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OBJECTIVE: Serial measurements of anti-double-stranded DNA (anti-dsDNA) and complement are routine in the management of systemic lupus erythematosus (SLE), but their utility as biomarkers in preemptive treatment to prevent flares remains a subject of controversy. We hypothesized that concomitant elevation of anti-dsDNA and C3a can predict SLE activity in patients with stable or inactive disease and that short-term treatment with corticosteroids can avert flares. METHODS: In this prospective, randomized, double-blind, placebo-controlled trial, 154 patients were evaluated monthly for up to 18 months, with measurements of C3a, C3, C4, CH50, and anti-dsDNA levels. Patients who remained clinically stable but showed serologic evidence of an SLE flare (elevation of both the anti-dsDNA level by 25% and the C3a level by 50% over the previous 1-2 monthly visits) were randomized to receive either prednisone or placebo therapy at a dosage of 30 mg/day for 2 weeks, 20 mg/day for 1 week, and 10 mg/day for 1 week. RESULTS: Forty-one patients (21 randomized to prednisone and 20 randomized to placebo) experienced a serologic flare. Analysis of severe flares occurring 40 mg/day and/or the addition of an immunosuppressive agent. Furthermore, improvement in scores on the Systemic Lupus Erythematosus Disease Activity Index, decreased levels of anti-dsDNA antibodies, and increased levels of C4 occurred 1 month after initiation of prednisone treatment. CONCLUSION: These preliminary data support our hypothesis that in a subset of clinically stable SLE patients with a combination of elevated C3a and anti-dsDNA levels, short-term corticosteroid therapy may avert a severe flare. [ABSTRACT FROM AUTHOR]

Objective: Given fibromyalgia (FM) frequently co-occurs with autoimmune disease, this study was initiated to objectively evaluate FM in a multiracial/ethnic cohort of patients with systemic lupus erythematosus (SLE)., Methods: Patients with SLE were screened for FM using the 2016 FM classification criteria during an in-person rheumatologist visit. We evaluated hybrid Safety of Estrogens in Lupus National Assessment (SELENA)-SLE Disease Activity Index (SLEDAI) scores, SLE classification criteria, and Systemic Lupus International Collaborating Clinics damage index. We compared patients with and without FM and if differences were present, compared patients with FM with patients with non-FM related chronic pain., Results: 316 patients with SLE completed the FM questionnaire. 55 (17.4%) met criteria for FM. The racial composition of patients with FM differed from those without FM (P = 0.023), driven by fewer Asian patients having FM. There was no difference in SLE disease duration, SELENA-SLEDAI score, or active serologies. There was more active arthritis in the FM group (16.4%) versus the non-FM group (1.9%) (P < 0.001). The Widespread Pain Index and Symptom Severity Score did not correlate with degree of SLE activity (r = -0.016; 0.107) among patients with FM or non-FM chronic pain (r = 0.009; -0.024). Regarding criteria, patients with FM had less nephritis and more malar rash. Systemic Lupus International Collaborating Clinics damage index did not differ between groups., Conclusion: Except for arthritis, patients with SLE with FM are not otherwise clinically or serologically distinguishable from those without FM, and Widespread Pain Index and Symptom Severity Score indices do not correlate with SLEDAI. These observations support the importance of further understanding the underlying biology of FM in SLE., (© 2024 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Metastatic castration-resistant prostate cancer (mCRPC) is challenging to treat. Virus-like particles (VLPs), originating from JC polyomavirus (JCPyV) and carrying a suicide gene driven by the PSA promoter (PSAtk-VLPs), can inhibit tumor growth in animal models of human prostate cancer. However, the efficacy of suppression of orthotopic PCa growth and metastasis by PSAtk-VLPs remains undetermined. Here, we established an iRFP stable expression CRPC cell line suitable for deep-tissue observation using fluorescence molecular tomography (FMT). These cells were implanted into murine prostate tissue, and PSAtk-VLPs were systemically administered via the tail vein along with the prodrug ganciclovir (GCV), allowing for the real-time observation of orthotopic prostate tumor growth and CRPC tumor metastasis. Our findings demonstrated that systemic PSAtk-VLPs administration with GCV and subsequent FMT scanning facilitated real-time observation of the suppressed growth in mouse iRFP CRPC orthotopic tumors, which further revealed a notable metastasis rate reduction. Systemic PSAtk-VLPs and GCV administration effectively inhibited orthotopic prostate cancer growth and metastasis. These findings suggest the potential of JCPyV VLPs as a promising vector for mCRPC gene therapy. Conclusively, systemically administered JCPyV VLPs carrying a tissue-specific promoter, JCPyV VLPs can protect genes within the bloodstream to be specifically expressed in specific organs., (© 2023. The Author(s).)

(1) Background: PADI2 is a post-translational modification (PTM) enzyme that catalyzes citrullination, which then triggers autoimmune disease and cancer. This study aimed to evaluate the prognostic value of peptidylarginine deiminase 2 (PADI2) protein expression in biliary tract cancer (BTC) patients. (2) Methods: Using immunohistochemistry, the PADI2 protein expression in BTC tissues was analyzed. The correlations between PADI2 protein expression and clinicopathologic characteristics were analyzed using Chi-square tests. The Kaplan-Meier procedure was used for comparing survival distributions. We used Cox proportional hazards regression for univariate and multivariate analyses. From 2014 to 2020, 30 resected BTC patients were enrolled in this study. (3) Results: Patients with high PADI2 protein expression were associated with shorter progress-free survival (PFS; p = 0.041), disease-specific survival (DSS; p = 0.025), and overall survival (OS; p = 0.017) than patients with low PADI2 protein expression. (4) Conclusions: The results indicated that PADI2 protein expression was an independent poor prognostic factor for BTC patients regarding PFS, DSS, and OS.

Background: Anhedonia is hypothesized to be associated with blunted mesocorticolimbic dopamine (DA) functioning in samples with major depressive disorder. The purpose of this study was to examine linkages between striatal DA, reward circuitry functioning, anhedonia, and, in an exploratory fashion, self-reported stress, in a transdiagnostic anhedonic sample., Methods: Participants with (n = 25) and without (n = 12) clinically impairing anhedonia completed a reward-processing task during simultaneous positron emission tomography and magnetic resonance (PET-MR) imaging with [ 11 C]raclopride, a DA D2/D3 receptor antagonist that selectively binds to striatal DA receptors., Results: Relative to controls, the anhedonia group exhibited decreased task-related DA release in the left putamen, caudate, and nucleus accumbens and right putamen and pallidum. There were no group differences in task-related brain activation (fMRI) during reward processing after correcting for multiple comparisons. General functional connectivity (GFC) findings revealed blunted fMRI connectivity between PET-derived striatal seeds and target regions in the anhedonia group. Associations were identified between anhedonia severity and the magnitude of task-related DA release to rewards in the left putamen, but not mesocorticolimbic GFC., Conclusions: Results provide evidence for reduced striatal DA functioning during reward processing and blunted mesocorticolimbic network functional connectivity in a transdiagnostic sample with clinically significant anhedonia., Competing Interests: Declaration of Competing Interest Over the past 3 years, Dr. Pizzagalli has received consulting fees from Albright Stonebridge Group, Boehringer Ingelheim, Compass Pathways, Engrail Therapeutics, Neumora Therapeutics (formerly BlackThorn Therapeutics), Neurocrine Biosciences, Neuroscience Software, Otsuka, Sunovion, and Takeda; he has received honoraria from the Psychonomic Society (for editorial work) and from Alkermes; he has received research funding from the Brain and Behavior Research Foundation, the Dana Foundation, Millennium Pharmaceuticals, and NIMH; he has received stock options from Compass Pathways, Engrail Therapeutics, Neumora Therapeutics, and Neuroscience Software. No funding from these entities was used to support the current work, and all views expressed are solely those of the authors. The other authors have no conflicts of interest or relevant disclosures., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Competing Interests: AS, AJE, JPB, and PMI contributed equally to this work. AS, AJE, NF, RMC, JPB, and PMI conceived the study. AS, BB, GHa, and PMI performed the literature search. AS, AJE, BB, GHa, NF, DZ, MM, GHo, JL, PR, C-ET, HMB, RMC, JPB, and PMI performed data collection. AS, AJE, JPB, and PMI created the figures and wrote the original draft. All authors performed interpretation and analysis of data, reviewed or edited the manuscript, approved the final version for publication, and agree to be accountable for all aspects of the work. AS, AJE, and PMI verified the underlying data. AS, AJE, JPB, and PMI had final responsibility for the decision to submit for publication. AS has received consulting fees from AstraZeneca, Bristol-Myers Squibb, Eli Lilly and Company, GlaxoSmithKline, and Kezar Life Sciences. RHH has received consulting compensation from Janssen. JUS has served as a consultant for Janssen, Amgen, Pfizer, Sanofi, UCB, Bristol-Myers Squibb, and Abbvie; and has received funding for investigator-initiated studies from Pfizer and Janssen. RMC has received consulting fees from Momenta–Janssen. JPB has received consulting fees and served on data and safety monitoring boards for Momenta–Janssen, Ventus, Equillium, and GlaxoSmithKline. PMI has received consulting fees from GlaxoSmithKline and Momenta–Janssen. All other authors declare no competing interests. Deidentified participant data will be made available upon request by email to the corresponding author. This work was supported by the National Institutes of Health–National Institute of Arthritis and Musculoskeletal and Skin Diseases (P50 AR07059) to JPB and PMI and Bloomberg Philanthropies COVID-19 Response Initiative Grant to JUS and PMI. The funders of the study had no role in study design, data collection, data analysis, data interpretation, writing of the report, or decision to submit for publication.

Primary intestinal T-cell lymphoma (PITL) is highly aggressive and includes celiac disease-related enteropathy-associated T-cell lymphoma (EATL), monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), and primary intestinal peripheral T-cell lymphoma, not otherwise specified (ITCL-NOS). MEITL is the most common PITL in Asia, comprising of monomorphic medium-sized cells typically expressing CD8, CD56, and cytotoxic granules. Occasional cases with intermediate features between MEITL and ITCL-NOS are difficult to be classified and warrant further investigation. We collected 54 surgically resected PITLs from Taiwan, with 80% presenting with bowel perforation. The overall outcome was poor with a median survival of 7 months. Based on histopathology (monomorphic vs. pleomorphic) and immunophenotype, we classified these cases into 4 groups: MEITL with typical immunophenotype (n=34), MEITL with atypical immunophenotype (n=5), pleomorphic PITL with MEITL-like immunophenotype (n=6), and ITCL-NOS (n=9). There was no EATL in our cohort. Targeted next-generation sequencing of the first 3 groups showed highly prevalent loss-of-function mutations for SETD2 (85%, 80%, and 83%, respectively) and frequent activating mutations for STAT5B (64%, 60%, and 50%, respectively) and JAK3 (38%, 20%, and 50%, respectively). In contrast, ITCL-NOS cases had less frequent mutations of SETD2 (56%) and STAT5B (11%) and rare JAK3 mutations (11%). Our results suggest that there is a wider morphologic and immunophenotypic spectrum of MEITL as currently defined in the 2017 WHO classification. MEITL with atypical immunophenotype and PITL with MEITL-like immunophenotype shared clinicopathologic and molecular features similar to MEITL but distinct from ITCL-NOS, indicating that such cases may be considered as immunophenotypic or histopathologic variants of MEITL., Competing Interests: Conflicts of Interest and Source of Funding: Supported by the Ministry of Science and Technology, Taiwan (107-2320-B-384-002). The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Lung cancer is one of the most common causes of cancer-related deaths worldwide. During or after the treatment of lung cancer, patients might develop another malignant neoplasm. To our knowledge, synchronous pulmonary adenocarcinoma and leptomeningeal large B-cell lymphoma have not been reported in the literature. Herein, we report the first case of synchronous pulmonary adenocarcinoma and primary leptomeningeal lymphoma, which is challenging in cytological diagnosis using cerebrospinal fluid (CSF). Knowledge of this rare situation by cytopathologists might avoid misdiagnosis or erroneous tumor classification during the cytological diagnosis of CSF in the future., (© 2022 Wiley Periodicals LLC.)

While COVID-19 research has seen an explosion in the literature, the impact of pandemic-related societal and lifestyle disruptions on brain health among the uninfected remains underexplored. However, a global increase in the prevalence of fatigue, brain fog, depression and other "sickness behavior"-like symptoms implicates a possible dysregulation in neuroimmune mechanisms even among those never infected by the virus. We compared fifty-seven 'Pre-Pandemic' and fifteen 'Pandemic' datasets from individuals originally enrolled as control subjects for various completed, or ongoing, research studies available in our records, with a confirmed negative test for SARS-CoV-2 antibodies. We used a combination of multimodal molecular brain imaging (simultaneous positron emission tomography / magnetic resonance spectroscopy), behavioral measurements, imaging transcriptomics and serum testing to uncover links between pandemic-related stressors and neuroinflammation. Healthy individuals examined after the enforcement of 2020 lockdown/stay-at-home measures demonstrated elevated brain levels of two independent neuroinflammatory markers (the 18 kDa translocator protein, TSPO, and myoinositol) compared to pre-lockdown subjects. The serum levels of two inflammatory markers (interleukin-16 and monocyte chemoattractant protein-1) were also elevated, although these effects did not reach statistical significance after correcting for multiple comparisons. Subjects endorsing higher symptom burden showed higher TSPO signal in the hippocampus (mood alteration, mental fatigue), intraparietal sulcus and precuneus (physical fatigue), compared to those reporting little/no symptoms. Post-lockdown TSPO signal changes were spatially aligned with the constitutive expression of several genes involved in immune/neuroimmune functions. This work implicates neuroimmune activation as a possible mechanism underlying the non-virally-mediated symptoms experienced by many during the COVID-19 pandemic. Future studies will be needed to corroborate and further interpret these preliminary findings., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Primary cutaneous gamma/delta T-cell lymphoma (PCDG-TCL) is aggressive, frequently presenting as multiple plaques, tumors, and/or subcutaneous nodules., Methods: In this study, we conducted a retrospective study in a tertiary center in Taiwan to characterize this rare tumor., Results: We identified six patients. Five presented with a solitary lesion, including two with clinical impression of epidermal inclusion cyst or lipoma. Two of four evaluable cases exhibited epidermotropism, with one mimicking Pautrier microabscess. The neoplastic cells were pleomorphic and mostly medium- to large-sized. In all cases, the neoplastic cells expressed T-cell receptor (TCR)-γ and/or TCR-δ, with four co-expressing βF1. Two of these βF1+ cases co-expressed TCR-γ but not TCR-δ (two different clones). All were negative for Epstein-Barr virus (EBV), low stage, and treated with radiotherapy alone or combined chemotherapy and radiotherapy. In two patients, lymphoma relapsed in 3 and 7 months, respectively, and one patient died of the disease in 7 months. Four other patients were free of disease for 6 to 126 months., Conclusion: PCGD-TCL cases in Taiwan are more commonly solitary, frequently with indolent courses. The two currently available TCR-δ clones alone might be insufficient to detect all tumors., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Metanephric adenoma (MA) and Wilms tumor (WT) represent 2 prototypes of primary renal neoplasms closely resembling embryonal renal tubules. Tumors with overlapping features may occur, requiring differential diagnoses between the 2. Evidence of divergent oncogenic pathways has been reported, suggesting that MA is driven by BRAF mutation while most WT is of the BRAF wild-type. We collected 4 MA cases, 3 cases of monophasic epithelial WT, and 1 overlap metanephric tumor that contains both conventional MA and high-grade components similar to epithelial WT. Whole-exome sequencing and whole transcriptome sequencing were performed to discover mutations, somatic copy number variation, and differential expression. The findings were compared with those of WT of the TARGET database (WT-TARGET). BRAF V600E mutation was detected in all MAs as well as the overlap tumor but was undetectable in all epithelial WTs and WT-TARGET. The overlap tumor showed an additional pathogenic mutation of SETD2. Three frequent gene mutations observed in WT-TARGET were not common in epithelial WT, in which the mutations appeared sporadic. The profiles of recurrent copy number variations were all different among MA, epithelial WT, and WT-TARGET. Differential expression and unsupervised hierarchical cluster analyses revealed distinct clusters of the 3 categories. Remarkably, the overlap tumor coclustered with MA, separated from epithelial WT and WT-TARGET. The distinctiveness of MA and WT were demonstrated corresponding to BRAF-mutated and non-BRAF-mutated pathways from the molecular perspective. BRAF assay has diagnostic implication for overlap tumors., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To evaluate seroreactivity and disease flares after COVID-19 vaccination in a multiethnic/multiracial cohort of patients with systemic lupus erythematosus (SLE)., Methods: Ninety SLE patients and 20 healthy controls receiving a complete COVID-19 vaccine regimen were included. IgG seroreactivity to the SARS-CoV-2 spike receptor-binding domain (RBD) and SARS-CoV-2 microneutralization were used to evaluate B cell responses; interferon-γ (IFNγ) production was measured by enzyme-linked immunospot (ELISpot) assay in order to assess T cell responses. Disease activity was measured by the hybrid SLE Disease Activity Index (SLEDAI), and flares were identified according to the Safety of Estrogens in Lupus Erythematosus National Assessment-SLEDAI flare index., Results: Overall, fully vaccinated SLE patients produced significantly lower IgG antibodies against SARS-CoV-2 spike RBD compared to fully vaccinated controls. Twenty-six SLE patients (28.8%) generated an IgG response below that of the lowest control (<100 units/ml). In logistic regression analyses, the use of any immunosuppressant or prednisone and a normal anti-double-stranded DNA antibody level prior to vaccination were associated with decreased vaccine responses. IgG seroreactivity to the SARS-CoV-2 spike RBD strongly correlated with the SARS-CoV-2 microneutralization titers and correlated with antigen-specific IFNγ production determined by ELISpot. In a subset of patients with poor antibody responses, IFNγ production was similarly diminished. Pre- and postvaccination SLEDAI scores were similar in both groups. Postvaccination flares occurred in 11.4% of patients; 1.3% of these were severe., Conclusion: In a multiethnic/multiracial study of SLE patients, 29% had a low response to the COVID-19 vaccine which was associated with receiving immunosuppressive therapy. Reassuringly, severe disease flares were rare. While minimal protective levels remain unknown, these data suggest that protocol development is needed to assess the efficacy of booster vaccination., (© 2021, American College of Rheumatology.)

Toxic and nontoxic volatile organic compound (VOC) gases are emitted into the atmosphere from certain solids and liquids as a consequence of wastage and some common daily activities. Inhalation of toxic VOCs has an adverse effect on human health, so it is necessary to monitor their concentration in the atmosphere. In this work, we report on the fabrication of inorganic nanotube (INT)-tungsten disulfide, paper-based graphene-PEDOT:PSS sheet and WS 2 nanotube-modified conductive paper-based chemiresistors for VOC gas sensing. The WS 2 nanotubes were fabricated by a two-step reaction, that is oxide reduction and sulfurization, carried out at 900 °C. The synthesized nanotubes were characterized by FE-SEM, EDS, XRD, Raman spectroscopy, and TEM. The synthesized nanotubes were 206-267 nm in diameter. The FE-SEM results show the length of the nanotubes to be 4.5-8 µm. The graphene-PEDOT:PSS hybrid conductive paper sheet was fabricated by a continuous coating process. Then, WS 2 nanotubes were drop-cast onto conductive paper for fabrication of the chemiresistors. The feasibility and sensitivity of the WS 2 nanotube-modified paper-based chemiresistor were tested in four VOC gases at different concentrations at room temperature (RT). Experimental results show the proposed sensor to be more sensitive to butanol gas when the concentration ranges from 50 to 1000 ppm. The limit of detection (LOD) of this chemiresistor for butanol gas was 44.92 ppm. The WS 2 nanotube-modified paper-based chemiresistor exhibits good potential as a VOC sensor with the advantages of flexibility, easy fabrication, and low fabrication cost.

Background: Although hydroxychloroquine (HCQ) is a mainstay of treatment for patients with systemic lupus erythematosus (SLE), ocular toxicity can result from accumulated exposure. As the longevity of patients with SLE improves, data are needed to balance the risk of ocular toxicity and the risk of disease flare, especially in older patients with quiescent disease. Accordingly, this study was initiated to examine the safety of HCQ withdrawal in older SLE patients., Methods: Data were obtained by retrospective chart review at three major lupus centers in New York City. Twenty-six patients who discontinued HCQ and thirty-two patients on HCQ matched for gender, race/ethnicity, and age were included in this study. The primary outcome was the occurrence of a lupus flare classified by the revised version of the Safety of Estrogens in Lupus Erythematosus: National Assessment version of the Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) Flare composite index, within 1 year of HCQ withdrawal or matched time of continuation., Results: Five patients (19.2%) in the HCQ withdrawal group compared to five (15.6%) in the HCQ continuation group experienced a flare of any severity (odds ratio [OR] = 1.28; 95% CI 0.31, 5.30; p = 0.73). There were no severe flares in either group. The results were similar after adjusting for length of SLE, number of American College of Rheumatology criteria, low complement levels, and SELENA-SLEDAI score, and in a propensity score analysis (OR = 1.18; 95% CI 0.23, 6.16; p = 0.84). The analysis of time to any flare revealed a non-significant earlier time to flare in the HCQ withdrawal group (log-rank p = 0.67). Most flares were in the cutaneous and musculoskeletal systems, but one patient in the continuation group developed pericarditis. The most common reason for HCQ withdrawal was retinal toxicity (42.3%), followed by patient's preference (34.6%), other confirmed or suspected adverse effects (15.4%), ophthalmologist recommendation for macular degeneration (3.8%), and rheumatologist recommendation for quiescent SLE (3.8%)., Conclusions: In this retrospective study of older stable patients with SLE on long-term HCQ, withdrawal did not significantly increase the risk of flares.

Computed tomography (CT) of a 68-year-old man showed multiple small nodules in the bilateral lungs (maximum 14 mm in the left upper lobe). CT-guided biopsy of left upper lobe lesion showed no tumor or granuloma. Fluorodeoxyglucose (FDG) PET/CT showed multiple nodules with background-to-mild FDG-avid activity, and an incidental left scrotal skin lesion with intensely increased accumulation of F-FDG (SUVmax, 11.7), suspected malignant. After urologist consultation, local dermatological findings suggested a huge wart. Excision was done, and pathology concluded nodular papillary fibroepithelial polyp with acute and chronic inflammation.

Background: Controversy is not uncommon in the diagnosis of discogenic low back pain (DLBP) and in the identification of the location of the pain source for the symptomatic disc in patients with DLBP. Various techniques, from minimally invasive procedures to fusion surgery, are used to treat chronic DLBP, but the clinical outcomes are variable. Percutaneous endoscopic discectomy by transforaminal or interlaminar approach is considered to be an effective method to treat DLBP, but the evidence is limited; the lack of clear evidence may be associated with patient selection and surgical technique., Objectives: The purpose of this study is to evaluate the clinical results of percutaneous endoscopic treatment for annular tear in selected patients with DLBP by using the outside-in technique., Study Design: A prospective study and retrospective observations were performed on 24 consecutive patients with a minimum 2 years of follow-up. This study was approved by the Institutional Review Board (IRB) of Buddhist Dalin Tzu-Chi General Hospital Foundation (IRB number: 10504004) and written informed consent was obtained from all patients., Setting: This research took place within an interventional pain management and spine practice., Methods: Twenty-four consecutive patients with single-level DLBP diagnosed by positive high-intensity zone on magnetic resonance imaging, positive provocative discography, and block test underwent a percutaneous endoscopic procedure from January 2014 to December 2015. The transforaminal approach or interlaminar approach was selected according to the location of the annular tear. The torn lesions were visualized directly and treated by puncture and debridement of the inflammatory tissues from the outer annulus fibrosus to the inner nucleus using the outside-in technique. The Visual Analog Scale (VAS) score and Oswestry Disability Index (ODI) score were evaluated before and after surgery. The clinical global outcomes were assessed on the basis of modified MacNab criteria., Results: These patients included 13 men and 11 women with a mean age of 43.8 years (range, 32-55 yrs). There were 15 lesion levels at L4/L5 and 9 lesion levels at L5/S1. Among them, 15 levels were accessed by transforaminal approach and 9 levels by interlaminar approach. No serious complications were observed during the follow-up periods. All except 2 patients experienced significant symptomatic and functional improvements at the 2-year follow-up with a success rate of 91.7%., Limitations: Significant limitations include nonrandom format and small sample size. Future research may focus on controlled prospective studies with larger sample sizes and long-term follow-up to examine the validity of this protocol., Conclusions: The percutaneous endoscopic procedure provides a safe and effective treatment for selected patients with DLBP. The outside-in technique allows the surgeons to visualize and treat the torn or inflammatory lesions directly, and the success rate is high at 2 years follow-up., Key Words: Transforaminal, interlaminar, outside-in technique, endoscopic discectomy, discogenic low back pain.

Very preterm birth (VPT; <32 weeks of gestation) has been associated with impairments in memory abilities and functional neuroanatomical brain alterations in medial temporal and fronto-parietal areas. Here we investigated the relationship between structural connectivity in memory-related tracts and various aspects of memory in VPT adults (mean age 19) who sustained differing degrees of perinatal brain injury (PBI), as assessed by neonatal cerebral ultrasound. We showed that the neurodevelopmental consequences of VPT birth persist into young adulthood and are associated with neonatal cranial ultrasound classification. At a cognitive level, VPT young adults showed impairments specific to effective organization of verbal information and visuospatial memory, whereas at an anatomical level they displayed reduced volume of memory-related tracts, the cingulum and the fornix, with greater alterations in those individuals who experienced high-grade PBI. When investigating the association between these tracts and memory scores, perseveration errors were associated with the volume of the fornix and dorsal cingulum (connecting medial frontal and parietal lobes). Visuospatial memory scores were associated with the volume of the ventral cingulum (connecting medial parietal and temporal lobes). These results suggest that structural connectivity alterations could underlie memory difficulties in preterm born individuals., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: Unilateral mesial temporal lobe epilepsy and hippocampal sclerosis have structural and functional abnormalities in the mesial temporal regions. To gain insight into the pathophysiology of the epileptic network in mesial temporal lobe epilepsy with hippocampal sclerosis, we aimed to clarify the relationships between hippocampal atrophy and the altered connection between the hippocampus and the posterior cingulate cortex in patients with mesial temporal lobe epilepsy with hippocampal sclerosis., Materials and Methods: Fifteen patients with left mesial temporal lobe epilepsy with hippocampal sclerosis and 15 healthy controls were included in the study. Multicontrast MR imaging, including high-resolution T1WI, diffusion spectrum imaging, and resting-state fMRI, was performed to measure the hippocampal volume, structural connectivity of the inferior cingulum bundle, and intrinsic functional connectivity between the hippocampus and the posterior cingulate cortex, respectively., Results: Compared with controls, patients had decreased left hippocampal volume (volume ratio of the hippocampus and controls, 0.366% ± 0.029%; patients, 0.277% ± 0.063%, corrected P = .002), structural connectivity of the bilateral inferior cingulum bundle (generalized fractional anisotropy, left: controls, 0.234 ± 0.020; patients, 0.193 ± 0.022, corrected P = .0001, right: controls, 0.226 ± 0.022; patients, 0.208 ± 0.017, corrected P = .047), and intrinsic functional connectivity between the left hippocampus and the left posterior cingulate cortex (averaged z-value: controls, 0.314 ± 0.152; patients, 0.166 ± 0.062). The left hippocampal volume correlated with structural connectivity positively (standardized β = 0.864, P = .001), but it had little correlation with intrinsic functional connectivity (standardized β = -0.329, P = .113). On the contralesional side, the hippocampal volume did not show any significant correlation with structural connectivity or intrinsic functional connectivity ( F 2,12 = 0.284, P = .757, R 2 = 0.045)., Conclusions: In left mesial temporal lobe epilepsy with hippocampal sclerosis, the left inferior cingulum bundle undergoes degeneration in tandem with the left hippocampal volume, whereas intrinsic functional connectivity seems to react by compensating the loss of connectivity. Such insight might be helpful in understanding the development of the epileptic network in left mesial temporal lobe epilepsy with hippocampal sclerosis., (© 2017 by American Journal of Neuroradiology.)

Myelodysplastic syndromes are a heterogeneous group of clonal disorders of hematopoietic progenitors and have potentiality to progress into acute myelogenous leukemia. Development of effective treatments has been impeded by limited insight into pathogenic pathways. In this study, we applied RNA-seq technology to study the transcriptome on 20 MDS patients and 5 age-matched controls, and developed a pipeline for analyzing this data. After analysis, we identified 38 mutated genes contributing to MDS pathogenesis. 37 out of 38 genes have not been reported previously, suggesting our pipeline is critical for identifying novel mutated genes in MDS. The most recurrent mutation happened in gene IFRD1, which involved 30% of patient samples. Biological relationships among these mutated genes were mined using Ingenuity Pathway Analysis, and the results demonstrated that top two networks with highest scores were highly associated with cancer and hematological diseases, indicating that the mutated genes identified by our method were highly relevant to MDS. We then integrated the pathways in KEGG database and the identified mutated genes using our novel rule-based mutated driver pathway scoring approach for detecting mutated driver pathways. The results indicated two mutated driver pathways are important for the pathogenesis of MDS: pathway in cancer and in regulation of actin cytoskeleton. The latter, which likely contributes to the hallmark morphologic dysplasia observed in MDS, has not been reported, to the best of our knowledge. These results provide us new insights into the pathogenesis of MDS, which, in turn, may lead to novel therapeutics for this disease.

Myoepithelioma/myoepithelial carcinomas are not commonly found in soft tissues and are especially rare at visceral sites. This report describes a case of a rare low-grade myoepithelial carcinoma of the stomach. A 61-year-old female patient presented with postprandial abdominal discomfort. Endoscopy revealed a 1.1 cm submucosal lesion. Local excision was performed after malignancy was confirmed by biopsy. The resection margin is free of tumor and she received no adjuvant therapy. The tumor was characterized by multinodular growth with biphasic epithelioid and spindle components. Infiltrative margin and nuclear pleomorphism are seen. Tumor cells were positive for both epithelial and myoepithelial markers. Evidence of epithelial differentiation was confirmed by electron microscopy. No EWSR1 rearrangement was detected. The final diagnosis was low-grade myoepithelial gastric carcinoma. The patient is currently well, and no evidence of recurrence or metastasis was found after ten-month of follow-up. Myoepithelial carcinoma should be considered in the differential diagnosis of a biphasic gastric tumor.

The mirror neuron system (MNS) may be implicated in schizophrenia. This study investigated MNS structures, including the pars opercularis (Pop), the supramarginal gyrus (SMg), the third branch of the superior longitudinal fasciculus, and callosal fibers interconnecting bilateral Pop (CC-Pop) and SMg (CC-SMg), and clarified their relationships with positive and negative symptoms of schizophrenia. Participants comprised 32 schizophrenia patients and 32 matched controls who received T1-weighted structural magnetic resonance imaging (MRI, T1WI) and diffusion spectrum imaging (DSI). The cortical measures were computed from the T1WI data. Tract integrity was assessed using a tractography-based analysis of the generalized fractional anisotropy (GFA) derived from the DSI data. Pearson׳s correlations and multiple linear regression analysis were used to investigate the associations between MNS structures and positive and negative symptom scores of schizophrenia. Cortical thickness in bilateral Pop and SMg were significantly thinner and mean GFA of CC-Pop was significantly decreased in patients. Negative symptoms were significantly correlated with left SMg volume, and positive symptoms were significantly correlated with right SMg thickness. Multiple linear regression analysis showed left SMg volume to be the strongest contributor to the negative symptoms. The association between left SMg volume and negative symptoms may reflect the degree of social cognition impairment in schizophrenia., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Diffuse large B-cell lymphoma (DLBCL) is one of the most common types of aggressive B-cell non-Hodgkin lymphoma. About one-third of patients are either refractory to the treatment or experience relapse afterwards, pointing to the necessity of developing other effective therapies for DLBCL. Human B-lymphocytes are susceptible to JC polyomavirus (JCPyV) infection, and JCPyV virus-like particles (VLPs) can effectively deliver exogenous genes to susceptible cells for expression, suggesting the feasibility of using JCPyV VLPs as gene therapy vectors for DLBCL., Methods: The JCPyV VLPs packaged with a GFP reporter gene were used to infect human DLBCL cells for gene delivery assay. Furthermore, we packaged JCPyV VLPs with a suicide gene encoding thymidine kinase (TK) to inhibit the growth of DLBCL in vitro and in vivo., Results: Here, we show that JCPyV VLPs effectively entered human germinal center B-cell-like (GCB-like) DLBCL and activated B-cell-like (ABC-like) DLBCL and expressed the packaged reporter gene in vitro. As measured by the MTT assay, treatment with tk-VLPs in combination with gancyclovir (GCV) reduced the viability of DLBCL cells by 60%. In the xenograft mouse model, injection of tk-VLPs through the tail vein in combination with GCV administration resulted in a potent 80% inhibition of DLBCL tumor nodule growth., Conclusions: Our results demonstrate the effectiveness of JCPyV VLPs as gene therapy vectors for human DLBCL and provide a potential new strategy for the treatment of DLBCL.

Radioresistance is still an emerging problem for radiotherapy of oral cancer. Aberrant epigenetic alterations play an important role in cancer development, yet the role of such alterations in radioresistance of oral cancer is not fully explored. Using a methylation microarray, we identified promoter hypermethylation of FHIT (fragile histidine triad) in radioresistant OML1-R cells, established from hypo-fractionated irradiation of parental OML1 radiosensitive oral cancer cells. Further analysis confirmed that transcriptional repression of FHIT was due to promoter hypermethylation, H3K27me3 and overexpression of methyltransferase EZH2 in OML1-R cells. Epigenetic interventions or depletion of EZH2 restored FHIT expression. Ectopic expression of FHIT inhibited tumor growth in both in vitro and in vivo models, while also resensitizing radioresistant cancer cells to irradiation, by restoring Chk2 phosphorylation and G2/M arrest. Clinically, promoter hypermethylation of FHIT inversely correlated with its expression and independently predicted both locoregional control and overall survival in 40 match-paired oral cancer patient samples. Further in vivo therapeutic experiments confirmed that inhibition of DNA methylation significantly resensitized radioresistant oral cancer cell xenograft tumors. These results show that epigenetic silencing of FHIT contributes partially to radioresistance and predicts clinical outcomes in irradiated oral cancer. The radiosensitizing effect of epigenetic interventions warrants further clinical investigation.

Epstein-Barr Virus (EBV) is a herpesvirus usually infecting B-cells but may occasionally infect T- or natural killer (NK)-cells. EBV-associated T- or NK-cell lymphoproliferations represent a continuous spectrum of diseases ranging from asymptomatic infection, infectious mononucleosis (IM), to clonal and malignant lymphoproliferations including systemic EBV-positive T/NK-cell lymphoproliferative disease (EBV-T/NK-LPD) of childhood and hydroa-vacciniforme-like lymphoma of the skin. The clonal diseases are more prevalent in East Asia and exhibit overlapping clinical and pathological features with chronic active EBV infection. Here we report our experience on 10 cases of EBV-associated T-cell lymphoproliferation from Taiwan including five males and five females with a median age of 18 years old (range, 15-28). The most common clinical symptoms were fever, neck mass and hepatosplenomegaly. Eight of these patients showed elevated lactate dehydrogenase level and half of the patients had cytopenia. All patients had either elevated EBV antibody titers or increased serum EBV DNA levels. Five cases were clinically IM-like with polyclonal (3 cases) or clonal (2 cases) T-cell lymphoproliferation. Two patients each had chronic active EBV infection (CAEBV) and hemophagocytic lymphohistiocytosis (HLH). One patient had both CAEBV and HLH. One of the HLH patients with marrow infiltration by intra-sinusoidal large atypical lymphocytes experienced a fulminant course. In a median follow-up time of 21.5 months, seven patients were free of disease, one was alive with disease, and two died of disease in 31 and 3 months, respectively, despite chemotherapy. We confirmed a wide clinicopathological range of EVB-associated T-cell lymphoproliferation in Taiwan. Furthermore, monomorphic LPD and the single case with fulminant course as defined by Ohshima et al (Pathol Int 2018) as categories A3 and B, respectively, died of disease despite chemotherapy. Our report, the largest series in the recent decade from Taiwan, adds to the understanding of these rare diseases with variable clinical and histopathological presentations.

Previous studies have demonstrated that infection with human polyomavirus, such as JCPyV and BKPyV, might be associated with various human tumors. However, an association between human JCPyV and BKPyV infection and diffuse large B-cell lymphoma (DLBCL) has not been reported. The purpose of this study was to examine DLBCLs of the gastrointestinal tract for evidence of human polyomavirus infection. Nested PCR and DNA sequencing were employed for viral DNA detection and viral genotype identification. In addition, two viral proteins, the large tumor antigen (LT) and the major structural protein (VP1), were detected by immunohistochemistry (IHC). Human JCPyV and BKPyV DNA was detected in 14 out of 16 tissue samples (87.5%), whereby nine cases were infected with JCPyV and five cases were infected with BKPyV. Both archetypal and rearranged genotypes of JCPyV and BKPyV were detected in the tissues. LT was detected in 11 tissue samples (68.75%). However, VP1 was not detected in any of the tissue samples. The presence of human JCPyV and BKPyV DNA and protein in DLBCL tissues of gastrointestinal tract were first reported in this study. The current results provide evidence of a possible association between human JCPyV and BKPyV infection and DLBCL.

Malignant mesonephric mixed tumor (MMMT), or mesonephric carcinosarcoma, is a rare tumor with malignant epithelial and mesenchymal components, and is found mostly in the uterine cervix. While diagnosed at the early stage in most cases, MMMT can have an aggressive course. The clinical significance of the presence of sarcomatous components remains unsettled. We report a case of MMMT of the uterine cervix in a patient who presented with tumor rupture, instead of the common presentation, vaginal bleeding. This unusual presentation has not been reported in the literature. It implies that MMMT may progress rapidly without any prodrome and pose a surgical emergency. Unlike most cervical adenocarcinomas, both mesonephric adenocarcinoma and MMMT are not related to human papilloma virus (HPV) infection. Because mesonephric neoplasms have a different etiology, their prevention, screening, and treatment should be further investigated. Thirteen cases of MMMT reported in the literature are also reviewed.

To explore the feasibility of computer-aided monitoring of the workflow in surgical pathology. We collected 5-year data about computer-aided monitoring of the workflow in surgical pathology and analyzed the four subprocesses in the surgical pathologic process: 1) from arranging surgical pathology examination to receipt of the examination sheet and sample by the laboratory; 2) from receipt of the sample to issuance of the pathology report; 3) from issuance of the pathology report to automatic computer forwarding of positive pathology reports by e-mail to the physician who ordered the examination; 4) from receipt of the positive report by the physician to his/her response of acknowledging receipt. A total 115,648 surgical pathological cases were reviewed in this study. The overdue rate of delivery of samples was 0.82%. The most common cause (62.92%) of overdue delivery was clinicians in the outpatient department arranging for the examination more than 1 day in advance of specimen collection. The cumulative rates of report completion within 1, 2, 3, 4 and 5 work days were 12.82%, 53.56%, 86.42%, 95.90% and 98.85%, respectively. The rate of overdue reporting was 1.15% over the 5-year study. The most common cause (56.30%) of overdue reporting was case complexity. The learning time for adapting this subprocess of report issuance was 7 months. There were 12,151 positive reports (10.51% of all cases) that required automatic computer forwarding to the physicians' e-mail boxes. A total of 113 cases (0.93%) failed in automatic computer forwarding during the 5-year period. The learning time for constructing a stable automatic computer forwarding system was 2.5 years. Of the 12,038 reports successfully forwarded, 10,107 (83.96%) were received by physicians and acknowledged by automated receipt within 120 h, and the other 1,931 (16.04%) showed no response within 120 h. The major reason for an overdue reply was that the physicians did not check their e-mail boxes (94.89%). We used a preliminary computer-aided system to monitor the workflow in surgical pathology. This system might be used as one of the methods of quality assurance in surgical pathology.

Cryptococcosis occurring within 30 days after transplant is unusual. We present a case of cryptococcosis diagnosed within 2 weeks of liver transplant and cryptococcal infection transmitted by liver transplant is considered as the cause. A 63-year-old woman with hepatitis C virus-related cirrhosis and hepatocellular carcinoma had an orthotopic liver transplant from a 45-year-old donor. The immediate postoperative course was smooth, although she was confused with a fever, tachycardia, respiratory failure of 1 week's duration after the orthotopic liver transplant. A liver biopsy was performed for hyperbilirubinemia 2 weeks after the orthotopic liver transplant that showed a Cryptococcus-like yeast. Her blood culture was reexamined, and it was confirmed as Cryptococcus neoformans that had been misinterpreted as candida initially. At the time of the re-examination, her sputum was clear. We checked her preoperative blood sample, retrospectively, for serum cryptococcal antigen with negative result. She was on liposomal amphotericin treatment for 1 month when her blood culture became negative. She was discharged home, with good liver function and a low antigen titer for cryptococcal infection. Cryptococcal disease usually develops at a mean of 5.6 months after transplant. However an early occurrence is rare. Apart from that, its variable clinical presentations make early detection difficult. It might be an early reactivation or a donor-derived infection. The latter usually occurs in unusual sites (eg, the transplanted organ as the sole site of involvement). Our case presented as cryptococcoma and liver involvement was diagnosed by an unintentional liver biopsy.

DNA hypermethylation of promoter CpG islands is associated with epigenetic silencing of tumor suppressor genes in oral squamous cell carcinomas (OSCCs). We used a methyl-CpG-binding domain protein capture method coupled with next-generation sequencing (MBDCap-seq) to survey global DNA methylation patterns in OSCCs with and without nodal metastasis and normal mucosa (total n = 58). Of 1462 differentially methylated CpG islands identified in OSCCs relative to normal controls, MBDCap-seq profiling uncovered 359 loci linked to lymph node metastasis. Interactive network analysis revealed a subset of these loci (n = 23), including the anaplastic lymphoma kinase (ALK) gene, are potential regulators and effectors of invasiveness and metastatic progression. Promoter methylation of ALK was preferentially observed in OSCCs without node metastasis, whereas relatively lower methylation levels were present in metastatic tumors, implicating an active state of ALK transcription in the latter group. The OSCC cell line, SCC4, displayed reduced ALK expression that corresponded to extensive promoter CpG island methylation. SCC4 treatment with demethylating agents induced ALK expression and increased invasion and migration characteristics. Inhibition of ALK activity in OSCC cells with high ALK expression (CAL27, HSC3 and SCC25), decreased cell growth and resulted in changes in invasive potential and mesenchymal marker expression that were cell-line dependent. Although ALK is susceptible to epigenetic silencing during oral tumorigenesis, overwriting this default state may be necessary for modulating invasive processes involved in nodal metastases. Given the complex response of OSCC cells to ALK inhibition, future studies are required to assess the feasibility of targeting ALK to treat invasive OSCCs.

Objectives: In resected buccal cancer patients, an unexpected close surgical margin has been observed to correlate with poor clinical outcomes. However, close surgical margin alone does not independently guide post-operative therapies, revealing a clinical debate. Hence, the present study intended to explore epigenetic-based bio-predictors for further stratifying this debating patient population., Materials and Methods: Between 2000 and 2008, we retrospectively recruited 44 resected buccal cancer patients with a close surgical margin of ≤5 mm. All patients had post-operative radiotherapy. Genomic DNA was extracted from tumor-enrich areas that contained cancer cells of >70%. Methylation-specific PCR was performed to detect promoter methylation of four tumor suppressor genes, including RASSF1A, DAPK, IRF8, and SFRP1. Post-irradiation locoregional control was defined as the primary end point., Results: There were 40 males and 4 females, with a median age of 53.5 years (range, 32-82 years). Multivariate analysis identified two independent predictors for locoregional recurrence: very close margin of ≤1 mm (HR: 4.96; 95% CI, 1.63-15.09; P=0.018) and promoter hypermethylation of DAPK (HR: 2.83; 95% CI, 1.05-7.63; P=0.042). The highest risk of locoregional recurrence was observed in patients with both of the two factors (HR, 8.05; 95% CI, 2.56-25.82; P=0.002) when compared with patients with none. Shorter disease-free survival, but not overall survival, was also observed., Conclusion: More aggressive managements should be considered in resected buccal cancer patients with both very close margin and DAPK promoter hypermethylation rather than post-operative observation or radiotherapy alone., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Extranodal natural killer/T-cell lymphoma (ENKTL) is a distinct subtype of non-Hodgkin's lymphoma and is rare in the colon. Synchronous adenocarcinoma and ENKTL of the colon has not been reported in the literature. In the present study, we report a 63-year-old male who suffered from intermittent bloody stools for 2 mo. He did not have fever, body weight loss or night sweat. Endoscopic and imaging studies revealed a 4.5-cm ulcerative mass in the ascending colon and a 3.0-cm polypoid, easy bleeding mass in the sigmoid colon, respectively. Thought to have double carcinoma of the colon, he received simultaneous right hemicolectomy and sigmoidectomy. The pathological diagnosis was a synchronous ENKTL (ascending colon) and adenocarcinoma (sigmoid colon). The literature on synchronous adenocarcinoma and malignant lymphoma of the colon was also reviewed.

Adult T-cell leukemia/lymphoma (ATLL) is a peripheral T-cell neoplasm caused by human T-cell lymphotropic virus type I (HTLV-I). The neoplastic cells are highly pleomorphic and are usually CD4+ and CD8- phenotypically. We reported the case of a 46-year-old woman presenting with fever, abdominal distention, lymphadenopathy, leukocytosis and hypercalcemia. Nodal biopsy showed diffuse infiltration by monomorphic small to medium-sized atypical lymphocytes expressing CD3, CD25, CD30 and CD99, but not CD1a, CD4, CD8, CD34, terminal deoxynucleotidyl transferase or ALK. An initial diagnosis of T-lymphoblastic leukemia/lymphoma was made based on cytomorphology, CD4 and CD8 double negativity, and the expression of CD99. The diagnosis was later revised to ATLL based on the positive serology study for anti-HTLV I/II antibody and confirmation by the clonal integration of HTLV-I proviral DNA into the tumor tissues by Southern blotting analysis. The patient had a stage IVB disease and died of septic shock after 2 courses of chemotherapy 3 months after diagnosis. Immunohistochemical staining for CD99 in archival ATLL tissues showed a positive rate of 67% (4 of 6 tumors). Our case showed that ATLL with atypical morphology and immunophenotype in HTLV non-endemic areas might pose a diagnostic challenge and CD99 expression is frequent in ATLL., (© 2013 The Authors. Pathology International © 2013 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd.)

Desmoid tumor is a locally invasive, myofibroblastic, nonmetastatic tumor. Its pathogenesis remains unclear and it may involve genetic abnormalities, sex hormones and traumatic injury, including surgery. Postoperative intra-abdominal desmoid tumor is rare, especially in the retroperitoneum. We report a case of postoperative retroperitoneal desmoid tumor that developed 29 mo after the first excision of a gastrointestinal stromal tumor. Sporadic trauma-related intra-abdominal desmoid tumors reported in the English literature are also reviewed. Despite an extremely low incidence, postoperative desmoid tumor should be considered in the differential diagnosis when a recurrent neoplasm is found at least one year after operation. However, it is a clinical challenge to distinguish recurrent malignant neoplasms from desmoid tumors, and surgical resection is the treatment option depending on the anatomic location.

Objective: The autopsy and clinical information on children dying with anti-SSA/Ro-associated cardiac manifestations of neonatal lupus (cardiac NL) were examined to identify patterns of disease, gain insight into pathogenesis and enhance the search for biomarkers and preventive therapies., Methods: A retrospective analysis evaluating reports from 18 autopsies of cardiac NL cases and clinical data from the Research Registry for Neonatal Lupus was performed., Results: Of the 18 cases with autopsies, 15 had advanced heart block, including 3 who died in the second trimester, 9 in the third trimester and 3 post-natally. Three others died of cardiomyopathy without advanced block, including two dying pre-natally and one after birth. Pathological findings included fibrosis/calcification of the atrioventricular (AV) node, sinoatrial (SA) node and bundle of His, endocardial fibroelastosis (EFE), papillary muscle fibrosis, valvular disease, calcification of the atrial septum and mononuclear pancarditis. There was no association of pathology with the timing of death except that in the third-trimester deaths more valvular disease and/or extensive conduction system abnormalities were observed. Clinical rhythm did not always correlate with pathology of the conduction system, and the pre-mortem echocardiograms did not consistently detect the extent of pathology., Conclusion: Fibrosis of the AV node/distal conduction system is the most characteristic histopathological finding. Fibrosis of the SA node and bundle of His, EFE and valve damage are also part of the anti-Ro spectrum of injury. Discordance between echocardiograms and pathology findings should prompt the search for more sensitive methods to accurately study the phenotype of antibody damage.

Primary aldosteronism (PA) may be missed in patients with chronic kidney disease (CKD), because CKD may disturb the renin-angiotensin-aldosterone system. Adrenal vein sampling has increased risks in patients with CKD. We report the case of a 58-year-old man with CKD and suspected PA. Left adrenal aldosteronism was diagnosed by NP-59 SPECT/CT. Left adrenalectomy demonstrated adrenocortical nodular hyperplasia. Plasma aldosterone normalized and blood pressure stabilized after surgery. NP-59 SPECT/CT may be a helpful diagnostic tool for detecting and lateralizing PA in CKD patients.

Accumulating evidence has shown the adverse effect of long-term hyperaldosteronism on cardiovascular morbidity that is independent of blood pressure. However, the diagnosis of primary aldosteronism (PA) remains a challenge for patients who present with subtle or atypical features or have chronic kidney disease (CKD). SPECT/CT has proven valuable in the diagnosis of a number of conditions. The aim of this study was to determine the usefulness of I-131 NP-59 SPECT/CT in patients with atypical presentations of PA and in those with CKD. The records of 15 patients with PA were retrospectively analyzed. NP-59 SPECT/CT was able to identify adrenal lesion(s) in CKD patients with suspected PA. Patients using NP-59 SPECT/CT imaging, compared with those not performing this procedure, significantly featured nearly normal serum potassium levels, normal aldosterone-renin ratio, and smaller adrenal size on CT and pathological examination and tended to feature stage 1 hypertension and non-suppressed plasma renin activity. These findings show that noninvasive NP-59 SPECT/CT is a useful tool for diagnosis in patients with subclinical or atypical features of PA and those with CKD.

Aim: To investigate the association of colorectal adenomas with both Helicobacter pylori (H. pylori) infection and metabolic syndrome., Methods: Using a cross-sectional hospital-based study, we analyzed physical examination data from 9311 healthy subjects with overnight physical examinations performed between January 2004 and December 2006. Examined data included gender, age, life style, anthropometric measurements, blood pressure, biochemical and hematological studies, H. pylori infection detected by esophagogastroduodenoscopy and biopsy urease tests, and colorectal adenomas detected with a complete total colonoscopy., Results: The prevalence values for H. pylori infection, metabolic syndrome, and colorectal adenoma were 39.2%, 18.7%, and 20.7%, respectively. Colorectal adenoma risk factors included male gender [odd ratio (OR): 2.005, 95% confidence interval (CI): 1.740-2.310, P < 0.001], advanced age (OR: 1.046, 95% CI: 1.040-1.052, P < 0.001), smoking (OR: 1.377, 95% CI: 1.146-1.654, P = 0.001), increased body fat (OR: 1.016, 95% CI: 1.007-1.026, P = 0.001), higher white blood cell count (OR: 1.038, 95% CI: 1.005-1.073, P = 0.025), H. pylori infection (OR: 1.366, 95% CI: 1.230-1.517, P < 0.001), and metabolic syndrome (OR: 1.408, 95% CI: 1.231-1.610, P < 0.001). In addition, concomitant H. pylori infection with metabolic syndrome further increased the probability of colorectal adenomas., Conclusion: Our study revealed H. pylori infection with concomitant metabolic syndrome might further increase the risk of colorectal adenomas.

Pancreatic tumors with combined exocrine and endocrine features are rare. Most reported cases are classified as mixed exocrine and endocrine carcinoma of the pancreas. We report the first case of solitary concomitant endocrine tumor and ductal adenocarcinoma of the pancreas. A 58-year-old patient was admitted for uncontrolled diabetes mellitus and body weight loss. The tumor was fortuitously discovered in the pancreatic tail after a tumor survey panel. Grossly, the solitary tumor had a central fibrous band that clearly divided it into two parts. On microscopic examination, the tumor contained both endocrine and exocrine components distinctly separated by the central fibrous band. The exocrine part showed a poorly-differentiated adenocarcinoma. The endocrine part was strongly immunoreactive to chromogranin, synaptophysin and glucagon. We reviewed the literature on pancreatic tumors with combined exocrine and endocrine features. A simple classification for this group of neoplasms is suggested, including five types: amphicrine, mixed, collision, solitary concomitant and multiple concomitant.

Unlabelled: The gross appearance and histological features of the medial plicae removed from 48 consecutive patients who had received total knee replacement for severe medial compartment osteoarthritis of their knees were investigated prospectively. The prevalence of the medial plica was 100%. A small branch of skeletal muscle originating from articularis genu inserting into the proximal synovial stroma of the medial plica was found in all knees. The synovial fold of the distal part of the medial plica was disclosed to have a close relationship with the gracilis tendon sheath. Histologically, the majority of advanced pathologic presentation was found at the middle and distal portion of the medial plica that might abrade on the articular cartilage of the medial femoral condyle. Noticeable cartilaginous lesion was found on the facing medial femoral condyle in all knees. The histomorphological findings of the medial plica imply the close interplay between this structure and the medial femoral condyle that might play a role in the pathogenesis of medial compartment osteoarthritis of the knee., Clinical Relevance: The findings of this study support the beneficial effect of some surgical procedure that would remove the pathologic medial plica for the treatment of medial compartment OA knee.

Background/purpose: Oral squamous cell carcinoma (OSCC) is an aggressive tumor and its occurrence in Taiwan is closely related to chronic smoking, alcohol consumption, and especially to betel quid chewing. It became the fourth most common malignant tumor of Taiwanese men in 2006. Unfortunately, there are few biomarkers for diagnosis and treatment of this disease., Methods: To find potential markers, two domestic cell lines (OC2 and OCSL) derived from different grades of OSCC were established and their proteins were compared by global proteomic analysis. The expression differences of GRP78 protein in these two cell lines and clinical samples from OSCC patients were verified., Results: Of the 11 candidate proteins expressed differentially in both cell lines, six [heat shock protein 90 kDa beta member 1 (94 kDa glucose-regulated protein; GRP94), protein disulfide-isomerase precursor, vimentin, tubulin beta-2C chain, 78 kDa glucose-regulated protein precursor (GRP78), and annexin A2] were increased in OC2 cells (low-grade OSCC), and five (heat shock protein 90-beta, annexin A1, stress-induced phosphoprotein 1, elongation factor-2, and integrin alpha-3 precursor) were increased in OCSL cells (high-grade OSCC). Some of these proteins have been previously associated with malignant tumors, but no previous association of GRP78 with OSCC has been reported. GRP78 protein expression in these two OSCC cell lines was confirmed by Western blotting. Immunohistochemical staining of clinical samples from OSCC patients revealed that decreased GRP78 protein expression was significantly correlated with advance tumor stage (p < 0.001) and neck lymph node metastasis (p = 0.001)., Conclusion: GRP78 protein is a possible biomarker of oral cancer in Taiwan., (Copyright 2010 Formosan Medical Association & Elsevier. Published by Elsevier B.V. All rights reserved.)

Angiolymphoid hyperplasia with eosinophilia (ALHE) describes a group of benign anomalous vascular hyperplasias which consist of epithelioid-like endothelial cells attached to dilated blood vessels, and infiltration of inflammatory cells, predominantly lymphocytes and some eosinophils. Here, we describe a healthy 34-year-old man, who had 10 well-defined, non-tender, red-to-brownish papules and subcutaneous nodules of 0.3-1.0 cm in diameter on his left forearm. The lesions started to appear about 4 months after an earlier electric welding rod burn had healed. The histopathologic diagnosis of the lesions was ALHE. Because the new lesions developed progressively and malignancy could not be excluded, the patient underwent a wide elliptical excision and received a split-thickness skin graft from his left thigh. His postoperative recovery was successful and has showed no evidence of recurrence after 5 years of follow-up. The forearm is an unusual site for ALHE; the antecedent burn was the key trigger for ALHE onset in this case., (Copyright (c) 2010 Elsevier. Published by Elsevier B.V. All rights reserved.)

Aims: Cytology fails to detect neoplastic cells in 40-50% of cases of malignant pleural effusion, a condition that frequently accompanies lung adenocarcinoma. Published reports of diagnostic sensitivity of various tumour markers are inconsistent, and optimal cut-off points have not been determined. This study aimed to evaluate the ability of three markers to discriminate lung adenocarcinoma-associated malignant pleural effusion (LAC-MPE) from benign effusion., Methods: Pleural effusion samples were collected from 41 patients with LAC-MPE, and from 93 with various benign conditions. The diagnostic sensitivity and specificity for Her-2/neu, Cyfra 21-1, and carcinoembryonic antigen (CEA) were evaluated. Cut-off points for these markers are optimally set at 3.6 microg/L, 60 microg/L, and 6.0 microg/L, respectively., Results: Her-2/neu, Cyfra 21-1, and CEA vary in their diagnostic accuracy to differentiate LAC-MPE from benign pleural effusion: 79.85%, 88.81%, and 94.03%, respectively. CEA combined with Cyfra 21-1 increases diagnostic sensitivity to 97.6%, with a specificity of 91.4%., Conclusions: With appropriate cut-off points, CEA currently provides the best diagnostic accuracy. Combining CEA with Cyfra 21-1 increases diagnostic sensitivity to nearly 100%. The results of the present study may help clinicians decide whether to obtain a cytological/histological specimen by invasive means to investigate a possible diagnosis of malignancy.

This paper describes a signal processing technique for ECG signal analysis based upon the combination of wavelet analysis and fuzzy c-means clustering. The signal analysis technique is implemented into a biomedical signal diagnostic unit that is the carry on device for the Wireless Nano-Bios Diagnostic System (WNBDS) developed at National Taiwan University. The WNBDS integrates mobile devices and remote data base servers to conduct online monitoring and remote healthcare applications. The signal analysis and diagnostic algorithms in this paper are implemented in an embedded mobile device to conduct mobile biomedical signal diagnostics. At this stage, the Electrocardiogram (ECG or EKG) is analyzed for patient health monitoring. The ECG signal processing is based on the wavelet analysis, and the diagnosis is based on fuzzy clustering. The embedded system is realized with the Windows CE operating system.