Aim of this study was to biomechanically compare two different acetabular cup fixation constructs in terms of fracture fixation for displaced acetabular fractures involving the anterior column with hemitransverse fracture under partial and full weight-bearing conditions.n = 6) and primary THA with Burch–Schneider reinforcement cage (BSRC) (n = 6).Two different reinforcement rings designed as cages for primary THA were biomechanically tested in terms of managing a complex acetabular fracture. Single-leg stance cyclic loading was performed to assess fracture gap movement and fragment rotation. Twelve hemi pelvis Sawbones were divided into two groups: primary THA with acetabulum roof reinforcement plate (ARRP) (p = 0.035) of the os ilium to os ischii gap compared to BSRC. Fracture gap movements between the os ilium and spina iliaca fragments were significantly reduced by 76% (p = 0.048) for ARRP in contrast to BSRC. The ARRP group also demonstrated significantly less movement in the fracture gaps os ischii to quadrilateral plate  and quadrilateral plate to spina iliaca . Significantly less rotational movement of the quadrilateral plate to the os ilium was exhibited by the ARRP group (p = 0.015).During loading under partial weight-bearing (250 N) fracture gap movement tended to be larger in the BSRC group as compared to the ARRP group. Under full weight-bearing conditions, the ARRP showed 60% significantly less motion (The presented acetabulum roof-reinforcement plate (ARRP) provides stable conditions at the acetabular component with adequate stabilization of a displaced acetabular fracture. The incidence of anterior column fractures combined with hemitransverse (ACPHT) fractures tremendously increases due to an aging society. Such fractures involve displacement of the quadrilateral plate (QLP) and are often associated with a higher degree of comminution and impaction in patients with osteoporotic bone quality , 25, 42.In the past, only a few biomechanical studies have analyzed the stability of acetabular fracture reconstruction methods underlining the necessity of stable osteosynthesis to prevent re-displacement of the QLP , 24. HowThis study compares two different reinforcement cages for displaced acetabular fractures providing fixation of the acetabular roof. Designed as a defect implant for revision surgery in hip bone defects, the Burch–Schneider reinforcement cage (BSRC) aims to restore the anatomical rotational center of the hip . The fixThe study was conducted using synthetic hemi pelvises . A CT scan of one synthetic hemi pelvis bone was performed and DICOM data of the scan was segmented. After data segmentation, a negative of the prepared hemi pelvis model was used to create a virtual sawing template. This template was 3D printed with PolyJet technology. Using this template, an anterior column combined with posterior hemitransverse (ACPHT) fracture with additional break out of the quadrilateral plate Fig.  was reprPrior to testing, specimens were attached to an artificial sacrum that consisted of a polyurethane cast  which was used to create an equal load distribution between the servohydraulic testing machine and synthetic bone, mimicking the sacroiliac joint. For correct placing of the sacrum substitute, anatomical correlations and geometric dimensions of a fourth generation Sawbones sacrum  corresponding to the hemi pelvis were used for manufacturing. The connection between sacrum and hemi pelvis was secured using three threaded rods (M8) with corresponding nuts. The artificial sacrum was reused for each test sample.The bones were randomly assigned to one of two methods of primary THA Fig. : ARRP imBiomechanical testing was conducted using an Instron 8874 servohydraulic testing machine . A single-leg stance model Fig.  was creaIn-vivo hip contact force angles resulting during single leg stance were obtained as according to Bergmann et al. . Loadingos ilium were determined and statistically analyzed . For statistical analysis, a Student’s t test for independent samples was performed to identify differences between the two groups. Distribution for normality was checked with Shapiron–Wilk test. Results are presented as mean value ± standard deviation (SD).Fracture gap movements and quadrilateral plate fragment rotation with respect to the os ilium and os ischii , and the os ilium and spina iliaca . In addition, the ARRP group showed significantly less fracture gap movement between the quadrilateral plate the spina iliaca .Fracture gap movements were analyzed after 1000 cycles under partial weight-bearing 250 N) and after 31,000 cycles of loading under full weight-bearing  and the os ilium and spina iliaca fracture gap . ARRP also demonstrated significantly less movement in the fracture gaps os ischii to quadrilateral plate  and quadrilateral plate to spina iliaca . Although ARRP fixation showed less motion in the fracture gaps os ilium to quadrilateral plate (p = 0.318) and os ischii to os pubis (p = 0.065), these differences were not statistically significant.Under full weight-bearing conditions movements between fracture gaps were always larger for the BSRC fixation as compared to the ARRP fixation. The improvements in fixation stability due to the ARRP fixation were most relevant for the os ilium (Table p = 0.771) was similar for ARRP and BSRC. Nevertheless, the ARRP demonstrated less rotation around the horizontal (p = 0.199) and the longitudinal axis (p = 0.135). Under full weight-bearing conditions fragment rotation around the sagittal axis was approximately three times larger when a BSRC was used instead of an ARRP (p = 0.015). The rotations around the horizontal (p = 0.071) and longitudinal axis (p = 0.070) tended to be larger for BSRC as compared to ARRP.The rotation of the quadrilateral plate was assessed with respect to the um Table . After 1This biomechanical study compared two different reinforcement techniques for severely displaced acetabular fractures typically seen in geriatric patients. The acetabulum roof-reinforcement plate (ARRP) which employs a special cage fixation at the intact iliac bone in combination with fixed-angle screws demonstrated a consistently improved biomechanical stability compared to the Burch–Schneider reinforcement cage (BSRC) technique. Even under unrestricted partial and full weight-bearing conditions, the ARRP resulted in interfragmentary fracture movements of typically less than 1 mm and can thus provide a biomechanically sound fracture healing environment.Displaced acetabular fractures with disruption of the quadrilateral plate frequently result in post-traumatic osteoarthrosis and long-term surgery outcome is directly related to accuracy of fracture reduction , 27. AnaThe indication for primary THA is often discussed and there is no need for primary THA in general cases . Howeveros ilium to os ischii, os ilium to spina iliaca, os ischii to quadrilateral plate and quadrilateral plate to spina iliaca. It was assumed that the cause for higher relative quadrilateral plate and fracture gap movement with BSRC is presumably due to a higher ARRP construct stiffness. The use of 13 angle stable screws fixed in the solid iliac bone seem to provide higher stability compared to the seven non-angle stable screws of the BSRC construct. Angular stability provided by the ARRP screws may be beneficial regarding the prevention of large fracture gap movements. Another reason for the higher stability of the ARRP might be caused by the fact that the monoaxial locking screws with different angles of the individual screws with respect to the implant might provide additional purchase in the iliac bone.In the postoperative simulation starting with partial and ending with full weight-bearing conducted in the present study, the comparison of construct stability among both groups revealed less quadrilateral plate movement for ARRP. Furthermore, the ARRP fixation stability was most significantly relevant under full weight-bearing conditions as compared to BSRC. Thus, protrusion of the femoral head  was sufficiently prevented by ARRP treated fractures. It is worth noting that testing showed that ARRP distinctly reduced the fracture gap movements in os ischii to os pubis was detected in both groups, although this may not be a disadvantage for both implants and could easily be addressed by methods such as additional plating. However, this would significantly increase operation time and be an unreliable method in geriatric patients favoring immediate postoperative full weight-bearing.A large movement in As the model studied represents loading under partial and full weight-bearing conditions, a single-leg stance model was chosen to evaluate fracture gap movement of both implants. In the presented test set-up fracture gap movements in both groups were analyzed at the beginning after 1000 cycles with 250 N and after 31,000 cycles, simulating long-term loading conditions. Egol et al.  indicateA cable was used to prevent the bones from collapsing and to achieve a hip joint load as according to Bergmann et al. . High loThis biomechanical study presents several strengths including (1) the use of a clinically relevant acetabular ACPHT fracture model; (2) utilization of fourth-generation Sawbones as a suitable biomechanical comparison for human bone , 37; (3)In conclusion, this biomechanical study compared two constructs in a clinically relevant scenario for cases of hip joint failure in the elderly with reduced bone quality. No clinically relevant implant failure or loss of reduction was noted in either construct. However, the acetabulum roof-reinforcement plate demonstrated increased fixation stability of the quadrilateral plate under partial and full weight-bearing conditions and provides a possible treatment option for anterior column with posterior hemitransverse acetabular fractures.


We read with great interest the recent article by Keith et al. who concluded that their retrospective, observational study in adult patients with septic shock and multiple organ failure demonstrated improved 28-day survival with adjunct therapeutic plasma exchange (TPE) compared to standard care alone . The 28-


A 72-year-old man presented with excruciating epigastric pain. A chest computed tomography angiography revealed an aortic intramural hematoma. A filling defect within the distal ascending aorta was noted. Images of an intramular hematoma and surgical details of an ascending aortic replacement under deep hypothermic circulatory arrest are provided. A 72-year-old man presented with excruciating epigastric pain not associated with exercise or trauma. After excluding myocardial ischemia, a chest computed tomography angiography revealed an aortic intramural hematoma (IMH) of 5 mm in thickness starting at the sinotubular junction (34 mm) and extending circumferentially to the diaphragm 27 mm;. A fillAn ascending aortic replacement was performed under deep hypothermic circulatory arrest. A thrombus covering a small intimal tear was found within the aortic lumen at the distal ascending aorta corresponding to the filling defect . No othDisruption of a vasa vasorum within the media or bleeding within the vicinity of a penetrating atherosclerotic ulcer are the mechanisms reported to cause IMH.


Goblint is a static analysis framework for C programs specializing in data race analysis. It relies on thread-modular abstract interpretation where thread interferences are accounted for by means of flow-insensitive global invariants.


With the recent increased use of lanthanum carbonate, several cases of lanthanum phosphate deposition to gastric mucosa in dialysis patients have been reported. However, the endoscopic appearance of the early-stage lesion and the over-time alterations of endoscopic findings due to the progression of lanthanum phosphate deposition remain unclear.An 80-year-old man receiving dialysis and taking lanthanum carbonate as a phosphate binder over a 4-year period underwent upper gastrointestinal endoscopy four times beginning 1 year after initiation of treatment. The first endoscopic examination (after 1 year of exposure to lanthanum carbonate) revealed rough mucosa with a few areas of white granular mucosa. Over the 3 years of endoscopic follow-up, the white granular mucosa spread and multiple erosions appeared. Histopathological findings of biopsy specimens from an erosion showed extensive infiltration by histiocytes containing deposits. Scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDX) revealed that the presence of the deposits containing phosphorus and lanthanum in the gastric mucosa.On the basis of these results, the patient was diagnosed with gastropathy associated with lanthanum phosphate deposition.Over a 3-year period, endoscopic findings associated with lanthanum deposition gradually changed and expanded from the early stage. Lanthanum carbonate is commonly used in dialysis patients to improve the hyperphosphatemia associated with chronic kidney disease. Specific gastric mucosal findings associated with the deposition of lanthanum have been reported in recent years in patients taking lanthanum carbonate –4. VarioWe herein report the gradual changes in endoscopic findings resulting from lanthanum deposition over a 3-year period in a patient receiving ongoing oral administration of lanthanum carbonate.An 80-year-old Japanese man diagnosed with chronic renal failure secondary to type 2 diabetes received dialysis for 4 years and took lanthanum carbonate at dose 750 mg/day orally as a phosphate binder during this 4-year period. The patient underwent upper gastrointestinal endoscopy 1 year after initiation of lanthanum carbonate because of epigastric discomfort.The endoscopic findings at this initial endoscopy included rough mucosa with a few white granular lesions in the lesser curvature of the gastric body with the atrophic change Fig. a. After Histopathological findings on biopsy of erosion in greater curvature showed atrophic mucosa, intestinal metaplasia, and regenerative change. Many histiocytes containing granular or crystalline eosinophilic deposits were found extensively infiltrating the lamina propria, consistent with the presence of inflammation Fig. .Fig. 2HScanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDX) identified the deposition of phosphorus and lanthanum in gastric mucosa. Figure We took biopsy specimens from erosion in greater curvature over time Fig. . It was Because the patient has no abdominal symptoms, gastrointestinal endoscopy has been continued annually for follow-up observation. The patient signed the explanation and consent forms in the informed consent process for endoscopic examination.Lanthanum carbonate is a therapeutic agent for hyperphosphatemia and is widely used for the management of chronic renal failure in dialysis patients. Lanthanum carbonate has been available in the UK since 2007 and in Japan since 2009. Lanthanum carbonate strongly binds with phosphate ions in the intestinal tract to form minimally soluble lanthanum phosphate. Although the absorption rate of lanthanum from the gastrointestinal tract to the bloodstream is considered safe at less than 0.00127% , there hWe observed that the area of whitish granular mucosa and erosions expanded and the appearance of lesions became more apparent over time while being exposed to lanthanum carbonate over 3 years. Interestingly, the lesion area spread on the atrophic area from near the pylorus toward the cardia. This spreading pattern seemed similar to the mucosal atrophy progress described by Takemoto et al. . This fiMeanwhile, the causality and the mechanism between lanthanum deposition and mucosal injury remains unestablished. Since the patient in this case report did not have an endoscopic examination before starting lanthanum carbonate, we could not assess the base-line gastric mucosa without the effect of the medication. Nonetheless, over-time endoscopic as well as histological observations clearly showed that the deposition of lanthanum and the number of histiocytes that infiltrated in the tissue were increasing and gastric inflammation became exacerbated during the treatment with lanthanum carbonate. Our findings imply the lanthanum deposition results in damaging the gastric mucosa. The studies to investigate the causal link and mechanisms of lanthanum deposition and mucosal injury are needed.One study found that 85.7% of dialysis patients treated with lanthanum carbonate had deposition in the gastrointestinal mucosa . Despite


Significance: Assessment of disease using optical coherence tomography is an actively investigated problem, owing to many unresolved challenges in early disease detection, diagnosis, and treatment response monitoring. The early manifestation of disease or precancer is typically associated with subtle alterations in the tissue dielectric and ultrastructural morphology. In addition, biological tissue is known to have ultrastructural multifractality.Aim: Detection and characterization of nanosensitive structural morphology and multifractality in the tissue submicron structure. Quantification of nanosensitive multifractality and its alteration in progression of tumor.Approach: We have developed a label free nanosensitive multifractal detrended fluctuation analysis(nsMFDFA) technique in combination with multifractal analysis and nanosensitive optical coherence tomography (nsOCT). The proposed method deployed for extraction and quantification of nanosensitive multifractal parameters in mammary fat pad (MFP).Results: Initially, the nsOCT approach is numerically validated on synthetic submicron axial structures. The nsOCT technique was applied to pathologically characterized MFP of murine breast tissue to extract depth-resolved nanosensitive submicron structures. Subsequently, two-dimensional MFDFA were deployed on submicron structural en face images to extract nanosensitive tissue multifractality. We found that nanosensitive multifractality increases in transition from healthy to tumor.Conclusions: This method for extraction of nanosensitive tissue multifractality promises to provide a noninvasive diagnostic tool for early disease detection and monitoring treatment response. The novel ability to delineate the dominant submicron scale nanosensitive multifractal properties may also prove useful for characterizing a wide variety of complex scattering media of non-biological origin. Subsequently, we have deployed two-dimensional multifractal detrended fluctuation analysis (2D-MFDFA)–ex vivo study on murine tissue, we found interesting change in depth-resolved nanosensitive multifractality in submicron structures after tumor formation in breast tissue samples. This method for extraction of nanosensitive tissue multifractality promises to develop a noninvasive diagnosis tool for the detection of cancer development. This newly developed method offers exciting depth-resolved ultrastructural detection for better treatment and monitoring if there is a tumor response to treatment.Early disease progression in living tissues expected to exhibit nanosensitive structural alteration at the submicron scale. It is highly desirable to develop noninvasive, label-free techniques to detect nanoscale changes in biological tissue for early diagnosis and better treatment. Recently, many optical nanoscopic techniques were developed based on labeling22.1Flowchart of nsOCT is shown in 2.2,,®) has been used for implementation of simulation. The OCT signal was constructed as an interference spectrum of the reflected light from different layers of synthetic sample with the reflected light from a gold mirror. We have also added suitable noise in detector and source spectra to mimic experimental reality. The signal-to-noise ratio was 86 dB in this simulation. The inverse Fourier transform was performed to form A-lines nsOCT of a synthetic volume as each lateral position of en face images to compare.In our recent publications,2.3en face images to extract nanosensitive multifractal parameters namely, Hurst exponent [–We have followed our established nsOCT methodology to construct depth-resolved dominant structures of synthetic and tissue volume. Flowchart of nsOCT processing displayed in Step 1:en face nsOCT image [size: The two-dimensional Step 2:Each square segment Step 3:en face nsOCT. The residual nanosensitive axial size variation or detrended subsurface is given by The local fit Step 4:The detrended fluctuation function en face image at each depth is en face image with size en face nsOCT map. Note that, in principle, we can calculate generalized Hurst exponents for The Step 5:The generalized Hurst exponents [en face nsOCT surface.From this above equation, the scaling exponent The classical multifractal scaling exponent en face nsOCT surface is related to en face image. The width of the singularity spectrum en face images. The higher value of en face indicates higher strength of multifractality. The Hurst scaling exponents: en face images at different depths. The The two-scaling exponent en face images.In this study, we have characterized (a) Hurst exponent [2.4All animal procedures were performed in accordance with the Guidelines for Care and Use of Laboratory Animals of the “Animal Care Research Ethics Committee (ACREC), National University of Ireland Galway (NUIG)” and approved by the “Health Product Regularity Authority (HPRA), Ireland”.ex vivo analysis. Harvested samples were taken out from PBS and mounted on a glass slide to bring them under the objective of spectral domain OCT system  to record OCT images.Female BALB/c mice (Charles River Laboratories Ltd.) aged between 6 and 8 weeks were employed. A mouse received a mammary fat pad  injection of 33.1en face map of submicron structure at en face map of submicron structure. en face and in nsOCT detected en face, we have applied state of the art 2D-MFDFA on each en face images throughout the depth. en face in en face in en face has a multifractality (blue color plot) and can be detected with almost no error (red color plot). In addition, Hurst exponent [en face is almost equal in values confirms our capability to detect submicron scale structural correlation within a complex tissue sample. Similarly, en face in en face in en face image proved our capability to detect submicron scale structural multifractality within a complex tissue sample.We have recently demonstrated an experimental and numerical approach for nsOCT validation and detection of submicron structure with few nanometer accuracy.en face structures. The upper part of en face structures. Detected depth-dependent Hurst exponent [en face structure is very close to each other. These results validated our capability to detect submicron scale structural multifractality through the proposed nsMFDFA methodology from a tissue-like complex submicron scale multifractal structure with greater accuracy.The lower part of 3.2ex vivo tissue with healthy MFP and tumor portion. en face for healthy [blue plot extracted from volume in After successful validation of nsMFDFA approach, we have applied this technique on en face images to find nanosensitive multifractal parameters.In these regards, it is known that tissues have multifractality in submicron structure. Therefore, it is always interesting to have depth-resolved quantitative submicron scale multifractal parameters for better understanding. Quantitative submicron scale multifractal parameters can also help to develop computer-assisted automated differentiation of tumor tissue from healthy tissue. In this direction, we have performed 2D-MFDFA on depth-resolved nsOCT constructed en face images at en face and tumor (red color) en face image. en face, and tumor (red color) en face image. Variation of In en face images at different depths. Vertical lines at each depth represent standard deviation from mean trends over 10 samples. In en face images as tumor progress. In en face images as tumor progress.For further verification and confirmation, we have applied this extraction method of nanosensitive multifractality on 10 healthy MFP and 10 tumor volume images in different areas of a tissue sample. We found consistence differences of nanosensitive correlation and strength of multifractality over different depths of tissue. 4in vivo deployment. Exploiting the interference spectra recorded from tissue depths with the reference mirror, in vivo applications of this approach should be realized with a fiber optic-based handheld probe assisted with scanning lens and galvo mirror. Finally, the developed nsMFDFA method represents as a novel approach with much potential for in vivo detection of cancer initiation and other non-biological application remain to be rigorously evaluated.A novel approach to quantify submicron scale nanosensitive multifractality in combination with nsOCT and multifractal analysis has been demonstrated. We validated the nsOCT technique numerically on synthetic submicron scale axial structures. We developed a novel nanosensitive submicron scale multifractal analysis technique to characterize tissue depth-resolved ultrastructural morphology. Reduction of the Hurst exponent [


Peripheral arterial disease (PAD) is a major cause of diminished functional capacity and quality of life in a large portion of western populations. While 3D contrast-enhanced (CE) MRA is becoming a modality of choice for clinical PAD examinations, the potential for nephrogenic systemic fibrosis (NSF) in patients with renal insufficiency has triggered a renaissance of interest in non-contrast enhanced (NCE) MRA. Various NCE-MRA strategies employing 3D half-Fourier FSE  or balanThe FSD module was modified by using bipolar gradient rather than unipolar gradient before and after the center 180-RF pulse to address the artifactual issue resulted from imperfect frequency response  to selectively suppress arterial blood and to avoid otherwise venous contamination. The feasibility of this approach was demonstrated on healthy distal lower extremities. Further investigation on PAD patients, with CE-MRA or x-ray angiography correlation, is warranted. It is anticipated that this strategy could be applied to other vascular territories where appropriate choice of m1 (magnitude and direction) would vary with the specific flow patterns.


Aortic coarctation is currently treated by both surgical and transcatheter methods. Patients can present with late complication of prior surgical repair including recoarctation and aneurysm formation. There are limited reports on safety and efficacy of thoracic endovascular aortic repair methods (TEVAR) in post-coarctation repair patients.We report an adult patient with aortic aneurysm formation following surgical coarctoplasty successfully treated with transcatheter TEVAR method obviating the need for open heart surgery.Endovascular repair of aneurysms in post-coarctoplasty patients is a promising method and should be considered in those with suitable anatomy based on prior imaging. Aortic coarctation refers to the congenitally stenotic aorta, more commonly found near the ligamentum arteriosum and adjacent to the left subclavian artery . CoarctaA 25-year-old female with history of surgical repair of coarctation in infancy and percutaneous device closure of a mid-muscular ventricular septal defect (VSD) at age eighteen presented to our adult congenital clinic for routine follow-up. She stated that she was asymptomatic and had normal functional capacity. Physical examination findings were within normal limits. Chest X-ray showed normal heart size and an abnormal bulging in the upper left heart border suggesting aneurysmal dilation of thoracic aorta Fig. . CardiacAortography was performed via femoral route, and injections were done using a radiopaque marker pigtail to get accurate measurements. Aortic angiography confirmed CMR findings Fig. .Fig. 3AInitially, the left subclavian artery ostium was occluded using a Occlutech® PDA occluder 8 × 10 mm to eliminate the risk of endoleaks Fig. .Then a 2Follow-up CT angiography showed complete exclusion of the aneurysm with no complications Fig. . At 1-yeRepair of aortic coarctation has traditionally been based on surgical methods although catheter interventions are progressively improving . DiffereAlthough endovascular stent grafting has been approached cautiously in the treatment of such young patients, newer stent graft designs offer better conformability and durability, and endovascular stent grafting could be considered as a safe option for treatment of these patients. Advantages of stent grafts include the fact that they could cover the total length of the diseased aorta. However, long-term efficacy and freedom of reintervention remain to be investigated.Yazar et al. in their series of 13 patients with TEVAR for treatment of late complications after aortic coarctation reported cases suffering mortality and morbidity . Lala etThe present case highlights the importance of considering percutaneous methods of aneurysm repair in patients who are optimal candidates based on prior imaging, over the routine open surgical alternatives and thereby averting the risks associated with repeat surgical procedures. Large and multi-center trials with long-term follow-up focusing on postsurgical patients are needed to further clarify the role and potential shortcomings of the endovascular stent grafts in the management of these patients.


Functional enrichment of genes and pathways based on Gene Ontology (GO) has been widely used to describe the results of various -omics analyses. GO terms statistically overrepresented within a set of a large number of genes are typically used to describe the main functional attributes of the gene set. However, these lists of overrepresented GO terms are often too large and contains redundant overlapping GO terms hindering informative functional interpretations.We developed GOMCL to reduce redundancy and summarize lists of GO terms effectively and informatively. This lightweight python toolkit efficiently identifies clusters within a list of GO terms using the Markov Clustering (MCL) algorithm, based on the overlap of gene members between GO terms. GOMCL facilitates biological interpretation of a large number of GO terms by condensing them into GO clusters representing non-overlapping functional themes. It enables visualizing GO clusters as a heatmap, networks based on either overlap of members or hierarchy among GO terms, and tables with depth and cluster information for each GO term. Each GO cluster generated by GOMCL can be evaluated and further divided into non-overlapping sub-clusters using the GOMCL-sub module. The outputs from both GOMCL and GOMCL-sub can be imported to Cytoscape for additional visualization effects.https://github.com/Guannan-Wang/GOMCL and www.lsugenomics.org.GOMCL is a convenient toolkit to cluster, evaluate, and extract non-redundant associations of Gene Ontology-based functions. GOMCL helps researchers to reduce time spent on manual curation of large lists of GO terms, minimize biases introduced by redundant GO terms in data interpretation, and batch processing of multiple GO enrichment datasets. A user guide, a test dataset, and the source code of GOMCL are available at  High-throughput “omics” approaches are frequently employed to investigate expression changes and regulation of genes at a genome-wide level. Use of these genomic data often results in the identification of large lists of genes of interest. A standard approach to summarize the functions of these genes is to determine the enriched functions represented by Gene Ontology (GO) terms and other functional associations extracted from databases such as KEGG –3, ReactGO resources have become the most widely used knowledge base in terms of gene functions , 9, whicGOMCL is implemented in Python and allows grouping of lists of individual GO terms of interest into GO clusters using MCL Fig. . GOMCL ehttp://geneontology.org/) as an input  or an Overlap Coefficient (OC) [Jaccard Coefficient (JC) is calculated as A∩B/A∪B, and preferred for clustering of similarly sized GO terms. The Overlap Coefficient (OC) is derived from A∩B/min , and works better to maximally reduce the redundancy between disproportionately sized GO terms. The construction of the GO term similarity network is initiated using only those interactions that pass a user-defined threshold for the Jaccard or Overlap coefficient of users’ choice. MCL algorithm is subsequently applied to identify cluster structure in the initial network and assigns more similar GO terms into one cluster. The resulting GO clusters are ordered based on the number of genes in each cluster. GO terms with largest number of genes, or smallest enrichment p-value, or most other GO terms connected are selected and offered as potential representative GO terms for each cluster. GOMCL also reproduces the hierarchy of GO terms from the provided ontology structure for any user-selected clusters upon command to assist identification and interpretation of the functional themes of these clusters. A novel functionality enabled in GOMCL that is unavailable in previous tools for GO-network analysis, is the evaluation of clustering results by visualizing the distribution of similarity indexes between GO terms for each cluster. Taking this one step further, GOMCL includes a second module, called GOMCL-sub, which provides users customizable options to break down selected clusters produced by GOMCL into sub-groups with more specific functional themes. These functionalities combined, allows users to determine if there are distinct functional themes present in primary clusters and further identify these sub-structures in clusters of interest.GOMCL first trims the input GO lists by removing overly broad GO terms whose size is greater than a user-defined threshold. For example, a large GO term such as biological regulation (GO:0065007) has over 12,000 child GO terms, including 15,000 genes in Arabidopsis and is often uninformative as a term representing a meaningful biological function. GOMCL also enables users to separate input GO lists into biological process, molecular function, and cellular component categories or any combinations of these categories if clustering within different categories is preferred. Each term in the trimmed GO lists is then compared to each other, and similarity between any two GO terms is computed based on the overlaps between the members of these two GO terms as either a ent (OC) . Given aThe standard GOMCL output consists of a heatmap Fig. a, a grapAs a proof of concept, we performed a GOMCL run on a list of over-represented GO terms identified from genes differentially expressed between two GFP tagged cell populations of Arabidopsis roots in a published study  to highlOverlap Coefficient of 0.5 and granularity of 1.5 were used for cluster identification. These cutoffs can be set by the user. Among the 244 GO terms, GOMCL identified five distinct clusters with minimal overlap between clusters and extensive overlaps among GO terms within each cluster  enriched in genes expressed higher in the cell population with high GFP intensity . GOMCL-sub further separated cluster C1 and C2 clusters in less than 2 mins with similar amount of memory used. Given the efficiency of the toolkit, this can be easily implemented to conduct batch processing of multiple datasets associated with large –omics datasets.While the proof of concept analyses described above using GOMCL is used to highlight functional associations drawn from a typical RNAseq experiment, the use of GOMCL is not limited to summarizing functional processes from RNAseq data. For example, it has been recently successfully used in summarizing gene functions associated with multiple epigenetic marks in rice under phosphorus starved conditions . AdditioGOMCL is an open-source Python toolkit to identify clusters among GO term similarity networks using the MCL clustering algorithm. This toolkit allows grouping of GO terms into functional clusters to further simplify the interpretation of large datasets, reduce redundancy of functional interpretations, and especially when visual identification of cluster structure is not feasible due to a large number of enriched GO terms often found in -omics data (see Table GOMCL can be used for batch processing of multiple enrichment test results defined by the user. It is applicable for any research project where lists of genes of interest are generated. It is compatible with a wide variety of GO enrichment analysis tools publicly available, which would reduce intermediate steps needed to convert different input formats to conform to GOMCL requirements.GOMCL currently uses the MCL algorithm for cluster identification and is compatible with commonly-used GO enrichment tools. For future versions, we consider implementing additional clustering methods, improving labeling of nodes, and supporting more GO enrichment analysis tools.Lists of overrepresented GO functions from GO enrichment analyses are often long and redundant. We present GOMCL as a convenient toolkit to identify functional clusters among GO term similarity networks and further separate the resulting clusters into more informative sub-groups. It enables the user to effectively summarize long lists of GO functions into biologically informative non-redundant clusters without hand-picked selections and look for major functional themes associated with the experiments. GOMCL assists with the unmet yet increasing need for interpreting large gene sets often produced from -omics studies.Additional file 1. GOMCL cluster information for each GO term.Additional file 2. Similarity connections of GOMCL clusters and hierarchical connections of GOMCL cluster C1.Additional file 3. GO hierarchical structure produced using GOMCL for cluster C2 described in Fig. Additional file 4. Summary for GOMCL-sub clustering results of C1 described in Fig. Additional file 5. GOMCL-sub sub-cluster information for each GO term in cluster C1 described in Fig.


Epithelial ovarian cancer is one of the most lethal cancers in women and is typically diagnosed at an advanced-stage. Historically, primary tumor reductive surgery was attempted followed by postoperative chemotherapy in most patients diagnosed with advanced ovarian cancer. However, neoadjuvant chemotherapy followed by interval tumor reductive surgery is an alternative approach for patients with advanced-stage ovarian cancer where primary tumor reductive surgery is not feasible. Here, we review proposed models that can assist in selecting patients who would benefit most from neoadjuvant chemotherapy followed by surgery.Epithelial ovarian cancer remains a leading cause of death amongst all gynecologic cancers despite advances in surgical and medical therapy. Historically, patients with ovarian cancer underwent primary tumor reductive surgery followed by postoperative chemotherapy; however, neoadjuvant chemotherapy followed by interval tumor reductive surgery has gradually become an alternative approach for patients with advanced-stage ovarian cancer for whom primary tumor reductive surgery is not feasible. Decision-making about the use of these approaches has not been uniform. Hence, it is essential to identify patients who can benefit most from neoadjuvant chemotherapy followed by interval tumor reductive surgery. Several prospective and retrospective studies have proposed potential models to guide upfront decision-making for patients with advanced ovarian cancer. In this review, we summarize important decision-making models that can improve patient selection for personalized treatment. Models based on clinical factors  and molecular markers (circulating and tumor-based) are useful, but laparoscopic staging is among the most informative diagnostic methods for upfront decision-making in patients medically fit for surgery. Further research is needed to explore more reliable models to determine personalized treatment for advanced epithelial ovarian cancer. Epithelial ovarian cancer remains the fifth leading cause of death among women in the United States, with an incidence of 10.4/100,000 women/year and a death rate of 6.9/100,000 women/year in the 2017 statistics report . OvarianPlatinum-based drugs with paclitaxel are part of standard NACT regimen that have been used for newly diagnosed advanced ovarian cancers; however, limited information is available on use of bevacizumab (anti-angiogenesis drug), poly (ADP-ribose) polymerase (PARP) inhibitors and immunotherapy in NACT setting. Combination of bevacizumab with standard regimen in NACT setting demonstrated improved PFS among patients with advanced ovarian cancer ,14. Few The purpose of NACT is to decrease the tumor load and to increase the likelihood of achieving optimal cytoreduction  or RD ≤ 1 cm) at interval tumor reductive surgery (iTRS). Various diagnostic models have been developed to determine the ideal upfront treatment strategy for patients with advanced-stage ovarian cancer with no clear “winner.” In this review, we provide a critical discussion of the available data and evolving models to aid in decision-making and guide future research.p = 0.586)  value = 0.846). Thus, the serum CA-125 to ascites leptin ratio could anticipate clinical response before primary treatment and could be helpful in selecting type of first-line treatment for patients with HGSOC [Serum CA-125 is the most common tumor marker used at diagnosis and subsequent surveillance visits. A retrospective study demonstrated that patients with a serum CA-125 of ≤100 U/mL after NACT (before iTRS) had a higher likelihood of achieving optimal cytoreduction . Anotherth HGSOC .One retrospective study assessed the prognostic value of human epididymis 4 (HE4) protein marker preoperatively and at various time points during primary treatment for ovarian cancer . In thisADLH1-positive cancer stem cells have been shown to have an important role in platinum sensitivity. Increased expression of ALDH1 after NACT treatment indicated a 4.18 times higher risk of death and increased risk of poor outcome .Analyses of two publicly available microarray datasets revealed that higher levels of fatty acid–binding protein 4 (FABP4) and alcohol dehydrogenase 1B (ADH1B) in primary tumors were associated with a higher incidence of RD after pTRS among patients with HGSOC . In The One study  analyzedExamination of samples from tumor tissues and ascites revealed that insulin-like growth factor (IGF)-I in ascitic fluid was an independent predictor of objective clinical response . The autOne study suggested that an increased level of serum calretinin (CRT), a calcium-binding protein, at the time of initial diagnosis was correlated with a higher amount of ascites and advanced FIGO staging. An increased level of serum CRT (sCRT level cutoff = 0.35 ng/mL) was associated with higher chances of suboptimal cytoreduction. Serum CRT levels were also found to be an independent predictor for PFS and OS .Results of a multicenter retrospective study  revealedIn another study , quantitThe heterogeneity and later stage of diagnosis make curative treatment difficult for patients with ovarian cancer. NACT followed by iTRS has been shown to be as effective as pTRS for advanced-stage ovarian cancers. NACT can be considered a primary treatment option for patients with FIGO stage IV and is preferred for patients with FIGO stage IIIc ovarian cancer for whom optimal cytoreduction is not achievable or for those with multiple comorbidities. Many models have been proposed based on clinical factors, radiology studies, laparoscopic triage, circulating molecular markers and tumor-based genetic markers to facilitate upfront decision-making. Among these, laparoscopic assessment is arguably the most informative surgical assessment tool available. Additional research is required to determine more reliable models and to direct decision-making in upfront clinical management for advanced epithelial ovarian cancer.


There were cases of sudden death in some patients infected with COVID-19 including a few of young physicians, which had a huge impact on medical community and society . It is nIn addition to lung injury, cardiac injury has often been reported in patients with COVID-19 . Some exWe found that sinus bradycardia often occurred during sleep. So, deep sleep or sedation may be an important risk factor for sinus bradycardia. A few patients had mild to moderate decreased thyroid function, which was consistent with secondary pathological thyroid syndrome and may also be one of the causes of sinus bradycardia. When viral nucleic acid tests gradually turned negative, the heart rate returned to normal no matter whether the patient’s condition improved or worsened and the uses of catecholamine were gradually discontinued. According to the results, we speculated that the inhibitory effect of virus on sinus node activity was the main cause of sinus bradycardia in these patients.https://www.genecards.org/). Biological processes (BP) for ACE2 gene showed that it not only promoted the contraction of cardiac muscle, but also regulated the cardiac conduction. Donoghue et al. demonstrated that cardiac ACE2 overexpression in transgenic mice caused sudden death in a gene dose-dependent fashion; they also found that increased ACE2 expression led to progressive conduction and rhythm disturbances with lethal ventricular arrhythmias via detailed electrophysiology [Previous study indicated that COVID-19 invaded host cells via the receptor angiotensin-converting enzyme 2 (ACE2) . Zou et ysiology . In lighTaken together, heart rate monitoring of severe COVID-19 pneumonia patients should be strengthened during treatment, and catecholamines should be appropriately applied when necessary. Moreover, a possible inhibitory influence of the virus on activity of cardiac nervous conduction system including sinus node via ACE2 should not be ignored when studying the pathogenic mechanisms among these patients.


Intraocular medulloepithelioma is commonly treated with primary enucleation. Conservative treatment options include brachytherapy, local resection and/or cryotherapy in selected cases. We report for the first time the use of targeted chemotherapy to treat a ciliary body medulloepithelioma with aqueous and vitreous seeding.ab interno trabeculotomy followed by 360° gonioscopy-assisted transluminal trabeculotomy 6 months later was performed for uncontrolled intraocular pressure despite antihypertensive drugs combined to cyclophotocoagulation and 7 intravitreal anti-VEGF injections for recurrent iris neovascularization. Cataract was removed at the same operative time. The child has remained disease- and metastasis-free at a 5-year follow-up since the last melphalan injection (25-month follow-up after the combined lensectomy-trabeculotomy) with a controlled intraocular pressure under topical quadritherapy and a best corrected Snellen visual acuity of 0.08.A 17-month-old boy with a diagnosis of ciliary body medulloepithelioma with concomitant seeding and neovascular glaucoma in the right eye was seen for a second opinion after parental refusal of enucleation. Examination under anesthesia showed multiple free-floating cysts in the pupillary area associated with iris neovascularization and a subluxated and notched lens. Ultrasound biomicroscopy revealed a partially cystic mass adjacent to the ciliary body between the 5 and 9 o’clock meridians as well as multiple nodules in the posterior chamber invading the anterior vitreous inferiorly. Fluorescein angiography demonstrated peripheral retinal ischemia. Left eye was unremarkable. Diagnosis of intraocular medulloepithelioma with no extraocular invasion was confirmed and conservative treatment initiated with combined intracameral and intravitreal melphalan injections given according to the previously described safety-enhanced technique. Ciliary tumor and seeding totally regressed after a total of 3 combined intracameral  and intravitreal  melphalan injections given every 7–10 days. Ischemic retina was treated with cryoablation as necessary. Three years later, We report for the first time complete regression of a non-infiltrating ciliary body medulloepithelioma with seeding achieved with only a small number of intracameral and intravitreal melphalan injections. Concomitant secondary neovascular glaucoma and cataract needed appropriate management to allow long-term eye and vision preservation. DICER1 mutations has been found [Intraocular medulloepithelioma is a rare, nonhereditary, neuroepithelial tumor, usually arising from the nonpigmented ciliary epithelium of the ciliary body, more rarely the optic nerve, the retina or the iris . Its exaen found .Characteristic features of ciliary body medulloepithelioma include a grey-white to fleshy pink mass with a various quantity of cysts adjacent to the ciliary body, a lens notching with or without subluxation and a neoplastic cyclitic membrane , 4. The Here we report for the first time a case of intraocular medulloepithelioma with seeding at presentation successfully treated with intracameral and intravitreal melphalan chemotherapy.ab interno trabeculotomy followed by a 360° gonioscopy-assisted transluminal trabeculotomy 6 months later to manage uncontrolled intraocular pressure despite antihypertensive drugs combined with cyclophotocoagulation and 7 intravitreal anti-VEGF injections for recurrent iris neovascularization. Cataract surgery with posterior capsulorhexis, anterior vitrectomy and sulcus implantation of a three-piece intraocular lens was performed during the first glaucoma surgery. Cytopathologic analysis of the vitrectomy fluid was negative for tumor cells. One year after the cataract was removed, YAG-laser capsulotomy was performed for posterior capsular lens opacification. The child has remained disease and metastasis-free at a 5-year follow-up since the last chemotherapy with a controlled intraocular pressure under topical quadritherapy and a best-corrected Snellen visual acuity of 0.08.A previously healthy 17-month-old boy was given topical antibiotics for a right eye redness appearing in the context of an ear, nose and throat infection. One week later, fixed mydriasis of the same eye was observed, and the child seen elsewhere for evaluation Fig. a. IntraoIntraocular medulloepithelioma is a rare tumor of unknown incidence but still represents the most frequent pediatric primary malignant intraocular tumor after retinoblastoma . StandarIn this report, we describe for the first time the conservative management of a non-infiltrating ciliary body medulloepithelioma complicated with seeding at presentation using intraocular melphalan injections. Presence of seeding was so far considered as an indication for enucleation . MelphalIn conclusion, we report herein for the first time a case of non-invasive ciliary body medulloepithelioma with seeding at presentation successfully treated with only a small number of intraocular melphalan injections. To our knowledge, this is the first case of intraocular medulloepthelioma with seeding to be managed conservatively. Concomitant secondary neovascular glaucoma and cataract needed appropriate management to allow long-term eye and vision preservation. Further studies will help to better define the role of targeted chemotherapy for intraocular medulloepithelioma in the future.


Osteoarthritis (OA) of the knee is one of the most common causes of pain in older adults. Recent evidence suggests that knee OA pain is characterized by alterations in central pain processing in the brain. Two nonpharmacological pain treatments, transcranial direct current stimulation (tDCS) and mindfulness-based meditation (MBM), have been shown to improve pain-related brain function in older adults with knee OA. Because tDCS promotes neuroplasticity, it may potentiate the effect of MBM that also stimulates adaptive changes in the brain. However, no studies have examined whether tDCS combined with MBM can reduce OA symptoms in older adults with knee OA. Thus, the purpose of this study was to examine the preliminary efficacy of tDCS combined with MBM in older adults with knee OA. Thirty participants with knee OA were randomly assigned to receive 10 daily sessions of home-based 2 mA tDCS combined with active MBM for 20 minutes (n=15) or sham tDCS combined with sham MBM (n=15). We measured OA-related clinical symptoms using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Participants  had a mean age of 59 years. Active tDCS combined with active MBM significantly reduced scores on the WOAMC . Participants tolerated tDCS combined with MBM well without serious adverse effects. Our findings demonstrate promising clinical efficacy of home-based tDCS combined with MBM for older adults with knee OA. Future studies with larger-scale randomized controlled trials with follow-up assessments are needed to validate our findings.


This letter describes the potential effect of B cell depletion on immune related adverse events associated with immune checkpoint inhibition. B cell depleting agents such as rituximab reduce B cell to plasma cell differentiation and antibody production. This treatment strategy is used in several immune mediated inflammatory diseases such as rheumatoid arthritis and small vessel vasculitis. The immune related adverse events associated with immune checkpoint inhibition resemble immune mediated inflammatory diseases. Here, we report a lower incidence of hypothyroidism in a trial of combined B cell depletion and immune checkpoint inhibitor treatment compared with studies of immune checkpoint inhibitor monotherapy. This letter aims to increase awareness of the immune related adverse events associated with immune checkpoint inhibition in future clinical trials of immune checkpoint inhibition together with B cell depletion . Hopefully, observations from these clinical trials can guide future treatment strategies to treat or prevent immune related adverse events associated with immune checkpoint inhibition. The next decade will bring fundamental knowledge about the immunology behind the immune related adverse events (irAEs) associated with immune checkpoint inhibition (ICI). This knowledge will come as a consequence of new clinical trials of ICI together with B cell depletion. These treatment regimens are designed to improve outcomes for patients with B cell hematologic malignancies. However, reports of the irAE profile will be a major add-on benefit from these clinical trials.During ICI 35% of cancer patients develop irAEs. This type of adverse events resembles immune mediated inflammatory diseases (IMIDs). When treating cancer, we try to induce immunological reactions against the tumor cells. When treating IMIDs, we try to dampen immunological reactions causing inflammation. Immune modulating therapy can therefore be a double-edged sword. However, the two processes might not be mutually exclusive.ICI refers to blocking antibodies targeting the programmed cell death protein 1 (PD1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA4) pathways. PD1 and CTLA4 are negative regulators of T cell activity and are upregulated in many malignancies. In this way, cancer cells evade immune surveillance. ICI results in increased activity of the immune system and increased recognition and elimination of cancer cells. Therefore, ICI is emerging as a potential treatment option for many malignancies including lymphoma. B cell depleting agents bind to B cell specific membrane proteins causing complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity. E.g. rituximab binds to CD20 found on mature B cells and is routinely used in the treatment of B cell lymphomas. This results in depletion of the cancerous B cells expressing the CD20 protein on their surface. However, depletion of all mature B cells will also reduce antigen presentation, B cell to plasma cell differentiation and antibody production. Therefore, rituximab is also used in the treatment of several IMIDs such as rheumatoid arthritis and small vessel vasculitis.Little is known about the immunological reactions causing irAEs. Some irAEs are associated with the presence of autoantibodies implying a role for B cells. The most frequent of these autoantibody-associated irAEs is thyroiditis.Until now, only one clinical trial combining ICI with B cell depletion has been completed. 2 To investigate whether rituximab alters the frequency of irAEs we compared the incidence of hypothyroidism in this phase II trial with the incidence of hypothyroidism in comparable studies of PD1 inhibitor monotherapy.2 intravenously 17 days after the first infusion of pidilizumab and weekly for 4 weeks. Of the 32 patients, two were ineligible and not treated. Thirty patients were available for toxicity analysis, but only 29 received the therapy. The incidence of hypothyroidism in the 29 patients that received combination therapy was 0% .The completed phase II clinical trial was a study of 32 patients with rituximab-sensitive follicular lymphoma treated with pidilizumab and rituximab . PidilizThis incidence contrasts with larger studies with PD1 inhibition monotherapy reporting between 6% and 10% of patients experiencing hypothyroidism  is a major limitation. Thyroiditis was chosen because it is one of the most frequent irAE. We did not compare any of the other irAEs. This letter primarily aims to increase awareness of the irAEs associated with ICI in future clinical trials of ICI together with B cell depletion. A list of these ongoing trials and their completion dates can be seen in Table


The conventional orthotopic heart transplantation (OHT)  results in atrial enlargement. The variability of atrial size and function in these patients has not been previously reported.1. Determine the variability in the post-OHT size and function of left and right atria; 2. Analyze the relationship of donor and native atria; 3. Compare cardiac MRI (CMR) with transthoracic echocardiogram (TTE).This is a retrospective observational study. Nine patients who had undergone OHT via biatrial anastomosis technique and had both CMR as well TTE within one month of each other were selected. Using the optimized apical 4-chamber views in both TTE and CMR cine images (SSFP), endocardial borders of the native and donor, right atrial (RA) and left atrial (LA) free wall and septum were traced from base to the valvular annulus and areas were determined in late systole when atrial volumes are maximal and late diastole when atrial volumes are minimal. RA and LA function was assessed quantitatively using percentage of change in cavity area or fractional area change (FAC). FAC was defined using the formula ([end-systolic area] - [end-diastolic area])/[end-systolic area] × 100). Native and donor areas were also combined to calculate the total area of the right and left atria. Comparison was made between the TTE and CMR values. Data for continuous variables are expressed as mean value +/- SD.See Tables Left atrial volumes consistently predict outcome in most patient groups studied. LA size is frequently severely distorted after OHT and is dependent upon extent of retained pulmonary vein cuffs or associated donor lung preparation, individual cardiac surgeon preferences, and cardiac recipient organ status. Knowing the variations in atrial sizes may provide a new avenue for clinical investigation Figure . A CMR aIt appears that the retained native atrium does not contribute to atrial contraction. This resulted in a negative total FAC% in 45% (4/9) of our patients. Given the large retained native atria, and its poor contribution to atrial contraction, this report suggests that minimizing this atrial reservoir may be valuable and warrants additional study. The underestimation of native atrial size reported by TTE is most likely due to apical fore-shortening of the true long-axis and the far field ultrasound imaging.This observational study suggests that despite a generally reasonable correlation between TTE and CMR measures of OHT atria, significant differences exist. Furthermore, because of suspected intra-atrial (donor versus native) mechanical dysynchrony, some patients surprisingly had a negative FAC% suggesting that the native atria is larger during donor atrial contraction – acting as a non-functioning reservoir. The association of this to the clinical outcome has yet to be determined.


Embolic events are rare presentation of myxoma, which is one of the most prevalent benign cardiac tumors. Here we report the case of a 53-year-old man with presentation of acute anterior infarction and occlusion of the left anterior descending artery in association with left atrial myxoma. Intracoronary aspiration thrombectomy along with frequent balloon inflation was failed to recover distal coronary blood flow. Cardiac myxomas are the most common benign cardiac neoplasm. The exact etiology of the tumor has yet to be fully determined. Hemodynamic instability, intermittent syncope, congestive heart failure, pulmonary hypertension, sudden death and systemic embolization are some presentations of myxoma -3. CardiA 53-year-old man referred to emergency department with typical angina. Neither history of heart diseases in his past medical history nor any risk factors of cardiac diseases was seen in the patient. Electrocardiogram (ECG) showed hyper acute ST elevation in anterolateral and inferior leads. He was a candidate for Primary percutaneous coronary intervention (PCI). Coronary angiography revealed left anterior descending artery (LAD) occlusion at far mid portion. After wiring with some difficulties regarding to thrombotic manifestation of the lesion, thrombosuction (with Export® AP aspiration catheter medtronic) performed which was unsuccessful and despite several efforts of balloon inflation by the mini trek RX 2*15mm coronary dilation catheter, Abbott vascular, the thrombolysis in myocardial infarction flow grade (TIMI) was 0-1. TIMI grade 0 reveals no penetration of contrast beyond stenosis (100% stenosis) and TIMI grade 1 reveals penetration of contrast beyond stenosis without perfusion of distal vessel (99% stenosis).The procedure terminated unsuccessfully and the patient was admitted to cardiac care unit (CCU). His chest pain resolved 5 hours later and he was both hemodynamically and electrically stable. The day after admission echocardiography showed left ventricle ejection fraction (LVEF) 45% with some regional wall motion abnormalities in LAD territory and a large homogenous LA mass (3.5 × 3.5cm) attached to inter atrial septum that was protruded to mitral valve inflow . To prevThe present case was an acute anterior ST elevation myocardial infarction (STEMI) with unsuccessful PCI and diagnosis of left atrial myxoma. Non-sclerotic coronary artery diseases (NA-CAD) have several etiologies: coronary vasospasm, Kounis syndrome and coronary embolisms . CoronarData on this area is only based on case reports or case reviews . CoronarTransthoracic echocardiography (TTE) is helpful in diagnosis of myxoma. Initial treatment depends on etiology and amount of the blockage. In some cases, thrombus aspiration is alone sufficient to re-establish the blood flow. In other cases balloonangioplasty or stent insertion is essential to access a TIMI grade 3. Underlying conditions of embolism should be treated uniquely. Anticoagulant treatments in cases of atrial fibrilation, synthetic valve thrombosis and intracardiac thrombosis recommended. Surgery interventions suggested as the best option for some cases including tumors. Embolism caused by myxoma is rare and manifestations are often cerebral. Since in patients with acute myocardial infarction reperfusion time is very decisive, echocardiography may not be the first therapeutic priority. Exactly, like this case that PCI was preceding the echocardiography. To improve prognosis and prevent embolism, surgery is the only treatment of atrial myxoma. Complete resection is recommended to prevent tumor recurrence.The present case was an acute anterior ST elevation myocardial infarction (STEMI) with unsuccessful PCI and diagnosis of left atrial myxoma. Non-sclerotic coronary artery diseases (NA-CAD) should be taken into account in young people with no atherosclerotic risk factors who refer to emergency with acute myocardial infarction.The authors declare no competing interests.


Hashimoto's thyroiditis can be present with a localized palpable nodule though presentation as a hyperfunction "nodule" is extremely rare. The first case of Hashimoto's thyroiditis and hot nodule was reported in 1971 by Warner.131scintigraphy. The nodule disappeared after eight months of sufficient thyroid hormone replacement therapy.We reported a 26-year-old hypothyroid woman in Hashimoto's thyroiditis background with a hyperactive thyroid nodule in both 99mTc and IToxic adenoma in hypothyroid patients can be resolved after levothyroxine (L-T4) replacement therapy. Hashimoto's thyroiditis (HT) is the most common cause of hypothyroidism in iodine-sufficient areas. Hypothyroidism is seen in up to 10 percent of the population, and its prevalence increases with age . This raA 26-year-old woman with family history of hypothyroidism on her mother side was referred to our endocrine clinic because of clinical hypothyroidism and a thyroid hot nodule . After hThe final cytological diagnosis was “suggestive of thyroid neoplasm”. The patient was referred to our clinic because of hot area in the thyroid gland isthmus (compatible with thyroid nodule) according to 99mTc pertechnetate thyroid scintigraphy report. Residual thyroid tissue had low uptake . We requested an I131 thyroid scintigraphy to rule out the false hot nodule report by 99mTc scintigraphy, which confirmed the hot condition of nodule . So we dL-T4 substitution therapy was started again with full dose (700 micg/week) and fine needle aspiration (FNAC) was repeated because of increase in nodule size. Cytology report revealed an adenomatous nodule in background of lymphocytic thyroiditis. The thyroid function tests were acceptable in follow-up .The nodule size diminished to 11*5 mm at the four months full dose levothyroxine replacement therapy and disappeared after 8 months follow-up according to sonography report .Hashimoto thyroiditis is the most common cause of primary hypothyroidism in rich iodine area. The diagnosis of Hashimoto thyroiditis can be confirmed when a patient with hypothyroidism had firm consistency thyroid on palpation and high level of thyroid peroxidase antibody .We reported a young hypothyroid female due to Hashimoto thyroiditis and a thyroid hot nodule in scintigraphy which disappeared with sufficient thyroid hormone therapy. Although there are numerous reports about thyroid nodule associated with Hashimoto's thyroiditis, but the association of hypothyroidism in Hashimoto thyroiditis background with thyroid hot nodule is rare. Scintigraphic findings in Hashimoto thyroiditis are very different such as multinodular goiter, diffuse hyperplasia and some of them mimic solitary nodule but the toxic adenoma is rare condition . To the The first US guided fine needle aspiration cytology (FNAC) report was suggestive of thyroid neoplasm whereas the second FNAC after 6 months reported an adenomatous nodule in a background of lymphocytic thyroiditis. Only available cytology report by Mousavi et al. in three cases showed normal follicular cells with lymphocytic infiltration in two of them . In some reports after six months follow-up, the nodule size decreased between 40-60 % on adequate thyroid hormone replacement therapy , 11 whicIn conclusion thyroid adequate replacement therapy has been advised for hypothyroid patients in Hashimoto thyroiditis background and toxic adenoma.


Age-friendly environments aim to promote healthy and active aging by building and maintaining capacity across the life course and allow people who have a loss of capacity to continue engaging in activities that they value. Age-friendly community assessments are being conducted worldwide. This qualitative interpretive meta-synthesis (QIMS) aims to create a rich description of older adults’ experiences with outdoor spaces and buildings as well as transportation as part of an age-friendly assessment. The themes that emerged regarding older adults’ experiences with outdoor space and buildings included 1) accessibility and 2) appropriate infrastructure. Regarding transportation, the theme of accessibility included subthemes of 1) availability and 2) affordability. Further reduction indicated that age-friendliness can be conceptualized as environmental justice (EJ). The three areas of EJ including distributional justice, procedural justice, and recognition provide a helpful framework for social workers and their interdisciplinary partners to systematically document and evaluate their age-friendly community efforts.


Coronary ostial stenosis is an uncommon but potentially lethal complication following aortic root replacement with or without aortic valve replacement . This manifests clinically as acute myocardial ischaemia in the early or late post-operative period. Traditionally, this might be managed with redo open-heart surgery.This case series describes two presentations where urgent percutaneous coronary intervention was used to manage myocardial infarction complicating aortic root surgery with coronary reimplantation. This series highlights the risk of acute myocardial infarction after cardiac surgery involving coronary reimplantation. Emergency percutaneous coronary intervention is feasible and illustrates the importance of shared post-operative care involving the cardiac surgeons and the cardiology team. Acute myocardial infarction is an unusual complication in the days to months following aortic root replacement with coronary reimplantation  and can be due to obstruction of the reimplanted artery. PCI can be considered as a salvage treatment for these patients.Cardiothoracic centres should perform complex aortic root surgery within the setting of an experienced multidisciplinary team involving cardiac surgeons, cardiologists with allied health professional input.Coronary ostial stenosis is an uncommon but recognized complication of aortic root surgery involving reimplantation of the coronaries to a graft and usually presents within the first 6 months following aortic root surgery.This 38-year-old woman with background of Marfan’s syndrome was admitted to hospital following an episode of syncope. Echocardiography (ECHO) showed severe dilation of the ascending aorta with mild mitral and aortic regurgitation (AR) and normal left ventricular systolic function. Computed tomography confirmed dilation at 57 mm. Valve sparing aortic root replacement (David procedure) was carried out 2 months later after which she made an unremarkable recovery, being discharged home 5 days post -operatively. She was not on any regular medications prior to admission and refused any medications on discharge from hospital.Figure 1]. Prior to this, she had experienced a short history of exertional chest pain. Angiography showed the right coronary artery (RCA) was occluded proximally with thrombus and appearance of mechanical disruption of the aorto-ostial anastomosis . Reperfusion was achieved after wiring and export of a large thrombus, followed by ventricular fibrillation (VF) cardiac arrest after which an intra-aortic balloon pump was inserted and the patient intubated. After discussion with the multidisciplinary team (MDT) in the catheterization lab, the decision was to proceed with intravascular ultrasound (IVUS)-guided percutaneous intervention. IVUS confirmed extrinsic mechanical compression at the right coronary neo-ostium with no atherosclerosis present. This was successfully treated with one drug-eluting stent (DES) . Emergency ECHO in the catheterization lab showed severe right and left ventricular systolic dysfunction (LVSD). She was extubated the next day. Echocardiography on the 8th day of admission showed a dilated left ventricle with moderate segmental function and notably dilated failing right ventricle. Her recovery was complicated by ventilator acquired pneumonia and atrial fibrillation (AF) and she was discharged home after 3-week hospital admission.She was readmitted 10 days post -operatively directly from home to interventional cardiology via our regional optimal reperfusion service with an inferior ST-elevation myocardial infarction (STEMI) and cardiogenic shock .This 53-year-old gentleman with known bicuspid aortic valve and dilated aortic root developed decompensated heart failure related to severe AR in the setting of severely dilated aortic root (70 mm). His left ventricular (LV) function was moderately impaired which improved with medical therapy prior to operation. Computed tomography coronary angiography (CTCA) showed trivial plaque without obstructive coronary artery disease. Three weeks later after optimizing his medical treatment, he underwent aortic valve repair with valve-sparing aortic root replacement (David procedure). Post-procedure ECHO showed no AR with good LV function. Aspirin was started in the post -operative period with plan to continue for 3 months. After developing AF, he commenced on treatment dose low- molecular-weight heparin, amiodarone, and beta-blocker. His other medications included an angiotensin-converting enzyme inhibitor, statin, and omeprazole.Figure 3). Therefore, a CTCA was performed which was suggestive of distortion of the proximal RCA . Urgent invasive angiography showed proximal RCA stenosis which was treated with one DES with good angiographic results. Echocardiography at Day 5 showed basal to mid-infero-lateral akinesia with overall moderate LVSD. The right ventricle size was normal with mildly impaired systolic function. Recovery was complicated by lower respiratory tract infection and ongoing AF but he was discharged home 12 days later. At clinic review 2 months post-operatively, he was well with no symptoms of angina or syncope and with mild shortness of breath only on moderate exertion. At follow-up, there was moderate segmental LVSD (consistent with the target vessel infarction), whilst RV function was normal.His inpatient recovery was complicated by recurrent chest pain on mobilizing. Levels of high-sensitivity troponin remained elevated at levels higher than expected in the post-operative period ( high-sensitivity troponin T peak 489 ng/mL) raising clinical concern regarding ongoing ischaemia. ECG showed AF with an uncontrolled ventricular rate and new right bundle branch block  may be identified and corrected including possible refashioning of the coronary button. If this is not possible bypass may be an alternative, however, long-term outcome of a graft may be reduced given the potential for competitive flow through the coronary ostium which would vary through the cardiac cycle.PCI was felt to offer the best emergency salvage and the acute success of the procedure was supported by prompt improvement in haemodynamics with ST-segment resolution. In general, minimization of time to revascularization is the primary driver behind choice of revascularization in STE MI with cardiac bypass surgery being considered when the patient is not suitable for PCI.Cardiogenic shock in these cases may result from the target vessel myocardial infarction with contribution from potential suboptimal myocardial protection which is of vital importance in lengthy aortic root reconstructions (e.g. the lengthy David procedure).Of note, Patient 1 was not on antiplatelet or anticoagulation at time of discharge postoperatively having refused medications. Patient 2 was started on Aspirin post -operatively with a plan to continue for 3 months. Often post -operative patients would be treated with either antiplatelet or anticoagulation for 3 months to reduce the risk of thromboembolic complication and this may have contributed to the acute presentation of Patient 1 .Alongside early revascularization, both patients were treated with IV fluid to expand plasma volumes and treat RV infarction. In patients with RV infarction, hypotension and absence of pulmonary oedema should be treated with plasma expansion, ideally with invasive monitoring. Both these patients also had a degree of LV impairment which can make resuscitation more challenging as RV dilatation can increase diastolic LV pressures and contribute to low output state.These cases demonstrate the potential efficacy of PCI in management of both emergency STEMI and a high-risk non-STEMI. Prompt diagnosis and early multidisciplinary team discussion including with the operating surgeon allowed the patients to receive early and successful revascularization with PCI. Good communication was key to each of these decisions specifically collaboration between the surgical and cardiology teams.Acute myocardial infarction is an uncommon but important complication following aortic root replacement with coronary reimplantation. Extrinsic compression or distortion of the replanted coronary neo-ostium may result in vessel occlusion. Urgent PCI may facilitate emergency revascularization in these patients.Dr Carly Adamson graduated with MBChB from the University of Dundee in 2013. She has developed a keen interest in pursuing a career in cardiology during general medical training and is currently working as a Cardiology Clinical Fellow.European Heart Journal - Case Reports online.This study received grant funding from the British Heart Foundation (RE/13/5/30177).Slide sets: A fully edited slide set detailing this case and suitable for local presentation is available online as Consent: The author/s confirm that written consent for submission and publication of this case report including image(s) and associated text has been obtained from the patient in line with COPE guidance. Conflict of interest: none declared.ytz181_Supplementary_Slide_SetClick here for additional data file.


The HOPE Project is an ongoing RCT testing whether Senior Corps volunteering for lonely older adults (age 60+) leads to reduced loneliness and improved quality of life—outcomes associated with suicide in later life. We have randomly assigned 130 participants to 12-months of volunteering or active control. We will describe the trial as well as baseline characteristics of participants that may predict non-compliance with volunteering/control. We found no difference between conditions nor demographic characteristics  on non-compliance. Participants demonstrated wide variability in depression at baseline (PROMIS t-score range 38.9 to 71.4) and 18% reported suicide ideation; neither were associated with compliance (p>.20). These preliminary findings indicate that those with more severe mental health symptoms were equally willing/able to engage in volunteering as those without depression and suicide ideation. Volunteering is a highly scalable intervention (given nationwide Senior Corps infrastructure) that may function as upstream suicide prevention.


Modern laser surgery uses Nd:YAG laser capsulotomy for posterior capsule opacification (PCO) and Nd:YAG laser vitreolysis for symptomatic vitreous floaters (VF). We report a case of acute retinal detachment seven days after Nd:YAG laser capsulotomy combined with Nd:YAG laser vitreolysis and analyze the cause of this complication.A 58-year-old myopic woman complained of decreased visual acuity and symptomatic floaters with her left eye for 3 months. We found she had significant PCO and VF in the posterior vitreous. She underwent neodymium-doped yttrium aluminum (Nd:YAG) laser vitreolysis immediately after Nd:YAG capsulotomy. After 7 days, she complained of rapid vision decline and dark shadows in her treated eye. We found she had a acute severe rhegmentogenous retinal detachment (RD) involving the macula. Then she underwent vitrectomy, retinal reattchment and silicone oil tamponade surgery immediately. Six months later, silicone oil was removed and the best corrected visual acuity (BCVA) of her left eye gradually improved to 10/20 and maintained during a 1-year follow-up period.As myopic patients are at risk of developing retinal detachment, Nd:YAG vitreolysis and capsulotomy should be performed with caution. The laser energy should be as low as possible and careful focus is necessary to reduce interference to the retina. Symptomatic floater is the common disease of the ophthalmological clinics. Because it may interfere with the patients’ quality of vision, many patients are eager to remove their floaters. Webb  reportedA 58-year-old myopic woman visited our clinic, complaining of blurred vision and symptomatic floaters in her left eye for 3 months. Ophthalmologic examination revealed significant Elsching pearl like PCO in her left eye and VF like a thick string in the posterior segment of the vitreous cavityFig. a. The BCIn this case, the patient was treated with Nd:YAG laser capsulotomy and vireolysis therapy for PCO and VF in one procedure. Powell et al.  reported


Sleep studies examine how pain is associated with poor sleep. However, emergent research suggests poor sleep increases pain and may interfere with activities of daily living (ADL) among older adults. This study will examine how poor sleep may affect next-day pain interference and how this relationship may vary by cognitive function. Ten community-dwelling older adults with lower extremity chronic pain wore an Actigraph GT9X Link for 7 days to measure poor sleep and next-day pain interference . Multi-level mixed models accounted for intra-individual changes in sleep and pain interference and controlled for age, mild cognitive impairment (MCI) and depressive symptoms. Poor sleep among older adults with MCI  was also explored. Across 79 observations, increased number of awakenings  and movement index scores  were associated with increased next-day pain interference. In exploratory analyses, MCI intensified relationships between sleep efficiency , increased awakenings after sleep onset  and increased length of sleep awakenings  on next-day pain interference. This study’s findings suggest poor sleep is associated with next-day pain interference and the ability to perform ADL. Older adults with MCI may be at an increased risk for poor sleep and pain-related interference in ADL. Interventions designed to moderate the association between poor sleep and pain in general and for adults with MCI in particular may be warranted.


Platelet satellitism is a rare in vitro phenomenon that occurs when an immunoglobulinG antibody directed against the glycoprotein IIb/IIIa complex on the platelet membrane forms in ethylenediaminetetraacetic acid-treated peripheral blood at room temperature ,2. As thThe images presented here were obtained from a 5-year-old child with an upper respiratory tract infection accompanying asthma. Thrombocytopenia was not detected in complete blood count .


Combined hepatocellular-cholangiocarcinoma (CHC) is a primary hepatic malignancy with heterogeneously combined histological features of putative hepatic progenitor cells (HPC) origin. We describe a mouse model that exhibits the heterogenous histological and phenotypic finding similar to human CHC.−/− C57BL/6 mice into syngeneic wild-type pre-conditioned C57BL/6 mice. We confirmed that p53−/− murine hepatoblasts act as tumor-initiating cells (TICs) that generate CHC both in situ and within metastases. For comparative pathological study, 8 human cases of CHC with stem cell features were recruited by immunohistochemistry and multicolor fluorescence immunostaining.We injected hepatoblasts isolated from p53We identified corresponding areas in murine tumors matching each WHO criteria-described subtype of human CHC. In both murine and human tumors, HPC-like cells in tumor nests and associated stem cell features/traits are suggested histologically to be the progenitor origin of the cancerThe pathological characteristics of murine tumors recapitulate human CHC with stem cell features. These data provide additional comparative pathological evidence that CHC with stem cell features originate from HPCs and validate a model to study this cancer type in vivo. Combined hepatocellular-cholangiocarcinoma (CHC) represents fewer than 3% of human primary liver malignancies. CHC manifests combined histological features of both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) . AlthougAlthough the debate whether hepatocellular carcinoma (HCC) arises from stem cells that undergo malignant transformation or alternatively from de-differentiated, transformed mature hepatocytes continues , most evDuring the last 2 decades, there has been active research on tumorigenic role of liver parenchymal cells in experimental animals. A milestone study demonstrated that HPCs, hepatoblasts, and mature hepatocytes all can be transformed in vivo , suggestA minority of these studies have observed tumors with the marked heterogeneity typical of CHC –17. One −/− C57BL/6 fetal hepatoblasts) trans-splenically into livers of inflammatory pre-conditioned syngeneic C57BL/6 mice ..6]. Chol+ tumor cells in murine tumors. Furthermore, the few AFP+ tumor cells are always found to be negative for EpCAM staining confirmed by double immunofluorescence  with hepatocyte regeneration . Specifically, every described subtype of human CHCs matched with corresponding areas in murine tumors. In both murine and human tumors, small, hyperchromatic, ‘oval-like’ cells in peripherally located tumor nests with stem-like features are suggested histologically to be the progenitor origin of the cancer, since the nests of cells appear to be at the head of a progressive maturation process from the undifferentiated small cells at the periphery to the mature cells at the center [Accumulating evidence from human tissues support the HPC origin of CHC, by identifying HPC-associated traits in tumor architecture; however, the observational nature of the pathological studies precludes drawing hard conclusions regarding cell origin of CHC since histological and biomarker profiles do not necessarily predict the cell of origin . Most exe center . These ae center –31.Genetic lineage tracing mediated by Cre recombinase has opened up the door for scientists to explore the cellular events in hepatocarcinogenesis. Numerous mouse models of hepatocarcinogenesis have demonstrated mature hepatocytes primarily generate HCC through malignant transformation under selective pressure induced by chronic inflammatory milieu , 32, 33.4, potentially limiting the genesis of CAFs in our model. It is also possible that the inflammatory milieu created by CCl4 administration cannot fully mimic human chronic liver disease, since liver tumor phenotype has been suggested defined by nature of chronic liver inflammation. Broad desmoplastic stroma found in our margin area of subcutaneous metastasis may support the idea. However, detailed mechanism will be interesting and should be investigated in the future.It is noteworthy that formation of fibrous stroma within murine orthotopic tumor was modest in our model. In human CC, the presence of a dense desmoplastic stroma is a prominent phenotype . The strThe pathological characteristics of murine hepatoblast-derived tumors recapitulate human CHC with stem cell features. The current study provides additional comparative pathological evidence that CHC with stem cell features originate from a progenitor cell. It is not surprising that causal relationship still cannot be demonstrated unless a convincing endogenous biomarker is innovated for in vivo tracking of HPC. Further study into the mechanisms by which HPC participate hepatocarcinogenesis, including epigenetic or somatic changes of tumor initiating cells during malignant transformation and interactions between microenvironment and tumor-initiating cells, will clarify the causal relationship between HPC and hepatocarcinogenesis.Additional file 1: Supporting Tables. List of antibodies and primers.Additional file 2. Supporting materials and methods.


Vestibular symptoms such as vertigo and imbalance are known to occur in some cochlear implant patients during the immediate postoperative period; however, acute vertigo in implanted children occurring remotely from the postoperative period has not been previously well-described.A three-year-old girl with a history of bilateral sequential cochlear implantation presented with acute labyrinthitis associated with sudden onset of vertigo, balance impairment, and decline in right cochlear implant function 2 years after her most recent implant surgery. We describe her audiological and vestibular testing results during both the acute phase and following medical management and recovery.Acute labyrinthitis should be considered when sudden onset vertigo and/or imbalance presents in children with cochlear implants outside of the perioperative period. Such symptoms should prompt early assessment of cochlear implant function, so that the device can be reprogrammed accordingly. Vestibular loss is common in children with sensorineural hearing loss and with cochlear implants (CI) . FurtherA three-year-old girl with bilateral profound congenital sensorineural hearing loss of unknown etiology underwent right cochlear implantation (CI) at 12 months old and left cochlear implantation at 16 months old. Both implant surgeries were uneventful. Preoperative magnetic resonance imaging showed unremarkable cochlear and vestibular anatomy. Preoperative cervical vestibular evoked myogenic potential (VEMP) testing was normal.Two years post-implantation, the patient experienced the sudden onset of room-spinning vertigo and imbalance, accompanied by a parent-reported change in hearing performance. Cochlear implant programming 4 days after symptom onset demonstrated an increase in right-sided impedances, resulting in non-compliance across 4/22 channels Fig. . Device All symptoms resolved entirely by 10 days post-onset. At 29 days post-onset, cochlear implant programming demonstrated that right impedance and stimulation levels returned to baseline. Audiological testing indicated baseline right CI soundfield puretone thresholds and word recognition scores. There were no residual balance deficits on clinical examination 4 weeks after symptom onset. Vestibular retesting 1 year later showed a recovery of peripheral vestibular function, except for continued absence of ocular VEMP responses.Acute labyrinthitis in the setting of a cochlear implant has been described in a limited number of cases in adults, but this is the first pediatric case reported to our knowledge. Itayem and colleagues were the first to describe the clinical and electrophysiological constellation in adults, which they refer to as “cochlear implant associated labyrinthitis.”  They repEndocochlear inflammation has been implicated in other cases of suspected soft device failure. Benatti et al. reported a case of gradual performance decline plus acute onset facial nerve paralysis in an eight-year-old CI recipient, ultimately necessitating explantation . HistoloThis case highlights the utility of preoperative vestibular testing in the pediatric CI population, in which vestibular and balance impairment is common , 3, 7. TLabyrinthitis should be considered when acute onset vertigo occurs in children with cochlear implants remote from the perioperative period. Early device reprogramming and administration of systemic corticosteroids are interventions that may help to expedite recovery. Further research is needed to expand our knowledge of this presentation with regard to etiology and optimal management.


A 74-year-old diabetic woman presented to the Emergency Department with a high fever and prostration. She had been recently admitted three times for acute urinary retention resulting from an infection with negative urine culture. Laboratory tests at admission showed high C-reactive protein level (16.7 mg/dL), impaired renal function (Cr 2.42 mg/dL), and pus cells (>70/ high-power field). A kidney ultrasound  revealedCandida glabrata. The patient was administered intravenous caspofungin and referred for bilateral nephrostomies with amphotericin instillations. Systemic amphotericin B was to be avoided to prevent further deterioration of her renal function. While under medical treatment, the patient refused surgical treatment and died. The blood cultures were negative and the urine culture yielded fluconazole-resistant Upper urinary tract fungal infections are uncommon and fungal bezoar formation is particularly rareAwareness of the various radiological findings of this rare clinical entity and an increased suspicion in high-risk individuals will help to overcome the challenges related to early diagnosis and proper treatment


As cancer management evolves into precision medicine national/international cancer meetings bring novel therapeutic approaches and potentially practice-changing results of clinical studies are presented. This year, the ASCO GI Symposium 2020 had also several updates from ongoing and finalized clinical trials. Although there were no groundbreaking results that impact the daily practice directly, several highly important data from ongoing studies were shared with the audience. In this report, the highlights of the ASCO GI Symposium 2020 are presented with a future perspective. The management of gastrointestinal cancers has substantially evolved into personalized medicine in the last decade, due to a better understanding of molecular underpinnings of each and unique gastrointestinal cancer . While tThe first day of the ASCO GI 2020 Symposium had mostly presentations and discussions on upper gastrointestinal (GI) cancers. The FLOT4 trial . At thisHER2 amplification (KEYNOTE 811) . OThe targetability of the pancreatic cancer microenvironment has been investigated in multiple studies. Multiple agents that targeting dense stroma at multiple levels have failed to demonstrate any clinical activity including sonic hedgehog inhibitors and stroma modifying agents . One theBRCA1/2 and PALB2 mutations), which makes it an alternative to FOLFIRINOX in this subset of patients [The progress in homologous recombination deficient pancreatic cancer continues to evolve. The addition of veliparib to cisplatin and gemcitabine did not result in improvement in PFS or OS. However, cisplatin and gemcitabine combination arm achieved an objective response rate of 65.2% among pancreatic cancer patients with homologous recombination deficient (patients .IDH 1/2 mutations are currently actionable mutations with US FDA-approved drugs and are highly detected in biliary tract cancers with most notably among intrahepatic cholangiocarcinoma (approximately 17% of patients) among all biliary cancers [IDH mutations [HER2 amplification, BRAF V600 mutations and HRD pathway [The efficacy of immune checkpoint inhibitors in hepatocellular carcinoma (HCC) continues to evolve with different combinations. Recently, the IMPOWER 150 trial changed the standard of care of advanced-stage hepatocellular carcinoma to the combination of atezolizumab and bevacizumab as a first-line treatment . The com cancers . Current pathway , which wBRAF V600 mutations and specific types of MMR genes as a predictor of worse 12- and 24-month PFS rates [BRAF V600 mutations in MMR-D colorectal cancer patients who are treated with immune checkpoint inhibitors. This novel finding may trigger novel therapeutic approaches for BRAF-mutant MMR-D colorectal cancer patients.The efficacy of immune checkpoint inhibitors in mismatch repair deficient (MMR-D) colorectal cancer has been well established as a subsequent line of therapy. Currently, clinical trials investigating these agents in the first-line setting with promising clinical outcomes . Most ofFS rates . Future BRAF V600 mutations are now among targetable genomic alterations in metastatic colorectal cancer patients. The combination of BRAF ± MEK inhibitors with anti-EGFR monoclonal antibodies has achieved promising responses in this highly aggressive subset of colorectal cancer patients leading to improvement in survival and quality of life outcomes [BRAF box is now open and outcomes . Locoregoutcomes . Proceedoutcomes . On the outcomes  suggestioutcomes . These aAnother growing scientific discussion in cancer research embraces the type of biopsy utilized for molecular profiling. Currently, the gold standard of molecular profiling is tissue biopsy. However, at the time of disease progression, performing liquid biopsy-based circulating tumor DNA analysis may provide further information perhaps particularly on disease heterogeneity, as well as novel mutations evolved through the progression of disease that may be actionable. Circulating tumor DNA can be also considered where tissue biopsy is not available or accessible in current clinical practice. Liquid biopsies are often being used in clinical trial protocols where specific molecular alterations are tested during the initial evaluation of patients for biomarker-driven trials. More research is indicated in that field to better characterize the use of liquid-based molecular profiling perhaps, more importantly, their sensitivity to specific molecular alterations such as HER2 amplification and microsatellite instability status.Collectively, the advances in the management of gastrointestinal cancers are highly promising for the future. The cancer management is evolving into personalized medicine than ever before as we better understand disease heterogeneity led by distinct molecular alterations for individual tumor type. Although this progress may bring some challenges such as financial toxicity and requirement more collaborative work to identify patients with specific molecular alterations to successfully conduct biomarker-driven clinical trials, precision medicine provides significant hope for cancer patients for improved quality and length of life.