Tailgut Cyst in a Child: A Case Report and Review of Literature.

ABSTRACT: Tailgut cysts are rare congenital abnormalities that develop due to failure of embryologic tailgut to involute. This generally manifests as a presacral, retrorectal and multicystic mass. It has a high propensity in female patients including paediatric age group. The clinical presentation varies depending on the age of patient, location and size of the cyst. The symptoms are mostly due to mass effects and rarely complications such as malignancy. Being a rare entity, it is generally misdiagnosed. Differential diagnosis mostly includes rectal duplication cyst, sacrococcygeal teratoma and anterior meningocele. Radiological imaging such as computed tomography scan and magnetic resonance imaging is useful in the diagnosis. The treatment of choice is complete excision to prevent recurrence, infection and malignant degeneration. We have reviewed previous literature and given our valuable information regarding the same.

Patient-specific arterial wall generation for intracranial aneurysms with a variable and a near realistic vessel wall thickness for FSI studies.

BACKGROUND AND OBJECTIVE: Imaging methodologies such as, computed tomography (CT) aid in three-dimensional (3D) reconstruction of patient-specific aneurysms. The radiological data is useful in understanding their location, shape, size, and disease progression. However, there are serious impediments in discerning the blood vessel wall thickness due to limitations in the current imaging modalities. This further restricts the ability to perform high-fidelity fluid structure interaction (FSI) studies for an accurate assessment of rupture risk. FSI studies would require the arterial wall mesh to be generated to determine realistic maximum allowable wall stresses by performing coupled calculations for the hemodynamic forces with the arterial walls. METHODS: In the present study, a novel methodology is developed to geometrically model variable vessel wall thickness for the lumen isosurface extracted from CT scan slices of patient-specific aneurysms based on clinical and histopathological inputs. FSI simulations are carried out with the reconstructed models to assess the importance of near realistic wall thickness model on rupture risk predictions. RESULTS: During surgery, clinicians often observe translucent vessel walls, indicating the presence of thin regions. The need to generate variable vessel wall thickness model, that embodies the wall thickness gradation, is closer to such clinical observations. Hence, corresponding FSI simulations performed can improve clinical outcomes. Considerable differences in the magnitude of instantaneous wall shear stresses and von Mises stresses in the walls of the aneurysm was observed between a uniform wall thickness and a variable wall thickness model. CONCLUSION: In the present study, a variable vessel wall thickness generation algorithm is implemented. It was shown that, a realistic wall thickness modeling is necessary for an accurate prediction of the shear stresses on the wall as well as von Mises stresses in the wall. FSI simulations are performed to demonstrate the utility of variable wall thickness modeling.

Influence of framing coil orientation and its shape on the hemodynamics of a basilar aneurysm model.

Aneurysms are bulges of an artery, which require clinical management solutions. Due to the inherent advantages, endovascular coil filling is emerging as the treatment of choice for intracranial aneurysms (IAs). However, after successful treatment of coil embolization, there is a serious risk of recurrence. It is well known that optimal packing density will enhance treatment outcomes. The main objective of endovascular coil embolization is to achieve flow stasis by enabling significant reduction in intra-aneurysmal flow and facilitate thrombus formation. The present study numerically investigates the effect of framing coil orientation on intra-aneurysmal hemodynamics. For the purpose of analysis, actual shape of the embolic coil is used, instead of simplified ideal coil shape. Typically used details of the framing coil are resolved for the analysis. However, region above the framing coil is assumed to be filled with a porous medium. Present simulations have shown that orientation of the framing coil loop (FCL) greatly influences the intra-aneurysmal hemodynamics. The FCLs which were placed parallel to the outlets of basilar tip aneurysm (Coil A) were found to reduce intra-aneurysmal flow velocity that facilitates thrombus formation. Involving the coil for the region is modeled using a porous medium model with a packing density of 20 % . The simulations indicate that the framing coil loop (FCL) has a significant influence on the overall outcome.

Awareness, Perception, and Practice Regarding Needle-Stick Injury and Its Prevention Among Healthcare Workers in a Tertiary Care Hospital in Southern India.

Background Needle stick injuries caused by various sharp and other items like hypodermic needles and intravenous cannulas are important occupational hazards for healthcare workers (HCW). Preventing injuries is the most effective way to protect workers and requires good awareness and perceptions associated with practice on a daily basis. Therefore, we did a descriptive cross-sectional study involving healthcare workers in a tertiary care hospital to find the level of awareness, perception, and practice associated with needle stick injury and its prevention. Methodology A descriptive cross-sectional study was conducted in a tertiary care hospital, in south India. 400 healthcare workers (doctors, nurses, technicians, and housekeeping staff) with more than one year of experience were randomly selected. An anonymous, self-reporting, semi-structured questionnaire was administered. Results are expressed in mean, standard deviation, frequency, and percentages. Results Out of 400 respondents, 89% had good awareness about proper disposal practices. However,44% of the participants had the misbelief that recapping needles was recommended to prevent needle stick injury (NSI), and 30.5% practiced it, with the doctors being the majority. The majority (79.8%) knew that HIV, Hepatitis B & C are blood-borne pathogens that HCWs are most commonly exposed to through needle-stick injury (NSI). However, only 49% knew that Hepatitis B has the highest risk of transmission following a needle prick. 75% were aware of the correct Hepatitis B vaccination doses. Most of the healthcare workers (89.5%) claimed to be aware of the procedure and guidelines to be followed after a needle stick injury and 96% felt that they would report NSI immediately. Awareness regarding Hepatitis C prevention was comparatively poor, with only 47% having knowledge regarding the non-availability of Hepatitis C Vaccination and& 46% about the non-availability of post-exposure prophylaxis for Hepatitis C. Among the healthcare workers, 61% were worried about having needle stick injuries but 56.5% felt that their own personal safety is secondary to patient care. Among the HCWs, 91.3% believed that needle stick injuries can be prevented. Most of the participants (93.5%) ensure that others around them take extra precautions while handling sharp/ needles. The majority, i.e. 88%, utilized a designated container for disposal of sharp items, while only 53% of respondents utilized a needle cutter or shredder. 85% of HCWs had attended specific training programs on the usage of safe devices/sharps in the preceding one-year period and 72.8% had completed the vaccination against Hepatitis B. Conclusion Awareness regarding needle stick injury and its prevention is patchy and not adequate across different sections of healthcare workers. Perceptions regarding needle stick injury and its prevention revealed an overall positive attitude. Practices related to needle stick injury and its prevention seem to be reasonably good except when related to recapping and waiting to dispose of until the completion of the session. Training sessions need to be tailored for specific participant groups and a 'one size fits all' philosophy cannot be followed.

Pathway level subtyping identifies a slow-cycling biological phenotype associated with poor clinical outcomes in colorectal cancer.

Molecular stratification using gene-level transcriptional data has identified subtypes with distinctive genotypic and phenotypic traits, as exemplified by the consensus molecular subtypes (CMS) in colorectal cancer (CRC). Here, rather than gene-level data, we make use of gene ontology and biological activation state information for initial molecular class discovery. In doing so, we defined three pathway-derived subtypes (PDS) in CRC: PDS1 tumors, which are canonical/LGR5+ stem-rich, highly proliferative and display good prognosis; PDS2 tumors, which are regenerative/ANXA1+ stem-rich, with elevated stromal and immune tumor microenvironmental lineages; and PDS3 tumors, which represent a previously overlooked slow-cycling subset of tumors within CMS2 with reduced stem populations and increased differentiated lineages, particularly enterocytes and enteroendocrine cells, yet display the worst prognosis in locally advanced disease. These PDS3 phenotypic traits are evident across numerous bulk and single-cell datasets, and demark a series of subtle biological states that are currently under-represented in pre-clinical models and are not identified using existing subtyping classifiers.

Numerical investigation of unruptured middle cerebral artery bifurcation aneurysms: influence of aspect ratio.

An aneurysm is a disease condition, which is due to the pathological weakening of an arterial wall. These aneurysms are often found in various branch points and bifurcations of an artery in the cerebral circulation. Most aneurysms come to medical attention, either due to brain hemorrhages caused by rupture or found unruptured. To consider surgically invasive treatment modalities, clinicians need scientific methods such as, hemodynamic analysis to assess rupture risk. The arterial wall loses its structural integrity when wall shear stress (WSS) and other hemodynamic parameters exceed a certain threshold. In the present study, numerical simulations are carried out for unruptured middle cerebral artery (MCA) aneurysms. Three distinct representative sizes are chosen from a larger patient pool of 26 MCA aneurysms. Logically, these aneurysms represent three growth stages of any patient with similar anatomical structure. Simulations are performed to compare the three growth phases (with different aspect ratios) of an aneurysm and correlate their hemodynamic parameters. Simulations with patient specific boundary conditions reveal that, aneurysms with a higher aspect ratio (AR) correspond to an attendant decrease in both time-averaged wall shear stress (TAWSS) and spatial wall shear stress gradients (WSSG). Smaller MCAs were observed to have higher positive wall shear stress divergence (WSSD), exemplifying the tensile nature of arterial wall stretching. Present study identifies positive wall shear stress divergence (PWSSD) to be a potential biomarker for evaluating the growth of an aneurysm.

PLAC8-Mediated Activation of NOX4 Signalling Restores Angiogenic Function of Endothelial Colony-Forming Cells in Experimental Hypoxia.

Ischaemic cardiovascular disease is associated with tissue hypoxia as a significant determinant of angiogenic dysfunction and adverse remodelling. While cord blood-derived endothelial colony-forming cells (CB-ECFCs) hold clear therapeutic potential due to their enhanced angiogenic and proliferative capacity, their impaired functionality within the disease microenvironment represents a major barrier to clinical translation. The aim of this study was to define the specific contribution of NOX4 NADPH oxidase, which we previously reported as a key CB-ECFC regulator, to hypoxia-induced dysfunction and its potential as a therapeutic target. CB-ECFCs exposed to experimental hypoxia demonstrated downregulation of NOX4-mediated reactive oxygen species (ROS) signalling linked with a reduced tube formation, which was partially restored by NOX4 plasmid overexpression. siRNA knockdown of placenta-specific 8 (PLAC8), identified by microarray analysis as an upstream regulator of NOX4 in hypoxic versus normoxic CB-ECFCs, enhanced tube formation, NOX4 expression and hydrogen peroxide generation, and induced several key transcription factors associated with downstream Nrf2 signalling. Taken together, these findings indicated that activation of the PLAC8-NOX4 signalling axis improved CB-ECFC angiogenic functions in experimental hypoxia, highlighting this pathway as a potential target for protecting therapeutic cells against the ischaemic cardiovascular disease microenvironment.

A novel parameter for the prediction of rupture risk of cerebral aneurysms based on morphology.

Neurosurgeons often encounter dilemmas in the clinical management of cerebral aneurysms owing to an uncertainty of their rupture status and rupture risk. This study evaluates the influence of natural frequency of an aneurysm, as a novel morphological parameter to understand and analyze rupture status and risk prediction. In this work, we employ the natural frequency of 20 idealized and 50 patient specific aneurysms. The natural frequency of patient specific aneurysms is then compared against their rupture status. A strong correlation was observed between various morphological indicators and natural frequency for ideal and patient specific geometries. A statistical analysis with both Mann Whitney U test and T-test for rupture status against natural frequency has given a p-value less than 0.01 indicating a strong correlation between them. The correlation of morphological parameters with natural frequency from Pearson correlation coefficient and T-test suggests a holistic reflection of their effects on the natural frequency of an aneurysm. Thus, natural frequency could be a good indicator to discern the rupture potential of an aneurysm. The correlation between rupture status and natural frequency makes it a novel parameter that can differentiate between ruptured and unruptured patient specific aneurysms.

Profile of Splash, Sharp and Needle-Stick Injuries Among Healthcare Workers in a Tertiary Care Hospital in Southern India.

Background and objective Among biological hazards faced by healthcare workers, one of the most commonly reported is sharp-related injury. Needle-stick and sharp injuries transmit infectious diseases, especially blood-borne viruses. The conditions in which these exposures occur vary. Reporting of exposure and proper post-exposure prophylactic measures are important in controlling blood-borne infections in healthcare workers. Better analysis of such accidents is an important tool to reinforce exposure preventive measures. Hence, we conducted a study to describe the profile of splash, sharp and needle-stick injuries among healthcare workers in a tertiary care hospital. Methods A record-based cross-sectional study was done in a tertiary care hospital, in south Tamil Nadu. All healthcare workers who have reported needle stick, sharp, or splash injuries during the last five years in the hospital were included. Data was extracted from post-exposure reports maintained in the hospital. Results are expressed in mean, standard deviation and percentages. Results A total of 189 healthcare workers (HCWs) had reported instances of splash, sharp and needle stick injuries in the last five years. The most common exposure was needle prick (86.2%), followed by splash of fluids (7.4%). The majority of HCWs were from the nursing department (44.4%), and the most commonly reported place of exposure was the Emergency Department and Intensive Care Unit (ICU) (30.3%), followed by inpatient wards. The associated activity in the majority of the injuries/exposures was the transfer of sharps or cleaning surfaces (26.4%), followed by blood withdrawal (25.7%). After the exposure, 99.5% of HCWs washed the wound immediately. In a total of 135 exposures, the identity of the source, and thus, the serological status was known. Among these, hepatitis B was the most common (17.8%), followed by HIV (11.9%). All exposures related to unknown sources were considered positive exposure and were managed accordingly. Among the HCWs with possible seropositive exposure to hepatitis B, antibody titres were recorded and HBV Immunoglobulin (low titre), and vaccination were administered accordingly. Among the possible HIV exposures, 97.1% of HCWs initiated post-exposure prophylaxis (PEP). All probable hepatitis C exposures were given counseling and advised to follow up. No seroconversion at six months of follow-up has been recorded till now. Conclusion Healthcare workers are constantly at risk of exposure to splash, sharp and needle stick injuries, and although all categories of workers are at risk, nurses are at particularly high risk. A variety of activities can result in injury or a splash of fluids and so preventive activities, including health education, should be focused on all areas of healthcare and for all healthcare workers. More awareness is needed among healthcare workers regarding post-exposure prophylaxis.

MmCMS: mouse models' consensus molecular subtypes of colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) primary tumours are molecularly classified into four consensus molecular subtypes (CMS1-4). Genetically engineered mouse models aim to faithfully mimic the complexity of human cancers and, when appropriately aligned, represent ideal pre-clinical systems to test new drug treatments. Despite its importance, dual-species classification has been limited by the lack of a reliable approach. Here we utilise, develop and test a set of options for human-to-mouse CMS classifications of CRC tissue. METHODS: Using transcriptional data from established collections of CRC tumours, including human (TCGA cohort; n = 577) and mouse (n = 57 across n = 8 genotypes) tumours with combinations of random forest and nearest template prediction algorithms, alongside gene ontology collections, we comprehensively assess the performance of a suite of new dual-species classifiers. RESULTS: We developed three approaches: MmCMS-A; a gene-level classifier, MmCMS-B; an ontology-level approach and MmCMS-C; a combined pathway system encompassing multiple biological and histological signalling cascades. Although all options could identify tumours associated with stromal-rich CMS4-like biology, MmCMS-A was unable to accurately classify the biology underpinning epithelial-like subtypes (CMS2/3) in mouse tumours. CONCLUSIONS: When applying human-based transcriptional classifiers to mouse tumour data, a pathway-level classifier, rather than an individual gene-level system, is optimal. Our R package enables researchers to select suitable mouse models of human CRC subtype for their experimental testing.

Hemodynamics and bio-mechanics of morphologically distinct saccular intracranial aneurysms at bifurcations: Idealised vs Patient-specific geometries.

BACKGROUND AND OBJECTIVE: Understanding the factors that influence the rupture of aneurysms is of primary concern to the clinicians, who are grappled with patient management. It is important to know how the relation between morphological features of the cerebral aneurysm, and the mechanical stresses on the containing arterial walls are influenced by the hemodynamic forces. Present study investigates three different shapes, which have been identified correspondingly in patient-specific scenarios as well. The primary objective is to categorize the bifurcation aneurysms into standard shapes such as, spherical, beehive and pear-shaped, based on patient-specific clinical studies and further compare and contrast the model aneurysms with the patient specific configurations, for their hemodynamic factors as well as the attendant stresses on the wall. MethodsComputational fluid dynamic simulations are performed accounting for the fluid-structure interaction (FSI) effects between the flowing fluid and the containing vessel wall. Blood is assumed to be Newtonian, while the arterial walls are assumed to be linearly elastic. A commercial solver is used for performing detailed calculations. Hemodynamic and bio-mechanical rupture predictions are carried out for the three different shapes. Observations derived from the idealised simulations are compared and contrasted against their patient-specific counterparts. ResultsFrom detailed numerical simulations, it was observed that pear-shaped aneurysms exhibit large re-circulation bubble and flow stagnation zone, with higher residence time for the particles, which may lead to atherosclerotic lesions. Beehive shape allows for maximum flow into the aneurysmal sac with concentrated jet impinging on the dome, leading to high values of maximum WSS (MWSS) resulting in great propensity to form a secondary bleb. However, flow field inside a spherical aneurysm is found to be stable with fewer vortices, and nearly uniform distribution of wall stresses are observed though-out the sac, which perhaps signifies hemodynamically and bio-mechanically stable condition. ConclusionCategorizing patient-specific intracranial aneurysms into standard shapes viz, spherical, beehive and pear could generalize the process of prediction of hemodynamic and bio-mechanical rupture indicators. Comparative assessment of the flow field and stresses reported from the simulations on idealised models, with corresponding patient-specific simulations reveal that, these studies could aid in understanding the generalised shape dependence of hemodynamic and bio-mechanical behaviour of aneurysms.

Calcific Myonecrosis: Solving the Diagnostic Dilemma.

We report the clinico radiological presentation of an unusual case of an ossified soft tissue mass in the leg in a 74-year-old man. Calcific myonecrosis is a rare soft tissue condition characterized by calcified mass within a compartment. Differential diagnosis of myonecrosis include myositis ossificans and sarcomas with propensity for extra-osseous calcification like extra-skeletal osteosarcoma, Ewing's sarcoma and epithelioid sarcoma. This entity is a late complication to trauma and prolonged high pressure state within the leg compartments. With imaging alone, the differential of soft tissue sarcoma could be ruled out but typical natural history of disease and radiopathological features aided in the diagnosis.

Isolated duodenal duplication cyst in a neonate.

Duodenal duplication cysts are a rare subtype of alimentary tract duplications cysts, consisting of 7% of all the duplications. We report a rare case of neonatal duodenal duplication cyst presenting as a palpable abdominal mass and features of gastric outlet obstruction. A 27-day-old male child presented with complaints of icterus, non-bilious vomiting after every feed and right-sided abdominal lump for the last 15 days. A computed tomography scan of the abdomen revealed well-defined peripherally enhancing cystic lesion noted in the subhepatic region extending up to the right lumbar region. On surgical exploration, a cystic mass was found attached to the pyloric part of the stomach along the mesenteric border of the first, second and third part of the duodenum, which was marsupialised, and no communication was found with the duodenum. On histopathological analysis, a duodenal duplication cyst was diagnosed without any heterotopic mucosa. The literature was reviewed and the approach to duodenal duplication cyst in neonates is discussed.

Biological Misinterpretation of Transcriptional Signatures in Tumor Samples Can Unknowingly Undermine Mechanistic Understanding and Faithful Alignment with Preclinical Data.

PURPOSE: Precise mechanism-based gene expression signatures (GES) have been developed in appropriate in vitro and in vivo model systems, to identify important cancer-related signaling processes. However, some GESs originally developed to represent specific disease processes, primarily with an epithelial cell focus, are being applied to heterogeneous tumor samples where the expression of the genes in the signature may no longer be epithelial-specific. Therefore, unknowingly, even small changes in tumor stroma percentage can directly influence GESs, undermining the intended mechanistic signaling. EXPERIMENTAL DESIGN: Using colorectal cancer as an exemplar, we deployed numerous orthogonal profiling methodologies, including laser capture microdissection, flow cytometry, bulk and multiregional biopsy clinical samples, single-cell RNA sequencing and finally spatial transcriptomics, to perform a comprehensive assessment of the potential for the most widely used GESs to be influenced, or confounded, by stromal content in tumor tissue. To complement this work, we generated a freely-available resource, ConfoundR; https://confoundr.qub.ac.uk/, that enables users to test the extent of stromal influence on an unlimited number of the genes/signatures simultaneously across colorectal, breast, pancreatic, ovarian and prostate cancer datasets. RESULTS: Findings presented here demonstrate the clear potential for misinterpretation of the meaning of GESs, due to widespread stromal influences, which in-turn can undermine faithful alignment between clinical samples and preclinical data/models, particularly cell lines and organoids, or tumor models not fully recapitulating the stromal and immune microenvironment. CONCLUSIONS: Efforts to faithfully align preclinical models of disease using phenotypically-designed GESs must ensure that the signatures themselves remain representative of the same biology when applied to clinical samples.

Activation of innate-adaptive immune machinery by poly(I:C) exposes a therapeutic vulnerability to prevent relapse in stroma-rich colon cancer.

OBJECTIVE: Stroma-rich tumours represent a poor prognostic subtype in stage II/III colon cancer (CC), with high relapse rates and limited response to standard adjuvant chemotherapy. DESIGN: To address the lack of efficacious therapeutic options for patients with stroma-rich CC, we stratified our human tumour cohorts according to stromal content, enabling identification of the biology underpinning relapse and potential therapeutic vulnerabilities specifically within stroma-rich tumours that could be exploited clinically. Following human tumour-based discovery and independent clinical validation, we use a series of in vitro and stroma-rich in vivo models to test and validate the therapeutic potential of elevating the biology associated with reduced relapse in human tumours. RESULTS: By performing our analyses specifically within the stroma-rich/high-fibroblast (HiFi) subtype of CC, we identify and validate the clinical value of a HiFi-specific prognostic signature (HPS), which stratifies tumours based on STAT1-related signalling (High-HPS v Low-HPS=HR 0.093, CI 0.019 to 0.466). Using in silico, in vitro and in vivo models, we demonstrate that the HPS is associated with antigen processing and presentation within discrete immune lineages in stroma-rich CC, downstream of double-stranded RNA and viral response signalling. Treatment with the TLR3 agonist poly(I:C) elevated the HPS signalling and antigen processing phenotype across in vitro and in vivo models. In an in vivo model of stroma-rich CC, poly(I:C) treatment significantly increased systemic cytotoxic T cell activity (p<0.05) and reduced liver metastases (p<0.0002). CONCLUSION: This study reveals new biological insight that offers a novel therapeutic option to reduce relapse rates in patients with the worst prognosis CC.