Morphological,Functional, and Tissue Characterization of Silent Myocardial Involvement in Patients With Primary Biliary Cholangitis

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How structural and functional MRI can inform dual-site tACS parameters: A case study in a clinical population and its pragmatic implications

BackgroundAbnormalities in frontoparietal network (FPN) were observed in many neuropsychiatric diseases including substance use disorders. A growing number of studies are using dual-site-tACS with frontoparietal synchronization to engage this network. However, a computational pathway to inform and optimize parameter space for frontoparietal synchronization is still lacking. In this case study, in a group of participants with methamphetamine use disorders, we proposed a computational pathway to extract optimal electrode montage while accounting for stimulation intensity using structural and functional MRI.MethodsSixty methamphetamine users completed an fMRI drug cue-reactivity task. Four main steps were taken to define electrode montage and adjust stimulation intensity using 4x1 high-definition (HD) electrodes for a dual-site-tACS; (1) Frontal seed was defined based on the maximum electric fields (EF) predicted by simulation of HD montage over DLPFC (F3/F4 in EEG 10–10), (2) frontal seed-to-whole brain context-dependent correlation was calculated to determine connected regions to frontal seeds, (3) center of connected cluster in parietal cortex was selected as a location for placing the second set of HD electrodes to shape the informed montage, (4) individualized head models were used to determine optimal stimulation intensity considering underlying brain structure. The informed montage was compared to montages with large electrodes and classic frontoparietal HD montages (F3-P3/F4-P4) in terms of tACS-induced EF and ROI-to-ROI task-based/resting-state connectivity.ResultsCompared to the large electrodes, HD frontoparietal montages allow for a finer control of the spatial peak fields in the main nodes of the FPN at the cost of lower maximum EF (large-pad/HD: max EF[V/m] = 0.37/0.11, number of cortical sub-regions that EF exceeds 50% of the max = 77/13). For defining stimulation targets based on EF patterns, using group-level head models compared to a single standard head model results in comparable but significantly different seed locations (6.43 mm Euclidean distance between the locations of the frontal maximum EF in standard-space). As expected, significant task-based/resting-state connections were only found between frontal-parietal locations in the informed montage. Cue-induced craving score was correlated with frontoparietal connectivity only in the informed montage (r = ?0.24). Stimulation intensity in the informed montage, and not in the classic HD montage, needs 40% reduction in the parietal site to reduce the disparity in EF between stimulation sites.ConclusionThis study provides some empirical insights to montage and dose selection in dual-site-tACS using individual brain structures and functions and proposes a computational pathway to use head models and functional MRI to define (1) optimum electrode montage for targeting FPN in a context of interest (drug-cue-reactivity) and (2) proper transcranial stimulation intensity.     

Five-year clinical outcomes using the bioresorbable vascular scaffold: Insights from the FRANCE ABSORB registry

Central illustration: cumulative major adverse cardiac events (MACE) and bioresorbable vascular scaffold (BVS) thrombosis rates after 1, 2, 3, 4 and 5 years.

     

Immunisation with the BCG and DTPw vaccines induces different programs of trained immunity in mice

In addition to providing pathogen-specific immunity, vaccines can also confer nonspecific effects (NSEs) on mortality and morbidity unrelated to the targeted disease. Immunisation with live vaccines, such as the BCG vaccine, has generally been associated with significantly reduced all-cause infant mortality. In contrast, some inactivated vaccines, such as the diphtheria, tetanus, whole-cell pertussis (DTPw) vaccine, have been controversially associated with increased all-cause mortality especially in female infants in high-mortality settings. The NSEs associated with BCG have been attributed, in part, to the induction of trained immunity, an epigenetic and metabolic reprograming of innate immune cells, increasing their responsiveness to subsequent microbial encounters. Whether non-live vaccines such as DTPw induce trained immunity is currently poorly understood. Here, we report that immunisation of mice with DTPw induced a unique program of trained immunity in comparison to BCG immunised mice. Altered monocyte and DC cytokine responses were evident in DTPw immunised mice even months after vaccination. Furthermore, splenic cDCs from DTPw immunised mice had altered chromatin accessibility at loci involved in immunity and metabolism, suggesting that these changes were epigenetically mediated. Interestingly, changing the order in which the BCG and DTPw vaccines were co-administered to mice altered subsequent trained immune responses. Given these differences in trained immunity, we also assessed whether administration of these vaccines altered susceptibility to sepsis in two different mouse models. Immunisation with either BCG or a DTPw-containing vaccine prior to the induction of sepsis did not significantly alter survival. Further studies are now needed to more fully investigate the potential consequences of DTPw induced trained immunity in different contexts and to assess whether other non-live vaccines also induce similar changes.     

Improving Surgical Training

Improving Surgical Training is a programme piloting an innovative, evidence-based approach to training. It was developed in response to the Shape of Training report which reviewed postgraduate training and recommended changes in medical education to meet the demands of the modern NHS. A series of initiatives have been developed to enhance the experience for surgical trainees not only to encourage a more focussed and supported method, but also to improve their job satisfaction. The initiatives have combined a greater emphasis on time for training provided by trainers with allocated time for training with multidisciplinary teamworking and the use of technology enhanced learning with simulation of both technical and non-technical skills. The pilot started in 2018 with core training in general surgery and has been expanded to include vascular surgery, urology and trauma and orthopaedics over the last 2 years. Initial feedback from both trainees, trainers and schools of surgery have identified different challenges to aid implementation. The programme is being very carefully evaluated by an independent company as well as careful oversight by the General Medical Council which are paramount to its success.     

空间频域成像在皮肤病定量评估中的研究

利用空间频域成像技术搭建的成像系统检测多种皮肤病组织的光学参数和生理参数信息，并对比分析讨论不同类型的皮肤病与光学参数、生理参数之间的关系。实验结果表明，病变皮肤组织与正常皮肤组织之间在光学参数、生理参数上存在较大差异，这将为临床医生对皮肤病诊治提供一种新颖、可靠、科学的评估方法。     

The Lausanne forensic pathology approach to post-mortem imaging for natural and non-natural deaths

Post-mortem imaging by computed tomography (PMCT) and post-mortem CT angiography (PMCTA) are used routinely in forensic practice as components to the autopsy. PMCT is efficient for gas detection, foreign body visualization and skeleton analysis. Various parameters can lead to the indication for contrast agent injection. Contrast injection into the vascular system can overcome the disadvantages of non-contrast PMCT by visualization of solid organ parenchyma and vessels. This can also assist the conventional autopsy, allowing one to investigate the vascular system. It is the method of choice for the analysis of the blood vessels by showing vascular pathology, congenital or postsurgical anatomical variations and an exact source of bleeding. By knowing the artefacts linked to the angiographic technique, we limit the risk of misinterpretation. The use of post-mortem MRI (PMMR) for diagnostic purposes is still limited to rare indications. These include review of the neck in cases of death by mechanical asphyxia, total-body PMMR in neonatal and pediatric death and cardiac PMMR in case of suspected myocardial infraction. Currently, in our daily practice, the vast majority or PMMR is only performed for research purposes.     

Optimal combination of antiangiogenic therapy for hepatocellular carcinoma

The success of sorafenib in prolonging survival of patients with hepatocellular carcinoma (HCC) makes therapeutic inhibition of angiogenesis a component of treatment for HCC. To enhance therapeutic efficacy, overcome drug resistance and reduce toxicity, combination of antiangiogenic agents with chemotherapy, radiotherapy or other targeted agents were evaluated. Nevertheless, the use of antiangiogenic therapy remains suboptimal regarding dosage, schedule and duration of therapy. The issue is further complicated by combination antiangiogenesis to other cytotoxic or biologic agents. There is no way to determine which patients are most likely respond to a given form of antiangiogenic therapy. Activation of alternative pathways associated with disease progression in patients undergoing antiangiogenic therapy has also been recognized. There is increasing importance in identifying, validating and standardizing potential response biomarkers for antiangiogenesis therapy for HCC patients. In this review, biomarkers for antiangiogenesis therapy including systemic, circulating, tissue and imaging ones are summarized. The strength and deficit of circulating and imaging biomarkers were further demonstrated by a series of studies in HCC patients receiving radiotherapy with or without thalidomide.     

The Effect of Helicobacter pylori on Gastric Cancer Treated with Adjuvant Chemotherapy After Curative Resection

Helicobacter pylori has been associated with diverse pathologies of varying severity. We investigated the H. pylori infection status and its association with the pathologic features and clinical outcomes in stage III gastric cancer patients treated with adjuvant therapy after curative resection. Between 2004 and 2009, the records of 76 consecutive patients were retrospectively reviewed. H. pylori infection was confirmed by examination of pathological specimen. The relationship between H. pylori and the clinicopathological features was analyzed by Fisher exact test, Student’s t test, and Kaplan-Meier method. Of the 76 patients, 16 patients (21.1 %) were confirmed for H. pylori infection. The median age was 59 years. Twenty-three patients received chemotherapy and remainder received chemoradiotherapy. H. pylori status did not correlate with the clinicopathologic features. It was greater in non-neoplastic tissue than the tumor tissue (21.1 vs 7.9 %). Median follow-up was 21 months. During this period, 88.2 % patients had experienced tumor recurrence, and 85.5 % patients had died. Recurrence was observed in 87.5 % patients and in 88.3 % patients in H. pylori-positive and H. pylori-negative patients, respectively (P = 0.92). Disease-free survival was 28.4 ± 7.9 months and overall survival was 31.5 ± 7.4 months in H. pylori-positive patients compared with 28.3 ± 3.7 and 33.2 ± 3.4 months, respectively, in H. pylori-negative patients. H. pylori infection status did not have effect on the overall or disease-free survival (p = 0.85 and P = 0.86), respectively. H. pylori status might not be useful as a prognostic and predictive factor for clinical outcomes.