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diagnosis - Top 30 Publications

A Policy Analysis on the Proactive Prevention of Chronic Disease: Learnings from the Initial Implementation of Integrated Measurement for Early Detection (MIDO).

Mexico, like many low- and middle-income countries (LMICs), faces an epidemic of chronic non-communicable diseases (NCDs), specifically diabetes, hypertension, obesity, and lipid disorders. Many people with these NCDs may not be aware that they have a disease, pointing to the need for broader screening programs. The traditional prevention policy in Mexico was based on screening with a paper-based risk factor questionnaire. However, this was used to screen patients already seeking healthcare services at facilities, and screening goals were set as a function of the number of questionnaires applied, not number of individuals screened. Due to this, Fundación Carlos Slim developed Medición Integrada para la Detección Oportuna (MIDOTM), or Integrated Measurement for Early Detection, an NCD screening and proactive prevention policy. This document is a policy analysis based on early learnings from the initial implementation of MIDO in eight primary healthcare centers in two central Mexican states. MIDO was found to expand screening programs beyond clinic walls, systematize community screening strategies, emphasize the detection of pre-disease phases, incorporate lifestyle counseling, and propose screening goals based on population targets. In collaboration with the Mexican Ministry of Health, MIDO has successfully screened over 500 000 individuals-about 40% of whom would not have been screened under previous policies. Of these more than 500 000 screened individuals, 13.4% had pre-diabetes (fasting glucose between 100 and 125 mg/dL), and 5.8% had undiagnosed diabetes (defined as fasting glucose above 126 mg/dL or random glucose above 200 mg/dL). However, there is still room for improvement in linking positive results from screening with disease confirmation and with patient incorporation into disease management. The experience of implementing MIDO in Mexico suggests that primary and secondary prevention programs in other parts of the world should consider the need for population-based screening targets, a greater focus on pre-disease stages, and the streamlining of the transition between screening, confirmation of diagnosis, and incorporation of patients into the healthcare system.

A facile synthesis of CuFe2O4/Cu9S8/PPy ternary nanotubes as peroxidase mimics for the sensitive colorimetric detection of H2O2 and dopamine.

Synergistic effects play an important role in improving the catalytic activity for enzyme-like reactions. Compared to individual nanomaterials, a system consisting of multiple components usually exhibits enhanced catalytic activity as an enzyme mimic. Herein we describe the synthesis of CuFe2O4/Cu9S8/polypyrrole (PPy) ternary nanotubes as an efficient peroxidase mimic via a three-step approach involving an electrospinning process, annealing treatment and hydrothermal reaction. The remarkably enhanced catalytic activity of CuFe2O4/Cu9S8/PPy ternary nanotubes as peroxidase mimics over individual CuFe2O4 nanofibers, CuFe2O4/CuO composite nanofibers, CuFe2O4/CuS composite nanofibers, and PPy materials has been achieved, demonstrating the presence of a synergistic effect among the components. The steady-state kinetic experiment suggests a good catalytic efficiency of the CuFe2O4/Cu9S8/PPy ternary nanotubes. On the basis of high catalytic activity, a colorimetric platform for the sensitive detection of H2O2 and dopamine has been developed. This work not only offers a simple approach for the fabrication of a high performance peroxidase-like nanocatalyst, but also provides its promising potential applications in biosensors, medical diagnosis, and environmental monitoring.

Autosomal recessive cone-rod dystrophy can be caused by mutations in the ATF6 gene.

Inherited retinal dystrophies (IRDs) are clinically and genetically highly heterogeneous, making clinical diagnosis difficult. The advances in high-throughput sequencing (ie, panel, exome and genome sequencing) have proven highly effective on defining the molecular basis of these disorders by identifying the underlying variants in the respective gene. Here we report two siblings affected by an IRD phenotype and a novel homozygous c.1691A>G (p.(Asp564Gly)) ATF6 (activating transcription factor 6A) missense substitution identified by whole exome sequencing analysis. The pathogenicity of the variant was confirmed by functional analyses done on patients' fibroblasts and on recombinant p.(Asp564Gly) protein. The ATF6(Asp564Gly/Asp564Gly) variant shows impaired production of the ATF6 cleaved transcriptional activator domain in response to endoplasmic reticulum stress. Detailed phenotypic examination revealed extinguished cone responses but also decreased rod responses together with the ability to discriminate some colours suggestive rather for cone-rod dystrophy than achromatopsia.European Journal of Human Genetics advance online publication, 16 August 2017; doi:10.1038/ejhg.2017.131.

Throw caution to the wind: is refeeding syndrome really a cause of death in acute care?

Refeeding syndrome (RFS), a life-threatening medical condition, is commonly associated with acute or chronic starvation. While the prevalence of patients at risk of RFS in hospital reportedly ranges from 0 to 80%, the prevalence and types of patients who die as a result of RFS is unknown. We aimed to measure the prevalence rate and examine the case histories of patients who passed away with RFS listed as a cause of death.

Leveraging network analytics to infer patient syndrome and identify causal genes in rare disease cases.

Next-generation sequencing is widely used to identify disease-causing variants in patients with rare genetic disorders. Identifying those variants from whole-genome or exome data can be both scientifically challenging and time consuming. A significant amount of time is spent on variant annotation, and interpretation. Fully or partly automated solutions are therefore needed to streamline and scale this process.

Immunoreactivity of Canine Liposarcoma to Muscle and Brown Adipose Antigens.

Liposarcoma, rhabdomyosarcoma, and hibernoma share some overlapping histologic and immunohistochemical features. Although immunohistochemistry (IHC) is commonly used in the diagnosis of these neoplasms, expression of muscle markers has been reported in human liposarcoma and canine hibernoma in addition to rhabdomyosarcoma. Thus, these neoplasms are a diagnostic challenge but important to distinguish because of differences in prognosis and treatment. Rhabdomyosarcoma and liposarcoma are both malignant, but rhabdomyosarcoma has a higher potential for metastasis. In contrast, hibernomas are benign with low risk of recurrence. This study investigated expression of the muscle markers desmin, myogenin, and α-smooth muscle actin (α-SMA) and the brown fat marker uncoupling protein 1 (UCP1) in 25 cases of canine liposarcoma using IHC. Oil red O histochemistry was performed to confirm the presence of lipid and the diagnosis of liposarcoma in cases that were not well-differentiated. The 25 cases included 15 well-differentiated, 5 pleomorphic, 3 myxoid, and 2 dedifferentiated subtypes of liposarcoma. By IHC, 23 of 25 expressed UCP1, 7 of 25 expressed α-SMA, 7 of 25 expressed desmin, and 3 of 25 expressed myogenin with no clear relationship of antigen expression and tumor subtype. These findings clarify the immunohistochemical profile of canine liposarcoma and suggest overlap in the expression of several muscle antigens and UCP1 between liposarcoma, hibernoma, and rhabdomyosarcoma.

Prolactinoma in a Dog.

A 12-year-old male Yorkshire Terrier was presented because of decreased appetite. Physical examination revealed mammary gland swelling and galactorrhea. Contrast-enhanced computed tomographic scanning of the skull indicated an enlarged pituitary gland, compatible with a pituitary tumor. The serum prolactin concentration was markedly elevated. One week after the start of treatment with the dopamine agonist cabergoline, the serum prolactin concentration normalized and the galactorrhea resolved. Cabergoline was administered for approximately 4 months and then discontinued. Subsequently, serum prolactin concentration increased again, and mammary gland swelling and galactorrhea reappeared. The dog was euthanized 10 months after the first detection of the galactorrhea because of problems not directly related to pituitary disease. Postmortem examination revealed an infiltrative adenoma of the pituitary gland with immunolabeling for prolactin. The clinical and histopathologic findings indicated the diagnosis of a functional prolactinoma in a male dog.

Acute Leukemia in Horses.

Leukemia is broadly divided into acute and chronic lymphocytic and myeloid types based on the proportion of blasts, morphology of cells, and expression of specific antigens on neoplastic cells. Classifying leukemia in horses can be challenging if blasts predominate and since few antibodies to identify cell types are available. The objective of this study was to describe in detail the clinical and pathologic features of acute leukemia in horses. Twelve horses ranging from 0.2 to 25.9 years of age were diagnosed with acute leukemia. Six cases were classified as acute lymphocytic leukemia (ALL) based on predominance of blasts, lack of granulocytic or monocytic differentiation, and detection of CD3, CD20, and/or CD79a antigens by immunohistochemistry. Six other cases were classified as acute myeloid leukemia (AML) with myelomonocytic ( n = 4), basophilic ( n = 1), and eosinophilic ( n = 1) differentiation based on > 20% bone marrow blasts and partial leukocytic differentiation. Reactivity with antibodies to Iba-1/AIF-1, CD172a, and CD163 was determined for all cases of AML. Eleven horses had thrombocytopenia, 10 had neutropenia, 8 had anemia, all had blasts on blood films, and none had leukocytosis. Ten horses had increased serum acute phase proteins. Bone marrow cellularity ranged from 30% to 100%, and the proportion of blasts ranged from 80% to 100% and 30% to 60% in ALL and AML, respectively. Horses were severely ill at diagnosis and euthanized within days or weeks. Unique features of acute leukemia in horses compared to other species were variable lymphocyte antigen expression (ALL) and frequent inflammation (ALL and AML).

Cytokine Concentrations Measured by Multiplex Assays in Canine Peripheral Blood Samples.

Cytokines are known to play important roles in a wide range of pathologic conditions spanning all organ systems in every species studied. As our knowledge of the physiology of individual cytokines expands and our ability to measure multiple cytokines in smaller biological samples increases, we gain more insight into the significance and function of each cytokine and the importance of cytokine networks. Previous studies that reported measurements of cytokine concentrations from serum or plasma in dogs with infectious, autoimmune, metabolic, endocrine, and neoplastic diseases yield an appreciation for the complexity of cytokine control and potential applications for cytokine measurements in the diagnosis, prognosis, and therapy of a variety of disease conditions. In this review, we highlight the benefits of multiplex cytokine analysis, summarize clinical and experimental reports that have used this technology in dogs, and discuss the strengths and limitations of data analysis for the interpretation of results in these studies. We describe how differences in technical acuity, data reporting tactics, statistical analysis, study population selection criteria, and cross-sectional experimental design methods may affect interpretation of results from this technology. We also suggest methods for analysis in future studies, such as reporting median fluorescence intensity values, analyzing the proportion of patients above population medians, and performing longitudinal studies.

Parvovirus Infection Is Associated With Myocarditis and Myocardial Fibrosis in Young Dogs.

Perinatal parvoviral infection causes necrotizing myocarditis in puppies, which results in acute high mortality or progressive cardiac injury. While widespread vaccination has dramatically curtailed the epidemic of canine parvoviral myocarditis, we hypothesized that canine parvovirus 2 (CPV-2) myocardial infection is an underrecognized cause of myocarditis, cardiac damage, and/or repair by fibrosis in young dogs. In this retrospective study, DNA was extracted from formalin-fixed, paraffin-embedded tissues from 40 cases and 41 control dogs under 2 years of age from 2007 to 2015. Cases had a diagnosis of myocardial necrosis, inflammation, or fibrosis, while age-matched controls lacked myocardial lesions. Conventional polymerase chain reaction (PCR) and sequencing targeting the VP1 to VP2 region detected CPV-2 in 12 of 40 cases (30%; 95% confidence interval [CI], 18%-45%) and 2 of 41 controls (5%; 95% CI, 0.1%-16%). Detection of CPV-2 DNA in the myocardium was significantly associated with myocardial lesions ( P = .003). Reverse transcription quantitative PCR amplifying VP2 identified viral messenger RNA in 12 of 12 PCR-positive cases and 2 of 2 controls. PCR results were confirmed by in situ hybridization, which identified parvoviral DNA in cardiomyocytes and occasionally macrophages of juvenile and young adult dogs (median age 61 days). Myocardial CPV-2 was identified in juveniles with minimal myocarditis and CPV-2 enteritis, which may indicate a longer window of cardiac susceptibility to myocarditis than previously reported. CPV-2 was also detected in dogs with severe myocardial fibrosis with in situ hybridization signal localized to cardiomyocytes, suggesting prior myocardial damage by CPV-2. Despite the frequency of vaccination, these findings suggest that CPV-2 remains an important cause of myocardial damage in dogs.

The First Reported Case of Meckel-Gruber Syndrome Associated With Abnormal Karyotype Mosaic Trisomy 17.

Meckel-Gruber syndrome (MKS) is a rare lethal autosomal recessive disorder with typical anomalies including encephalocele, multicystic renal dysplasia, congenital liver fibrosis, and polydactyly. MKS is caused by mutations of genes localized on different chromosomes. Karyotypes of published Meckel-Gruber syndrome cases are without any aberrations. We present a male fetus with meningoencephalocele, multicystic renal dysplasia, congenital liver fibrosis, and other anomalies. Standard cytogenetic examination of cultured fetal skin and muscle fibroblasts showed mosaic trisomy 17. Homozygous deletion in CC2D2A gene was found by Sanger sequencing. This is to our knowledge the first case of genetically confirmed Meckel-Gruber syndrome with incidental cofinding of mosaic trisomy 17. Abnormal karyotype does not exclude diagnosis of MKS with risk of recurrence 25% in next pregnancy. In the case of anomalies typical for Meckel-Gruber syndrome, genetic analysis is indicated.

Vessel Perforation and False Tracking Resulting From Umbilical Artery Catheterization: A Case Report and Literature Review.

We report an extremely low-birth-weight neonate who developed umbilical artery perforation and false tracking. There was no life-threatening event relating to the complication. Diagnosis was made at postmortem examination. Little information exists regarding the anatomic and vascular effects of umbilical artery catheterization placement in newborns. We report a new complication of umbilical artery catheterization. We raise the awareness regarding the potential life threat due to this rare but very serious complication.

Melanotic Neuroectodermal Tumor of Infancy Presenting With Fast-Growing Scrotal Swelling: A Case Report and Literature Review.

Testicular melanotic neuroectodermal tumor of infancy (MNTI) is extremely rare, with 2 cases reported in the literature. Its rarity and rapid and infiltrative growth pattern pose a diagnostic challenge. A previously healthy 3-month-old male, presented with a history of worsening left hemiscrotal swelling for 1 week. An outside ultrasound was suggestive of testicular torsion. Left orchiectomy demonstrated a mass occupying almost entire testicle with a variegated cut surface, with areas of pigmentation, necrosis, and hemorrhage. Histological examination confirmed MNTI of the testis and epididymis. MNTI should be included in differential diagnosis in infants presenting with fast-growing scrotal swelling.

Novel COL1A1 Mutation c.3290G>T Associated With Severe Form of Osteogenesis Imperfecta in a Fetus.

Osteogenesis imperfecta is a genetically and clinically heterogenous group of skeletal dysplasias characterized by bone fragility. Its severity ranges from nearly asymptomatic individuals to perinatal lethality. The majority of cases are caused by mutations in either the COL1A1 or the COL1A2 gene coding for alpha 1 and alpha 2 chains of collagen type 1, respectively, and a large number of pathogenic variants of these genes has been identified. We describe a novel COL1A1 mutation associated with prenatally diagnosed severe form of osteogenesis imperfecta.

Soft Tissue Perineurioma in a Child With Neurofibromatosis Type 1: A Case Report and Review of the Literature.

Soft tissue perineurioma is a rare benign peripheral nerve sheath tumor, especially in children. This manuscript presents an unusual case of soft tissue perineurioma in a 10-year-old boy with neurofibromatosis type 1. The patient presented with a lump in the region of the right breast. A subcutaneous, well circumscribed mass was removed. The cut surface was cream with a vaguely nodular appearance. Histology showed a spindle cell lesion with variable architecture and biphasic morphology. There was no nuclear atypia or pleomorphism. The differential diagnosis and other soft tissue lesions that can be seen in neurofibromatosis type 1 are discussed.

ALOX15 Immunohistochemistry Aids in the Diagnosis of Eosinophilic Esophagitis on Pauci-eosinophilic Biopsies in Children.

Histologically, esophageal biopsies should have ≥15 intraepithelial eosinophils (IEEs) per high power field (HPF) to support a clinicopathologic diagnosis of eosinophilic esophagitis (EoE). Children with clinically apparent EoE may show pauci-eosinophilic biopsies due to patchy involvement. Immunostaining (Immunohistochemistry) for arachidonate-15 lipooxygenase (ALOX15) has been demonstrated to be a sensitive marker for EoE. We retrospectively assessed the expression of ALOX15 in 48 biopsies from 21 patients with established diagnosis of EoE and with tissue fragments below the threshold of 15 IEEs/HPF. Fragments were classified into pauci-eosinophilic and non-pauci-eosinophilic groups using cutoffs of 10 and 15 IEEs/HPF. Controls included patients with reflux and normal biopsies. Sixty-five (43.9%) fragments showed <10 IEEs/HPF and 83 (56.1%) showed ≥10 IEEs/HPF. Using a cutoff of 15 IEEs/HPF, 87 (58.7%) fragments showed <15 IEEs/HPF while 61 fragments (41.2%) had ≥15 IEEs/HPF. ALOX15 was positive in 53/65 (81.5%) of fragments with <10 IEEs/HPF versus 82/83 (98.8%) of fragments with ≥10 IEEs/HPF ( P < .001). For a cutoff of 15 IEEs/HPF, 75/87 (86.2%) of pauci-eosinophilic fragments were ALOX15-positive, while 60/61(98.4%) of biopsies meeting the threshold were positive ( P < .001). In 3/21 (14.3%) patients with EoE, all of the fragments (n = 7) were pauci-eosinophilic and all of them were positive for ALOX15. Two of 24 patients with reflux (one with 9 and one with 14 IEEs/HPF) were also positive. Fragments from normal controls (0 IEEs/HPF) were negative. Our results support the utility of ALOX15 immunohistochemistry in supporting the diagnosis of EoE in rare situations with strong clinical suspicion where no fragments reach 15 IEEs/HPF.

Congenital Cystic Lung Lesions: Evolution From In-utero Detection to Pathology Diagnosis-A Multidisciplinary Approach.

Congenital cystic lung lesions are a group of rare pathologies that are usually diagnosed in the prenatal period. The majority of these lesions are diagnosed at pathology examination as congenital pulmonary airway malformations (CPAM) and bronchopulmonary sequestration (BPS). These lesions are typically managed by surgical intervention within the first year of life and have an excellent prognosis. We examined the evolution of imaging appearances from prenatal diagnosis to postnatal work-up of these lesions and correlate imaging and pathological findings. An 8-year retrospective review of the perinatal and pathology database of a single tertiary care center identified 42 cases of congenital cystic lung lesions of which 36 had known prenatal ultrasound and prenatal course available. Final pathologic diagnoses were 15 CPAM (41%), 7 BPS (19%), and 9 hybrid BPS and CPAM lesions (25%). Five cases with bronchial atresia were also identified (either in isolation or associated with CPAM or BPS). The overall characteristics of these lesions by prenatal ultrasound, postnatal imaging, and ultimate histopathologic diagnosis are described.

Good outcome scores and high satisfaction rate after primary total ankle replacement.

Background and purpose - Total ankle replacement (TAR) is gaining popularity for treatment of end-stage ankle arthritis. Large patient-centered outcome studies are, however, few. Here, we report data from the Swedish Ankle Registry. Patients and methods - We examined outcomes after primary TAR in patients from the Swedish Ankle Registry using PROMs (Patient Reported Outcome Measures; generic: EQ-5D and SF-36, region specific: SEFAS (Self-Reported Foot and Ankle Score), and a question on satisfaction). We included 241 patients registered with primary TAR between 2008 and 2016 and who completed PROMs preoperatively and postoperatively up to 24 months. We evaluated changes in PROMs following surgery and estimated effects of age, diagnosis, prosthetic design, and preoperative functional score on the outcomes. Results - All absolute scores improved from preoperative to 24 months after surgery (p ≤ 0.001). 71% of the patients were satisfied or very satisfied at the latest follow-up and 12% dissatisfied or very dissatisfied. Postoperative SEFAS correlated with age (r = 0.2, p = 0.01) and preoperative SEFAS (r = 0.3, p < 0.001), as did patient satisfaction (r = -0.2; p ≤ 0.03). Postoperative SEFAS and EQ-5D were similar between different diagnoses or prosthetic designs. Preoperative SF-36 was associated with diagnosis (p ≤ 0.03), postoperative SF-36 with age (r = 0.2, p = 0.01) and diagnosis (p < 0.03). Interpretation - We found statistically and clinically significant improvements in patient-reported outcomes following TAR surgery. The postoperative region-specific SEFAS was positively associated with older age. Prosthetic design seemed not to influence patient-reported outcome, whereas diagnosis partly did. Studies with longer follow-up are necessary to establish the long-term outcome of TAR and to elucidate whether short- and mid-term outcomes may predict implant failure.

Current research on circular RNAs associated with colorectal cancer.

Representing a novel type of endogenous noncoding RNAs, circular RNAs (circRNAs) have recently gained much attention for their involvement in multiple biological processes. CircRNAs are ubiquitously expressed in eukaryotic cells and modulate gene expression by acting as sponges of microRNAs (miRNAs) or other proteins, such as RNA-binding proteins (RBPs). Due to their unique structure, circRNAs are more stable than linear RNAs. Expression profiles of circRNAs are associated with clinicopathological characteristics of colorectal cancer patients, such as differentiation, TNM classification and distant metastasis. Furthermore, circRNAs play crucial roles in multiple processes associated with malignant phenotypes, including cell proliferation/cycle, apoptosis and invasion. Improvements in RNA-sequencing methods have helped researchers to elucidate molecular interactions between circRNAs and colorectal cancer. This review provides a comprehensive overview of the features and functions of circRNAs, as well as insights into their roles in the onset and development of colorectal cancer. Combined with the reported results, the identification of circRNAs associated with colorectal cancer will certainly contribute to early detection and help to design treatment strategies for colorectal cancer. Screening for circRNAs may provide an accessible, noninvasive yet highly sensitive diagnosis for colorectal cancer. Furthermore, a better understanding of the roles of circRNAs may also provide a novel predictive feature in colorectal cancer therapy and prognosis.

Ultrasensitive and Accurate Assay of Human Methyltransferase Activity at the Single-Cell Level Based on A Single Integrated Magnetic Microprobe.

Human DNA methyltransferase (MTase) activity expression patterns and inhibition response are linked to related cancer initiation, progression and therapeutic responses. Sensitive and accurate human MTase activity assay in cancer cells, especially at the single-cell level, is essential for biological study, clinical diagnosis and therapy. Here, we developed an ultrasensitive and accurate DNA (cytosine-5)-methyltransferase 1 (Dnmt1) activity assay at the single-cell level based on a single integrated magnetic microprobe of functionalized double-stranded DNA (dsDNA) anchored to a single magnetic microbead surface. Functionalized dsDNA is designed with a hemimethylated DNA site for Dnmt1 recognition and a single-stranded tail to trigger in situ rolling circle amplification (RCA). Under the action of Dnmt1, hemimethylated dsDNA could be recognized and catalyzed to fully methylated dsDNA, which would protect them from the cleavage of BssHII. But the dsDNA without full methylation would be cut by BssHII, making single-stranded tail separated from the single integrated microprobe. Subsequently, full methylation-protected in situ RCA could be performed and multiple signal probes were hybridized to the single integrated microprobe for amplified signal accumulation. Finally, Dnmt1 activity could be evaluated by reading the fluorescence of the single integrated microprobe. Meanwhile, to minimize matrix interferences, magnetic separation was performed in the process. In this strategy, the single integrated magnetic microprobe was provided with integrated capacities of target recognition, signal amplification, signal accumulation and matrix isolation. Therefore, an ultralow detection limit of 0.007 U/mL Dnmt1 was obtained and accurate Dnmt1 activity assays in multiple cell lysates at the single-cell level were achieved. Furthermore, the inhibition effect of RG108 was evaluated conveniently. These results indicate that the single integrated magnetic microprobe-based strategy is an excellent candidate for sensitive monitoring of Dnmt1 activity and screening of anticancer drugs.

AMBIGUITY IN A MASCULINE WORLD: Being a BRCA1/2 mutation carrier and a man with prostate cancer.

Increased risk of prostate cancer(PCa) is observed in men with BRCA1/BRCA2 mutations. Sex and gender are key determinants of health and disease although unequal care exists between the sexes. Stereotypical male attitudes are shown to lead to poor health outcomes.

Poorly differentiated chordoma with loss of SMARCB1/INI1 expression in pediatric patients: A report of two cases and review of the literature.

Identification of loss of SMARCB1/INI1 expression in poorly differentiated (PD) chordoma in pediatric patients suggests that PD chordoma is an entity molecularly distinct from conventional chordoma or atypical teratoid/rhabdoid tumor, which is also characterized by loss of SMARCB1/INI1 expression by inactivating mutation of the SMARCB1/INI gene. So far, around 20 cases of pediatric PD chordoma with loss of SMARCB1/INI1 expression have been reported. Here, we report two cases of pediatric PD chordoma with loss of SMARCB1/INI1 expression, which is very rare among the pediatric chordoma types. Both patients presented clival masses on preoperative MRI. Histologically, both tumors had nonclassic histologic features for conventional chordoma: sheets of large epithelioid to spindle cells with vesicular nuclei and prominent nucleoli. Both cases revealed nuclear expression of brachyury, loss of SMARCB1/INI1 expression and lack of embryonal, neuroectodermal, or epithelial component. One case showed heterozygous loss of EWSR1 gene by break-apart fluorescence in situ hybridization that reflected loss of SMARCB1/INI1 gene. Based on the clival location and histologic findings along with the loss of SMARCB1/INI1 expression and positivity for nuclear brachyury staining, the final pathologic diagnosis for both cases was PD chordoma.

Gliosarcoma arising from oligodendroglioma, IDH mutant and 1p/19q codeleted.

Herein, we present a rare case of gliosarcoma arising from oligodendroglioma, isocitrate dehydrogenase (IDH) mutant and 1p/19q codeleted. A 36-year-old man presented with a non-enhanced calcified abnormal lesion on the right frontal lobe. The patient underwent subtotal surgical resection, PAV chemotherapy (procarbazine, nimustine (ACNU) and vincristine), and fractionated radiotherapy with 50 Gy. The pathological diagnosis was oligodendroglioma, IDH mutant and 1p/19q codeleted, World Health Organization 2016 grade II. Six years later, a new enhanced lesion appeared, and the recurrent tumor was surgically removed. Although the histopathological findings indicated gliosarcoma, the recurrent tumor still demonstrated the IDH mutation and 1p/19q codeleted. Thus, the recurrent tumor was considered to originate from oligodendroglioma, rather than being newly generated after chemoradiotherapy. Interestingly, the second recurrent tumor responded well to temozolomide chemotherapy. Based on the findings of this case, oligodendrogliomas have the potential for mesenchymal transformation on progression, while keeping their genotype.

Circulating Tumor DNA as a Liquid Biopsy: Current Clinical Applications and Future Directions.

Tumor genomic sequencing has become part of routine oncology practice in many tumor types, in order to identify potentially targetable mutations and to personalize cancer care. Plasma genotyping via circulating tumor DNA analysis is a noninvasive and rapid alternative method of detecting and monitoring genomic alterations throughout the course of disease. Multiple assays have been developed to date, each with different test characteristics and degrees of clinical validation. Here we review the clinical data supporting these different plasma genotyping methodologies, and present a practical approach to the interpretation of the results of these tests. While the clinical application of plasma genotyping has been most extensively validated in the metastatic setting-for the detection of targetable alterations at the time of initial diagnosis or disease progression-this technology holds significant promise across many tumor types and stages of disease. We will also review emerging applications of plasma genotyping that are currently under clinical investigation.

Changing Treatment Paradigms for Brain Metastases From Melanoma-Part 1: Diagnosis, Prognosis, Symptom Control, and Local Treatment.

Melanoma is the third most common cause of brain metastases, after lung and breast cancer. The management of melanoma brain metastases can be broadly divided into symptom control and therapeutic strategies. Supportive treatments include corticosteroids to reduce peritumoral edema, antiepileptics for seizure control, and medications to preserve cognitive function. Until recently, therapeutic strategies consisted primarily of local treatments, including surgery, whole-brain radiation therapy (WBRT), and stereotactic radiosurgery (SRS). Surgery, WBRT, and SRS-alone and in various combinations-still play an important role in treatment, especially in patients with few and/or smaller brain lesions. Much work has been done recently to try to determine the optimal settings for these therapies, the most effective ways to combine them, and ideal radiation dose and fractions.

Long-term disability and progression in spinal onset multiple sclerosis.

The aim of this study is to investigate the long-term effects of the initial spinal cord (SC) involvement in MS patients. In this retrospective, single-center study, 824 patients with definite MS were screened. A total of 348 patients were excluded for ambiguous documentation of the initial relapse, pediatric onset, diagnosis of primary progressive disease, irregular assessments or visits causing doubt on the onset of progression time, and clinical follow-up duration less than 12 months. Eventually, 476 MS patients were included. Data regarding the demographics, initial symptoms, the degree of recovery from the initial relapse, neuroimaging, cerebrospinal fluid analysis, long-term disability, and progression were collected from the medical registry. The mean duration of follow-up was 7.49 ± 5.30 years. The percentage of patients entering the progressive disease course was 23.3 in the whole group. A total of 157 patients (33.0%) had SC involvement during the first clinical relapse. These patients were significantly older at disease onset (31.69 ± 10.18 vs. 29.55 ± 9.49; p = 0.028), had higher rates of progression (32.5 vs. 18.8%; p = 0.001), and had higher disability scores in long-term follow-up (3.41 ± 2.19 vs. 2.62 ± 1.81; p < 0.001). Mean age at the transition of progressive phase was 41.4 ± 11.2 years. The degree of recovery from the initial relapse significantly affected the long-term disability. The poor recovery from the initial relapse was associated with older onset age and higher EDSS scores. Being older than 40 years during MS onset and poor recovery from the initial relapse exerted an increased risk for progression. The initial SC involvement was related to a more severe relapse with less chance of complete recovery and higher risk for progression. Confirmation of risk factors in different MS cohorts would increase our understanding of the complex disease mechanisms.

Genetic Testing in Inherited Heart Diseases: Practical Considerations for Clinicians.

Genetic testing has become an important element in the care of patients with inherited cardiac conditions (ICCs). The purpose of this review is to provide clinicians with insights into the utility of genetic testing as well as challenges associated with interpreting results.

Multivariable Adaptive Artificial Pancreas System in Type 1 Diabetes.

The review summarizes the current state of the artificial pancreas (AP) systems and introduces various new modules that should be included in future AP systems.

Diagnosis of inguinal hernia by prone- vs. supine-position computed tomography.

The aim of this study was to investigate the efficacy of prone-position computed tomography (CT) for detecting and classifying inguinal hernia relative to supine-position CT before laparoscopic inguinal hernia repair.

Laparoscopic colectomy reduces complications and hospital length of stay in colon cancer patients with liver disease and ascites.

Ascites increases perioperative complications and risk of death, but is not an absolute contraindication for colectomy in patients with colon cancer. It remains unclear whether postoperative risks can be minimized using a laparoscopic versus open approach.