Value In Pathology Research Articles

Влияние соединений на основе янтарной кислоты и хитозана на активность аконитатгидратазы и содержание цитрата в тканях крыс при ишемии/реперфузии головного мозга

При введении фармакологических средств на основе янтарной кислоты и хитозана в различных дозах крысам с ишемией/реперфузией головного мозга было отмечено снижение в ткани мозга уровня лактата — маркера развития ишемического состояния — по сравнению со значением при патологии. В этих условиях также выявлено возрастание активности аконитазы — чувствительной мишени действия свободных радикалов — и снижение уровня цитрата в головном мозге и сыворотке крови животных в сторону контрольных значений. Выявленные изменения носят дозозависимый характер. Полученные результаты свидетельствуют о способности данных соединений снижать степень метаболических повреждений и развитие окислительного стресса при постишемической реперфузии. Вследствие этого исследуемые средства могут представлять значительный интерес с точки зрения фармакологической коррекции изменений метаболизма при развитии патологий подобного рода. Более выраженный нейропротекторный и антиоксидантный эффект был обнаружен для сукцината хитозана (по сравнению с N-сукцинилхитозаном).

Evaluation of cell-free DNA as a biomarker for pancreatic malignancies

Currently, no reliable blood-based assay for early detection of pancreatic ductal adenocarcinoma (PDAC) is available. Cell-free DNA (cfDNA) quantitation in patients' plasma has been recently applied in monitoring several cancer types. This study evaluates the diagnostic potential of cfDNA in PDAC patients. Plasma cfDNA levels and integrity ratio were assayed using quantitative real-time PCR of Alu-repeat amplicons in patients with pancreatic ductal adenocarcinoma (n=50), pancreatic neuroendocrine tumor (n=23), and chronic pancreatitis (n=20), as well as in healthy volunteers without evidence of pancreatic disease (n=23). The total load of cfDNA, obtained by Alu83 quantitation, was the highest in PDAC patients than in any of the other patient groups (Welch t test; p<0.001) and was an average predictor of PDAC disease (AUC=0.664; CI, 0.56-0.77). A nonlinear association between Alu83 levels and subjects' age was detected (Spearman's rho=0.35; p<0.001) in the overall population, as well as within the PDAC patients' group (Spearman's rho=0.47; p<0.001). Necrosis-derived cfDNA fragments, quantitated with the Alu244 amplicon, were barely detectable in any of the samples and, in that respect, comparable between the different subject groups. CfDNA integrity estimation (Alu244/Alu83 ratio) was significantly affected by the limited detectability of plasma Alu244 levels. The lack of detectable levels of necrosis-derived cfDNA in pancreatic pathologies considerably affects the clinical use of such biomarker in PDAC patients. Different methods of analysis should be applied in the evaluation of the cfDNA diagnostic value in pancreas pathology.

The value of clinical pathology in pet rabbit medicine

AS rabbits become a more mainstream companion animal and are no longer considered merely a children's or ‘exotic’ pet, rabbit medicine is at last beginning to catch up with other...

Validation of the Oxford classification of IgA nephropathy in cohorts with different presentations and treatments

The Oxford Classification of IgA Nephropathy (IgAN) identified mesangial hypercellularity (M), endocapillary proliferation (E), segmental glomerulosclerosis (S), and tubular atrophy/interstitial fibrosis (T) as independent predictors of outcome. Whether it applies to individuals excluded from the original study and how therapy influences the predictive value of pathology remain uncertain. The VALIGA study examined 1147 patients from 13 European countries that encompassed the whole spectrum of IgAN. Over a median follow-up of 4.7 years, 86% received renin–angiotensin system blockade and 42% glucocorticoid/immunosuppressive drugs. M, S, and T lesions independently predicted the loss of estimated glomerular filtration rate (eGFR) and a lower renal survival. Their value was also assessed in patients not represented in the Oxford cohort. In individuals with eGFR less than 30 ml/min per 1.73 m2, the M and T lesions independently predicted a poor survival. In those with proteinuria under 0.5 g/day, both M and E lesions were associated with a rise in proteinuria to 1 or 2 g/day or more. The addition of M, S, and T lesions to clinical variables significantly enhanced the ability to predict progression only in those who did not receive immunosuppression (net reclassification index 11.5%). The VALIGA study provides a validation of the Oxford classification in a large European cohort of IgAN patients across the whole spectrum of the disease. The independent predictive value of pathology MEST score is reduced by glucocorticoid/immunosuppressive therapy.

GATA3

GATA3 is a transcription factor important in the differentiation of breast epithelia, urothelia, and subsets of T lymphocytes. It has been suggested to be useful in the evaluation of carcinomas of mammary or urothelial origin or metastatic carcinomas, but its distribution in normal and neoplastic tissues is incompletely mapped. In this study, we examined normal developing and adult tissues and 2040 epithelial and 460 mesenchymal or neuroectodermal neoplasms for GATA3 expression to explore its diagnostic value in surgical pathology, using monoclonal antibody (clone L50-823) and Leica Bond automated immunohistochemistry. GATA3 was expressed in trophoblast, fetal and adult epidermis, adult mammary and some salivary gland and sweat gland ductal epithelia, urothelia, distal nephron in developing and adult tissues, some prostatic basal cells, and subsets of T lymphocytes. It was expressed stronger in fetal than in adult mesothelia and was absent in respiratory and gastrointestinal epithelia. In epithelial neoplasms, GATA3 was expressed in >90% of primary and metastatic ductal and lobular carcinomas of the breast, urothelial, and cutaneous basal cell carcinomas and trophoblastic and endodermal sinus tumors. In metastatic breast carcinomas, it was more sensitive than GCDFP. Among squamous cell carcinomas, the expression was highest in the skin (81%) and lower in cervical (33%), laryngeal (16%), and pulmonary tumors (12%). Common positivity was found in skin adnexal tumors (100%), mesothelioma (58%), salivary gland (43%), and pancreatic (37%) ductal carcinomas, whereas frequency of expression in adenocarcinomas of lung, stomach, colon, endometrium, ovary, and prostate was <10%. Chromophobe renal cell carcinoma was a unique renal tumor with frequent positivity (51%), whereas oncocytomas were positive in 17% of cases but other types only rarely. Among mesenchymal and neuroectodermal tumors, paragangliomas were usually positive, which sets these tumors apart from epithelial neuroendocrine tumors. Mesenchymal tumors were only sporadically positive, except epithelia of biphasic synovial sarcomas. GATA3 is a useful marker in the characterization of not only mammary and urothelial but also renal and germ cell tumors, mesotheliomas, and paragangliomas. The multiple specificities of GATA3 should be taken into account when using this marker to detect metastatic mammary or urothelial carcinomas.

Preoperative Patient and Injury Factors of Successful Rehabilitation After Anterior Cruciate Ligament Reconstruction With Single-Bundle Techniques

The aim of this systematic review was to determine which patient determinants and injury factors, before anterior cruciate ligament reconstruction by arthroscopic single-bundle techniques, affect postoperative rehabilitation. A search of PubMed, Embase, and the Cochrane Database of Clinical Trials was performed up to February 2013. After application of our inclusion criteria, a final selection was made based on studies' methodologic score assessed with the Newcastle-Ottawa Scale. Meta-analysis was planned for each prognostic factor when data were considered clinically and statistically homogeneous. Meta-analysis showed that male patients have better functional outcomes. Qualitative synthesis from 18 high-quality studies showed that patients operated on before 30 years of age reach higher activity levels. Patients with high baseline body mass index have lower activity levels after surgery. Smoking results in more symptoms and lower activity levels and subjective scores. Reconstruction before 3 months results in higher activity levels. Preoperatively, a less than 20% quadriceps strength difference, 50° of tibial external rotation or less, absence of flexion deficits, low knee influence on the patient's activity level, and less anterior knee pain result in higher functional scores. Preoperative anterior laxity difference does not predict functional scores. The prognostic value of preoperative activity and competition level for postoperative functional outcome is controversial. Patients with concomitant meniscal injuries have worse functional outcomes. The prognostic value of concomitant chondral pathology for postoperative functional outcome is controversial. Collateral ligament injury could predict functional scores or activity level. Male gender, patient age younger than 30 years, reconstruction before 3 months, and high baseline activity level contribute to better functional outcomes. Smoking, high body mass index, quadriceps strength, and range-of-motion deficits affect rehabilitation negatively. Preoperative anterior laxity does not influence rehabilitation. The role of preoperative prognostic injury factors remains unclear because of limited evidence. Level III, systematic review of Level II and III studies.

The costs and utility of imaging in evaluating dizzy patients in the emergency room

To determine the usefulness and the costs of computed tomography (CT) and magnetic resonance imaging (MRI) in the evaluation of patients with dizziness in the emergency department (ED). Retrospective chart review. Charts of patients with a specific health maintenance insurance plan presenting with dizziness and vertigo to a large health system's ED between January 2008 and January 2011 were reviewed. Patient demographics, signs/symptoms, and CT and MRI results were assessed. CT and MRI charges were determined based on positive versus unremarkable findings. Data analysis included stepwise logistic regressions. Of 1681 patients identified, 810 (48%) received CT brain/head scan totaling $988,200 in charges. Of these, only 0.74% yielded clinically significant pathology requiring intervention. However, 12.2% of MRI studies yielded discovery of significant abnormalities. Logistic regression analysis revealed that older patients (P = .001) were more likely to receive a CT scan. In the 3-year period studied, CT scans for ED patients with dizziness and vertigo yielded a low predictive value for significant pathology. These data reveal a great opportunity for cost savings by developing stricter guidelines for ordering CT scans for this set of ED patients. The use of MRI in all cases of dizziness was found to be neither practical nor useful. However, appropriately directed MRI of the brain is recommended in patients with dizziness and other neurological signs or symptoms.

Fine Needle Aspiration of Parotid Tumors: Diagnostic Utility From a Clinical Perspective

The utility of fine needle aspiration (FNA) for parotid tumors is limited owing to its low diagnostic accuracy. In this study, the authors sought to analyze and interpret FNA results for parotid tumors from a clinical perspective. Parotid tumors subjected to preoperative FNA and subsequent complete excision were the subject of this study. Patient demographics, medical records, FNA findings, and final pathology of 158 consecutive cases were analyzed. The accuracy of FNA was 77.8%. The positive predictive value and likelihood ratio for malignancy were 90.0% and 52.8% (95% confidence interval, 7.02-397), respectively. The positive predictive value and likelihood ratio for benign pathology of Warthin tumor plus pleomorphic adenoma were 97.8% and 7.67% (2.03-29.0), respectively. The FNA diagnosis of Warthin tumor or pleomorphic adenoma is reliable and can be safely regarded as a benign tumor. Based on the high positive predictive value and likelihood ratio, FNA of the parotid gland can offer valuable information in surgical planning and patient counseling in many centers.

Plusoptix photoscreening may replace cycloplegic examination in select pediatric ophthalmology patients

To determine whether children presenting to a pediatric ophthalmologist and found to have a normal Plusoptix photoscreener (PlusoptiX GmbH, Nuremberg, Germany) result, normal visual acuity (children age 3+), and normal alignment/motility receive additional benefit from a dilated fundus examination. The medical records of all children seen at one pediatric ophthalmology practice between 2007 and 2010 who were coded as having had a photoscreening were retrospectively reviewed. Of the total number of records identified, one-half were selected randomly for review. Patients who underwent plusoptiX screening on the first visit were included. Patients with abnormal alignment and/or abnormal vision as well as those referred for examination as determined by a medical or ophthalmic condition that required a dilated fundus examination were excluded. Of 1,377 patients identified, 697 were selected randomly for record review. Of these, 451 had had an initial plusoptiX screening. A total of 222 had a normal result. Of the 190 patients analyzed, cycloplegic examination provided additional diagnostic information for only 4 children: 1 with nonvisually significant congenital cataract, 1 with refractive amblyopia from moderate astigmatism, 1 with moderate hyperopia who later was found to have accommodative esotropia, and 1 with increased cupping but normal IOP. A normal plusoptiX result, combined with normal alignment/motility evaluation and visual acuity was found to have a 98% negative predictive value for ophthalmic pathology, including significant refractive error. The plusoptiX and an abbreviated eye examination may obviate the need for dilation in select children.

Impact of White Matter Lesions and Cognitive Deficits on Conversion from Mild Cognitive Impairment to Alzheimer's Disease

Mild cognitive impairment (MCI) may represent a prodromal stage of dementia and confers a particularly high annual risk of 10-15% for conversion to Alzheimer's disease (AD). Recent findings suggest that white matter lesion pathology (WML) can negatively influence conversion from MCI to AD. In this study, we examined the predictive value of neuropsychological test results and WML pathology on conversion of MCI to AD. Retrospective neuropsychological and magnetic resonance imaging data were collected for MCI patients seen at the University Clinic of Innsbruck between 2005 and 2011. WML were visually rated using the Fazekas and Scheltens scales. Of the 60 subjects, 31 converted to AD during a follow-up of 18.3 ± 7.4 months and 29 remained stable. Orientation, MMSE score, word list learning and recall, visual memory, and naming scores were significantly lower in MCI patients converting to AD than in non-converters. Converters had significantly higher Fazekas scores and more WML in periventricular regions. Periventricular WML were negatively associated with psychomotor speed, and subcortical WML were negatively correlated with visual memory at baseline in all MCI patients. Low scores in orientation and verbal delayed recall were predictors of progression from MCI to AD. Periventricular WML correlate with lower cognitive function in patients with MCI. However, deficits in orientation and verbal memory, but not vascular changes, turned out as predictive for conversion from MCI to AD. Consequently, a higher WML burden may represent a serious risk factor but not an early symptom for the imminent conversion to AD.

Defining communication disability in under-served communities in response to the World Report on Disability

The World Report on Disability takes a broad emphasis on disability. In their paper on the implications of this report for speech-language pathology and for people with communication disabilities, Wylie, McAllister, Davidson, and Marshall (2013) emphasize the importance of promoting a broader view of communication disability. This commentary explores the challenges of investigating the epidemiology of communication disability, in particular, the difficulties defining the disability and then measuring it in a valid and reliable manner. The two interpretations are discussed of the concept medically under-served as it relates to speech-language pathology: service availability and service accessibility. Bourdieu's forms of capital were then explored as a way of understanding an individual's perception of capital and how service provision can enhance perceived capital and minimize loss of capital. It is important services are mindful of the variations of capital and engage with communities to facilitate access and increase their perceptions of the value of speech-language pathology (SLP) services. The focus throughout is on pre-school children with communication disability in the context of a program of research in England, called Child Talk–What Works.

Is There Any Additional Benefit of Contrast-Enhanced CT as Part of Routine PET/CT Protocols for the Differentiation of Suspicious Incidental Gastrointestinal 2-Deoxy-18F-FDG Uptake?

ObjectiveSuspicious incidental gastrointestinal FDG uptake during positron-emission tomography/computed tomography (PET/CT) examinations can be caused by different diseases, including malignancies. However, differentiation with PET alone is difficult. The aim of this study was to investigate the potential of PET alone, contrast-enhanced CT (ceCT), and low-dose CT (ldCT) in routine PET/CT protocols for differentiation of incidental gastrointestinal lesions.Materials and MethodsSixty patients with incidental gastrointestinal lesions who underwent a routine PET/CT protocol with ldCT and ceCT were retrospectively analysed. The PET lesions were evaluated regarding their FDG uptake patterns and the standard uptake value. The anatomical correlates in both CT protocols were compared in regard to the correct lesion classification with the reference standard endoscopy.ResultsSixty-two lesions were found in 60 patients (17 malignant, 10 premalignant, 5 benign, 13 inflammatory, 17 physiological). The differentiation of the FDG uptake patterns did not enable reliable lesion classification. The positive predictive value for pathology was 0.81 for ceCT in PET/CT and 0.70 for ldCT. Malignancies were detected in 100% of the patients by ceCT vs. 29.4% by ldCT. The false negative rate of ceCT for all pathologies was 31.1%, vs. 68.9% for ldCT. False positive results (17/62) could not be excluded sufficiently by either CT protocol.ConclusionPET/ceCT protocols provide additional benefit especially in detecting gastrointestinal malignancies as a cause of suspicious incidental gastrointestinal FDG uptake. However, since follow-up endoscopy cannot be forgone due to the considerable false negative rate even with ceCT, the addition of ceCT to a routine PET/ldCT protocol cannot be recommended for this purpose.

Response to Guest Editorial (“Veterinary Pathology Under the Microscope: Planning for the Future”)

Several interesting and important issues were raised in a recent editorial published in Veterinary Pathology regarding possible future directions and emphases of the ACVP/ECVP/JCVP’s official publication. One of the principal reasons for publishing Veterinary Pathology, as outlined in that editorial, is its indispensible role in disseminating scientific information that is relevant to the field of veterinary pathology and to practicing veterinary pathologists, veterinary pathologists in training, and nonpathologists alike. I applaud the establishment of a Strategic Planning Task Force that will produce a plan designed to ensure the continued success of the journal in what promises to be a challenging future in the world of scientific publications. The wide range of interests and needs of ACVP/ECVP/ JCVP members makes this a daunting task and one that will have a large impact on the future of our specialty. Perhaps the primary consideration is that as the official publication of the ACVP/ECVP/JCVP, Veterinary Pathology affects the image and prestige of our profession/specialty. Fairly or not, the inordinately weak impact factor of the journal probably does not influence perceptions of our specialty in a positive way. At the very least, on the basis of personal experiences with coauthors, I can attest that a weak impact factor does not encourage submission of some potentially important papers to Veterinary Pathology. In this regard, the large improvement in the journal’s impact factor in the past year reflects well on the concerted efforts of the journal editors to improve the quality of papers accepted for publication. As the editors continue this effort and if ACVP/ECVP/JCVP members will increase their support of the journal by submitting more of their best work for publication, it is very likely that a ‘‘virtuous cycle’’ can be established in which researchers are incentivized to submit their probable ‘‘high impact’’ papers to a journal having a higher impact factor. One of the challenges facing the Strategic Planning Task Force will be to figure out how to publish a journal with global importance that still provides real value to its supporting members. I believe that it is possible to reconcile the seemingly conflicting requirements to provide useful information for ACVP/ECVP/JCVP members having a wide range of professional interests and job requirements while simultaneously raising the profile of veterinary pathology and veterinary pathologists in the global biomedical research community. I believe that this is an achievable goal, but some changes will be necessary. The strategic plan must continue to recognize and address the especially critical role that the journal plays in the training and continuing education of veterinary pathologists. Veterinary Pathology is one of the few existing venues in which detailed descriptive reports that focus on the pathology and/or pathogenesis of disease in animals can be published. Although veterinary pathologists often make valuable contributions to studies published in many different top-tier journals, the pathology itself is often shortchanged in those reports. The strict space constraints in many journals too often result in severely condensed pathology descriptions, generally accompanied by postage stamp–sized images that function more as colorful decorations felt necessary for a ‘‘real science’’ paper. In contrast, because Veterinary Pathology is published by organizations and editors that understand and appreciate the value of pathology, papers can include detailed morphologic descriptions of lesions, as well as high-quality images large enough to actually convey useful information. Following are some specific suggestions to consider in mapping a strategy to increase the impact factor of Veterinary Pathology, without negating the distinct services it provides to our profession.

Focused Transthoracic Echocardiography Predicts Perioperative Cardiovascular Morbidity

The aim of this study was to assess the risk and predictive value of cardiac pathology detected on an anesthesiologist-performed focused transthoracic echocardiogram with adverse cardiac outcomes in the perioperative period. A retrospective review of 222 patients having a focused transthoracic echocardiogram and evaluating the incidence and echocardiographic risk factors associated with perioperative adverse cardiac events. A single tertiary referral university teaching hospital. Two hundred twenty patients who had a focused transthoracic echocardiogram performed by an anesthesiologist. All patients who had a focused transthoracic echocardiogram had their discharge summary and any perioperative troponin levels reviewed, looking for evidence of adverse cardiac events, including cardiac death before discharge, myocardial infarction, pulmonary edema, hypotension requiring vasoactive drug infusion, or new arrhythmia. Data were collected on the 222 patients who had an anesthesiologist-performed focused transthoracic echocardiogram, with 39 (18%) having an adverse cardiac event. There were 24 (11%) myocardial infarctions, 6 (2.7%) new arrhythmias, 5 (2.3%) deaths, and 4 (1.8%) episodes of severe hypotension. High-risk pathology detected on echocardiography included adverse cardiac events in 64% of the patients with pulmonary hypertension, 56% of the patients with left or right ventricular dysfunction, and 17% of the patients with stenotic valvular disease. In particular, patients with a combination of pulmonary hypertension, ventricular dysfunction, and/or stenotic valvular disease had a 77% risk of an adverse cardiac event. In contrast, no patients with a completely normal study, flow murmur, or isolated regurgitant valvular disease had adverse cardiac events. Anesthesiologist-performed focused transthoracic echocardiography predicts perioperative adverse cardiac events in noncardiac surgical patients.

Site-specific pathology in breast reduction mammoplasty.

To investigate the feasibility and clinical value of site-specific pathology in breast reduction mammoplasty. Totally 127 patients who underwent breast reduction mammoplasty from June 2007 to June 2010 were included. Pathologic specimens were sent for frozen pathology according to the clock-wise method. Patients with confirmed cancer were arranged for conservative breast surgery. Of the 127 patients, 53 patients (41.7%) had gland hyperplasia; 7 had fibroadenoma (5.5%); 1 (0.79%) had ductal carcinoma in situ, who underwent breast conserving surgery, following by chemotherapy and radiotherapy, no relapse was noted during the three-year follow-up. Clock-wise method is useful to locate the tumor and ensure the patients to receive skin-spared breast resection even cancer is detected.

917 NOVEL PREDICTORS OF BENIGN PATHOLOGY IN STAGE IA OR IB PATIENTS WITH NON-SEMINOMATOUS TESTICULAR GERM CELL MALIGNANCY UNDERGOING PRIMARY RETROPERITONEAL LYMPH NODE DISSECTION

INTRODUCTION AND OBJECTIVES: There is no consensus on the optimal treatment for Stage I testicular non seminomatous germ cell tumors (T NSGCT), partly due to the inaccuracy of clinical staging methods. Prior reports have demonstrated that the presence of embyronal carcinoma (EC), lymphovascular invasion (LVI), and absence of yolk sac tumor (YST) in the orchiectomy specimen are important risk factors predicting occult metastatic disease. We assessed whether a novel combination of the above factors could predict the presence of benign retroperitoneal pathology. METHODS: We reviewed an institutional database of patients with T NSGCT and included all patients with Stage IA or IB NSGCT who underwent primary RPLND. Logistic regression analysis was used to compare patients with benign pathology versus germ cell tumor (GCT). A combination of significant pathologic factors was used as internal validation to predict the presence of benign or GCT pathology. Significance was determined at p 0.05. No financial funding was obtained. RESULTS: Among 55 patients with Stage IA or IB NSGCT managed with primary RPLND, 44(80%) had benign pathology and 11 (20%) had occult GCT in the retroperitoneum. No specimens revealed retroperitoneal teratoma in this cohort. Predictors of benign pathology were higher preorchiectomy alpha fetoprotein levels (p 0.03), larger percentage of YST (p 0.02), lower embryonal carcinoma to YST (E/Y) ratio (p 0.001), presence of teratoma and absence of LVI in the primary orchiectomy specimen (both p 0.01). Multivariate analysis demonstrated an E/Y ratio 4 to be a strong predictor of benign pathology in the retroperitoneum, with an area under the receiver operating curve of 0.71 0.08 (p 0.04), and a sensitivity and specificity of 37% (16/43) and 100% (12/12), respectively. In combination with absence of LVI, an E/Y ratio 4 had a 100%(10/10) positive predictive value for benign pathology on internal validation. Conversely, presence of LVI and an E/Y ratio of 4 revealed a 64% (7/11) predictive value for GCT. CONCLUSIONS: In our cohort, patients with Stage IA or IB NSGCT who had benign pathology on the primary RPLND had a significantly higher proportion of YST to EC in the preorchiectomy specimen. An E/Y cutoff value of 4 appears to be discriminatory for predicting benign pathology. Emphasis on the proportion of YST in the primary orchiectomy specimen in addition to other previously established risk factors may allow for improved risk stratification.

Using the Electronic Medical Record to Better Define “No Products of Conception” as a Critical Value in Anatomic Pathology

At present, the College of American Pathologists checklist requires documentation of communication of critical values in anatomic pathology to caregivers. Recently, our institution has begun using the electronic medical record to document the lack of imminent danger or emergency associated with the case rather than calling the caregiver. I sought to document this trend. The results of all critical values and all endometrial curettings with a diagnosis of "no products of conception seen" for the last 3 years at 1 hospital were reviewed. During the first 18 months, 0 of 11 critical cases were documented by reference to the electronic medical record. During the second 18 months 5 of 14 cases (36%; P = .02) were documented to have an intrauterine pregnancy by ultrasound and the physician was not notified. In our laboratory, cases without products of conception and a documented intrauterine pregnancy are no longer considered critical values in anatomic pathology. Documentation of the lack of imminent danger to the patient through reference to the electronic medical record is an increasingly common and acceptable means of ensuring patient safety and more accurately defining critical values in anatomic pathology.

Does Transvaginal Ultrasonography Have Good Diagnostic Value in Endometrial Pathology?

Introduction: Endometrial biopsy is usually considered unnecessary in post-menopausal uterine bleeding when the endometrial thickness (ET) is less than 5 mm because the risk of endometrial hyperplasia or cancer is low. However, there is still much controversy from this as some believe that the diagnostic value of ET in diagnosis of endometrial pathology (EP) in postmenopausal bleeding is necessary. In this study, the diagnostic value of ET for diagnosis of EP in post-menopausal bleeding was evaluated. Materials and methods: Sixty post-menopausal women with uterine bleeding were evaluated. Transvaginal ultrasonography (TVS) was used for measurement of ET followed by dilatation and curettage in a one-day interval. According to the EP, patients were divided in two groups, normal and abnormal. Endometrial atrophy was considered as normal and hyperplasia, polyps and carcinoma was considered as abnormal. Results: Twenty nine cases had ET more than 6 mm, among them, 25 cases had abnormal pathology (hyperplasia, polyp, cancer) and 4 cases were normal (atrophy). Thirty-one patients had ET equal or less than 6mm, among them, 26 cases were normal (atrophy) and 5 cases had abnormal pathology. The sensitivity, specifi ty, positive and negative predictive values of TVS in the diagnosis of uterine pathology were 83.3%, 86.7%, 86.2%, 83.9% respectively. Conclusion: We suggest that an ET of less than 6 mm in TVS is unlikely to indicate EP in post-menopausal women with uterine bleeding.

Regulation of proton-coupled folate transporter in retinal Müller cells by the antipsoriatic drug monomethylfumarate

Fumaric acid esters are used to treat psoriasis, an inflammatory skin disease characterized by keratinocyte proliferation. Inflammation and proliferation are hallmarks of retinal disease; hence, fumaric acid esters may have therapeutic value in retinal pathology. In diseased retinas, Müller glial cells (MCs) undergo reactive gliosis, a hyperproliferative state. MCs take up folate, a vitamin necessary for cell proliferation, via the proton-coupled folate transporter (PCFT). Here we examined the effect of monomethylfumarate (MMF), the active metabolite of fumaric acid esters, on expression and function of PCFT in MCs. Primary MCs, isolated from neonatal mouse retinas, were treated with MMF, and PCFT function was monitored by measuring uptake of radiolabeled methyltetrahydrofolate (MTF) at pH 5.5. Dose-response and time-course analyses were performed to identify optimal conditions for maximal effect. The influence of MMF treatment on kinetic parameters of PCFT was studied, and PCFT expression was analyzed at the mRNA and protein level. MTF uptake in MCs decreased by ˜50% following 18 h treatment with 1 mM MMF. This effect was specific to fumaric acid esters. MMF treatment decreased the maximal velocity of the transporter without altering substrate affinity. The decrease in PCFT function following MMF treatment was accompanied by attenuated PCFT expression. This is the first report that an antipsoriatic compound can regulate folate transport in MCs and may have potential for the treatment of reactive gliosis in retinal disease.

Validating the Oxford Classification of IgA Nephropathy

The evolution of patients with IgA nephropathy (IgAN) varies greatly, and predictive tools are needed to assess confidently the risk for progression. Although in many studies clinical risk factors such as hypertension and proteinuria have consistently been linked to outcome, the independent value of pathology remains debated. Pathologists have developed a number of classifications over the years, at times with seemingly conflicting results. In 2009, the International IgA Nephropathy Network Group, working in collaboration with the Renal Pathology Society, proposed a set of four predictive renal biopsy findings independent of clinical assessment, the MEST score (M, mesangial hypercellularity; E, endocapillary proliferation; S, segmental glomerulosclerosis/adhesion;