Complexity Matters: Normalization to Prototypical Viewpoint Induces Memory Distortion along the Vertical Axis of Scenes.

Scene memory is prone to systematic distortions potentially arising from experience with the external world. Boundary transformation, a well-known memory distortion effect along the near-far axis of the three-dimensional space, represents the observer's erroneous recall of scenes' viewing distance. Researchers argued that normalization to the prototypical viewpoint with the high-probability viewing distance influenced this phenomenon. Herein, we hypothesized that the prototypical viewpoint also exists in the vertical angle of view (AOV) dimension and could cause memory distortion along scenes' vertical axis. Human subjects of both sexes were recruited to test this hypothesis, and two behavioral experiments were conducted, revealing a systematic memory distortion in the vertical AOV in both the forced choice (n = 79) and free adjustment (n = 30) tasks. Furthermore, the regression analysis implied that the complexity information asymmetry in scenes' vertical axis and the independent subjective AOV ratings from a large set of online participants (n = 1,208) could jointly predict AOV biases. Furthermore, in a functional magnetic resonance imaging experiment (n = 24), we demonstrated the involvement of areas in the ventral visual pathway (V3/V4, PPA, and OPA) in AOV bias judgment. Additionally, in a magnetoencephalography experiment (n = 20), we could significantly decode the subjects' AOV bias judgments ∼140 ms after scene onset and the low-level visual complexity information around the similar temporal interval. These findings suggest that AOV bias is driven by the normalization process and associated with the neural activities in the early stage of scene processing.

Workplace violence in radiology: results of a systematic review.

BACKGROUND: Workplace violence (WPV) is a growing issue in health care with far-reaching consequences for health workers' physical and psychological well-being. While some medical specialities like emergency medicine have always been considered at higher risk for WPV, several studies have also reported its occurrence in radiology. AIMS: This systematic review aimed to comprehensively synthesize the types of WPV in radiology, its psychological impact, and the underlying risk and protective factors. METHODS: We searched five electronic databases (PubMed, Web of Science Core Collection, Scopus, PsycINFO and CINAHL) and additional literature, including grey literature, and established weekly search alerts. Two reviewers independently conducted all methodological steps, involving a third reviewer in case of disagreement. RESULTS: Of the 12 205 retrieved records, 103 full-text articles were evaluated, and 15 studies were included. Across studies, verbal aggression, sexual harassment (mostly against women) and physical violence were experienced by up to 100%, 85% and 46% of health workers, respectively. Perpetrators were patients and patients' caregivers, followed by co-workers. Victims suffered from various psychological symptoms, such as anxiety (22%-54%), fear (6%-39%), depression (32%) and repeated disturbing memories (21%). Risk factors included female gender, understaffing, worker inexperience, poor communication and lengthy waiting times. Social support and security personnel presence were among the identified protective factors. CONCLUSIONS: Health workers are at high risk of experiencing WPV in the radiological setting, with a strong psychological impact. Radiological departments should create a safe healthcare environment that actively manages the identified risk factors and offers psychological support to affected workers.

[Predictive value of CONUT score and dialysis age for peritoneal dialysis-associated peritonitis].

Objective: To explore the predictive value of controlling nutritional status (CONUT) score and dialysis age for peritoneal dialysis-associated peritonitis (PDAP). Methods: This study was a follow-up study. Patients with end-stage renal disease who received peritoneal dialysis (PD) for the first time in the Department of Nephrology, the Third Affiliated Hospital of Suzhou University from January 2010 to December 2020 were enrolled in the study. Patients were divided into non-peritonitis group, mono group (only once PDAP occurred in one year) and frequent group (twice or more PDAP occurred in one year) according to the occurrence and frequency of PDAP during follow-up. The demographic, clinical and laboratory data of patients were collected, and the body mass index and CONUT score were recorded after half a year. Cox regression analysis was used to screen the relevant factors, and receiver operating characteristic (ROC) curve was used to analyze the predictive value of CONUT score and dialysis age for PDAP. Results: A total of 324 PD patients were included, with 188 males (58.0%) and 136 females (42.0%), and aged［M（Q1，Q3）］48 (37, 60) years old. The follow-up time was 33 (19, 56) months. PDAP occurred in 112 patients (34.6%), including 63 patients (19.4%) in mono group and 49 patients (15.1%) in frequent group. Multivariate Cox regression analysis showed that half-year CONUT score (HR=1.159, 95%CI: 1.047-1.283, P=0.004) was a risk factor for PDAP, and the baseline CONUT score (HR=1.194, 95%CI: 1.012-1.408, P=0.036) was a risk factor for frequent peritonitis. The area under ROC curve of baseline CONUT score combined with dialysis age in predicting PDAP and frequent peritonitis was 0.682 (95%CI: 0.628-0.733) and 0.676 (95%CI: 0.622-0.727), respectively. Conclusion: CONUT score and dialysis age have certain predictive value for PDAP, and the predictive value of combined diagnosis is higher, which may be used as a potential predictor for PDAP in PD patients.

[Analysis of prognosis and influencing factors of No. 253 lymph node metastasis in descending colon, sigmoid colon, and rectal cancer: a multicenter study].

Objectives: To analyze the influencing factors of No. 253 lymph node metastasis in descending colon cancer, sigmoid colon cancer, and rectal cancer, and to investigate the prognosis of No. 253 lymph node-positive patients by propensity score matching analysis. Methods: A retrospective analysis was performed on clinical data from patients with descending colon cancer, sigmoid colon cancer, rectosigmoid junction cancer, and rectal cancer who underwent surgery between January 2015 and December 2019 from the Cancer Hospital of the Chinese Academy of Medical Sciences, China-Japan Friendship Hospital, Peking Union Medical College Hospital, General Hospital of the Chinese People's Liberation Army, and Peking University Cancer Hospital. A total of 3 016 patients were included according to inclusion and exclusion criteria, comprising 1 848 males and 1 168 females, with 1 675 patients aged≥60 years and 1 341 patients aged<60 years. Clinical and pathological factors from single center data were subjected to univariate analysis to determine influencing factors of No. 253 lymph node metastasis, using a binary Logistic regression model. Based on the results of the multivariate analysis, a nomogram was constructed. External validation was performed using data from other multicenter sources, evaluating the effectiveness through the area under the receiver operating characteristic curve and the calibration curve. Using data from a single center, the No. 253 lymph node-positive group was matched with the negative group in a 1∶2 ratio (caliper value=0.05). Survival analysis was performed using the Kaplan-Meier method and Log-rank test. The Cox proportional hazards model was used to determine independent prognostic factors. Results: (1) The tumor diameter≥5 cm (OR=4.496,95%CI:1.344 to 15.035, P=0.015) T stage (T4 vs. T1: OR=11.284, 95%CI:7.122 to 15.646, P<0.01), N stage (N2 vs. N0: OR=60.554, 95%CI:7.813 to 469.055, P=0.043), tumor differentiation (moderate vs. well differentiated: OR=1.044, 95%CI:1.009 to 1.203, P=0.044; poor vs. well differentiated: OR=1.013, 95%CI:1.002 to 1.081, P=0.013), tumor location (sigmoid colon vs. descending colon: OR=9.307, 95%CI:2.236 to 38.740, P=0.002), pathological type (mucinous adenocarcinoma vs. adenocarcinoma: OR=79.923, 95%CI:15.113 to 422.654, P<0.01; signet ring cell carcinoma vs. adenocarcinoma: OR=27.309, 95%CI:4.191 to 177.944, P<0.01), and positive vascular invasion (OR=3.490, 95%CI:1.033 to 11.793, P=0.044) were independent influencing factors of No. 253 lymph node metastasis. (2) The area under the curve of the nomogram prediction model was 0.912 (95%CI: 0.869 to 0.955) for the training set and 0.921 (95%CI: 0.903 to 0.937) for the external validation set. The calibration curve demonstrated good consistency between the predicted outcomes and the actual observations. (3) After propensity score matching, the No. 253 lymph node-negative group did not reach the median overall survival time, while the positive group had a median overall survival of 20 months. The 1-, 3- and 5-year overall survival rates were 83.9%, 61.3% and 51.6% in the negative group, and 63.2%, 36.8% and 15.8% in the positive group, respectively. Multivariate Cox analysis revealed that the T4 stage (HR=3.067, 95%CI: 2.357 to 3.990, P<0.01), the N2 stage (HR=1.221, 95%CI: 0.979 to 1.523, P=0.043), and No. 253 lymph node positivity (HR=2.902, 95%CI:1.987 to 4.237, P<0.01) were independent adverse prognostic factors. Conclusions: Tumor diameter ≥5 cm, T4 stage, N2 stage, tumor location in the sigmoid colon, adverse pathological type, poor differentiation, and vascular invasion are influencing factors of No. 253 lymph node metastasis. No. 253 lymph node positivity indicates a poorer prognosis. Therefore, strict dissection for No. 253 lymph node should be performed for colorectal cancer patients with these high-risk factors.

An evaluation of the outcome metric 'days alive and at home' in older patients after hip fracture surgery.

'Days alive and at home' is a validated measure that estimates the time spent at home, defined as the place of residence before admission to hospital. We evaluated this metric in older adults after hip fracture surgery and assessed two follow-up durations, 30 and 90 days. Patients aged ≥ 70 years who underwent hip fracture surgery were identified retrospectively via hospital admission and government mortality records. Patients who successfully returned home and were still alive within 90 days of surgery were distinguished from those who were not. Regression models were used to examine which variables were associated with failure to return home and number of days at home among those who did return, within 90 days of surgery. We analysed the records of 825 patients. Median (IQR [range]) number of days at home within 90 days (n = 788) was 54 (0-76 [0-88]) days and within 30 days (n = 797) it was 2 (0-21 [0-28]) days. Out of these, 274 (35%) patients did not return home within 90 days and 374 (47%) within 30 days after surgery. Known peri-operative risk-factors such as older age, pre-operative anaemia and postoperative acute renal impairment were associated with failure to return home. This study supports days alive and at home as a useful patient-centred outcome measure in older adults after hip fracture surgery. We recommend that this metric should be used in clinical trials and measured at 90, rather than 30, postoperative days. As nearly half of this patient population did not return home within 30 days, the shorter time-period catches fewer meaningful events.

[Imaging study on the safety of axial pedicle screw placement by the position of the screw trajectory tip on the anteroposterior and lateral radiographs].

Objective: To propose a method to judge the safety of axial pedicle screw placement based on the position of the tip of the screw trajectory on the anteroposterior and lateral X-ray radiographs. Methods: The cervical CT data of 40 patients admitted to the Second Affiliated Hospital of Wenzhou Medical University from December 2020 to December 2021 were selected, including 24 males and 16 females, with a mean age of (47.6±13.2) years. Based on the three-dimensional model reconstruction of Mimics software and its function of X-ray, the transmission of the axial pedicle screw and its anteroposterior and lateral films was simulated. The position of the tip of the simulated screw trajectory was divided into 5 regions (regions Ⅰ-Ⅴ) from the inside to the outside on the anteroposterior virtual radiographs, and the upper and lower regions (regions a, b) on the lateral virtual radiographs. By adjusting the direction of the screw, the tip of the screw was located in the corresponding 10 regions (80 screws in each area) on the virtual projections of the anteroposterior and lateral virtual radiographs respectively, and its accuracy was analyzed by CT to determine whether each screw penetrated the medial wall of the pedicle or vertebral artery foramen. The anteroposterior and lateral X-rays and postoperative CT data of 34 patients who underwent axial pedicle screw placement (67 axial pedicle screws were placed in total) from January 2014 to December 2021 were collected, including 18 males and 16 females, with a mean age of (45.8±14.1) years. The position of the tip of the screw trajectory on the anteroposterior and lateral films was divided in the same way. The number of screws in the corresponding 10 positions was counted, and CT analysis was used to determine whether each screw penetrated the medial wall of the axial pedicle or the vertebral artery foreman. Results: The results of the imaging simulation screw placement study showed that the perforation rate of the vertebral artery foramen in region Ⅳ and Ⅴ was 75.0% (120/160) and 100% (160/160), respectively, while the perforation rate of the medial wall of the axial pedicle in the region Ⅰ was 85.6%(137/160). The failure rate in regions Ⅱ and Ⅲ was relatively lower, and the performance of simulated screws located in the region a was better than those in region b. The perforation rates of the medial wall in regions (a-Ⅱ) and (a-Ⅲ) was 7.5% (6/80) and 0 (0/80), respectively, and the perforation rates of the vertebral foramen was 0 (0/80) and 21.3% (17/80), respectively. The retrospective imaging study also showed a higher rate of placement failure in regions Ⅰ, Ⅳ and Ⅴ, and relatively lower in regions Ⅱ and Ⅲ. There were total of 15 screws in region a-Ⅱ and a-Ⅲ, and no destruction of the medial wall of the axial pedicle and the vertebral artery foreman occurred there. Conclusions: Regions a-Ⅱ and a-Ⅲ are the "safety areas" of the tip of the pedicle screw trajectory in the axial vertebra. By analyzing the tip of the pedicle screw trajectory on the anteroposterior and lateral radiographs, the operator can determine the reasonable trajectory of axial pedicle screw placement, prevent the injury of the cervical spinal cord and vertebral artery, and reduce the risk of operation.

Senolytic agent Quercetin ameliorates intervertebral disc degeneration via the Nrf2/NF-κB axis.

OBJECTIVE: Intervertebral disc degeneration (IDD) represents major cause of low back pain. Quercetin (QUE) is one of the approved senolytic agents. In this study, we evaluated the protective effects of QUE on IDD development and its underlying mechanism. METHODS: Effects of senolytic agent QUE on the viability of nucleus pulposus cells (NPCs) were measured by CCK-8 assays and EdU staining. The senescence associated secreted phenotype (SASP) factors expressions were measured by qPCR, western blot, and ELISA; and NF-κB pathway was detected by immunofluorescence and western blot. Molecular docking was applied to predict the interacting protein of QUE; while Nrf2 was knocked down by siRNAs to confirm its role in QUE regulated senescence phenotype. X-ray, MRI, Hematoxylin-Eosin and Safranin O-Fast green staining were performed to evaluate the therapeutic effects of QUE on IDD in the puncture-induced rat model. RESULTS: In in vitro experiments, QUE inhibited SASP factors expression and senescence phenotype in IL-1ß-treated NPCs. Mechanistically, QUE suppressed IL-1ß induced activation of the NF-κB pathway cascades; it was also demonstrated in molecular docking and knock down studies that QUE might bind to Keap1-Nrf2 complex to suppress NF-κB pathway. In vivo, QUE ameliorated the IDD process in the puncture-induced rat model. CONCLUSIONS: Together the present work suggests that QUE inhibits SASP factors expression and senescence phenotype in NPCs and ameliorates the progression of IDD via the Nrf2/NF-κB axis, which supports senolytic agent QUE as a potential therapeutic agent for the treatment of IDD.

Prognosis after neoadjuvant chemoradiation or chemotherapy for locally advanced gastro-oesophageal junctional adenocarcinoma.

BACKGROUND: Trials typically group cancers of the gastro-oesophageal junction (GOJ) with oesophageal or gastric cancer when studying neoadjuvant chemoradiation and perioperative chemotherapy, so the results may not be fully applicable to GOJ cancer. Because optimal neoadjuvant treatment for GOJ cancer remains controversial, outcomes with neoadjuvant chemoradiation versus chemotherapy for locally advanced GOJ adenocarcinoma were compared retrospectively. METHODS: Data were collected from all patients who underwent neoadjuvant treatment followed by surgery for adenocarcinoma located at the GOJ at a single high-volume institution between 2002 and 2017. Postoperative major complications and mortality were compared between groups using Fisher's exact test. Overall survival (OS) and disease-free survival (DFS) were assessed by log rank test and multivariable Cox regression analyses. Cumulative incidence functions were used to estimate recurrence, and groups were compared using Gray's test. RESULTS: Of 775 patients, 650 had neoadjuvant chemoradiation and 125 had chemotherapy. These groups were comparable in terms of clinical tumour and lymph node categories, although the chemoradiation group had greater proportions of white men, complete pathological response to chemotherapy, and smaller proportions of diffuse cancer, poor differentiation, and neurovascular invasion. Postoperative major complications (20.0 versus 17.6 per cent) and 30-day mortality (1.7 versus 1.6 per cent) were not significantly different between the chemoradiation and chemotherapy groups. After adjustment, type of therapy (chemoradiation versus chemotherapy) was not significantly associated with OS (hazard ratio (HR) 1.26, 95 per cent c.i. 0.96 to 1.67) or DFS (HR 1.27, 0.98 to 1.64). Type of recurrence (local, regional, or distant) did not differ after neoadjuvant chemoradiation versus chemotherapy. CONCLUSION: In patients undergoing surgical resection for locally advanced adenocarcinoma of the GOJ, OS and DFS did not differ significantly between patients who had neoadjuvant chemoradiation compared with chemotherapy.

Treating advanced cancer of the gastro-oesophageal junction (GOJ) poses a challenge given its location in the distal oesophagus and proximal stomach, and whether it should be treated as oesophageal or gastric cancer. Given the indistinct location, it is unclear whether GOJ cancer should be treated with neoadjuvant chemoradiation, which is the treatment of choice for advanced oesophageal cancers, or perioperative chemotherapy, which is the treatment of choice for advanced gastric cancers. Few studies have addressed treatment options specifically for GOJ cancers. This study investigated whether there was a difference in survival between patients with GOJ cancer who were treated with chemoradiation versus chemotherapy.

Healing of sub-critical femoral osteotomies in mice is unaffected by tacrolimus and deletion of recombination activating gene 1.

Clinical management of delayed healing or non-union of long bone fractures and segmental defects poses a substantial orthopaedic challenge. There are suggestions in the literature that bone healing may be enhanced by inhibiting the activities of T and B lymphocytes, but this remains controversial. To examine this matter in more detail, sub-critical-sized segmental defects were created in the femora of mice and it was assessed whether there might be a benefit from the administration of a Food and Drug Administration (FDA)-approved drug that blocks T cell activation (tacrolimus). Defects were stabilised using an internal plate. In certain groups of animals, 1 mg/kg or 10 mg/kg tacrolimus was delivered locally to the defect site for 3 or 7 d using an implanted osmotic pump with a silicon catheter directing drug delivery into the defect area. Healing was monitored by weekly X-ray and assessed at 12 weeks by mechanical testing, µCT and histology. Radiographic and histological evaluations revealed that 100 % of defects healed well regardless of tacrolimus dosage or duration. A comparison of healed C57BL/6 and Rag1-/- femora by µCT and ex vivo torsion testing showed no differences within mouse strains in terms of bone volume, tissue volume, bone volume/tissue volume ratio, shear modulus, torsional rigidity or torsional stiffness. These data failed to support an important role for tacrolimus in modulating the natural healing of segmental defects under those experimental conditions.

[Impact of enhanced recovery after surgery strategy on early postoperative quality of recovery in patients undergoing laparoscopic surgery for gynecologic malignancy].

Objective: To investigate the impact of perioperative anesthesia management with enhanced recovery after surgery (ERAS) strategy on postoperative recovery in patients undergoing laparoscopic surgery for gynecologic malignancy. Methods: Ninety patients undergoing laparoscopic surgery for gynecologic malignancies from April 2018 to April 2019,aged 18-65 years,with American Society of Anesthesiologists (ASA) physical status Ⅰ or Ⅱ, were recruited and randomly divided into two groups (n=45) using a random number table:ERAS group (group E) and control group (group C). Patients in group E received general anesthesia combined with transverses abdominis plane block and a series of interventions to optimize anesthetic and perioperative management, while patients in group C were treated with routine anesthesia management. Quality of Recovery-40 questionnaire (QoR-40) was administered to assess the early postoperative quality of recovery on 1 day before surgery, and at 24 and 48h after surgery. C-reactive protein (CRP) before and after the operation were evaluated. The incidence of nausea, vomiting and shivering, the time of first exhaust, ambulation, resumption of normal diet, postoperative hospital stay and complications were recorded. Results: The scores of QoR-40 [M(Q1, Q3)] in Group E were 175(171, 179) and 185(183, 189) at 24 h and 48 h after operation, which were higher than those in group C [162(160, 167) and 180(179, 183)] (both P<0.01). The levels of CRP in both group E and group C increased at 24 h and 72 h after operation. Moreover, the extent of increasing level of CRP in group C was much higher than that in group E [(39.8±18.0) mg/L vs (13.4±6.3) mg/L, (16.6±8.6) mg/L vs (6.7±2.5) mg/L] at 24 h and 48 h after operation (both P<0.01). Compared with group C, the numerical rating scale (NRS) for nausea decreased significantly in group E [0(0, 2) vs 3 (0, 5), P<0.01]. Meanwhile, the incidence of vomiting and shivering in group E was lower than that in group C [8.9% (4/45) vs 26.7% (12/45); 11.1% (5/45) vs 31.1% (14/45); both P<0.05]. The time of first exhaust, ambulation and resumption of normal diet in group E was (14±6) h, 6(6, 13) h and 1(1, 2) d, respectively, which was markedly shorter than that in group C [(25±10) h, 21(19, 27) h and 3(2, 3) d] (all P<0.01). Overall, the postoperative length of hospital stay reduced significantly for patients who followed the ERAS protocol [7(5, 11) d vs 10(7, 14) d, P<0.01]. The incidence of postoperative complications was 17.8% (8/45) and 37.8% (17/45) in group E and group C, respectively, with a significant difference (P<0.05). Conclusion: Implementation of ERAS anesthesia management in gynecologic oncology patients undergoing minimally invasive surgery alleviates perioperative discomfort, decreases surgical stress response, and improves the early postoperative quality of recovery.

[Analysis of factors affecting live birth outcome of frozen-thawed embryo transfer cycle].

Objective: To analyze the related factors affecting the success of frozen-thawed embryo transfer (FET). Methods: A total of 563 couples treated in the Reproductive Medicine Center of Guangdong Hospital of Traditional Chinese Medicine from January 2017 to March 2020 were selected as subjects. A total of 736 FET cycles were included to analyze the live birth outcomes of FET. Pregnancy outcomes, pregnancy complications and embryo status of patients between the live birth group and the non-live birth group were compared. A multivariate logistic regression model was used to evaluate the association between the 15 candidate factors and live birth outcomes for identifying independent factors associated with the live birth outcomes of the FET. Results: Among the enrolled subjects, the men were (33±5) years old at sperm extraction while the women were (31±4) years old at ovum pick-up (OPU) and (32±4) years old at embryo transfer (ET) and their infertility duration were (3.5±2.6) years. There were 333 (45.2%) live birth cycles and 403 (54.8%) non-live birth cycles in the 736 FET cycles. Pregnancy complications occurred in 49 cases (14.7%) of the live birth group. The age of the women at ET ((31±4) vs (32±4) years), the age of the women at OPU ((30±4) vs (32±4) years) and the age of the men at sperm extraction ((33±4) vs (34±5) years) in the live birth group were all lower than those in the non-live birth group. The infertility duration was shorter ((3.2±2.2) vs (3.6±2.8) years), and the proportion of primary infertility was higher ((63.1%, 210 cases) vs (49.6%, 200 cases)) in the live birth group (P<0.05) than those in the non-live birth group. Multivariate logistic regression analyses showed that the age of woman at ET (OR (95%CI): 0.50 (0.27-0.92), P=0.026), the types of infertility (0.62 (0.43-0.88), P=0.008), the numbers of optimal embryos transferred (1.60(1.11-2.31), P=0.012), and the types of embryos transferred (2.43 (1.46-4.01), P=0.001) were statistically significant related factors for live birth outcome of FET. Conclusion: The age of the woman at ET, the types of infertility, the numbers of optimal embryos transferred and the types of embryos transferred are associated factors for the outcomes of live birth after FET.

Safety of thoracic radiotherapy in patients with prior immune-related adverse events from immune checkpoint inhibitors.

BACKGROUND: Immune checkpoint inhibitors (ICIs) and thoracic radiotherapy are increasingly used to treat advanced cancers. Despite data indicating exaggerated radiation toxicities in patients with autoimmune disease, the safety of thoracic radiotherapy in patients with prior ICI-associated immune-related adverse events (irAEs) is undefined. PATIENTS AND METHODS: Patients treated from 2014 to 2020 with ICIs were queried for receipt of corticosteroids and radiotherapy. Patients who received thoracic radiation after symptomatic irAEs were assessed for ≥grade 2 radiation pneumonitis (RP). Characteristics predictive of RP were assessed using logistic regression and response relationships were modeled. RESULTS: Among 496 assessed patients, 41 with irAE history subsequently treated with thoracic radiotherapy were analyzed. Most irAEs were grade 2 (n = 21) and 3 (n = 19). Median time from irAE onset to radiotherapy was 8.1 months. Most patients received stereotactic body radiation therapy (n = 20) or hypofractionated radiotherapy (n = 18). In total, 25 patients (61%) developed ≥grade 2 RP at a median of 4 months from radiotherapy and 11 months from onset of irAEs. Three months from RP onset, 16 of 24 (67%) assessable patients had persistent symptoms. Among patients with prior ICI pneumonitis (n = 6), five patients (83%) developed ≥grade 2 RP (grade 2, n = 3; grade ≥3, n = 2). The mean lung radiation dose (MLD) predicted for RP (odds ratio: 1.60, P = 0.00002). The relationship between MLD and RP was strong (area under the receiver-operating characteristic curve: 0.85) and showed an exaggerated dose-response. Among patients with an MLD >5 Gy (n = 26), 21 patients (81%) developed ≥grade 2 RP. CONCLUSION: This is the first study assessing the toxicity of radiotherapy among patients with prior irAEs from ICIs. Patients with prior irAEs were found to be at very high risk for clinically significant and persistent RP from thoracic radiotherapy. Careful consideration should be given to the possibility of an increased risk of RP, and close monitoring is recommended in these patients.

Gait training with Achilles ankle exoskeleton in chronic incomplete spinal cord injury subjects.

Powered exoskeletons (EXOs) have emerged as potential devices for Spinal Cord Injury (SCI) to support the intervention of physical therapists during therapy (rehabilitation EXOs) as well as to assist lower limb motion during the daily life (assistive EXOs). Although the ankle is considered a key joint for gait restoration after SCI, very few ankle exoskeletons were developed and tested in incomplete SCI (iSCI) population. Among those, the Achilles ankle exoskeleton is the only one embedding a Controller inspired by the neuromuscular system (NeuroMuscular Controller, NMC). In a previous study we demonstrated that a period dedicated to train iSCI subjects in using the Achilles EXO as an assistive aid, improved robot-aided walking speed and surprisingly also generated a positive trend in free walking speed on long and short distances thus suggesting a possible unexpected rehabilitation effect. To further investigate this result, a case-control longitudinal study was conducted in the present work. The aim of this study was to test the hypothesis that Achilles-aided training could improve performance of free walking of chronic iSCI people more than conventional intensity-matched gait rehabilitation. Before and after conventional and robot-aided rehabilitation a number of variables were analyzed, including spatiotemporal parameters, joint kinematics, ground reaction forces, muscle force, spasticity and its related symptoms, balance and personal experience about the training. Results showed that only the NMC-controlled Achilles training allowed participants to significantly walk faster, with a longer step length and a reduced gait cycle time. A slight force and spasticity improvements were also experienced. In terms of subjects' personal experience, Achilles training was perceived more interesting and less physically demanding than conventional rehabilitation.

Imaging of spindle cell lipoma.

AIM: To review the evaluation, diagnosis, and treatment of spindle cell lipoma (SCL) with emphasis on the location of these tumours and the spectrum of magnetic resonance imaging (MRI) and computed tomography (CT) appearances. MATERIALS AND METHODS: The MRI and CT findings of 27 histopathologically proven SCLs were evaluated retrospectively. Imaging features evaluated included margins, percentage visible fat, MRI signal characteristics, oedema, and contrast enhancement patterns. RESULTS: Patient ages ranged from 18 to 80 years with an average age of 56.5 years. Men were affected twice as frequently as women (M=18, F=9). SCLs ranged in size from 2 to 10 cm, with an average greatest dimension of 5.5 cm. Five lesions (19%) contained no visible fat on CT or MRI, and the leading differential diagnosis of high-grade soft-tissue sarcoma diagnosis was suggested by referring surgeons. Five lesions (19%) had <50% fatty areas, nine lesions (52%) demonstrated >50% but <90% fat at MRI or CT. Only three of 25 lesions (12%) had an appearance of a typical lipoma on unenhanced MRI sequences. All SCLs that were imaged with contrast medium (n = 18) demonstrated some degree of enhancement, with eight (44%) showing marked enhancement, four (22%) showing moderate, and six (33%) minimal enhancement. CONCLUSION: SCLs have considerably variable imaging appearances and may have minimal or no visible fat at MRI or CT. Imaging features may make it difficult to distinguish this benign tumour from a potentially higher-grade malignant tumour.

ABCA1 transporter reduces amphotericin B cytotoxicity in mammalian cells.

Amphotericin B (AmB) belongs to a group of polyene antibiotics commonly used in the treatment of systemic mycotic infections. A widely accepted mechanism of action of AmB is based on the formation of an oligomeric pore structure within the plasma membrane (PM) by interaction with membrane sterols. Although AmB binds preferentially to ergosterol, it can also bind to cholesterol in the mammalian PM and cause severe cellular toxicity. The lipid content and its lateral organization at the cell PM appear to be significant for AmB binding. Several ATP-binding cassette (ABC) transporters, including ABCA1, play a crucial role in lipid translocation, cholesterol redistribution and efflux. Here, we demonstrate that cells expressing ABCA1 are more resistant to AmB treatment, while cells lacking ABCA1 expression or expressing non-active ABCA1MM mutant display increased sensitivity. Further, a FLIM analysis of AmB-treated cells reveals a fraction of the antibiotic molecules, characterized by relatively high fluorescence lifetimes (> 6 ns), involved in formation of bulk cholesterol-AmB structures at the surface of ABCA1-expressing cells. Finally, lowering the cellular cholesterol content abolishes resistance of ABCA1-expressing cells to AmB. Therefore, we propose that ABCA1-mediated cholesterol efflux from cells induces formation of bulk cholesterol-AmB structures at the cell surface, preventing AmB cytotoxicity.

Low pretreatment PNI correlates with worse survival in patients with stage III/IV NSCLC who received chemotherapy.

The aim of this study was to investigate the prognostic value of the prognostic nutritional index (PNI) on the long-term survival of non-small cell lung cancer (NSCLC) patients who received platinum-based chemotherapy. Data on nutritional parameters and clinicopathological characteristics [e.g., albumin, total protein, body mass index (BMI), eastern cooperative oncology group (ECOG) performance status, stage, pathology, treatment strategy] were analyzed and retrospectively correlated with overall survival (OS). The PNI was calculated based on the concentration of albumin and lymphocyte count [10 × albumin, (g/dl) + 0.005 × lymphocyte (count/mm3)]. A receiver operating characteristic curve (ROC) analysis was used to find the optimal cut-off value of PNI. Univariate and multivariate analyses were used to evaluate the prognostic value of PNI. A total of 186 patients met the inclusion criteria. The optimal cut-off value for PNI was 50.45. Compared with the parameters of the low PNI group (n=76), high PNI was significantly associated with adenocarcinoma type, stage III, better ECOG and comprehensive treatment modality. The univariate analysis demonstrated that OS was superior when PNI ≥50.45, albumin ≥35 g/l, platelet-lymphocyte ratio (PLR) ≥163 and ECOG <2, and when the patient received a comprehensive treatment modality. In the multivariate analysis, PNI, TNM stage and treatment strategy were identified as independent predictors of survival in this study. This retrospective study demonstrated that a low PNI was related to worse overall survival in patients with stage III/IV NSCLC who received platinum-based chemotherapy. These data provided a conceptual basis for further research on the clinical application of the PNI index for patients receiving chemotherapy for intermediate- and advanced-stage NSCLC.

Burden of pneumococcal disease: 8-year retrospective analysis from a single centre in Hong Kong.

PURPOSE: Streptococcus pneumoniae is a common pathogen involved in community-acquired pneumonia. Invasive pneumococcal disease is often associated with higher co-morbidity rates, but mortality-related findings have been inconclusive. This study investigated predictors of 30-day mortality and invasive pneumococcal disease. METHODS: This retrospective analysis included adults with pneumococcal disease who were admitted to Pamela Youde Nethersole Eastern Hospital from 1 January 2011 to 31 December 2018. Demographics, microbiological characteristics, and outcomes were compared between 30-day survivors and non-survivors, and between patients with invasive disease and those with non-invasive disease. Intensive care unit (ICU) subgroup analysis was performed. The primary outcome was 30-day all-cause mortality; secondary outcomes were ICU and hospital mortalities, and ICU and hospital lengths of stay. RESULTS: In total, 792 patients had pneumococcal disease; 701 survived and 91 (11.5%) died within 30 days. Notably, 106 (13.4%) patients had invasive pneumococcal disease and 170 (21.5%) patients received intensive care. Vasopressor use (odds ratio [OR]=4.96, P<0.001), chronic kidney disease (OR=3.62, P<0.001), positive urinary antigen test results (OR=2.57, P=0.001), and advanced age (OR=2.19, P=0.010) were independent predictors for 30-day mortality by logistic regression analysis. Among critically ill patients, chronic kidney disease (OR=4.64, P<0.001), higher APACHE IV score (OR=3.73, P=0.016), and positive urinary antigen test results (OR=2.94, P=0.008) were predictors for 30-day mortality. Logistic regression analysis revealed that chronic kidney disease (OR=3.10, P<0.001) was a risk factor for invasive pneumococcal disease. CONCLUSION: Advanced age, vasopressor use, chronic kidney disease, and positive urinary antigen test results were independent predictors for 30-day mortality in patients with pneumococcal disease.

[Analysis of imaging features of age-related cerebral small vessel disease with idiopathic normal pressure hydrocephalus].

Objective: To explore the imaging features in age-related cerebral small vessel disease (ArCSVD) with idiopathic normal pressure hydrocephalus (INPH). Methods: Ten cases of age-related cerebral small vessel disease (CSVD) with idiopathic normal pressure hydrocephalus admitted to the Third Affiliated Hospital of Sun Yat-sen University from December 2015 to March 2020 were retrospective analyzed, all patients met the inclusion and exclusion criteria, and completed the head Magnetic resonance angiography plain scan, T2 fluid attenuated inversion recovery and Susceptibility Weighted Imaging sequence. Deep marrow venous signs (DMVs), INPH severity (DESH score), cortical/subcortical and deep microhemorrhages (CMBs) statistics, paraventricular and deep white matter damage (WMH) severity and CSVD imaging burden score were acquired, and correlations of DMVs and DESH scores with CMBs, WMH and Burden scores were evaluated using Spearman correlation analysis. Results: DMVs and DESH scores were significantly and positively correlated (r=0.965 9, P<0.000 1). DMVs and DESH scores were not significantly correlated with cortical/subcortical CMBs and deep CMBs. Likewise, DMVs and DESH scores were not significantly correlated with deep WMH. The WMH score of paraventricular of the 10 cases was 3 points, and the Burden score was 4 points. Conclusion: DMVs may be an indicator of the severity of ArCSVD with INPH, due to the small sample size of the current study, more cases are needed for further verification.

[Gunsight closure versus purse-string closure techniques in loop stoma reversal: a multicenter prospective randomized controlled trial].

Objective: To compare the wound healing time, Surgical site infection (SSI) rate and other postoperative outcomes between the gunsight closure and purse-string closure technique in loop stoma closure. Methods: Between November 2013 and December 2017, a total of 143 patients who underwent gunsight stoma reversal were included in this multicenter prospective randomized controlled trial. The patients were randomized to undergo gunsight (gunsight group, n=72) or purse-string closure technique (purse-string group, n=71). The primary endpoint was wound healing time. The second endpoints were the incidence of SSI, morbidity, and patient satisfaction. Statistical analysis between groups was performed using the t-test, repeated measures analysis of variance, Mann-Whitney U test, χ(2) test or Fisher's exact test. Results: There were 45 males and 27 females with age of 67 (11) (M(Q(R))) years in gunsight group, 42 males and 29 females with age of 65 (20) years in purse-string group. The body mass index, American Society of Anesthesiologist classification, comorbidities, primary diagnosis, the type of ostomy, intraoperative blood loss, perioperative complications, postoperative hospital stay, hospitalization cost, SSI rate and incisional hernia (stoma site) between the 2 groups were not significantly different (P>0.05). Although had a statistically longer operating time (80(10) minutes vs. 70(10) minutes, Z=-2.381, P=0.017), patients who underwent gunsight procedure and a significantly shorter wound healing time (17(2) days vs. 25(4) days, Z=-10.199, P<0.01), higher patient satisfaction score with regards to wound healing time (3(1) vs. 3(1), Z=-4.526, P<0.01), and higher total patient satisfaction score (25(3) vs. 25(3), Z=-2.529, P=0.011) compared with those who underwent purse-string procedure. Conclusions: The gunsight and purse-string techniques are effective procedures for stoma reversal and both have low SSI rate. The gunsight technique is associated with shorter wound healing time, higher levels of patient satisfaction compared with purse-string technique, and is recommended as the closure technique of choice.

Duration of EEG suppression does not predict recovery time or degree of cognitive impairment after general anaesthesia in human volunteers.

BACKGROUND: Burst suppression occurs in the EEG during coma and under general anaesthesia. It has been assumed that burst suppression represents a deeper state of anaesthesia from which it is more difficult to recover. This has not been directly demonstrated, however. Here, we test this hypothesis directly by assessing relationships between EEG suppression in human volunteers and recovery of consciousness. METHODS: We recorded the EEG of 27 healthy humans (nine women/18 men) anaesthetised with isoflurane 1.3 minimum alveolar concentration (MAC) for 3 h. Periods of EEG suppression and non-suppression were separated using principal component analysis of the spectrogram. After emergence, participants completed the digit symbol substitution test and the psychomotor vigilance test. RESULTS: Volunteers demonstrated marked variability in multiple features of the suppressed EEG. In order to test the hypothesis that, for an individual subject, inclusion of features of suppression would improve accuracy of a model built to predict time of emergence, two types of models were constructed: one with a suppression-related feature included and one without. Contrary to our hypothesis, Akaike information criterion demonstrated that the addition of a suppression-related feature did not improve the ability of the model to predict time to emergence. Furthermore, the amounts of EEG suppression and decrements in cognitive task performance relative to pre-anaesthesia baseline were not significantly correlated. CONCLUSIONS: These findings suggest that, in contrast to current assumptions, EEG suppression in and of itself is not an important determinant of recovery time or the degree of cognitive impairment upon emergence from anaesthesia in healthy adults.