Search

After the 2013 International Congress of Cytology in Paris, consensus groups were formed to establish an international reporting system for urinary tract ( UT) specimens. The recommended guidelines, known as The Paris System ( TPS) for Reporting Urinary Cytology, focus on reducing the rate of unnecessary indeterminate diagnoses while maintaining the excellent performance UT cytology has for identifying high-grade urothelial carcinoma. This review highlights the major features of TPS. [ABSTRACT FROM AUTHOR]

By reducing the rate of indeterminate (atypical) diagnoses and standardising reporting terminology, The Paris System for Reporting Urine Cytology helps focus the application of cytology towards the detection primarily of high‐grade urothelial carcinoma. We present a urology‐based perspective of how the new system has influenced clinical decision‐making. [ABSTRACT FROM AUTHOR]

Introduction L’atteinte rénale touche jusqu’à 80 % des patients ayant une vascularite associée aux ANCA, avec un risque d’évolution vers l’insuffisance rénale terminale dans 25 % des cas. Deux types d’ANCA pathogènes sont décrits, MPO et PR3. Le but de notre étude est d’évaluer l’impact de la spécificité des ANCA sur la survie rénale. Patients/matériels et méthodes Cette étude observationnelle multicentrique rétrospective a recruté les patients de centres hospitaliers des Hauts-de-France présentant une vascularite à ANCA avec atteinte rénale. Les patients étaient traités selon les recommandations du GFEV. Les données de deux groupes distincts par le type des ANCA, MPO ou PR3, étaient comparées : clinique, biologie et histologie au diagnostic et évolution. Résultats Ont été inclus 114 patients avec des ANCA positifs (50 PR3 et 64 MPO), dont 104 ont eu une relecture de la biopsie rénale. Le BVAS médian au diagnostic était plus élevé dans le groupe PR3 versus MPO (20 ± 8 versus 17,8 ± 4,6, p = 0,004). Le taux médian de créatinine au diagnostic était 37,5 ± 44,5 mg/L dans le groupe PR3 et 30 ± 30 mg/L dans le groupe MPO (p = 0,775). Selon la classification de Berden, on observait un glomérulonéphrite extracapillaire focale chez 26,2 % et 25,8 %, mixte chez 26,2 % et 40,3 %, à croissants prédominants chez 38,1 % et 24,2 %, scléreuse chez 9,5 % et 9,7 % des patients dans les groupes PR3 et MPO respectivement (p = 0,381). Les lésions de fibrose interstitielle et d’atrophie tubulaire n’étaient pas significativement différentes. La créatinine à la rémission était à 15,5 ± 10,95 mg/L et 16 ± 9,95 mg/L (p = 0,47), et l’incidence de l’insuffisance rénale terminale était à 26 % et 26,56 % pour les groupe PR3 et MPO respectivement. Durant le suivi, on notait la survenue de 17 et 11 rechutes rénales dans les groupes PR3 et MPO respectivement (p = 0,05). Les survies globales à l’issue du suivi étaient comparables. Discussion L’impact de la spécificité des ANCA a été étudié [1] , certains rapportant une moins bonne survie rénale et globale chez les patients MPO, en rapport avec des lésions plus chroniques. Dans cette étude, le pronostic rénal et global sont similaires dans les groupes PR3 et MPO, avec au diagnostic une présentation histologique comparable. Le groupe PR3 fait plus de rechutes dans notre cohorte que le groupe MPO, sans impact sur la survie rénale et globale. Conclusion La survie rénale et globale n’étaient pas significativement différentes en fonction de la spécificité des ANCA dans cette série de patients ayant une vascularite à ANCA avec atteinte rénale. [ABSTRACT FROM AUTHOR]

Introduction Les lésions de fibrose rénales représentent une caractéristique commune des maladies rénales chroniques et participent, à terme, au développement d’insuffisance rénale chronique terminale. Bien que miR-21 soit un microARN communément impliqué dans le processus de fibrose rénale, les données expérimentales de la littérature restent contradictoires et suggèrent que ce miARN joue un rôle complexe et ambivalent, protecteur ou délétère, selon le contexte des pathologies rénales, aiguës ou chroniques. L’objectif de ce travail est de préciser l’implication de miR-21 dans deux modèles murins de néphrotoxicité induite par le tacrolimus et le cisplatine. Patients/matériels et méthodes Dans un premier modèle, des souris ont été exposées pendant 28 jours au tacrolimus (1 mg/kg/j). Le second modèle repose sur l’utilisation de souris invalidées pour miR-21 exposées au cisplatine de manière aiguë (injection d’une dose unique de 10 mg/kg) ou subaiguë (injections répétées de 7 mg/kg de cisplatine). La fonction rénale des animaux a été évaluée. Les reins prélevés ont permis de réaliser des analyses histologiques et de mesurer l’expression de miR-21, de marqueurs de souffrance rénale, d’inflammation et de stress oxydant dans les deux modèles. Résultats Dans le premier modèle, les souris exposées au tacrolimus ont une surexpression de miR-21 associée à des lésions rénales (surexpression de marqueurs de stress, d’inflammation et fibrotiques). De plus l’expression de miR-21, dans les coupes tissulaires, est localisée au niveau des tubules et dans le compartiment interstitiel, suggérant l’implication de ce dernier dans les lésions de fibrose induites par le tacrolimus. Dans le second modèle, les souris ayant reçu une injection unique de cisplatine ne présentent pas de différence significative d’urémie, de marqueurs de souffrance rénale, d’inflammation et de stress oxydant quel que soit leur statut sauvage ou invalidé pour miR-21. En revanche, les injections répétées de cisplatine induisent des lésions rénales plus sévères chez les souris miR-21-/- que chez les souris sauvages. Conclusion Ces résultats confirment ainsi que miR-21 joue un rôle ambivalent au cours des lésions rénales : protecteur à la phase précoce d’une agression rénale aiguë et délétère lorsque le processus se prolonge dans le temps. Des études complémentaires sont nécessaires afin d’évaluer l’intérêt potentiel de miR-21 en tant que cible thérapeutique innovante. [ABSTRACT FROM AUTHOR]

Background: Several scores have been developed to predict mortality at anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) diagnosis. Their prognostic value in Caucasian patients with kidney involvement (AAV-GN) remains uncertain as none has been developed in this specific population. We aimed to propose a novel and more accurate score specific for them., Methods: This multicentric study included patients diagnosed with AAV-GN since January 2000 in four nephrology centers (recorded in the Maine-Anjou AAV-GN Registry). Existing scores and baseline characteristics were assessed at diagnosis before any therapeutic intervention. A multivariable analysis was performed to build a new predictive score for death. Its prognosis performance (area under receiving operating curve and C-index) and accuracy (Brier score) was compared with existing scores. One hundred and eighty-five patients with AAV-GN from the RENVAS registry were used as a validation cohort., Results: A total of 228 patients with AAV-GN from the Maine-Anjou registry were included to build the new score. It included the four components most associated with death: age, history of hypertension or cardiac disease, creatinine and hemoglobin levels at diagnosis. Overall, 194 patients had all the data available to determine the performance of the new score and existing scores. The new score performed better than the previous ones in the development and in the validation cohort. Among the scores tested, only Five-Factor Score and Japanese Vasculitis Activity Score had good performance in predicting death in AAV-GN., Conclusions: This original score, named DANGER (Death in ANCA Glomerulonephritis-Estimating the Risk), may be useful to predict the risk of death in AAV-GN patients. Validation in different populations is needed to clarify its role in assisting clinical decisions., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Context.—: The College of American Pathologists (CAP) surveys provide national benchmarks of pathology practice., Objective.—: To investigate pancreaticobiliary cytology practice in domestic and international laboratories in 2021., Design.—: We analyzed data from the CAP Pancreaticobiliary Cytology Practice Supplemental Questionnaire that was distributed to laboratories participating in the 2021 CAP Nongynecologic Cytopathology Education Program., Results.—: Ninety-three percent (567 of 612) of respondent laboratories routinely evaluated pancreaticobiliary cytology specimens. Biliary brushing (85%) was the most common pancreaticobiliary cytology specimen evaluated, followed by pancreatic fine-needle aspiration (79%). The most used sampling methods reported by 235 laboratories were 22-gauge needle for fine-needle aspiration (62%) and SharkCore needle for fine-needle biopsy (27%). Cell block was the most used slide preparation method (76%), followed by liquid-based cytology (59%) for pancreatic cystic lesions. Up to 95% (303 of 320) of laboratories performed rapid on-site evaluation (ROSE) on pancreatic solid lesions, while 56% (180 of 320) performed ROSE for cystic lesions. Thirty-six percent (193 of 530) of laboratories used the Papanicolaou Society of Cytopathology System for Reporting Pancreaticobiliary Cytology in 2021. Among all institution types, significant differences in specimen volume, specimen type, ROSE practice, and case sign-out were identified. Additionally, significant differences in specimen type, slide preparation, and ROSE practice were found., Conclusions.—: This is the first survey from the CAP to investigate pancreaticobiliary cytology practice. The findings reveal significant differences among institution types and between domestic and international laboratories. These data provide a baseline for future studies in a variety of practice settings., Competing Interests: The authors are or were members of the College of American Pathologists Cytopathology Committee. Nwosu and Souers are employees of the College of American Pathologists., (© 2024 College of American Pathologists.)

Background & Aims: Next-generation sequencing (NGS) of pancreatic cyst fluid is a useful adjunct in the assessment of patients with pancreatic cyst. However, previous studies have been retrospective or single institutional experiences. The aim of this study was to prospectively evaluate NGS on a multi-institutional cohort of patients with pancreatic cyst in real time., Methods: The performance of a 22-gene NGS panel (PancreaSeq) was first retrospectively confirmed and then within a 2-year timeframe, PancreaSeq testing was prospectively used to evaluate endoscopic ultrasound-guided fine-needle aspiration pancreatic cyst fluid from 31 institutions. PancreaSeq results were correlated with endoscopic ultrasound findings, ancillary studies, current pancreatic cyst guidelines, follow-up, and expanded testing (Oncomine) of postoperative specimens., Results: Among 1933 PCs prospectively tested, 1887 (98%) specimens from 1832 patients were satisfactory for PancreaSeq testing. Follow-up was available for 1216 (66%) patients (median, 23 months). Based on 251 (21%) patients with surgical pathology, mitogen-activated protein kinase/GNAS mutations had 90% sensitivity and 100% specificity for a mucinous cyst (positive predictive value [PPV], 100%; negative predictive value [NPV], 77%). On exclusion of low-level variants, the combination of mitogen-activated protein kinase/GNAS and TP53/SMAD4/CTNNB1/mammalian target of rapamycin alterations had 88% sensitivity and 98% specificity for advanced neoplasia (PPV, 97%; NPV, 93%). Inclusion of cytopathologic evaluation to PancreaSeq testing improved the sensitivity to 93% and maintained a high specificity of 95% (PPV, 92%; NPV, 95%). In comparison, other modalities and current pancreatic cyst guidelines, such as the American Gastroenterology Association and International Association of Pancreatology/Fukuoka guidelines, show inferior diagnostic performance. The sensitivities and specificities of VHL and MEN1/loss of heterozygosity alterations were 71% and 100% for serous cystadenomas (PPV, 100%; NPV, 98%), and 68% and 98% for pancreatic neuroendocrine tumors (PPV, 85%; NPV, 95%), respectively. On follow-up, serous cystadenomas with TP53/TERT mutations exhibited interval growth, whereas pancreatic neuroendocrine tumors with loss of heterozygosity of ≥3 genes tended to have distant metastasis. None of the 965 patients who did not undergo surgery developed malignancy. Postoperative Oncomine testing identified mucinous cysts with BRAF fusions and ERBB2 amplification, and advanced neoplasia with CDKN2A alterations., Conclusions: PancreaSeq was not only sensitive and specific for various pancreatic cyst types and advanced neoplasia arising from mucinous cysts, but also reveals the diversity of genomic alterations seen in pancreatic cysts and their clinical significance., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Renal involvement is a severe manifestation of antineutrophil cytoplasmic antibody-associated vasculitis. Patients often progress to end-stage renal disease. The potential for renal recovery after the first flare has seldom been studied. Our objectives were to describe the evolution of the estimated glomerular filtration rate (eGFR) and identify factors associated with the change in the eGFR between diagnosis and the follow-up at 3 months (ΔeGFRM0-M3)., Methods: This was a retrospective study over the period 2003-2018 of incident patients in the Nord-Pas-de-Calais (France). The primary outcome was the ΔeGFRM0-M3., Results: One hundred and seventy-seven patients were included. The eGFR at 3 months was significantly higher than at diagnosis (mean ± standard deviation, 40 ± 24 vs. 28 ± 26 mL/min/1.73 m2, p < 0.001), with a ΔeGFRM0-M3 of 12 ± 19 mL/min/1.73 m2. The eGFR at 12 months was higher than at 3 months (44 ± 13 vs. 40 ± 24 mL/min/1.73 m2, p = 0.003). The factors significantly associated with the ΔeGFRM0-M3 in multivariate analysis were the percentage of cellular crescents and neurological involvement. The mean increase in the eGFR was 2.90 ± 0.06 mL/min/1.73 m2 for every 10-point gain in the percentage of cellular crescents., Conclusions: Early renal recovery after the first flare of pauci-immune glomerulonephritis occurred mainly in the first 3 months of treatment. The percentage of cellular crescents was the main independent predictor of early renal recovery., (© 2022 S. Karger AG, Basel.)

Background: Renal involvement in ANCA-associated vasculitis (AAV) is associated with poor outcomes. The clinical significance of arteritis of the small kidney arteries has not been evaluated in detail., Methods: In a multicenter cohort of patients with AAV and renal involvement, we sought to describe the clinicopathologic characteristics of patients with AAV who had renal arteritis at diagnosis, and to retrospectively analyze their prognostic value., Results: We included 251 patients diagnosed with AAV and renal involvement between 2000 and 2019, including 34 patients (13.5%) with arteritis. Patients with AAV-associated arteritis were older, and had a more pronounced inflammatory syndrome compared with patients without arteritis; they also had significantly lower renal survival ( P =0.01). In multivariable analysis, the ANCA renal risk score, age at diagnosis, history of diabetes mellitus, and arteritis on index kidney biopsy were independently associated with ESKD. The addition of the arteritis status significantly improved the discrimination of the ANCA renal risk score, with a concordance index (C-index) of 0.77 for the ANCA renal risk score alone, versus a C-index of 0.80 for the ANCA renal risk score plus arteritis status ( P =0.008); ESKD-free survival was significantly worse for patients with an arteritis involving small arteries who were classified as having low or moderate risk, according to the ANCA renal risk score. In two external validation cohorts, we confirmed the incidence and phenotype of this AAV subtype., Conclusions: Our findings suggest AAV with renal arteritis represents a different subtype of AAV with specific clinical and histologic characteristics. The prognostic contribution of the arteritis status remains to be prospectively confirmed., (Copyright © 2021 by the American Society of Nephrology.)

Preoperative staging of suspicious axillary lymph nodes (ALNs) allows patients to be triaged to ALN dissection or to sentinel lymph node biopsy (SLNB). Ultrasound-guided fine needle aspiration (FNA) and cytology of ALN is moderately sensitive but its clinical utility relies heavily on the cytologist's experience. We proposed that the 5-h automated GeneXpert system-based prototype breast cancer detection assay (BCDA) that quantitatively measures DNA methylation in ten tumor-specific gene markers could provide a facile, accurate test for detecting cancer in FNA of enlarged lymph nodes. We validated the assay in ALN-FNA samples from a prospective study of patients (N = 230) undergoing SLNB. In a blinded analysis of 218 evaluable LN-FNAs from 108 malignant and 110 benign LNs by histology, BCDA displayed a sensitivity of 90.7% and specificity of 99.1%, achieving an area under the ROC curve, AUC of 0.958 (95% CI: 0.928-0.989; P < 0.0001). Next, we conducted a study of archival FNAs of ipsilateral palpable LNs (malignant, N = 72, benign, N = 53 by cytology) collected in the outpatient setting prior to neoadjuvant chemotherapy (NAC). Using the ROC-threshold determined in the prospective study, compared to cytology, BCDA achieved a sensitivity of 94.4% and a specificity of 92.5% with a ROC-AUC = 0.977 (95% CI: 0.953-1.000; P < 0.0001). Our study shows that the automated assay detects cancer in suspicious lymph nodes with a high level of accuracy within 5 h. This cancer detection assay, scalable for analysis to scores of LN FNAs, could assist in determining eligibility of patients to different treatment regimens.

To increase the knowledge about S. capitis in the neonatal setting, we conducted a nationwide 3-month survey in 38 neonatal intensive care units (NICUs) covering 56.6% of French NICU beds. We demonstrated 14.2% of S. capitis BSI (S.capBSI) among nosocomial BSIs. S.capBSI incidence rate was 0.59 per 1000 patient-days. A total of 55.0% of the S.capBSIs were late onset catheter-related BSIs. The S. capitis strains infected preterm babies (median gestational age 26 weeks, median birth weight 855 g). They were resistant to methicillin and aminoglycosides and belonged to the NRCS-A clone. Evolution was favorable in all but one case, following vancomycin treatment.

The aims of this study were to determine whether tubulointerstitial damage in the form of interstitial fibrosis/tubular atrophy and total interstitial inflammation predicted progression to end stage renal disease (ESRD) and/or renal relapse (RR) in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). One hundred thirteen patients with AAV from six French centers with an index biopsy performed between 2003 and 2013 were included. Histological assessments using the AAV glomerular classification and the kidney allograft Banff classification were performed on pathological review. Biopsy tissues were also investigated by CD3, CD20, CD68, CD163, FOXP3 and RORγt immunohistochemical staining. Competing risks models were calculated. Of the 113 patients, 26 (23.0%) died during follow-up and 29 (25.6%) developed ESRD. Among the 94 patients who achieved remission by the end of induction therapy without developing ESRD, 26 (27.6%) experienced RR. The two independent prognostic factors for ESRD were the estimated glomerular filtration rate at presentation (HR 0.35; 95% CI 0.23-0.51; P < 0.0001) and IF/TA > 25% (HR 2.27; 95% CI 1.18-4.37; P = 0.014). When the distribution of interstitial immune cell phenotypes was included in a second multivariable model, the organization of lymphocytic infiltrates was also an independent predictor of ESRD (HR 2.86; 95% CI 1.35-6.1, P = 0.006). The independent risk factors for RR were a higher CD3/CD20 ratio (HR 1.39; 95% CI 1.05-1.85; P = 0.02) and the presence of RORγt positive cells (HR 2.70; 95% CI 1.11-6.54; P = 0.02). Our results highlight the prognostic value of initial histological evaluations in AAV. Measurements of tubulointerstitial damage and interstitial immune cell phenotype distributions should be considered to improve risk assessments for ESRD and RR.

Objective: To examine the incidence of lower genital tract dysplasia in women after solid organ transplantation, to evaluate risk factors associated with development of dysplasia, and to assess the timeline of disease development., Methods: This was a retrospective study of female patients who underwent solid organ transplantation at a large-volume tertiary care center between 2000 and 2015. Demographic and clinicopathologic factors were extracted from electronic medical records. Cumulative incidence of lower genital tract dysplasia was calculated, and univariate and multivariable logistic regression were performed to identify risk factors for the development of dysplasia., Results: Among 394 female solid organ transplant recipients, the median age was 41 years (interquartile range 29-53). Forty-seven (11.9%; 95% CI 8.8-15.9%) women developed lower genital tract dysplasia over a median follow-up of 7.8 years (interquartile range 4.6-12.9). Thirty-eight (9.6%) developed cervical intraepithelial neoplasia (CIN), with 14 (3.6%) diagnosed with CIN 2 or worse (one was cervical carcinoma). Nineteen (4.8%) developed noncervical lower genital tract dysplasia, including vulvar, vaginal, or anal dysplasia, with 13 (3.3%) diagnosed with high-grade dysplasia or worse (five were lower genital tract carcinoma [three anal, one vulvar, and one vaginal]). Ten (2.5%) developed both cervical and noncervical lower genital tract dysplasia. Black race was significantly associated with developing dysplasia (odds ratio [OR] 2.86; 95% CI 1.33-6.13) as was hydroxychloroquine use (OR 5.95; 95% CI 1.96-18.09). High-grade cervical dysplasia was diagnosed at a median interval of 3.18 years after transplant; noncervical high-grade lower genital tract dysplasia was diagnosed at a median interval of 3.94 years., Conclusions: One in eight transplant recipients developed lower genital tract dysplasia and approximately half were high-grade dysplasia or cancer. Black race and hydroxychloroquine use were associated with an increased risk of dysplasia. Yearly cervical screening and comprehensive lower genital examination beyond the cervix is indicated in this population.

Selective internal radiation therapy with Y-TheraSphere or Y-SIRSphere is used in the treatment of unresectable hepatic malignancies. To the best of our knowledge, this is the first Y-TheraSpheres series. BTG International Canada Inc. provided nonradiated microspheres from the Nordion manufacturer. The histologic processed microspheres were colorless, refractile, polarizable, 20 to 30 μm in diameter, and an occasional internal bulls'-eye seen with the condenser out and an internal cross seen with polarized light. Identical microspheres were identified in 15 hepatectomy specimens from four centers between February 2016 and March 2018. The patients were usually male (male=10, female=5) with a mean age of 59 years. All patients had a prior diagnosis of hepatocellular carcinoma (HCC) and documented Y-TheraSphere (mean duration from last deployment=32 wk). All surgical pathology specimens in these 15 patients were reviewed, but the microspheres were only identified in the hepatectomy specimens. During manuscript preparation, one case of Y-TheraSpheres gastritis was prospectively identified from a separate patient with a history of HCC and Y-TheraSpheres. In conclusion, recognition of Y-TheraSpheres is important so that one may consider the possibility of a nearby malignancy and or establish the cause of the background inflammatory or radiation-related injury. These structures can be easy to miss because the subtle morphology is distinct from previously reported Y-SIRSphere. Clues to the diagnosis include a history of HCC and background radiation change. We report the characteristic morphology as microspheres that overlap in size with Y-SIRSphere, but can be differentiated based on Y-TheraSpheres' colorless appearance with occasional internal bulls'-eyes with the condenser out and an internal cross with polarized light.

Background: Pauci-immune glomerulonephritis (PIGN) is a major prognostic factor in antineutrophil cytoplasmic antibodies-associated vasculitis (AAV). Renal remission is usually defined as improvement or stabilization of serum creatinine and proteinuria levels but the significance of hematuria is unclear. We evaluated the prognostic value of microscopic hematuria in patients in remission from a first flare of PIGN., Methods: A multicenter retrospective study was conducted of all patients with histologically proven PIGN in northern France who presented a first renal flare of AAV between 2003 and 2013. All patients received conventional induction treatment and were considered in remission. Two groups were defined by the presence (H+) or absence (H-) of hematuria (dipstick 1+ and/or cytology ≥10,000 erythrocytes/mL). The primary outcome measure was the occurrence of renal relapse (RR) and/or end-stage renal disease (ESRD)., Results: Eighty-six patients were included: 41 (48%) had hematuria at remission. The median follow-up time was 44 ± 34 months. There was no significant difference between the groups in terms of the primary endpoint or the number of RR. However, the survival rate without RR was significantly lower in the H+ group (p = 0.002). In multivariate analysis, risk factors for RR were hematuria at remission for relapses within 44 months (hazard ratio [HR] 4.15; 95% CI 1.15-15.01; p = 0.03) and the duration of maintenance immunosuppressive therapy (HR 0.96 per additional month; 95% CI 0.94-0.99; p = 0.002)., Conclusion: Hematuria at remission after a first PIGN flare was not associated with ESRD but with the occurrence of RR within 44 months of remission., (© 2019 S. Karger AG, Basel.)

Although Tacrolimus is an immunosuppressive drug widely used in renal transplantation, its chronic use paradoxically induces nephrotoxic effects, in particular renal fibrosis, which is responsible for chronic allograft dysfunction and represents a major prognostic factor of allograft survival. As molecular pathways and mechanisms involved in Tacrolimus-induced fibrogenic response are poorly elucidated, we assessed whether miRNAs are involved in the nephrotoxic effects mediated by Tacrolimus. Treatment of CD-1 mice with Tacrolimus (1 mg/kg/d for 28 days) resulted in kidney injury and was associated with alteration of a gene expression signature associated with cellular stress, fibrosis and inflammation. Tacrolimus also affected renal miRNA expression, including miRNAs previously involved in fibrotic and inflammatory processes as "fibromirs" such as miR-21-5p, miR-199a-5p and miR-214-3p. In agreement with in vivo data, Renal Proximal Tubular Epithelial cells exposed to Tacrolimus (25 and 50 µM) showed upregulation of miR-21-5p and the concomitant induction of epithelial phenotypic changes, inflammation and oxidative stress. In conclusion, this study suggests for the first time that miRNAs, especially fibromiRs, participate to Tacrolimus-induced nephrotoxic effects. Therefore, targeting miRNAs may be a new therapeutic option to counteract Tacrolimus deleterious effects on kidney.

Current non-invasive approaches for detection of urothelial cancers are suboptimal. We developed a test to detect urothelial neoplasms using DNA recovered from cells shed into urine. UroSEEK incorporates massive parallel sequencing assays for mutations in 11 genes and copy number changes on 39 chromosome arms. In 570 patients at risk for bladder cancer (BC), UroSEEK was positive in 83% of those who developed BC. Combined with cytology, UroSEEK detected 95% of patients who developed BC. Of 56 patients with upper tract urothelial cancer, 75% tested positive by UroSEEK, including 79% of those with non-invasive tumors. UroSEEK detected genetic abnormalities in 68% of urines obtained from BC patients under surveillance who demonstrated clinical evidence of recurrence. The advantages of UroSEEK over cytology were evident in low-grade BCs; UroSEEK detected 67% of cases whereas cytology detected none. These results establish the foundation for a new non-invasive approach for detection of urothelial cancer., Competing Interests: SS, CC, MR, LL, CD, YW, JC, DT, NS, JS, JP, LD, MP, IK, BA, AT, SB, CV, KF, DE, IC, LY, TB, AG, LD, RK, LD, CH, CS, RT, BY, TR, YP, RH, CT, KD, GN No competing interests declared, NP Founder of Personal Genome Diagnostics and PapGene and advises Sysmex-Inostics. These companies and others have licensed technologies from Johns Hopkins, of which BV, KK, and NP are inventors on a patent (U.S. 20140227705 A1) and receive royalties. The terms of these arrangements are managed by the university in accordance with its conflict of interest policies. Luis A Diaz: Member of the board of directors of Personal Genome Diagnostics (PGDx) and Jounce Therapeutics. LAD holds equity in PapGene, Personal Genome Diagnostics (PGDx) and Phoremost. He is a paid consultant for Merck, PGDx and Phoremost. LAD is an inventor of licensed intellectual property related to technology for ctDNA analyses and mismatch repair deficiency for diagnosis and therapy from Johns Hopkins University. These licenses and relationships are associated with equity or royalty payments to LAD. The terms of all these arrangements are being managed by Johns Hopkins and Memorial Sloan Kettering in accordance with their conflict of interest policies. In addition, in the past 5 years, LAD has participated as a paid consultant for one-time engagements with Caris, Lyndra, Genocea Biosciences, Illumina and Cell Design Labs. KK Ken W Kinzler: Founder of Personal Genome Diagnostics and PapGene and advises Sysmex-Inostics. These companies and others have licensed technologies from Johns Hopkins, of which BV, KK, and NP are inventors on a patent (U.S. 20140227705 A1) and receive royalties. The terms of these arrangements are managed by the university in accordance with its conflict of interest policies. BV Bert Vogelstein: Founder of Personal Genome Diagnostics and PapGene and advises Sysmex-Inostics. These companies and others have licensed technologies from Johns Hopkins, of which BV, KK, and NP are inventors on a patent (U.S. 20140227705 A1) and receive royalties. The terms of these arrangements are managed by the university in accordance with its conflict of interest policies., (© 2018, Springer et al.)

Objectives: The aims of the study were to investigate screening histories of women with adenocarcinoma in situ (AIS) and adenocarcinoma (AdCa) of the cervix and to further evaluate screening for glandular disease., Materials and Methods: Screening histories were retrospectively collected for patients with AIS or AdCa at a single large-volume academic institution from 2005 to 2015. Fisher exact and Wilcoxon rank sum tests were used to compare AIS with AdCa patient characteristics, distribution of preceding Pap (i.e., trigger Pap) results, and high-risk human papillomavirus testing. The association between Pap result and time to diagnosis was evaluated., Results: Eighty-seven cases, 50 AIS and 37 AdCa, met study criteria; median age was 31 and 43 years, respectively. Among the AIS cohort, 52.0% had a negative or low-risk trigger Pap result versus 24.3% of those with AdCa (p = .001). The time to diagnosis of AIS ranged from 8.4 to 18.8 weeks for those with high- versus low-risk or negative trigger Pap results, respectively (p = .002). The time to diagnosis of AdCa ranged from 14.6 to 44.7 weeks for those with high- versus low-risk or negative trigger Pap results, respectively (p = .003). Among those with high-risk human papillomavirus testing, 89.7% tested positive at the time of trigger Pap with 100% positivity among those with low-risk or negative trigger Pap results., Conclusions: Cervical AIS and AdCa affect many young nulliparous women and commonly preceded by low-risk or negative Pap testing. The interval to diagnosis increases with low-risk and negative Pap results, and therefore, further investigation into optimal screening for glandular lesions is needed.

Epithelioid hemangioendothelioma (EHE) is a rare mesenchymal tumor of vascular origin with variable morphological features and unpredictable biological behavior. EHE occasionally involves the pleural fluid. However, the cytomorphology of EHE found in pleural fluid has not been well characterized in the literature. Herein we describe a case of EHE, initially presenting as multiple liver lesions plus several small nodular densities at the bases of the lungs followed by bilateral pleural effusions., (© 2015 Wiley Periodicals, Inc.)

Exposure to toxicants leads to cumulative molecular changes that overtime increase a subject's risk of developing urothelial carcinoma. To assess the impact of arsenic exposure at a time progressive manner, we developed and characterized a cell culture model and tested a panel of miRNAs in urine samples from arsenic-exposed subjects, urothelial carcinoma patients, and controls. To prepare an in vitro model, we chronically exposed an immortalized normal human bladder cell line (HUC1) to arsenic. Growth of the HUC1 cells was increased in a time-dependent manner after arsenic treatment and cellular morphology was changed. In a soft agar assay, colonies were observed only in arsenic-treated cells, and the number of colonies gradually increased with longer periods of treatment. Similarly, invaded cells in an invasion assay were observed only in arsenic-treated cells. Withdrawal of arsenic treatment for 2.5 months did not reverse the tumorigenic properties of arsenic-treated cells. Western blot analysis demonstrated decreased PTEN and increased AKT and mTOR in arsenic-treated HUC1 cells. Levels of miR-200a, miR-200b, and miR-200c were downregulated in arsenic-exposed HUC1 cells by quantitative RT-PCR. Furthermore, in human urine, miR-200c and miR-205 were inversely associated with arsenic exposure (P = 0.005 and 0.009, respectively). Expression of miR-205 discriminated cancer cases from controls with high sensitivity and specificity (AUC = 0.845). Our study suggests that exposure to arsenic rapidly induces a multifaceted dedifferentiation program and miR-205 has potential to be used as a marker of arsenic exposure as well as a maker of early urothelial carcinoma detection., (©2015 American Association for Cancer Research.)

Introduction: There is currently substantial interest in dynamic telecytology-the presentation of microscopic findings by live video feed to a cytopathologist at a remote location. However, the initial costs of a telecytology system can be high. We present several low-cost alternatives along with their performance characteristics., Materials and Methods: We tested 3 low-cost telecytology systems: a Raspberry Pi with a webcam, an iPhone 4S with FaceTime, and an iPhone 4S with a live streaming app. Costs, resolution capacities, and latency periods for image transmission were determined., Results: At $85.55, the Raspberry Pi system is the least expensive telecytology solution described to date. When the cost per megapixel of resolution is considered, the cost of a Raspberry Pi system is 120× less than the most expensive commercially available option and about 7-fold less than the iPhone-based alternatives. Latency periods were substantially lower for the iPhone systems: 2.5 ± 1 seconds for FaceTime and 2.8 ± 0.3 seconds for iPhone live streaming versus 6.6 ± 0.6 seconds for the Raspberry Pi system at comparable frame rates., Conclusions: This proof-of-principle study demonstrates that inexpensive telecytology systems are able to stream live video feeds of cytology slides from a microscope to a remote location at useable resolutions., (Copyright © 2014 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.)

Study Objectives: To develop a simplified prognostic prediction rule for patients admitted to ICUs for severe community-acquired pneumonia (CAP)., Setting: Six ICUs in the north of France., Patients: Five hundred five patients admitted to ICUs over a 9-year period (from 1987 to 1995) for severe CAP., Interventions: Retrospective prognosis analysis and multivariate analysis using a credit scoring technique., Measurements: The primary outcome measure was ICU mortality., Results: Among the 505 patients, 472 were eligible for the prognosis study. The ICU mortality rate was 22.9%. Multivariate analysis identified, on the basis of the patient's medical history and initial examination on ICU admission, six independent predictors of mortality: age > or = 40 years, anticipated death within 5 years, nonaspiration pneumonia, chest radiograph involvement > 1 lobe, acute respiratory failure requiring mechanical ventilation, and septic shock. An initial risk score based on these factors classified patients into three risk classes of increasing mortality: 4% in class I, 25% in class II, and 60% in class III. Multivariate analysis of events occurring during ICU stay identified three independent predictors of mortality: hospital-acquired lower respiratory tract superinfections, nonspecific CAP-related complications, and sepsis-related complications. An adjustment risk score based on these factors was essential to accurately predict the final outcome of patients in the initial risk class II., Conclusions: As an aid to clinicians in stratifying the prognosis of patients with severe CAP, the simplified prediction rule used in this study could be useful for therapeutic decisions and appropriate care.

Objectives: To compare epidemiological data, etiology, and prognosis of severe community-acquired pneumonia (CAP) in the intensive care unit (ICU) according to age (< or > or = 65 years) and to determine prognostic factors of CAP in older people., Design: A retrospective (1987-1992) and prospective (1993-95) multicenter study., Setting: Six ICUs in the north of France., Patients: Five hundred five patients admitted to an ICU for severe CAP., Measurements: Patient characteristics were compared with regard to age. Prognosis of CAP in older patients was studied by stepwise discriminant analysis., Results: Two hundred seventy-eight patients (55%) were aged 65 years or older. Comparison of epidemiological data between older and younger patients revealed a higher prevalence of women (38% vs 29%), more severe underlying comorbidities (anticipated death within 5 years: 59% vs 26%), and more frequent chronic respiratory insufficiency (48% vs 33%) in the older patients. In this study group, 224 organisms were isolated from 172 patients (62%); those identified most frequently were Gram-negative bacilli (34%), S. pneumoniae (32%), and Staphylococcus sp. (19%). Compared with younger patients, no significant differences in bacteriological data were observed. However, crude and attributable mortality rates were significantly higher in the older patients (33% vs 21% and 30% vs 19%, respectively). Prognosis analysis identified four independent predictors of mortality in the older patients: initial septic shock (relative risk (RR) = 3), sepsis-related complications (RR = 4.3), hospital-acquired lower respiratory tract superinfections (RR = 2), and nonspecific pneumonia-related complications (RR = 2.8)., Conclusion: The bacterial etiology provides some approaches to empirical therapy for older patients with severe community-acquired pneumonia. In addition, the inappropriateness of withholding intensive care for reasons of age alone is emphasized.

Over a 9-yr period, among 505 patients exhibiting severe community-acquired pneumonia and admitted into a total of six medical ICUs in the north of France, we collected 116 patients (23%) meeting the usual criteria for aspiration pneumonia. Main medical grounds of ICU admission were respiratory distress in 54 patients and neurological disturbances in 62 patients. The main underlying risk factor for aspiration pneumonia was drug overdose (39%). Mechanical ventilation was required for 73 patients. Initial shock was present in 15 patients. Pulmonary involvement was bilateral in 27 patients. There were 94 aerobic organisms isolated from 70 patients (60%), the most frequent being gram-negative bacilli (n = 38), Staphyloccus spp. (n = 27) and Streptococcus pneumoniae (n = 22). Overall mortality was 22%, but only 11 (11%) deaths were directly or indirectly related to aspiration pneumonia. Stepwise multivariate analysis identified four independent predictors of mortality: ineffective initial antimicrobial therapy (p = 0.0001), positive initial blood culture (p = 0.0001), hospital-acquired lower respiratory tract superinfections (p = 0.0054), and use of inotropic support (p = 0.0078). The importance of prevention of hospital-acquired superinfections and permanent optimization of our antimicrobial strategies warranting efficacy of the initial antimicrobial therapy is underlined.

Minority peoples like the Romanies have divergent cultures. Typical cultural aspects for medical personnel to consider would include greetings and other communication, family and social support, dressing and habits of cleanliness, marriage and sexuality, honor, and other issues of importance to any human being. Some minority cultures have no geographic boundaries but they still may adopt the lifestyles of the country they live in. Physicians have to reckon with these different cultural patterns when dealing with patients. Patients must be treated equally at the same time when their personal needs require individual consideration. This consideration is reflected in both verbal and non-verbal communication with the other. Both the sender and the receiver of a message would need to know of the other. Minority groups tend to know more about the majority groups than vice versa. Most health care providers belong to the majority group and would be expected to learn more about the other. Problem-based learning can help students to understand attitudes of minority patients (like the Romanies) and handle the situation. In this instance, the students collected theory base from existing legal, cultural, and other resources and interviewed a Romany woman to verify that the information pertaining to the female case was correct. This combination of theory and experience was considered useful in preparing a case presented to a seminar with 116 medical and dental students in 1994.