 2-FL and 3-FL groups. The operation time of the two groups was significantly different (227.1±46.2 vs. 248.5±45.9 min, P=0.001); the operation time of the 3-FL group was about 20 minutes longer than that of the 2-FL group. The number of lymphatic nodes (LNs) obtained in the 3-FL group was significantly higher than that in the 2-FL group (31.3±12.9 vs. 54.6±18.0, P<0.001). Pathological N stage was also significantly different (P=0.002); the 3-FL group was more advanced than the 2-FL group. Conclusions: Compared to 2-FL MIE, 3-FL MIE does not increase postoperative complications, can obtain more LNs, and improves the accuracy of tumor LN staging.

Preparation of a Highly Flame-Retardant Urea-Formaldehyde Resin and Flame Retardance Mechanism.

Urea-formaldehyde (UF) resin is the most widely used adhesive resin. However, it is necessary to improve its flame-retardant performance to expand its applications. In this study, exploiting electrostatic interactions, anionic phytic acid and cationic chitosan were combined to form a bio-based intumescent flame-retardant, denoted phytic acid-chitosan polyelectrolyte (PCS). The molecular structure of the urea-formaldehyde resin was optimized by crosslinking with melamine and plasticizing with polyvinyl alcohol-124. Thus, by combining PCS with the urea-formaldehyde resin and with ammonium polyphosphate and ammonium chloride as composite curing agents, flame-retardant urea-formaldehyde resins (FRUFs) were prepared. Compared to traditional UF resin, FRUF showed excellent flame retardancy and not only reached the UL-94 V-0 level, but the limit of oxygen index was also as high as 36%. Compared to those of UF, the total heat release and peak heat release rate of FRUF decreased by 86.44% and 81.13%, respectively. The high flame retardancy of FRUF originates from the combination of oxygen and heat isolation by the dense carbon layer, quenching of phosphorus free radicals, and dilution of oxygen by a non-flammable gas. In addition, the mechanical properties of the FRUF remained good, even after modification. The findings of this study provide a reference for the flame-retardant application of FRUF for applications in multiple fields.

A case of Abernethy malformation type I combined with hepatoblastoma.

This article encountered an extremely rare case of a 2-year-old male with Abernethy malformation Type I combined with hepatoblastoma. Furthermore, the medical history was characterized by several other abnormalities: gross facial asymmetry and cardiac defects，thus, diagnosis of Goldenhar syndrome in the setting of Abernethy type I was made. In this article, we exhibit the typical clinical presentation and Pathology imaging features of this disease.

PD-L1 Expression and Its Modulating Factors in Anaplastic Thyroid Carcinoma: A Multi-institutional Study.

Anti-PD immunotherapy is currently under investigation in anaplastic thyroid carcinoma (ATC). Tumor cell surface PD-L1 expression is considered predictive of therapeutic response. Although papillary thyroid carcinoma has been widely studied for PD-L1 expression, there are limited data on ATC. In this retrospective multi-institutional study involving 9 centers across Asia, 179 ATCs were assessed for PD-L1 expression using the SP263 (Ventana) clone. A tumor proportion score (TPS) ≥1% was required to consider a case PD-L1-positive. PD-L1 expression was compared with the histological patterns, the type of specimen (small or large), tumor molecular profile (BRAF V600E and TERT promoter mutation status), and patient outcome. PD-L1 expression in any co-existent differentiated thyroid carcinoma (DTC) was evaluated separately and compared with ATC. Most ATCs (73.2%) were PD-L1-positive. The median TPS among positive cases was 36% (IQR 11% to 75%; range 1% to 99%). A high expression (TPS ≥ 50%) was noted in 30.7%. PD-L1-negative cases were more likely to be small specimens (P=0.01). A negative result on small samples, hence, may not preclude expression elsewhere. ATCs having epithelioid and pleomorphic histological patterns were more likely to be PD-L1-positive with higher TPS than sarcomatoid (P<0.01). DTCs were more frequently negative and had lower TPS than ATC (P<0.01). Such PD-L1 conversion from DTC-negative to ATC-positive was documented in 71% of cases with co-existent DTC. BRAF V600E, but not TERT promoter mutations, correlated significantly with PD-L1-positivity rate (P=0.039), reinforcing the potential of combining anti-PD and anti-BRAF V600E drugs. PD-L1 expression, however, did not impact the patient outcome.

Measurements of peri-prostatic adipose tissue by MRI predict bone metastasis in patients with newly diagnosed prostate cancer.

Objectives: To investigate the role of MRI measurements of peri-prostatic adipose tissue (PPAT) in predicting bone metastasis (BM) in patients with newly diagnosed prostate cancer (PCa). Methods: We performed a retrospective study on 156 patients newly diagnosed with PCa by prostate biopsy between October 2010 and November 2022. Clinicopathologic characteristics were collected. Measurements including PPAT volume and prostate volume were calculated by MRI, and the normalized PPAT (PPAT volume/prostate volume) was computed. Independent predictors of BM were determined by univariate and multivariate logistic regression analysis, and a new nomogram was developed based on the predictors. Receiver operating characteristic (ROC) curves were used to estimate predictive performance. Results: PPAT and normalized PPAT were associated with BM (P<0.001). Normalized PPAT positively correlated with clinical T stage(cT), clinical N stage(cN), and Grading Groups(P<0.05). The results of ROC curves indicated that PPAT and normalized PPAT had promising predictive value for BM with the AUC of 0.684 and 0.775 respectively. Univariate and multivariate analysis revealed that high normalized PPAT, cN, and alkaline phosphatase(ALP) were independently predictors of BM. The nomogram was developed and the concordance index(C-index) was 0.856. Conclusions: Normalized PPAT is an independent predictor for BM among with cN, and ALP. Normalized PPAT may help predict BM in patients with newly diagnosed prostate cancer, thus providing adjunctive information for BM risk stratification and bone scan selection.

Evaluating the Risk of Malignancies of the Diagnostic Categories Proposed by the World Health Organization System for Reporting Lung Cytopathology: A 2-Year Single Institutional Experience.

INTRODUCTION: The WHO System of Reporting Lung Cytopathology proposed a 5-tiered system in 2023. We report the risk of malignancies (ROMs) of bronchial washing/lavage and percutaneous fine-needle aspiration (FNA) specimens. We also evaluated the change of ROMs when image correlation is required. METHODS: Lung cytology cases in 2021 and 2022 with histologic follow-up were included. CT reports were reviewed to identify cases with a solid nodule/tumor but benign cytological findings. These were reassigned from the "benign" to "non-diagnostic" category, and the ROMs were re-estimated. RESULTS: A total of 1,031 bronchial washing/lavage and 206 FNAs were identified. The ROMs of bronchial washing/lavage were "non-diagnostic" 56.5% (13/23), "benign" 41.9% (320/764), "atypical" 71.7% (71/99), "suspicious for malignancy" 94.7% (72/76), and "malignant" 100% (70/70). The ROMs of FNAs were "non-diagnostic" 66% (33/50), "benign" 58.2% (39/67), "atypical" 70% (28/40), "suspicious for malignancy" 96.2% (25/26), and "malignant" 100% (70/70). When image finding was considered, cases initially assigned as "benign" were re-classified to "non-diagnostic" with decreases in ROMs for the "benign" category. CONCLUSIONS: Malignancy risks associated with the WHO System of Reporting Lung Cytopathology diagnostic groups were reported. Image correlation for the "benign" category led to a decrease in case number and ROM.

The effect of low-level laser therapy on the oxidative stress level and quality of life in patients with Hashimoto's thyroiditis.

This study aimed to examine the effects of low-level laser therapy (LLLT) combined with levothyroxine replacement therapy on thyroid function, oxidative stress (OS), and quality of life in patients with Hashimoto's thyroiditis (HT). Forty-six patients diagnosed with HT were randomized to receive active LLLT (n = 23) and sham LLLT (n = 23) twice a week for three weeks. Clinical and laboratory evaluations of the participants were performed before treatment and three months after treatment. Biochemical parameters were taken from the patient file requested by the physician as a routine examination. Malondialdehyde and nitricoxide indicating oxidant stress and superoxide dismutase, catalase, and glutathione, which indicate antioxidant capacity, were used in OS evaluation. The Oxidative Stress Index was calculated by measuring the Total Antioxidant Status and the Total Oxidant Status. At the end of our study, a significant improvement in oxidant and antioxidant biomarker levels showing OS and quality of life was observed in the treatment groups (p < 0.05). There was no change in thyroid function and autoimmunity at the end of the treatment between the two groups (p > 0.05). Improvements in glutathione levels and quality of life were significantly higher in the active treatment group than in the sham-controlled group. LLLT was found to be more effective on OS and quality of life in patients with HT than in patients in the sham-controlled group. It was concluded that LLLT is a safe and effective method that can be used in the treatment of patients with HT.

Next-Generation Sequencing in Lung Cancers-A Single-Center Experience in Taiwan.

Background and Objectives: Lung cancer is a leading cause of cancer mortality in Taiwan. With rapid advancement of targeted therapeutics in non-small cell lung cancers, next-generation sequencing (NGS) is becoming an important tool for biomarker testing. In this study, we describe institutional experience of NGS analysis in non-small cell carcinoma (NSCLC). Materials and Methods: A cohort of 73 cases was identified from the institutional pathology archive in the period between November 2020 and December 2022. Results: Adenocarcinoma was the most common histologic type (91.8%). Most patients presented with stage IIIB and beyond (87.7%). Twenty-nine patients (39.7%) were evaluated at the time of initial diagnosis, while the others had received prior chemotherapy or targeted therapy. The most frequently mutated gene was EGFR (63%), and this was followed by TP53 (50.7%), KRAS (13.7%), RB1 (13.7%), and CDKN2A (13.7%). Clinically actionable mutations associated with a guideline-suggested targeted therapy were identified in 55 cases (75.3%) overall, and in 47.1% of cases excluding EGFR TKI-sensitizing mutation. Biomarkers other than EGFR TKI-sensitizing mutations were compared. Cases without TKI-sensitizing EGFR mutation had more level 1 or 2 biomarkers (excluding EGFR TKI-sensitizing mutations) than cases with TKI-sensitizing EGFR mutations (47.1% versus 20.1%, p = 0.016). Progressive disease was associated with co-occurrence of clinically actionable mutations (20.5% versus 0%, p < 0.05). Eight of the nine cases with co-occurring actionable genetic alternations had an EGFR mutation. After an NGS test, 46.1% of actionable or potentially actionable genetic alternations led to patients receiving a matched therapy. Conclusions: Our study demonstrated that NGS analysis identifies therapeutic targets and may guide treatment strategies in NSCLC. NGS tests may be advantageous over multiple single-gene tests for optimization of treatment plans, especially for those with non-EGFR mutations or those with progressive disease.

Endovascular Management of Post-Irradiated Carotid Blowout Syndrome in Patients with Lower Neck Cancers.

OBJECTIVE: Lower neck cancers (LNCs) include specific tumour types and have some different vascular supply or collaterals from other head and neck cancers. This prospective study evaluated the outcome of endovascular management of post-irradiated carotid blowout syndrome (PCBS) in patients with LNC by comparing reconstructive management (RE) and deconstructive management (DE). METHODS: This was a single centre, prospective cohort study. Patients with LNC complicated by PCBS between 2015 and 2021 were enrolled for RE or DE. RE was performed by stent graft placement covering the pathological lesion and preventive external carotid artery (ECA) embolisation without balloon test occlusion (BTO). DE was performed after successful BTO by permanent coil or adhesive agent embolisation of the internal carotid artery (ICA) and ECA to common carotid artery, or ICA occlusion alone if the pathological lesion was ICA only. Cross occlusion included the proximal and distal ends of the pathological lesion in all patients. Re-bleeding events, haemostatic period, and neurological complications were evaluated. RESULTS: Fifty-nine patients (mean age 58.5 years; 56 male) were enrolled, including 28 patients undergoing RE and 31 patients undergoing DE. Three patients originally grouped to DE were transferred to RE owing to failed BTO. The results of RE vs. DE were as follows: rebleeding events, 13/28 (46%) vs. 10/31 (32%) (p = .27); haemostatic period, 9.4 ± 14.0 months vs. 14.2 ± 27.8 months (p = .59); neurological complication, 4/28 (14%) vs. 5/31 (16%) (p = .84); and survival time, 11.8 ± 14.6 months vs. 15.1 ± 27.5 months (p = .61). CONCLUSION: No difference in rebleeding risk or neurological complications was observed between the DE and RE groups. RE could be used as a potential routine treatment for PCBS in patients with LNC.

TSPO is a novel biomarker for prognosis that regulates cell proliferation through influencing mitochondrial functions in HCC.

The disorder of mitochondrial functions plays a key role in oncogenesis. It is known that TSPO (18-kDa translocator protein) lies in a peculiar location at the interface between the mitochondria and the cytosol. TSPO is found in many types of tissues and is associated with multiple cellular processes, including apoptosis, cell proliferation and the regulation of mitochondria. However, the involvement of TSPO in hepatocellular carcinoma (HCC) remains unclear. In this study, we found that TSPO is upregulated in HCC tissue and is associated with poor differentiation and poor survival. Multivariate analyses showed that TSPO was an independent predictive factor for poor prognosis in HCC patients. For the first time, we provided evidence that TSPO knockdown suppressed HCC cell proliferation in vitro. Hence, TSPO knockdown-induced apoptosis by disturbing mitochondrial function by enhancing the formation of reactive oxygen species (ROS) and decreasing the mitochondrial membrane potential (ΔΨm). An assay exploring the underlying mechanism revealed that TSPO knockdown modulated apoptotic regulatory proteins by regulating the ERK signaling pathway. Through a functional assay and an in vivo mouse model, the anti-cancer effect of PK11195, a specific ligand of TSPO, on HCC was revealed. In summary, TSPO may potentially serve as a prognostic biomarker, and TSPO might be a potential therapeutic target for HCC.

Ultrasound radiomics based on axillary lymph nodes images for predicting lymph node metastasis in breast cancer.

Objectives: To determine whether ultrasound radiomics can be used to distinguish axillary lymph nodes (ALN) metastases in breast cancer based on ALN imaging. Methods: A total of 147 breast cancer patients with 41 non-metastatic lymph nodes and 109 metastatic lymph nodes were divided into a training set (105 ALN) and a validation set (45 ALN). Radiomics features were extracted from ultrasound images and a radiomics signature (RS) was built. The Intraclass correlation coefficients (ICCs), Spearman correlation analysis, and least absolute shrinkage and selection operator (LASSO) methods were used to select the ALN status-related features. All images were assessed by two radiologists with at least 10 years of experience in ALN ultrasound examination. The performance levels of the model and radiologists in the training and validation subgroups were then evaluated and compared. Result: Radiomics signature accurately predicted the ALN status, achieved an area under the receiver operator characteristic curve of 0.929 (95%CI, 0.881-0.978) and area under curve(AUC) of 0.919 (95%CI, 95%CI, 0.841-0.997) in training and validation cohorts respectively. The radiomics model performed better than two experts' prediction of ALN status in both cohorts (P<0.05). Besides, prediction in subgroups based on baseline clinicopathological information also achieved good discrimination performance, with an AUC of 0.937, 0.918, 0.885, 0.930, and 0.913 in HR+/HER2-, HER2+, triple-negative, tumor sized ≤ 3cm and tumor sized>3 cm, respectively. Conclusion: The radiomics model demonstrated a good ability to predict ALN status in patients with breast cancer, which might provide essential information for decision-making.

Contrast-Enhanced Ultrasound Liver Imaging Reporting and Data System in Hepatocellular Carcinoma ≤5 cm: Biological Characteristics and Patient Outcomes.

Introduction: The present study aimed to evaluate the influence of biological characteristics of hepatocellular carcinoma (HCC) on the Liver Imaging Reporting and Data System (LI-RADS) v2017 category of contrast-enhanced ultrasound (CEUS) in patients with high risk and compare the outcomes among different categories after radical resection. Methods: Between June 2017 and December 2020, standardized CEUS data of liver nodules were prospectively collected from multiple centers across China. We conducted a retrospective analysis of the prospectively collected data on HCCs measuring no more than 5 cm, as diagnosed by pathology. LI-RADS categories were assigned after thorough evaluation of CEUS features. Then, CEUS LI-RADS categories and major features were compared in different differentiation, Ki-67, and microvascular invasion (MVI) statuses. Differences in recurrence-free survival (RFS) among different LI-RADS categories were further analyzed. Results: A total of 293 HCC nodules in 293 patients were included. This study revealed significant differences in the CEUS LI-RADS category of HCCs among differentiation (p < 0.001) and levels of Ki-67 (p = 0.01) and that poor differentiation (32.7% in LR-M, 12% in LR-5, and 6.2% in LR-4) (p < 0.001) and high level of Ki-67 (median value 30%) were more frequently classified into the LR-M category, whereas well differentiation (37.5% in LR-4, 15.1% in LR-5, and 11.5% in LR-M) and low levels of Ki-67 (median value 11%) were more frequently classified into the LR-4 category. No significant differences were found between MVI and CEUS LI-RADS categories (p > 0.05). With a median follow-up of 23 months, HCCs assigned to different CEUS LI-RADS classes showed no significant differences in RFS after resection. Conclusions: Biological characteristics of HCC, including differentiation and level of Ki-67 expression, could influence major features of CEUS and impact the CEUS LI-RADS category. HCCs in different CEUS LI-RADS categories showed no significant differences in RFS after resection.

The role of comorbidity indices and histochemical markers in surgically resected and non-resected primary central nervous system lymphoma.

The role of surgical resection in primary central nervous system lymphoma (PCNSL) was not recognized until recently. However, prognostic factors for surgically treated PCNSL remain unclear. In the present study, we aimed to identify and compare the prognostic value of comorbidity indices and immunohistochemical markers in patients with surgically and non-surgically treated PCNSL. This retrospective single-center study analyzed patients who underwent either surgical resection or stereotactic biopsy for newly diagnosed PCNSL between January 2012 and December 2021. Clinical demographics, comorbidity indices, and immunohistochemical markers were analyzed. We included 23 and 18 patients who underwent stereotactic biopsy and surgical resection, respectively. The median overall survival (OS) was 11.05 months. Using multivariate Cox regression, we identified pretreatment prognostic nutritional index (PNI) (p = 0.009), positive BCL2 staining (p = 0.026), and infratentorial involvement (p = 0.004) as independent prognostic factors of OS. Predictors of progression-free survival (PFS) included PNI (p = 0.040), infratentorial involvement (p = 0.021), and surgical resection for PCNSL (p = 0.048). Subgroup analyses revealed that positive BCL2 (p = 0.048) and PD-L1 (p = 0.037) staining were associated with worse OS in the biopsy group. PNI and infratentorial involvement could significantly impact both OS and PFS in patients with PCNSL. Surgical resection could predict favorable PFS but not OS. Moreover, BCL2 and PD-L1 expression can be employed as prognostic markers in these patients.

Towards the development of novel bicomponent phytosterol-based oleogels with natural phenolics.

Structuring liquid oils into edible oleogels from natural and abundant plant ingredients has great significance in fields ranging from foods to pharmaceuticals but has proven challenging. Herein, novel bicomponent phytosterol-based oleogels were developed with natural phenolics. Investigating diverse natural phenolics, cinnamic acid (CA) and ethyl ferulate (EF) successfully formed oleogels in combination with phytosterols (PS), where a synergistic effect on the oleogelation and crystallization was observed compared to the corresponding single component formulations. FTIR and UV-vis spectra showed that the gel network was primarily driven by hydrogen bonding and π-π stacking. Furthermore, oscillatory shear demonstrated oleogels featured higher elastic and network structure deformation at molar ratio of 5:5 and 3:7. Moreover, the bicomponent phytosterol-based oleogels displayed partially reversible shear deformation and a reversible solid-liquid transition. Such information was useful for engineering the functional properties of oleogel-based lipidic materials, providing significance for the application in foods, cosmetics and pharmaceuticals industries.

Mixed Mycobacterium kansasii and Mycobacterium smegmatis infection in an adult-onset immunodeficiency patient with anti-interferon-γ autoantibodies.

Anti-interferon-gamma autoantibody (AIGA) is a rare adult-onset immunodeficiency disease that increases the risk of occult infection. Nontuberculous mycobacteria (NTM) infections represent a diverse group of species and subspecies, and mixed infections with two or more NTM species have been reported. However, there is no consensus on the optimal antibiotics or immune modulator treatments for mixed NTM infections in AIGA patients. Here, we present the case of a 40-year-old female who initially presented with suspected lung cancer with obstructive pneumonitis. Tissue samples obtained through bronchoscopy, endoscopy, and bone marrow biopsy revealed disseminated mycobacterium infection. PCR-based testing confirmed a mixed pulmonary infection with Mycobacterium kansasii and Mycobacterium smegmatis, as well as M. kansasii bacteremia. The patient received 12 months of anti-NTM medications for M. kansasii, and the symptoms improved. Additionally, the images showed resolution after 6 months, even without the need for immune modulator treatment.

Clinical and imaging findings for the evaluation of large Rathke's cleft cysts and cystic craniopharyngiomas.

PURPOSE: Large Rathke's cleft cysts (LRCCs) and cystic craniopharyngiomas (CCPs) arise from the same embryological origin and may have similar MR presentations. However, the two tumors have different management strategies and outcomes. This study was designed to evaluate the clinical and imaging findings of LRCCs and CCPs, aiming to evaluate their pretreatment diagnosis and outcomes. METHODS: We retrospectively enrolled 20 patients with LRCCs and 25 patients with CCPs. Both tumors had a maximal diameter of more than 20 mm. We evaluated the patients' clinical and MR imaging findings, including symptoms, management strategies, outcomes, anatomic growth patterns and signal changes. RESULTS: The age of onset for LRCCs versus CCPs was 49.0 ± 16.8 versus 34.2 ± 22.2 years (p = .022); the following outcomes were observed for LRCCs versus CCPs: (1) postoperative diabetes insipidus: 6/20 (30%) versus 17/25 (68%) (p = .006); and (2) posttreatment recurrence: 2/20 (10%) versus 10/25 (40%) (p = .025). The following MR findings were observed for LRCCs versus CCPs: (1) solid component: 7/20 (35%) versus 21/25 (84%) (p = .001); (2) thick cyst wall: 2/20 (10%) versus 12/25 (48%) (p = .009); (3) intracystic septation: 1/20 (5%) versus 8/25 (32%) (p = .030); (4) snowman shape: 18/20 (90%) versus 1/25 (4%) (p < .001); (5) off-midline extension: 0/0 (0%) versus 10/25 (40%) (p = .001); and (6) oblique angle of the sagittal long axis of the tumor: 89.9° versus 107.1° (p = .001). CONCLUSIONS: LRCCs can be differentiated from CCPs based on their clinical and imaging findings, especially their specific anatomical growth patterns. We suggest using the pretreatment diagnosis to select the appropriate surgical approach and thus improve the clinical outcome.

Antibodies against Poly(ethylene glycol) Activate Innate Immune Cells and Induce Hypersensitivity Reactions to PEGylated Nanomedicines.

Nanomedicines and macromolecular drugs can induce hypersensitivity reactions (HSRs) with symptoms ranging from flushing and breathing difficulties to hypothermia, hypotension, and death in the most severe cases. Because many normal individuals have pre-existing antibodies that bind to poly(ethylene glycol) (PEG), which is often present on the surface of nanomedicines and macromolecular drugs, we examined if and how anti-PEG antibodies induce HSRs to PEGylated liposomal doxorubicin (PLD). Anti-PEG IgG but not anti-PEG IgM induced symptoms of HSRs including hypothermia, altered lung function, and hypotension after PLD administration in C57BL/6 and nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice. Hypothermia was significantly reduced by blocking FcγRII/III, by depleting basophils, monocytes, neutrophils, or mast cells, and by inhibiting secretion of histamine and platelet-activating factor. Anti-PEG IgG also induced hypothermia in mice after administration of other PEGylated liposomes, nanoparticles, or proteins. Humanized anti-PEG IgG promoted binding of PEGylated nanoparticles to human immune cells and induced secretion of histamine from human basophils in the presence of PLD. Anti-PEG IgE could also induce hypersensitivity reactions in mice after administration of PLD. Our results demonstrate an important role for IgG antibodies in induction of HSRs to PEGylated nanomedicines through interaction with Fcγ receptors on innate immune cells and provide a deeper understanding of HSRs to PEGylated nanoparticles and macromolecular drugs that may facilitate development of safer nanomedicines.