Do different types of stress differentially alter behavioural and neurobiological outcomes associated with depression in rodent models? A systematic review

Cataloguing the effects of different types of stress on behaviour and physiology in rodent models has not been comprehensively attempted. Here, we systematically review whether chronic exposure to physical stress, psychosocial stress, or both types of stress can induce different behavioural and neurobiological outcomes in male and female rodents. We found that physical stress consistently increased depressive-like behaviour, impaired social interaction and decreased body weight, while psychosocial stress consistently increased both anxiety- and depressive-like behaviour, impaired social interaction and learning and memory, increased HPA axis activity, peripheral inflammation and microglial activation, and decreased hippocampal neurogenesis in male rodents. Moreover, we found that the combined effect of both stress types resulted in a more severe pathological state defined by increased anxiety- and depressive-like behaviour, impaired social interaction and learning and memory, increased HPA axis activity and central inflammation, and reduced hippocampal neurogenesis and neural plasticity in male rodents. Phenotypes for females were less consistent, irrespective of the type of stress exposure, on account of the limited number of studies using females. This review highlights that the type of stress may indeed matter and will help animal researchers to more appropriately choose a stress/depression model that fits their research purposes.     

Impact of abdominal imaging on the diagnosis of acute pancreatitis in patients with painless lipase elevation

Abdominal pain is considered a cardinal feature of acute pancreatitis (AP), and abdominal imaging is only required to diagnose AP when the pain is atypical, or serum enzyme elevation does not match the clinical picture. While painless lipase elevation is being increasingly associated with worse outcomes in various diseases, the diagnostic approach to such elevation is so-far unclear. We thus aimed to learn the impact of pain on the diagnosis of AP.MethodsAll patients presenting to the Mayo Clinic Arizona Hospital emergency department with a serum lipase ≥3x upper limit of normal between April 2016 and January 2020 were prospectively followed. Their charts were reviewed for the nature of pain, serum lipase levels on presentation, abdominal imaging, and whether a diagnosis of AP was made. Chronic pancreatitis was excluded.ResultsAmong 320 patients, 85 (26.5%) had painless lipase elevation. These patients had abdominal imaging less often (56/85, 66%) than in those with abdominal pain (201/235, 83%; p = 0.001). The diagnosis of AP increased overall from 31/63 (49%) without imaging to 198/257 (77%) with imaging (P < 0.001). Imaging increased the diagnosis of AP in patients with painless lipase elevation from 2/29 (7%) without imaging to 16/56 (29%; p = 0.025) among those who were imaged.ConclusionsPainless lipase elevation >3-fold the upper limit of normal is common in emergency department patients. 1/3 to 1/4 of these may have AP. Abdominal imaging increases the diagnosis of AP in patients with painless lipase elevation. Therefore, abdominal imaging in such patients may help detect AP that otherwise eludes diagnosis.     

Radiomic analysis of liver grafts from brain-dead donors can predict early allograft dysfunction following transplantation: a proof-of-concept study

BackgroundSelection of liver grafts suitable for transplantation (LT) mainly depends on a surgeon's subjective assessment. This study aimed to investigate the role of radiomic analysis of donor-liver CTs after brain death (DBD) to predict the occurrence of early posttransplant allograft dysfunction (EAD).MethodsWe retrospectively extracted and analyzed the left lobe radiomic features from CT scans of DBD livers in training and validation cohorts. Multivariate analysis was performed to identify predictors of EAD.ResultsFrom 126 LTs included in the study in the training cohort, 27 (21.4%) had an EAD. For each patient, 279 radiomic features were extracted of which 5 were associated with EAD (AUC = 0.81) (95% CI 0.72–0.89). Among donor and recipient clinical characteristics, cardiac arrest, steatosis on donor's CT, cold ischemic time and age of recipient were also identified as independent risk factors for EAD. Combined radiomic signature and clinical risk factors showed a strong predictive performance for EAD with a C-index of 0.90 (95% CI 0.84–0.96). A validation cohort of 23 patients confirmed these results.ConclusionRadiomic signatures extracted from donor CT scan, independently or combined with clinical risk factors is an objective and accurate biomarker for prediction of EAD after LT.     

Combined hepatic and portal vein embolization as preparation for major hepatectomy: a systematic review

BackgroundSome patients remain deemed unsuitable for resection after portal vein embolization (PVE) because of insufficient hypertrophy of the future remnant liver (FRL). Hepatic and portal vein embolization (HPVE) has been shown to induce hypertrophy of the FRL. The aim of this study was to provide a systematic review of the available literature on HPVE as preparation for major hepatectomy.MethodsThe literature search was performed on online databases. Studies including patients who underwent preoperative HPVE were retrieved for evaluation.ResultsSix articles including 68 patients were published between 2003 and 2017. HPVE was performed successfully in all patients with no mortality and morbidity-related procedures. The degree of hypertrophy of the FRL after HPVE ranged from 33% to 63.3%. Surgical resection after preoperative HPVE could be performed in 85.3% of patients, but 14.7% remained unsuitable for resection because of insufficient hypertrophy of the FRL or tumor progression. Posthepatectomy morbidity and mortality rates were 10.3% and 5.1%, respectively. The postoperative liver failure rate was nil.ConclusionHPVE as a preparation for major hepatectomy appears to be feasible and safe and could increase the resectability of patients initially deemed unsuitable for resection because of absent or insufficient hypertrophy of the FRL after PVE alone.     

腹腔镜经腹腹膜前疝修补术与开放式腹膜前疝修补术治疗股疝的疗效比较

目的比较腹腔镜经腹腹膜前疝修补术（TAPP）与开放式腹膜前疝修补术治疗股疝的手术结果和对生活质量的影响。 方法回顾性分析2014年1月至2019年12月新疆医科大学第一附属医院收治的58例股疝患者的临床资料，根据手术方式不同分为TAPP组和开放式腹膜前疝修补术组（开放组），TAPP组31例，开放组27例。比较两组手术指标，采用卡罗来纳舒适量表（CCS）评估并比较两组患者术前及术后1、6、12和24个月的生活质量。 结果TAPP组在手术时间、术中出血量、术后住院天数及术后并发症发生率等方面和开放组相比差异无统计学意义（P>0.05）；TAPP组在术后24 h疼痛视觉模拟评分及术后镇痛药使用率方面明显优于开放组（P<0.05）；TAPP组术后离床时间及术后首次进食时间长于开放组（P<0.05）；2组患者术后随访24个月，均无复发病例。两种术式均能有效改善患者术前的疼痛、运动受限及总体生活质量（P<0.05）；TAPP组患者术后1个月疼痛及总体生活质量优于开放组（P<0.05）。 结论TAPP与开放式腹膜前疝修补术均可有效治疗股疝。TAPP可作为无全身麻醉禁忌股疝患者的首选治疗方法。股疝的治疗应依据患者的自身情况和手术医师的技术掌握程度制定个体化治疗方案。     

In silico repurposing the Rac1 inhibitor NSC23766 for treating PTTG1-high expressing clear cell renal carcinoma

The pituitary tumor-transforming gene 1 (PTTG1), also known as Securin, is considered an oncogene. This study aimed to investigate the role of PTTG1 in clear cell renal cell carcinoma (ccRCC) using in silico bioinformatics approaches. A pan-cancer analysis using The Cancer Genome Atlas (TCGA) data indicated that among all cancer types copy number amplification of PTTG1 gene was most frequently found in ccRCC. However, amplification of PTTG1 gene copy number did not correlate with the increase of mRNA level in ccRCC, and did not predict the patients' overall survival. Instead, ccRCC was correlated with overexpression of PTTG1 mRNA, and its expression level was stage-dependent increased in cancer patients. An outlier analysis using the Oncomine database suggested that PTTG1 mRNA expression served as a good biomarker for ccRCC. Pathway analysis for upregulated genes enriched in PTTG1-high expressing ccRCC patients found that PTTG1 overexpression was associated with mitotic defects. Mining drug sensitivity data using the Cancer Therapeutics Response Portal (CTRP) discovered that PTTG1-high expressing ccRCC cell lines were susceptible to a Rac1 (Ras-related C3 botulinum toxin substrate 1) inhibitor NSC23766. Therefore, this study provides an in silico insight into the role of PTTG1 in ccRCC, and repurposes the Rac1 inhibitor NSC23766 for treating PTTG1-high expressing ccRCC.     

Perioperative Bevacizumab-based Triplet Chemotherapy in Patients With Potentially Resectable Colorectal Cancer Liver Metastases

Background

In colorectal cancer liver metastases (CRCLM), bevacizumab-based neoadjuvant strategies provide increased pathologic response. We aimed at assessing the activity of perioperative capecitabine, oxaliplatin, irinotecan, and bevacizumab (COI-B regimen) in patients with potentially resectable CRCLM, and investigating biomarkers for early prediction of pathologic response.