Recent advances in computerized imaging and its vital roles in liver disease diagnosis, preoperative planning, and interventional liver surgery: A review.

The earliest and most accurate detection of the pathological manifestations of hepatic diseases ensures effective treatments and thus positive prognostic outcomes. In clinical settings, screening and determining the extent of a pathology are prominent factors in preparing remedial agents and administering appropriate therapeutic procedures. Moreover, in a patient undergoing liver resection, a realistic preoperative simulation of the subject-specific anatomy and physiology also plays a vital part in conducting initial assessments, making surgical decisions during the procedure, and anticipating postoperative results. Conventionally, various medical imaging modalities, e.g., computed tomography, magnetic resonance imaging, and positron emission tomography, have been employed to assist in these tasks. In fact, several standardized procedures, such as lesion detection and liver segmentation, are also incorporated into prominent commercial software packages. Thus far, most integrated software as a medical device typically involves tedious interactions from the physician, such as manual delineation and empirical adjustments, as per a given patient. With the rapid progress in digital health approaches, especially medical image analysis, a wide range of computer algorithms have been proposed to facilitate those procedures. They include pattern recognition of a liver, its periphery, and lesion, as well as pre- and postoperative simulations. Prior to clinical adoption, however, software must conform to regulatory requirements set by the governing agency, for instance, valid clinical association and analytical and clinical validation. Therefore, this paper provides a detailed account and discussion of the state-of-the-art methods for liver image analyses, visualization, and simulation in the literature. Emphasis is placed upon their concepts, algorithmic classifications, merits, limitations, clinical considerations, and future research trends.

Case report: Blotchy skin in a puffy neonate: is there a new association?

Introduction: Purpura fulminans in the neonatal population is a rare but potentially life-threatening condition complicated by thrombosis, resultant vital organ necrosis, and gangrene of the extremities. Considering the rapid evolution of the pathogenetic mechanism, an index of suspicion, early identification, and prompt intervention are imperative for improved outcomes. The majority of purpura fulminans cases have an infectious etiology, but it is essential to consider other congenital and acquired causes. Case description: We present a clinical case of a female neonate to emphasize the correlation between purpura fulminans, congenital chylothorax, involvement of the PAK2 gene, and the occurrence of retinal detachment in both eyes. After draining the congenital chylothorax, the neonate developed purpura fulminans due to a loss of protein C, S, and antithrombin factors, previously not reported in the literature. The purpuric lesions resolved after the administration of fresh frozen plasma. Subsequently, no recurring purpura fulminans lesions were noted following the normalization of the antithrombotic factor levels in the serum. Subsequently, the child also developed retinal detachment in both eyes.

Three Undescribed Iridoid Derivatives Isolated from the Fruits of Vitex trifolia with Their Cytotoxic and Antimicrobial Activities.

Vitex trifolia L. is a medicinal plant and widely distributed in the northern mountainous areas of Vietnam. Phytochemical study on the fruits of this plant led to the isolation of nine iridoid derivatives (1-9) including three undescribed compounds (1-3). Their structures were elucidated to be 3''-hydroxyscrophuloside A1 (1), 3''-hydroxycallicoside D (2), 2'-p-hydroxybenzoylaucubin (3), 6'-p-hydroxybenzoylmussaenosidic acid (4), nishindaside (5), agnuside (6), 10-O-vanilloylaucubin (7), 6'-O-p-hydroxybenzoyl-gardoside (8), and buddlejoside B (9) based on extensive analyses of HR-ESI-MS, 1D and 2D NMR spectra. Compounds 1, 2, 4, and 8 significantly posessed anti-barterial activity against Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa strains with MIC values in range of 16-64 µg/mL. At concentration of 20 µM, compounds 1-9 did not show cytotoxic effects against human lung cancer cells (PC9).

Lenient rate control versus strict rate control for atrial fibrillation: a statistical analysis plan for the Danish Atrial Fibrillation (DanAF) randomized clinical trial.

BACKGROUND: A key decision in the treatment of atrial fibrillation is choosing between a rhythm control strategy or a rate control strategy as the main strategy. When choosing rate control, the optimal heart rate target is uncertain. The Danish Atrial Fibrillation trial is a randomized, multicenter, two-group, superiority trial comparing strict rate control versus lenient rate control in patients with either persistent or permanent atrial fibrillation at inclusion. To prevent bias arising from selective reporting and data-driven analyses, we developed a predefined description of the statistical analysis. METHODS: The primary outcome of this trial is the physical component score of the SF-36 questionnaire. A total of 350 participants will be enrolled based on a minimal important difference of 3 points on the physical component score of the SF-36 questionnaire, a standard deviation of 10 points, a statistical power of 80% (beta of 20%), and an acceptable risk of type I error of 5%. All secondary, exploratory, and echocardiographic outcomes will be hypothesis-generating. The analyses of all outcomes will be based on the intention-to-treat principle. We will analyze continuous outcomes using linear regression adjusting for "site," type of atrial fibrillation at inclusion (persistent/ permanent), left ventricular ejection fraction (≥ 40% or < 40%), and the baseline value of the outcome (all as fixed effects). We define our threshold for statistical significance as a p-value of 0.05 and assessments of clinical significance will be based on the anticipated intervention effects defined in the sample size and power estimations. Thresholds for both statistical and clinical significance will be assessed according to the 5-step procedure proposed by Jakobsen and colleagues. DISCUSSION: This statistical analysis plan will be published prior to enrolment completion and before any data are available and is sought to increase the validity of the DANish Atrial Fibrillation trial. TRIAL REGISTRATION: Clinicaltrials.gov NCT04542785. Registered on Sept 09, 2020.

Functional outcomes and complications of tibial lengthening using unilateral external fixation and then plating. A prospective case series.

INTRODUCTION: and Importance: The purpose of this study was to assess the functional outcomes and complications of tibial lengthening using unilateral external fixation and then plating. MATERIAL AND METHODS: This was a prospective case series study that enrolled people of short stature or leg length discrepancy of more than 3 cm from January 2019 to January 2021. A total of 11 patients (one male and 10 females) were recruited for the study, including seven short statures and four patients with leg length discrepancies. The external fixaters in this study were Muller's frame or Nhan's frame. RESULTS: The average age of patients at the time of surgery was 25.89 years (range: 13-41 years). The study included 18 tibias that were lengthened and then plated. Average tibial lengthening was 6.89 ± 1.25 cm (21.87 ± 6.59%). The functional result was excellent in seven patients and good in four patients. Pin-track infection occurred in three tibias. There was one case of superficial infection. 12 legs (66.7%) developed ankle equinus after removing the external fixator. Four legs with severe equinus deformity were treated with percutaneous tendo-Achilles lengthening. Valgus deviation occurred in eight tibias. Peroneal nerve neuropraxia occurred in two legs during distraction. Distal migration of the fibula head occurred in four legs. CONCLUSION: Our study suggested that tibial lengthening using Nhan's external fixater or Muller frame then plating was safe and effective provided complications were looked for and kept in check. Equinus contracture, pin-site infection, and valgus alignment were the most common complications. LEVEL OF EVIDENCE: Level IV, prospective case series study.

Fibula lengthening then centralization for the treatment of pseudoarthrosis at the middle third of tibia with large leg-length discrepancy - A case report.

INTRODUCTION AND IMPORTANCE: Tibial dysplastic pseudoarthrosis associated with large leg-length discrepancy and extensive scarring was a great challenge for orthopedic surgeons. The treatment for these lesions was not defined. CASE PRESENTATION: We report a 24-year-old case of dysplastic pseudoarthrosis at the middle third of the right tibia with a 10 cm leg-length discrepancy and a 250 medial deviation and 200 internal torsion due to osteomyelitis 14 years previously. She was treated by fibula lengthening then centralization for the treatment of tibial pseudoarthrosis. Eight months after the operation, the patient reported no pain and became capable of walking without an orthosis. X-rays showed full bone union at the proximal tibiofibular synostosis and the lengthening site of the right fibula. The distal tibiofibular synostosis was healing. The range of movement of the knee and ankle was restored. CLINICAL DISCUSSION: This technique was different from the Huntington procedure. A good union between the transposed fibula and the remaining part of the fibula brought a better strength of the reconstructed tibia. The tibial pseudoarthrosis, leg-length discrepancy, and malalignment had been solved by our techniques. The procedure was easy, rapid, and inexpensive without requiring microsurgery skills and special devices. CONCLUSION: Leg lengthening then centralization of ipsilateral fibular graft is an excellent option for reconstruction of a tibial pseudarthrosis with a large leg-length discrepancy. It is a safe, rapid, and inexpensive procedure. The procedure was not difficult, and microvascular skills and special devices were not required. LEVEL OF EVIDENCE: A case report.

Occurrence of symptomatic lymphocele after open and robot-assisted radical prostatectomy.

INTRODUCTION: The aim of this article was to evaluate the prevalence and predictors of symptomatic lymphocele after open retropubic radical prostatectomy (RRP) and robot-assisted radical prostatectomy (RARP). MATERIAL AND METHODS: A total of 472 patients undergoing RRP (n = 241) or RARP (n = 231) were retrospectively analyzed with a 2-year follow-up for age, body mass index (BMI), total serum prostate-specific antigen (PSA), lymphocele formation and histopathological features. Univariate and multivariate logistic regression models were used to identify independent predictors of symptomatic lymphocele. RESULTS: Patients undergoing RRP developed significantly less overall lymphoceles than after RARP (8.2% vs 16.7%; p = 0.049), but no difference was determined for symptomatic events requiring intervention (7.4% vs 11.7%, p = 0.315). Although more pelvic lymph node dissections (PLND) were performed during RARP (70.1% vs 50.6%; p <0.001), significantly more cases with lymphatic invasion were observed after RRP (18% vs 6.2%, p = 0.002). The median lymph node yield during RRP and RARP were 11 and 10, respectively (p = 0.381). In multivariate logistic regression, we identified the number of dissected lymph nodes (n = 11) (OR 1.1; 95% Cl 1.055 - 1.147; p = 0.001), the Gleason score ≥ 8 (OR 4.7; 95% Cl 2.365 - 9.363; p = 0.001) and the total PSA ≥10 ng/ml (OR 1.05; 95% Cl 1.02 - 1.074; p = 0.001) as independent predictors for the development of symptomatic lymphocele. CONCLUSIONS: Next to an extended lymph node yield, high-grade disease was associated with a higher risk to develop symptomatic lymphocele irrespective of the technical approach. The identification of risk factors might prove valuable in clinical practice when assessing and counselling patients considering surgical treatment of prostate cancer.

Clinical evaluation of RB1 genetic testing reveals novel mutations in Vietnamese patients with retinoblastoma.

Clinical evaluation of the genetic testing strategy is essential for ensuring the correct determination of mutation carriers. The current study retrospectively analyzed genetic and clinicopathological data from 62 Vietnamese patients with retinoblastoma (RB) referred to the Vinmec Hi-Tech Center for RB transcriptional corepressor 1 (RB1) genetic testing between 2017 and 2019. The present study aimed to evaluate the sensitivity of the Next Generation Sequencing (NGS) method to identify novel RB1 mutations, and to consider using age at diagnosis as a risk factor. Genomic DNA was analyzed with custom panel based targeted NGS. NGS was performed on the Beijing Genomics Institute (BGI) sequencing platform, and pathogenic or likely pathogenic variants were confirmed by Sanger sequencing, quantitative PCR (qPCR) or Multiplex Ligation-dependent Probe Amplification assay (MLPA). Constitutional RB1 variants were identified in 100% (25/25) of the bilateral cases, while several common previously reported RB1 mutations were also recorded. In addition, in Vietnamese patients with RB, nine novel RB1 mutations were identified. Children aged between 0-36 months were more likely to be RB1 carriers compared with those aged >36 months. The current findings indicated that the NGS method implemented in the Vinmec Hi-Tech Center was highly accurate, and age at diagnosis may be used to assess the risk of hereditary RB. Furthermore, the newly identified RB1 mutations may provide additional data to improve the current understanding of the mechanisms underlying RB1 inactivation and the development of rapid assays for detecting RB1 mutations. Overall, the present study suggested that NGS may be applied for detecting germline RB1 mutations in routine clinical practice.

Hb Calgary (HBB: c.194G>T): A Highly Unstable Hemoglobin Variant with a ß-Thalassemia Major Phenotype.

We describe two unrelated patients, both heterozygous for an unstable hemoglobin (Hb) variant named Hb Calgary (HBB: c.194G>T) that causes severe hemolytic anemia and dyserythorpoietic, resulting in transfusion dependence and iron overload. The molecular pathogenesis is a missense variation on the ß-globin gene, presumed to lead to an unstable Hb. The phenotype of Hb Calgary is particularly severe presenting as transfusion-dependent anemia in early infancy, precluding phenotypic diagnosis and highlighting the importance of early genetic testing in order to make an accurate diagnosis.

Symmetric Reconstruction of Functional Liver Segments and Cross-Individual Correspondence of Hepatectomy.

Accurate localization and analyses of functional liver segments are crucial in devising various surgical procedures, including hepatectomy. To this end, they require the extraction of a liver from computed tomography, and then the identification of resection correspondence between individuals. The first part is usually impeded by inherent deficiencies, as present in medical images, and vast anatomical variations across subjects. While the model-based approach is found viable to tackle both issues, it is often undermined by an inadequate number of labeled samples, to capture all plausible variations. To address segmentation problems by balancing between accuracy, resource consumption, and data availability, this paper presents an efficient method for liver segmentation based on a graph-cut algorithm. One of its main novelties is the incorporation of a feature preserving a metric for boundary separation. Intuitive anatomical constraints are imposed to ensure valid extraction. The second part involves the symmetric conformal parameterization of the extracted liver surface onto a genus-0 domain. Provided with a few landmarks specified on two livers, we demonstrated that, by using a modified Beltrami differential, not only could they be non-rigidly registered, but also the hepatectomy on one liver could be envisioned on another. The merits of the proposed scheme were elucidated by both visual and numerical assessments on a standard MICCAI SLIVER07 dataset.

Semi-automatic liver segmentation based on probabilistic models and anatomical constraints.

Segmenting a liver and its peripherals from abdominal computed tomography is a crucial step toward computer aided diagnosis and therapeutic intervention. Despite the recent advances in computing methods, faithfully segmenting the liver has remained a challenging task, due to indefinite boundary, intensity inhomogeneity, and anatomical variations across subjects. In this paper, a semi-automatic segmentation method based on multivariable normal distribution of liver tissues and graph-cut sub-division is presented. Although it is not fully automated, the method minimally involves human interactions. Specifically, it consists of three main stages. Firstly, a subject specific probabilistic model was built from an interior patch, surrounding a seed point specified by the user. Secondly, an iterative assignment of pixel labels was applied to gradually update the probabilistic map of the tissues based on spatio-contextual information. Finally, the graph-cut model was optimized to extract the 3D liver from the image. During post-processing, overly segmented nodal regions due to fuzzy tissue separation were removed, maintaining its correct anatomy by using robust bottleneck detection with adjacent contour constraint. The proposed system was implemented and validated on the MICCAI SLIVER07 dataset. The experimental results were benchmarked against the state-of-the-art methods, based on major clinically relevant metrics. Both visual and numerical assessments reported herein indicated that the proposed system could improve the accuracy and reliability of asymptomatic liver segmentation.

Diffuse Intracerebral Hemorrhage in an Infant With a Novel Homozygous Variant Leading to Severe Protein C Deficiency.

Protein C is a circulating anticoagulant that inhibits factor Va and VIIIa and promotes fibrinolysis. Compound heterozygous or homozygous variants in the Protein C gene (PROC) lead to severe deficiency of protein C and affected neonates typically present shortly after birth with purpura fulminans. We describe an infant who suffered a diffuse intracranial hemorrhage as a neonate and presented with purpura fulminans as an older infant which led to investigations that were consistent with severe protein C deficiency. We demonstrate subacute findings on neuroimaging and suggest this condition should be considered with neonatal presentations of bilateral intraparenchymal hemorrhage.

Fludarabine, Campath, and Low-Dose Cyclophosphamide (FCClow) with or without TBI Conditioning Results in Excellent Transplant Outcomes in Children with Severe Aplastic Anemia.

Various reduced-intensity conditioning regimens are in use for allogeneic hematopoietic cell transplant (HSCT) in patients with idiopathic severe aplastic anemia (SAA). We describe the use of fludarabine, Campath, and low-dose cyclophosphamide (FCClow) conditioning in 15 children undergoing related or unrelated donor transplants. Total body irradiation (TBI) of 2 Gy was added for unrelated donor HSCT. At a median follow-up of 2.3 years, the failure-free survival was 100%, with low rates of infection and toxicity. There was no occurrence of grade III to IV acute graft-versus-host disease (GVHD). All patients had full donor myeloid chimerism post-HSCT, even with mixed chimerism in the T cell lineage. The absence of chronic GVHD and long-term stable mixed donor T cell chimerism confirms immune tolerance following FCClow (± TBI) conditioned transplantation in children with SAA.

Interactions between Curcumin Derivatives and Amyloid-ß Fibrils: Insights from Molecular Dynamics Simulations.

The aggregation of amyloid-ß (Aß) peptides into senile plaques is a hallmark of Alzheimer's disease (AD) and is hypothesized to be the primary cause of AD related neurodegeneration. Previous studies have shown the ability of curcumin to both inhibit the aggregation of Aß peptides into oligomers or fibrils and reduce amyloids in vivo. Despite the promise of curcumin and its derivatives to serve as diagnostic, preventative, and potentially therapeutic AD molecules, the mechanism by which curcumin and its derivatives bind to and inhibit Aß fibrils' formation remains elusive. Here, we investigated curcumin and a set of curcumin derivatives in complex with a hexamer peptide model of the Aß1-42 fibril using nearly exhaustive docking, followed by multi-ns molecular dynamics simulations, to provide atomistic-detail insights into the molecules' binding and inhibitory properties. In the vast majority of the simulations, curcumin and its derivatives remain firmly bound in complex with the fibril through primarily three different principle binding modes, in which the molecules interact with residue domain 17LVFFA21, in line with previous experiments. In a small subset of these simulations, the molecules partly dissociate the outermost peptide of the Aß1-42 fibril by disrupting ß-sheets within the residue domain 12VHHQKLVFF20. A comparison between binding modes leading or not leading to partial dissociation of the outermost peptide suggests that the latter is attributed to a few subtle key structural and energetic interaction-based differences. Interestingly, partial dissociation appears to be either an outcome of high affinity interactions or a cause leading to high affinity interactions between the molecules and the fibril, which could partly serve as a compensation for the energy loss in the fibril due to partial dissociation. In conjunction with this, we suggest a potential inhibition mechanism of Αß1-42 aggregation by the molecules, where the partially dissociated 16KLVFF20 domain of the outermost peptide could either remain unstructured or wrap around to form intramolecular interactions with the same peptide's 29GAIIG33 domain, while the molecules could additionally act as a patch against the external edge of the second outermost peptide's 16KLVFF20 domain. Thereby, individually or concurrently, these could prohibit fibril elongation.

Three new species of the genera Loxoconcha and Xestoleberis (Crustacea, Ostracoda, Podocopida) from central and southern Vietnam.

The present study reports three new species of Ostracoda, Loxoconcha damensis sp. nov., Xestoleberis vietnamensis sp. nov. and X. munensis sp. nov., from Phu Quoc Island, southwest Vietnam and Nha Trang Bay, central Vietnam. These species inhabit the coral reefs around isolated islands and can be easily distinguished from other known species based on their morphological differences, mainly in the male copulatory organ. Loxoconcha damensis sp. nov. belongs to Loxoconcha Group A, based on the distributional pattern of their pore system below the eye tubercle. Similarly, based on a combination of morphological types of pore systems, the two new Xestoleberis species belong to Xestoleberis Group A, because these species have two types of pore systems, i.e., sieve-type and lip-type. To the best of our knowledge, this study is the first report on Xestoleberididae and the second on Loxoconchidae from the Recent of Vietnam.

Feeling out a link between feeling and infant sociomoral evaluation.

Recent research has shown that infants selectively approach prosocial versus antisocial characters, suggesting that foundations of sociomoral development may be present early in life. Despite this, to date, the mental processes involved in infants' prosocial preferences are poorly understood. To explore a possible role of emotions in early social evaluations, the current studies examined whether four samples of infants and toddlers express different emotional reactions after observing prosocial (giving) versus antisocial (taking) events. Experimentally blind coders rated infants' and toddlers' emotional reactions to prosocial and antisocial interactions from video using a 1- to 7-point Likert scale of negative to positive emotion; reactions were rated as more positive after viewing prosocial compared to antisocial interactions in three of four samples. While the observed effects were small, a single-paper meta-analysis suggests that the findings are robust and stable across age. These results support the possibility that emotional reactions play some role in infants' sociomoral evaluations. Statement of contribution What is already known Infants prefer prosocial to antisocial individuals from the first year of life. Emotion plays some role in the sociomoral judgments of children and adults. What this study adds Infants and toddlers express more positive reactions after observing prosocial giving versus antisocial taking acts, though observed effect sizes are small. Naïve coders can predict at a better than chance rate what type of act an infant or toddler just viewed based on their facial expressions. Provides the first evidence that emotion plays some to-be-specified role in infants' and toddlers' sociomoral evaluations.

Social evaluation of intentional, truly accidental, and negligently accidental helpers and harmers by 10-month-old infants.

Whereas adults largely base their evaluations of others' actions on others' intentions, a host of research in developmental psychology suggests that younger children privilege outcome over intention, leading them to condemn accidental harm. To date, this question has been examined only with children capable of language production. In the current studies, we utilized a non-linguistic puppet show paradigm to examine the evaluation of intentional and accidental acts of helping or harming in 10-month-old infants. In Experiment 1 (n=64), infants preferred intentional over accidental helpers but accidental over intentional harmers, suggestive that by this age infants incorporate information about others' intentions into their social evaluations. In Experiment 2 (n=64), infants did not distinguish "negligently" accidental from intentional helpers or harmers, suggestive that infants may find negligent accidents somewhat intentional. In Experiment 3 (n=64), we found that infants preferred truly accidental over negligently accidental harmers, but did not reliably distinguish negligently accidental from truly accidental helpers, consistent with past work with adults and children suggestive that humans are particularly sensitive to negligently accidental harm. Together, these results imply that infants engage in intention-based social evaluation of those who help and harm accidentally, so long as those accidents do not stem from negligence.

[Osteocalcin and glucose metabolism: assessment of human studies]. / Ostéocalcine et métabolisme du glucose - Les leçons des études chez l'homme.

Osteocalcin, a protein secreted by osteoblasts, is recognized as a biomarker of bone mineralization. Besides, animal experimental studies have shown that osteocalcin could play an important role in glucose metabolism. Over the course of the last decade, this theory has been investigated in several human studies. Most of the results obtained from these reports support a positive correlation between total and undercarboxylated osteocalcin and insulin secretion/sensitivity. Studies also corroborate a reverse association with glycemic parameters such as fasting glucose and glycated hemoglobin. Nevertheless, because most of the studies published are observational, it is not possible to yet confirm a direct cause-effect relationship. Research in the field will surely contribute to the development of new pharmacological strategies for the treatment of endocrine diseases.