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Fonseca e Silva, Larissa, and Eliana da Conceição Tolentino. "Dulce Maria Cardoso, Lygia Bojunga Nunes e dois contos dosados pelo mesmo phármakon." Convergência Lusíada 31, no. 44 (December 30, 2020): 321–36. http://dx.doi.org/10.37508/rcl.2020.n44a409.
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Propõe-se neste ensaio uma leitura comparativa entre contos de duas escritoras: “A troca e a tarefa”, da brasileira Lygia Bojunga Nunes, e “A biblioteca”, da portuguesa Dulce Maria Cardoso. O aporte teórico dessa leitura se dá pelo phármakon de Platão (2000) retomado por Jacques Derrida (2005). Recorremos também às reflexões de Walter Benjamin (1994) em “O narrador: considerações sobre a obra de Nicolai Leskov”.
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Chagas, Carlos Alberto Araujo, Tulio Fabiano de Oliveira Leite, and Lucas Alves Sarmento Pires. "Post-injection embolia cutis medicamentosa – Nicolau Syndrome: case report and literature review." Jornal Vascular Brasileiro 15, no. 1 (April 5, 2016): 70–73. http://dx.doi.org/10.1590/1677-5449.008315.
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Abstract We report on the case of a 40-year-old male who was admitted to the clinic with a large ulcer on his left buttock, 3 days after an intramuscular benzathine penicillin injection. The patient was diagnosed with Nicolau syndrome, a rare vascular complication in which a lesion develops after intramuscular injection. Symptoms are intense pain at the injection site, erythema, and livedoid dermatitis, which leads to necrosis of skin, subcutaneous tissue and muscle tissue. It was described by Nicolau after intramuscular injections of bismuth salt for syphillis therapy. Nicolau syndrome is rare, but its symptoms are devastating and healthcare professionals must be aware of this clinical entity, since intramuscular injections are common procedures for administration of drugs.
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Dick, Mary K., Robert A. Elmore, and Poonam K. Sharma. "Nicolau syndrome appearing approximately one-year post bicillin injection treated with excision." International Journal of Research in Dermatology 5, no. 3 (July 24, 2019): 662. http://dx.doi.org/10.18203/issn.2455-4529.intjresdermatol20193248.
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<p class="Standard">Nicolau syndrome (livedoid dermatitis<strong>, </strong>embolia cutis medicamentosa) is a unique and painful reaction post intramuscular injection that often ends with necessary necrotic debridement and scarring. We present a case of a 25-year-old female who developed a tender golf ball size lesion with fat necrosis, confirmed by pathology, approximately one year after a Bicillin injection in the buttock. Excision of the mass was necessary for symptomatic relief. To our knowledge, there has never been a report entailing a slow development of Nicolau syndrome over an extended period of time. The pathophysiology of this condition has been attributed to a myriad of causes such as vascular trauma, drug embolism, inflammation, or inappropriate needle length. This syndrome often progresses through three generalized stages before ending in a necrotizing plaque. While there is no current standardized treatment to Nicolau syndrome there are methods for prevention making this important information across the medical field.</p>
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Gissoni de Santiago Lavelle, Patricia. "Walter Benjamin e o contador de histórias: (re)fundação do conto como gênero crítico." Gragoatá 22, no. 43 (August 30, 2017): 837–52. http://dx.doi.org/10.22409/gragoata.v22i43.33500.
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Contemporâneo de Dostoievski e de Tolstoi, Nicolai Leskov viveu e escreveu na época de apogeu do romance russo do século XIX. Entretanto, ao caracterizá-lo, logo nas primeiras linhas de seu célebre ensaio de 1936, Walter Benjamin o assimila à figura arcaica do contador de histórias, cujas origens pré-modernas se enraízam na tradição oral, na transmissibilidade da experiência de vida (Erfahrung), a qual estaria irremediavelmente perdida no mundo moderno. Assim, ele situa Leskov num passado anterior ao da modernidade que, no século XIX, encontra sua expressão literária no romance burguês. O anacronismo não é arbitrário: o contista russo se serve, de fato, de formas narrativas tradicionais que se alimentam de um farto material popular, e em particular da tipologia do conto de fadas. Entretanto, a partir da leitura de seus contos, Benjamin propõe a fundação de um novo gênero, radicalmente moderno, sobre as ruínas da arte de contar histórias. Para isto, ele explora e potencializa a produtividade reflexiva instaurada pela narrativa tradicional não apenas teoricamente, num ensaio crítico, mas também numa instigante produção ficcional. ---DOI: http://dx.doi.org/10.22409/gragoata.2017n43a934.
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Sanches, Eduardo Oliveira, and Divino José da Silva. "Reflexões sobre a noção de experiência na obra de Walter Benjamin." Comunicações 26, no. 3 (December 9, 2019): 151. http://dx.doi.org/10.15600/2238-121x/comunicacoes.v26n3p151-165.
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Tem-se por objetivo neste estudo analisar a noção de experiência na obra de Walter Benjamin como resultado de reflexões realizadas pelo autor sobre o tema desde sua sua juventude e até sua maturidade. Demonstou-se variações sobre qualidades do conceito de experiência, que foram sendo construídas, gradualmente, conforme o autor mudava seu foco de análise e observação social para falar de experiência e modernidade. Deste trânsito, foram feitas inferências para demonstrar que a noção desenvolvida pelo autor se caracteriza por meio dos desvios que ele mesmo faz durante a vida e que o ajudaram a construir seu entendimento sobre a ideia de experiência. Deste modo, Benjamin voltou-se para o conhecimento como um exercício que evoca o acontecimento, os agoras, os sentidos da aura. Essa dimensão conceitual congrega em si o conhecimento que se constitui a partir de se ter experiências e não apenas de fazê-las como visa a ciência moderna (AGANBEN, 2005). Foram utilizados seis ensaios para estabelecer esta análise, são eles: “Experiência” (1913); “Sobre o programa da filosofia do porvir” (1918); “Experiência e pobreza” (1933); “O narrador. Considerações sobre a obra de Nicolai Leskov” (1936); “Sobre alguns temas em Baudelaire” (1940) e “Infância Berlinense: 1900” (escrito entre 1926 e 1938).
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Kalic, Jovanka. "Srpska drzava i Ohridska arhiepiskopija u XII veku." Zbornik radova Vizantoloskog instituta, no. 44 (2007): 197–208. http://dx.doi.org/10.2298/zrvi0744197k.
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(francuski) L??poque des Comnene (1081-1185) voit le glissement progressif du centre de l?Etat serbe, depuis l?ancienne Dioclee et les contr?es du littoral adriatique plus a l?int?rieur de l?arri?re-pays, c?est-a-dire sur le territoire de l?archev?ch? grec d?Ohrid. Celui-ci correspondait alors une vaste r?gion dont les limites avaient ?t? fix?es au d?but du XIe si?cle lorsque, sous le r?gne de Basile II (976-1025), Byzance a r?tabli son autorit? sur le territoire des Balkans. De tous les souverains serbes, le grand Joupan Vukan (fin du XIe - d?but du XIIe si?cle) est le premier a avoir alors ?tendu son autorit? sur la contr?e de Ras, autrement dit le territoire de l??v?ch? du m?me nom qui entrait dans le dioc?se Ohrid et dont les ?v?ques si?geaient alors depuis plusieurs si?cles dans l??glise Saint-Pierre-et-Paul (aujourd?hui Saint-Pierre pr?s de Novi Pazar). Dans ce travail l?auteur observe les relations entretenues par l?Etat serbe et l?Eglise grecque sur le sol de la Serbie du XIIe si?cle, lesquelles ?taient avant tout fonction des relations politiques entre ce m?me Etat et Byzance. Pour l??poque m?me du joupan Vukan nous n?avons aucune donn?e concernant l?activit? des ?v?ques de Ras. Le pr?sent texte accorde donc une attention plus particuli?re a la situation enregistr?e vers le milieu du XIIe si?cle, a savoir sous le r?gne de Stefan Nemanja, fondateur de la dynastie des Nemanjic. D??pres le syst?me de pouvoir alors en vigueur en Serbie, Stefan Nemanja s?est tout d?abord vu confier l?administration d?une partie de l?Etat serbe (1158-1159). Il s?agissait en l?occurrence des r?gions appel?es Ibar, Rasina, Toplica et Reke, c?est-a-dire les contr?es orientales du pays jouxtant directement le territoire sous l?autorit? directe de Byzance. Pour cette p?riode, les sources serbes notent tout particuli?rement l?engagement de ce prince en faveur de l??rection de monast?res (un premier place sous le vocable de saint Nicolas et un second consacre au culte de la Vierge). On sait aussi que ces deux ?tablissements ont ?t? ?riges avec le consentement de l??v?que de l?archev?ch? d?Ohrid, et ce, dans les deux cas, avant 1166, ann?e ou Stefan Nemanja a ?tendu son pouvoir sur l?ensemble du pays. Or, de nouvelles donn?es nous r?v?lent que durant toute cette ?poque (plus pr?cis?ment jusqu?en 1164) l?archev?que d?Ohrid Jean (Adrien) Comn?ne, fils du sebastocrator Isaac Comn?ne, fr?re tr?s influent de l?empereur Alexis Ier Comnene, a joue un r?le de premier plan dans les relations serbe-byzantines. En l?occurrence, il a acc?de a cette fonction en 1140 et l?a exerc?e jusqu?a sa mort, en 1164, soit pr?cis?ment durant les d?cennies ayant vu d?importants ?v?nements pour l?avenir de l?Etat serbe. Nous apprenons ainsi qu?il ?tait pr?sent a Nis durant l??t? 1163, lors de la rencontre entre Manuel Ier Comn?ne et Stefan Nemanja, a l?occasion de laquelle l?empereur a d?cerne au prince serbe un titre ?l?ve de rang imp?rial et lui a remis, a titre de bien h?r?ditaire, la r?gion de la Dubocica (a savoir la r?gion de l?actuelle ville de Leskovac). Et il apparait qu?avant m?me cette rencontre, il soutenait d?j? les entreprises de Stefan Nemanja, avant tout s?agissant de l??rection d??glises dans la r?gion de Toplica (a savoir les ?glises Saint-Nicolas et de la Sainte-Vierge d?j? nomm?es). Par ailleurs, nous apprenons que ce m?me archev?que a aussi participe, cette m?me ann?e 1163, a des discussions en mati?re de dogme avec l??v?que russe en exil Leon, lors de son s?jour, avec l?empereur Manuel Ier, a Belgrade. L?auteur note que c?est assur?ment a cette p?riode d?activit? de fondateur de Stefan Nemanja qu?appartient l??rection de l??glise Saint-Nicolas dans la Toplica qui, selon les crit?res largement admis, se range dans le groupe des ?difices monumentaux de l?architecture sacr?e byzantine de l??poque des Comn?ne, d?notant de fortes influences de l?architecture de la capitale.
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Molokwu, Chidi N., Christos Gkikas, Nicola Lee, Joanna Lesniak-Buzon, Faisal Ali, and Harry Bardgett. "Abstract P067: Evaluating the risk of clinically significant prostate cancer in lesions detected on multiparametric MRI of the prostate." Cancer Prevention Research 16, no. 1_Supplement (January 1, 2023): P067. http://dx.doi.org/10.1158/1940-6215.precprev22-p067.
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Abstract Introduction: Multiparametric Magnetic Resonance Imaging (mpMRI) is a valuable tool in the prostate cancer diagnostic pathway. mpMRI has a negative predictive value (NPV) of approximately 90% for detecting clinically significant prostate cancer (csPCa), defined as the presence of any Gleason Grade (GG) 4 or 5. Lesions detected on mpMRI are scored using the PIRADS scoring system from 1 to 5. PIRADS-3, 4 and 5 lesions are recommended for biopsy. The use of mpMRI to guide prostate biopsy has been shown to be superior to systematic biopsy alone for detecting early csPCa as small lesions can be identified and accurately targeted. We analysed the outcome of targeted biopsy of prostate lesions detected on mpMRI, and systematic biopsy when no lesions were detected, to determine the risk of csPCa based on mpMRI findings. Methods: Men attending our prostate diagnostic pathway were offered mpMRI before biopsy. The criteria for pre-biopsy mpMRI were any man suitable for radical surgery or radiotherapy, plus one or more of PSA > 3, palpable lesion on digital rectal examination, or family history of PCa in a first degree relative (father or brother). mpMRI was performed with a 1.5-Tesla magnet and included T2, DWI and DCE sequences. Men with PIRADS 3, 4, and 5 lesions were offered targeted biopsy with 2-4 biopsy cores per lesion, and men with no lesion on MRI were offered systematic prostate biopsy with 8-16 biopsy cores. Results: 546 targeted lesions were biopsied in 349 men. 159 lesions were PIRADS-3, 226 were PIRADS-4, and 161 were PIRADS-5. 141 men with negative mpMRI had systematic prostate biopsy. Of the PIRADS-3 lesions, 84% were benign, 5% had GG 3, 11% had GG 4 and none had GG 5. Of the PIRADS-4 lesions, 44% were benign, 12% had GG 3, 42% had GG 4, and 2% had GG 5. Of the PIRADS-5 lesions, 23% were benign, 2% had GG 3, 62% had GG 4, and 13% had GG 5. Of the men with no lesion on mpMRI, 9% had GG 3, 4% had GG 4, and none had GG 5. Conclusion: Most men with negative mpMRI or PIRADS-3 lesions have benign tissue on biopsy or early PCa and are unlikely to have csPCa. A decision for biopsy vs PSA monitoring in these men should weigh the risks and benefits of biopsy and should be a shared decision taking into consideration individual risk factors for PCa, age and co-morbidities. Citation Format: Chidi N. Molokwu, Christos Gkikas, Nicola Lee, Joanna Lesniak-Buzon, Faisal Ali, Harry Bardgett. Evaluating the risk of clinically significant prostate cancer in lesions detected on multiparametric MRI of the prostate. [abstract]. In: Proceedings of the AACR Special Conference: Precision Prevention, Early Detection, and Interception of Cancer; 2022 Nov 17-19; Austin, TX. Philadelphia (PA): AACR; Can Prev Res 2023;16(1 Suppl): Abstract nr P067.
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Pizurica, Marija, Maarten Larmuseau, Kim Van der Eecken, Louise de Schaetzen van Brienen, Francisco Carrillo-Perez, Simon Isphording, Nicolaas Lumen, et al. "Abstract LB171: WSI based prediction of TP53 mutations identifies aggressive disease phenotype in prostate cancer." Cancer Research 83, no. 8_Supplement (April 14, 2023): LB171. http://dx.doi.org/10.1158/1538-7445.am2023-lb171.
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Abstract In prostate cancer, there is an urgent need for objective prognostic biomarkers that identify a tumor’s metastatic potential at an early stage. While recent analyses indicated TP53 mutations as candidate biomarker, molecular profiling in a clinical setting is complicated by tumor heterogeneity. Deep learning models that predict the spatial presence of TP53 mutations in Whole Slide Images (WSIs) offer the potential to mitigate this issue. To assess the potential of WSIs as proxy for spatially resolved profiling or as biomarker for aggressive disease, we developed TiDo, a deep learning model that achieves state-of-the-art performance in predicting TP53 mutations from WSIs of primary prostate tumors. On an independent multi-focal cohort, we could show successful generalization of the model, both at patient and lesion level. Hence, the model offers insight into which lesions on a WSI most likely contain a TP53 mutation. Analysis of model predictions revealed that false positive (FP) predictions could at least partially be explained by TP53 deletions. This suggests that some FP carry another alteration of which the effect converges in the same histological phenotype. Comparative expression analysis and histological cell type analysis identified such common phenotype (related to stromal composition) in both TP and FP predictions. This indicates that WSI-based models might not be able to perfectly predict the spatial presence of individual TP53 mutations. However, we show they have the potential of capturing a tumor’s aggressive potential by observing a downstream phenotype of the tumor cells and TME associated with a biomarker of aggressive disease (TP53). Citation Format: Marija Pizurica, Maarten Larmuseau, Kim Van der Eecken, Louise de Schaetzen van Brienen, Francisco Carrillo-Perez, Simon Isphording, Nicolaas Lumen, Jo Van Dorpe, Piet Ost, Sofie Verbeke, Olivier Gevaert, Kathleen Marchal. WSI based prediction of TP53 mutations identifies aggressive disease phenotype in prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB171.
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Schutte, Kathryn, Fabien Brulport, Sana Harguem-Zayani, Jean-Baptiste Schiratti, Ridouane Ghermi, Paul Jehanno, Alexandre Jaeger, et al. "Abstract 1924: PULS-AI: A multimodal artificial intelligence model to predict survival of solid tumor patients treated with antiangiogenics." Cancer Research 82, no. 12_Supplement (June 15, 2022): 1924. http://dx.doi.org/10.1158/1538-7445.am2022-1924.
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Abstract The need for developing new biomarkers is increasing with the emergence of many targeted therapies. In this study, we used artificial intelligence (AI) to develop a multimodal model (PULS-AI) predicting the survival of solid tumor patients treated with antiangiogenic treatments. Our retrospective, multicentric study included 616 patients with 7 different cancer types: renal cell carcinoma, colorectal carcinoma, hepatocellular carcinoma, gastrointestinal carcinoma, melanoma, breast cancer, and sarcoma. A set of 196 patients was left out of the study for validation. Clinical data including patient, treatment, and cancer metadata were collected at baseline for all patients, as well as computed tomography (CT) and ultrasound (US) images. Radiologists annotated all metastases on the CT images and the visible tumor lesion on the US images. AI models were used to extract relevant features from the regions of interest on CT and US images. In addition, handcrafted features related to the tumor burden were extracted from the annotations of all lesions on CT such as the number of lesions and the tumor burden volume per organ (lungs, liver, skull, bone, other). Finally, a Cox regression model was fitted to the set of imaging features and clinical features. The annotation process led to 1147 annotated US images with lesions delineation and 4564 reviewed CTs, of which 989 were selected and fully annotated with a total of 9516 annotated lesions.The developed model reaches an average concordance index of 0.71 (0.67-0.75, 95% CI). Using a risk threshold of 50%, PULS-AI model is able to significantly isolate (log-rank test P-value < 0.001) high-risk patients from low-risk patients (respective median OS of 12 and 32 months) with a hazard ratio of 3.52 (2.35-5.28, 95% CI). The results of this study show that AI algorithms are able to extract relevant information from radiology images and to aggregate data from multiple modalities to build powerful prognostic tools. Such tools may provide assistance to oncology clinicians in therapeutic decision-making. Citation Format: Kathryn Schutte, Fabien Brulport, Sana Harguem-Zayani, Jean-Baptiste Schiratti, Ridouane Ghermi, Paul Jehanno, Alexandre Jaeger, Talal Alamri, Raphael Naccache, Leila Haddag-Miliani, Teresa Orsi, Jean-Philippe Lamarque, Isaline Hoferer, Littisha Lawrance, Baya Benatsou, Imad Bousaid, Mickael Azoulay, Antoine Verdon, François Bidault, Corinne Balleyguier, Victor Aubert, Etienne Bendjebbar, Charles Maussion, Nicolas Loiseau, Benoit Schmauch, Meriem Sefta, Gilles Wainrib, Thomas Clozel, Samy Ammari, Nathalie Lassau. PULS-AI: A multimodal artificial intelligence model to predict survival of solid tumor patients treated with antiangiogenics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1924.
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Casanova Torres, Kristine M., Shilpi Relan, and Christina Tatsi. "ODP387 Hemihypertrophy: A Rare Clinical Presentation of Cushing's disease." Journal of the Endocrine Society 6, Supplement_1 (November 1, 2022): A603. http://dx.doi.org/10.1210/jendso/bvac150.1251.
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Abstract Background Hemihypertrophy is a rare clinical presentation of Cushing's disease. It has been described in three newborns with massive enlargement of adrenal glands in presence of other congenital abnormalities and in a 17-year-old female with pituitary adenoma with a genetic diagnosis of Beckwith Weidman syndrome. We describe a case of Cushing's disease with lower extremity hemihypertrophy in the absence of features suggestive of an underlying syndrome. 1,2 Clinical Case: A 12-year-old male with no significant past medical history presented with poor growth and rapid weight gain. In addition, he had hemihypertrophy of left lower extremity interfering with his physical activity. Physical exam showed Tanner Stage 1 for pubic hair and testicular volume of 4 ml bilaterally, with no signs of hirsutism, bruising or purplish striae. Initial work up showed normal thyroid hormone and growth factor levels. Midnight salivary cortisol levels were 238 ng/dl and 51 ng/dl respectively (range <100 ng/dl). One mg dexamethasone suppression test showed suppressed cortisol level of 1 mcg/dl. At the subsequent visit seven months later, he had gained 13.8 kg and grown 0.9 cm in height. Physical exam showed facial plethora and buffalo hump, which had not been present at the initial visit. Left and right leg circumference above the knee were 22 inches and 20 inches respectively. Repeat midnight cortisol levels on two separate occasions were 251 ng/dl and 441 ng/dl respectively. Repeat 1 mg dexamethasone suppression test showed suppressed cortisol levels of 1.2 mcg/dl. Because of clinical picture consistent with Cushing syndrome and elevated salivary cortisol levels, 24-hour urine cortisol levels were ordered that were 145 mcg and 276 mcg/24h respectively (range 1-45 mcg/24hours). ACTH was elevated at 65 pg/ml. CT scan of abdomen and pelvis was normal. Left leg ultrasound was normal. MRI of brain showed a 4 mm hypoenhancing lesion in the pituitary gland to the left of midline. A peripheral DDAVP stimulation test showed elevated ACTH and cortisol levels suggestive of pituitary origin. MRI of legs showed asymmetric fat deposition causing hemihypertrophy. Patient underwent transsphenoidal resection of pituitary adenoma with postoperative remission (postop cortisol nadir <1 mcg/dl). At follow up visit after surgery, patient had lost 0.2 kg, buffalo hump had disappeared, and left leg circumference had slightly improved. Genetic testing ispending. Conclusion This case demonstrates that hemihypertrophy can be a presenting symptom of Cushing's disease. References: (1)Brioude F, Nicolas C, Marey I, et al. Hypercortisolism due to a pituitary adenoma associated with beckwith-wiedemann syndrome. Horm Res Paediatr. 2016;86(3): 206-211. (2)Carney JA, Ho J, Kitsuda K, Young WF, Stratakis CA. Massive neonatal adrenal enlargement due to cytomegaly, persistence of the transient cortex, and hyperplasia of the permanent cortex: Findings in cushing syndrome associated with hemihypertrophy. Am J Surg Pathol. 2012;36(10): 1452-1463. Presentation: No date and time listed
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Mondani, Jo, Hamza Arabiyat, Stavroula Kastora, Mona Sulieman, Imran Abbas, Polly King, Rachel English, et al. "Abstract P3-04-09: 3-dimensional intraoperative analysis of screen-detected breast cancers reduce re-excision rates." Cancer Research 83, no. 5_Supplement (March 1, 2023): P3–04–09—P3–04–09. http://dx.doi.org/10.1158/1538-7445.sabcs22-p3-04-09.
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Abstract Introduction: Breast conserving therapy, has generally been accepted as treatment of choice for early invasive breast cancer. However adequate local control depends on obtaining negative margins and receipt of radiation In 20-30 % of patients with breast conserving surgery a second re-excision procedure is due to tumor-positive margins at histopathology. Margins re-excision rate are variable across the countries. Mean re-excision rate of 17.2% across units in UK. Intraoperative specimen radiography,used to evaluate partial mastectomy specimens ensure that the lesion is adequately removed. Objective: to determine whether 3D-intraoperative imaging better predicts margin status and reduces the re-excision rate than conventional 2D imaging. Methods: Retrospective study comparing two cohorts of patients 360 screen-detected breast cancer (2D cohort). April 2015 to March 2018 300 screen-detected breast cancer (3D cohort) April 2018 to March 2021 Royal Cornwall Hospital (RCHT) introduced a 3D intraoperative system for all cases in April 2018 Prior to the introduction of 3D intraoperative imaging at RCHT the re-excision rate was stable at approximately 15%. All patient had undergone preoperative digital mammogram and ultrasound. All patients had core biopsy diagnosis All malignancies were localised with ROLL (Radio-guided occult lesion localization) techniques. All wide local excision were performed by 5 fully trained oncoplastic breast surgeons (similar distribution within the two cohort) Specimen radiograph was performed intraoperatively using: 2D x-ray device (Faxitron system; Trident Hologic, Marlborough, MA) or 3D tomosynthesis (Mozart system; Kubtec Medical imaging, Stratford,CT). For both methods of assessment,specimen was placed in the device and auto exposed without any compression of tissue. All specimens were marked with orienting sutures and clips according to local protocol. All specimens were painted in theatre by the operating surgeon. All specimens were examined by the same pathologists. No change in margin protocol for 12 years(already compliant to ABS guidelines) • A clear margin for invasive cancer was defined as tumour found within 1mm of margin. For ductal carcinoma in situ (DCIS), a margin was classified as positive if ink on tumour, was classified as close ink is found in under 2 mm from tumour and as negative if more or equal to 2 mm, in accordance with NICE guidelines. (22) Statistical Analysis: • The study compares patient demographics, histology, and re-excision rates between 2D and 3D • Descriptive and comparative statistics are be calculated for all collected data TABLE 1: 3D/2D RR 0.59 (P:0.01), CI 0,3369-09068, Z -2.3473, P 0.0189 Conclusions: The use of intraoperative 3D specimen X-ray reduced the relative risk of re-excision rate by 41% (P=0.01) without any negative impact on other parameters. Table 1: Results 3D intraoperative imaging versus 2D intraoperative imaging Citation Format: Jo Mondani, Hamza Arabiyat, Stavroula Kastora, Mona Sulieman, Imran Abbas, Polly King, Rachel English, Iain Brown, Miklos Barta, Nicola Jackson, Philip Drew. 3-dimensional intraoperative analysis of screen-detected breast cancers reduce re-excision rates [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-04-09.
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Rajsri, Kritika Srinivasan, Michael P. McRae, Glennon W. Simmons, Alexander Ross Kerr, Nadarajah Vigneswaran, Spencer W. Redding, Malvin Janal, et al. "Abstract 785: A smart cytopathology risk-assessment platform for oral potentially malignant disorders and oral squamous cell carcinoma at the point-of-care." Cancer Research 83, no. 7_Supplement (April 4, 2023): 785. http://dx.doi.org/10.1158/1538-7445.am2023-785.
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Abstract Background & Objective: Oral squamous cell carcinoma (OSCC) affects over 400,000 individuals globally, every year. When diagnosed early, the 5-year survival rate for OSCC is 64%, but two-third of these lesions are diagnosed in later stages, leading to lower survival rates (<40%). Clinical diagnosis of these lesions is complicated by benign and Oral-Potentially-Malignant-Disorders (OPMD) like oral lichenoid conditions (OLC), mimicking OSCC in clinical presentation. Studies in literature demonstrate high rates of incorrect chair-side diagnosis for OSCC and OPMD, making their early and accurate detection challenging. This clinical gap prompts a strong need for clinical chair-side point-of-care (POC) platforms, to aid accurate screening of these lesions and prevent diagnostic delays. Methods: In this work we present a ‘smart diagnostic approach’ that combines three key capabilities into an integrated sensing modality as follows: i) powerful microfluidic engine that allows for cytology measurements to be completed outside of a sophisticated lab infrastructure, ii) cytomics platform that allows for single cell molecular imaging to be completed in a portable analyzer, iii) AI-linked diagnostic models for early disease detection using cyto-signatures. This platform has been clinically validated across a multi-site prospective clinical study. Results: Multiple parameters including cellular phenotypes, nuclear parameters, biomarker expressions were indexed. Further, combining these features allowed discrimination and stratification of these lesions with high accuracy (99.3%) and significance. Further examination using logistic regression and receiver operating characteristic curve analyses yielded significant lesion identifiers and AUC values towards positive discrimination of OLC and OSCC (0.824 and 0.95, respectively vs benign lesions), with high sensitivity and specificity. Conclusion: This rapid (<30 minutes) cytopathology POC solution has the potential to impact OSCC and OPMD screening accurately, characterizing subtle cellular changes to aid long-term monitoring of these lesions. Additionally, this platform has the capability to uncover new parameters that can further aid these assessments and improve confidence in clinicians’ decisions. Citation Format: Kritika Srinivasan Rajsri, Michael P. McRae, Glennon W. Simmons, Alexander Ross Kerr, Nadarajah Vigneswaran, Spencer W. Redding, Malvin Janal, Stella Kang, Leena Paloma, Nicolaos J. Christodoulides, John T. McDevitt. A smart cytopathology risk-assessment platform for oral potentially malignant disorders and oral squamous cell carcinoma at the point-of-care [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 785.
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Albrecht, Kim WorkowskiJoerg, Robin K. Avery, Robin K. Avery, Pranatharthi Chandrasekar, Roy F. Chemaly, Nicolas C. Issa, Camille Kotton, et al. "1060. Pritelivir in Immunocompromised Patients with Mucocutaneous Acyclovir-Resistant Herpes Simplex Virus-Infections – First Case Series." Open Forum Infectious Diseases 8, Supplement_1 (November 1, 2021): S622—S623. http://dx.doi.org/10.1093/ofid/ofab466.1254.
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Abstract Background HSV recurrences are usually managed effectively with existing antiviral drugs (nucleoside analogs such as acyclovir). However, in immunocompromised patients (e.g., malignancy, HIV, transplant), if lesions persist or recur while receiving antiviral treatment, acyclovir resistance should be suspected. In this population, there are limited treatment options. The helicase-primase inhibitor pritelivir is a novel oral antiviral, with a new mode of action and is active against both HSV-1 and HSV-2, including acyclovir and foscarnet-resistant strains. In this case series, we report the first clinical experiences with pritelivir in the treatment of immunocompromised patients with acyclovir resistant HSV infection. Methods All patient reported in this case series received pritelivir in a Phase 2 study. There were treated in an open-label design with a 400 mg pritelivir oral loading dose followed by a 100 mg oral maintenance dose daily for up to 28 days. Results Of the 23 patients, 11 had HIV infection and 12 had malignancy, transplant or an autoimmune disease. Of this cohort, 19 patients showed full resolution of their HSV-related lesions during the 28 day treatment period, while in 4 subjects lesions improved but did not completely heal during the observation period. Pritelivir was well tolerated without significant adverse effects.Reasons for incomplete lesion resolution during the 28 day treatment period, were extensive lesions in one patient, one patient with resistance development, and one patient with lesions in the oral cavity. Three patients subsequently experienced full resolution, while one patient required foscarnet due to CMV reactivation, necessitating early discontinuation. Conclusion Pritelivir is a promising novel treatment option for patients with severe mucocutaneous HSV-1/2 infections that are resistant to acyclovir and foscarnet. An international Phase 3 study is underway to evaluate pritelivir efficacy in immunocompromised patients. Disclosures Joerg Albrecht, MD/PhD, Biogen (Scientific Research Study Investigator)Investigator for AiCuris (Scientific Research Study Investigator) Robin K. Avery, MD, Aicuris (Grant/Research Support)Astellas (Grant/Research Support)Chimerix (Research Grant or Support)Merck (Grant/Research Support)Oxford Immunotec (Grant/Research Support)Qiagen (Grant/Research Support)Takeda/Shire (Grant/Research Support) Roy F. Chemaly, MD, MPH, FACP, FIDSA, AiCuris (Grant/Research Support)Ansun Biopharma (Consultant, Grant/Research Support)Chimerix (Consultant, Grant/Research Support)Clinigen (Consultant)Genentech (Consultant, Grant/Research Support)Janssen (Consultant, Grant/Research Support)Karius (Grant/Research Support)Merck (Consultant, Grant/Research Support)Molecular Partners (Consultant, Advisor or Review Panel member)Novartis (Grant/Research Support)Oxford Immunotec (Consultant, Grant/Research Support)Partner Therapeutics (Consultant)Pulmotec (Consultant, Grant/Research Support)Shire/Takeda (Consultant, Grant/Research Support)Viracor (Grant/Research Support)Xenex (Grant/Research Support) Nicolas C. Issa, MD, AiCuris (Scientific Research Study Investigator)Astellas (Scientific Research Study Investigator)GSK (Scientific Research Study Investigator)Merck (Scientific Research Study Investigator) Camille Kotton, MD, Shire/Takeda (Advisor or Review Panel member) Camille Kotton, MD, UpToDate (Individual(s) Involved: Self): I write chapters on zoonoses for UpToDate., Independent Contractor Princy N. Kumar, MD, AMGEN (Other Financial or Material Support, Honoraria)Eli Lilly (Grant/Research Support)Gilead (Grant/Research Support, Shareholder, Other Financial or Material Support, Honoraria)GSK (Grant/Research Support, Shareholder, Other Financial or Material Support, Honoraria)Merck & Co., Inc. (Grant/Research Support, Shareholder, Other Financial or Material Support, Honoraria) Moti Ramgopal, MD FACP FIDSA, Abbvie (Scientific Research Study Investigator, Speaker’s Bureau)Gilead (Consultant, Scientific Research Study Investigator, Speaker’s Bureau)Janssen (Consultant, Scientific Research Study Investigator, Research Grant or Support, Speaker’s Bureau)Merck (Consultant, Scientific Research Study Investigator)ViiV (Consultant, Scientific Research Study Investigator, Speaker’s Bureau) Anna Wald, MD, MPH, Aicuris (Consultant)Crozet (Consultant)GSK (Scientific Research Study Investigator)Merck (Other Financial or Material Support, DSMB)Sanofi (Scientific Research Study Investigator)X-Vax (Consultant) Michael G. Ison, MD, MS, Celltrion, Inc. (Consultant)
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Mukhopadhyay, Satabhisa, Tathagata Dasgupta, Elizabeth Walsh, Rebecca Millican-Slater, Andrew hanby, Joanne Stephenson, Craig A. Bunnell, and Nicolas M. Orsi. "Abstract P3-05-48: Prediction of disease recurrence in low risk Oncotype Dx breast cancers from digital H&E-stained whole slide images of pre-treatment resections alone." Cancer Research 83, no. 5_Supplement (March 1, 2023): P3–05–48—P3–05–48. http://dx.doi.org/10.1158/1538-7445.sabcs22-p3-05-48.
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Abstract Background Breast cancer patients with estrogen receptor (ER)+/HER2- (and usually node-negative) tumors can avail themselves of Oncotype DX Breast Recurrence Score (ODXRS) testing to predict their risk of distant recurrence within 9 years and, consequently, putative chemotherapy benefit. However, ODXRS testing requires sufficient tumour availability and specimen shipping, which imposes time and financial burdens to testing which have to be met by healthcare systems. The advent of digital pathology offers a potential avenue for exploring computer-aided diagnostic solutions which may overcome these hurdles by extracting the requisite information from hematoxylin and eosin (H&E)-stained tissue whole slide images (WSIs) alone. In turn, this technology could significantly reduce diagnostic turnaround times and cost, and improve accessibility and test reproducibility, thereby enabling healthcare systems to run more efficiently and offer patients more timely results. Ideally, such a platform should incorporate a measure of the underlying tumor biology to provide a fully explainable, white box solution, and may offer further insights into the identification of early recurrence events. Aims The aim of this study was to establish whether our computer-aided solution’s (Q-Plasia OncoReader Breast, QPORB) digital biomarker representing G1/S cell cycle deformations extracted from H&E WSIs was prognostic for disease-free survival (DFS) and could predict disease recurrence, particularly in the setting of low risk ODXRS breast cancers. Methods Primary breast cancer resection/excision specimens (n=70 cases) sent for ODXRS testing from St James’s University Hospital, UK (2016-2019) were collected. Anonymised diagnostic glass slides (n=198 slides) of H&E-stained tumors were scanned at x20 magnification on an Aperio AT2 scanner. In parallel, relevant clinical and histological data were collected from pathology reports and electronic patient records, including both ODXRS and recurrence events during follow-up. The QPORB recurrence scale (QPORB-RS), which combines statistical physics and tumor biology to identify image-based malignant cell cycle deformation, extracts prognostic information from WSIs. The contribution of potential confounders (age, stage, grade, lesion size, Nottingham prognostic index and Charlson score) were accounted for. Results The QPORB-RS was prognostic for DFS for patients with predominantly node-negative (including node micro-metastases) HR+/HER2- tumors over a median follow-up period of 5 years (P=0.02; dichotomized Kaplan Meyer with median cut-off). The QPORB-RS concurred with ODXRS’s high vs. low recurrence risk in 73% (19/26) and 61% (27/44) of cases, respectively, with an overall agreement of 66% (46/70). Moreover, the QPORB-RS identified all 5 patients who had recurrences (with ODXRS of 6, 9, 10, 21 and 26, and ages of 55, 66, 42, 35 and 50 years, respectively) as being high risk in the subset of those given a low (including historically intermediate) ODXRS and who did not receive chemotherapy. Conclusion The QPORB-RS is a good prognostic test of risk of disease recurrence in breast cancer patients with predominantly node-negative (including node micro-metastases) HR+/HER2- tumors within a median 5-year follow-up period. Our efforts are now focussed on extending this cohort and establishing the prognostic value of the QPORB-RS across all breast carcinomas, regardless of molecular subtype, stage/node positivity and menopausal status. Citation Format: Satabhisa Mukhopadhyay, Tathagata Dasgupta, Elizabeth Walsh, Rebecca Millican-Slater, Andrew hanby, Joanne Stephenson, Craig A. Bunnell, Nicolas M. Orsi. Prediction of disease recurrence in low risk Oncotype Dx breast cancers from digital H&E-stained whole slide images of pre-treatment resections alone [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-05-48.
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Dummer, Reinhard, Caroline Robert, Richard A. Scolyer, Janis M. Taube, Michael T. Tetzlaff, Andrew Hill, Jean-Jacques Grob, et al. "Abstract CT002: KEYMAKER-U02 substudy 02C: neoadjuvant pembrolizumab (pembro) + vibostolimab (vibo) or gebasaxturev (geba) or pembro alone followed by adjuvant pembro for stage IIIB-D melanoma." Cancer Research 83, no. 8_Supplement (April 14, 2023): CT002. http://dx.doi.org/10.1158/1538-7445.am2023-ct002.
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Abstract Background: The phase 1/2 KEYMAKER-U02 substudy 02C (NCT04303169) is evaluating neoadjuvant pembro + investigational agents or pembro alone followed by adjuvant pembro in stage IIIB-D melanoma. Results from patients treated with neoadjuvant pembro (anti-PD-1) + vibo (anti-TIGIT; arm 1), pembro + geba (coxsackievirus A21; arm 2), or pembro alone (arm 3) are presented. Methods: Eligible patients were ≥18 y with resectable stage IIIB, IIIC, or IIID melanoma per AJCC 8th ed criteria, ≥1 measurable lesion per RECIST v1.1, and ECOG PS ≤1. Patients were randomly allocated across open investigational arms. Before resection, patients in arm 1 received 2 administrations of pembro 200 mg Q3W + vibo 200 mg Q3W (cycle 1, day 1; cycle 2, day 1); patients in arm 2 received 1 administration of pembro 400 mg (cycle 1, day 8) + 5 administrations of geba at a fixed dose of 3 × 108 tissue culture infectious dose 50% during cycle 1 (days 1, 3, 5, 8, and 22); and patients in arm 3 received 1 administration of pembro 400 mg. Surgical resection was performed at week 6. At week 12, patients started adjuvant pembro 400 mg Q6W for ≤8 administrations (total treatment duration, ~1 y). Primary end points were safety and tolerability and pCR rate by central review. Secondary end points were near pCR rate and pPR rate by central review and RFS by investigator review. ORR per RECIST v1.1 and EFS by investigator review were exploratory. Results: At data cutoff (September 9, 2022), 66 patients had been assigned to treatment (arm 1 [pembro + vibo], n = 26; arm 2 [pembro + geba], n = 25; arm 3 [pembro alone], n = 15). Median follow-up was 14.1 mo (range, 8.0-26.1). Treatment-related AEs occurred in 92% of patients in arm 1, 84% in arm 2, and 80% in arm 3. Grade 3/4 treatment-related AEs occurred in 8%, 24%, and 7% of patients, respectively, with no grade 5 treatment-related AEs. 3 patients (12%) in arm 1, 5 (20%) in arm 2, and 0 in arm 3 discontinued any drug because of treatment-related AEs. Immune-mediated AEs or infusion reactions were reported in 31% of patients in arm 1, 32% in arm 2, and 27% in arm 3. The pCR rate was 38% (95% CI, 20-59) in arm 1, 28% (12-49) in arm 2, and 40% (16-68) in arm 3; the near pCR rate was 12% (2-30), 12% (3-31), and 7% (<1-32), respectively; and the pPR rate was 31% (14-52), 12% (3-31), and 27% (8-55), respectively. Median RFS was not reached in any arm; 18-mo RFS rates were 95% (95% CI, 70-99) in arm 1, 87% (56-97) in arm 2, and 73% (24-93) in arm 3. ORR was 50% (95% CI, 30-71), 32% (15-54), and 27% (8-55), respectively. Median EFS was not reached in any arm; 18-mo EFS rates were 81% (95% CI, 60-92), 61% (38-78), and 79% (47-93), respectively. Conclusions: Neoadjuvant pembro + vibo, pembro + geba, and pembro alone followed by adjuvant pembro had manageable safety and promising antitumor activity in patients with stage IIIB-D melanoma. Of the combination treatments, pembro + vibo showed the most promise. Citation Format: Reinhard Dummer, Caroline Robert, Richard A. Scolyer, Janis M. Taube, Michael T. Tetzlaff, Andrew Hill, Jean-Jacques Grob, David C. Portnoy, Celeste Lebbe, Muhammad A. Khattak, Jonathan Cohen, Gil Bar-Sela, Inderjit Mehmi, Ronnie Shapira Frommer, Nicolas Meyer, Yixin Ren, Mizuho Fukunaga-Kalabis, Clemens Krepler, Georgina V. Long. KEYMAKER-U02 substudy 02C: neoadjuvant pembrolizumab (pembro) + vibostolimab (vibo) or gebasaxturev (geba) or pembro alone followed by adjuvant pembro for stage IIIB-D melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT002.
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Lazzeroni, Matteo, Luca Nicosia, Elena Guerini Rocco, Sara Gandini, Sara Raimondi, Massimo Barberis, Nicola Fusco, et al. "Abstract PR004: Radiogenomics for predicting underestimation of invasiveness in ductal carcinoma in situ (DCIS) diagnosed with vacuum assisted breast biopsy: study rationale and design." Cancer Prevention Research 15, no. 12_Supplement_1 (December 1, 2022): PR004. http://dx.doi.org/10.1158/1940-6215.dcis22-pr004.
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Abstract Background: Concerns about overdiagnosis and overtreatment of DCIS have led to an interest in de-escalating treatment for DCIS. However, accruing patients to active surveillance trials poses several issues, the most pressing of which is the high risk of synchronous invasion at the biopsy level (~26%). Since DCIS-associated stromal changes and influx of immune cells might be mediators of progression to invasive breast cancer, the present project will investigate whether radiogenomics is able to predict the upstaging in patients preoperatively diagnosed with DCIS with Vacuum-Assisted Breast Biopsy (VABB). Hypothesis: We hypothesize a different immune gene expression signature between pure DCIS (p-DCIS) and DCIS with an invasive component at final surgery (i-DCIS). -We hypothesize to be able to identify these different immune gene expression signatures in VABB tissue samples. -We hypothesize that a subsequent gene expression profiling-derived immunohistochemistry signature in DCIS diagnosed on VABB, integrated with other histopathological characteristics and preoperative imaging - Standard Mammography (SM), Digital Breast Tomosynthesis (DBT), Contrast-Enhanced Spectral Mammography (CESM), and Magnetic Resonance (MR) - will predict with higher accuracy the upstaging at final surgery. We hypothesize that the implementation of a radiogenomic approach will reproduce all this information with ultimate precision. Aims: Aim 1: to investigate the relationship between immune gene expression signature at diagnosis of DCIS at VABB and at final surgery outcomes. -Aim 2: to investigate if the association of imaging plus genomics is better than genomics alone. -Aim 3: to create and validate a gene expression profiling-derived immunohistochemistry signature. -Aim 4: to implement radiomic in DCIS management. Experimental Design: Starting from a cohort of more than 2000 consecutive patients with a diagnosis of DCIS on VABB and subsequently operated at the European Institute of Oncology, training and testing datasets will be created. VABB p-DCIS and i-DCIS will be profiled using a next-generation sequencing gene expression assay, targeting 395 genes associated with tumor-immune systems interactions and performed on RNA extracted from DCIS samples. Gene expression and the subsequently derived immunohistochemistry profiles will be integrated with preoperative imaging (SM, DBT, CESM, MR). Finally, we will perform a radiomic feature analysis by SM, DBT (when available), and CESM-detected DCIS at VABB. Impact on Cancer: Patients with features that place them at low risk may be more likely to forego additional therapy. Clinicians would distinguish patients who are candidates to surveillance only, because the "pure" DCIS has been completely removed, from patients going to active surveillance plus endocrine treatment because the residual lesion is with high probability a DCIS, from patients to be sent to surgery because most certainly the invasive component will be present. Citation Format: Matteo Lazzeroni, Luca Nicosia, Elena Guerini Rocco, Sara Gandini, Sara Raimondi, Massimo Barberis, Nicola Fusco, Marta Cremonesi, Daniela Origgi, Enrico Cassano, Aliana Guerrieri Gonzaga, Davide Serrano, Debora Macis, Harriet Johansson, Bernardo Bonanni. Radiogenomics for predicting underestimation of invasiveness in ductal carcinoma in situ (DCIS) diagnosed with vacuum assisted breast biopsy: study rationale and design [abstract]. In: Proceedings of the AACR Special Conference on Rethinking DCIS: An Opportunity for Prevention?; 2022 Sep 8-11; Philadelphia, PA. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_1): Abstract nr PR004.
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Jayakumar, V., G. Kannamma Usha Rani, N. Amaresan, and S. Rajalakshmi. "First Report of Anthracnose Disease of Black Pepper (Piper nigrum) Caused by an Unknown Species of Colletotrichum." Plant Disease 93, no. 2 (February 2009): 199. http://dx.doi.org/10.1094/pdis-93-2-0199a.
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Black pepper is cultivated in Andaman and Nicobar Islands, India as a spice crop. During a survey performed in June of 2007 in South Andaman, two kinds of leaf anthracnose symptoms were observed. The classic symptom, angular to irregular or circular brownish lesions with a chlorotic halo and pinhead size acervuli on the leaves, was consistent with the disease previously reported on pepper caused by Colletotrichum gloeosporioides (2). This symptom also caused splitting and the production of hollow berries. The new symptom was novel, with leaves initially exhibiting pale green or yellowish green lesions. As the disease progressed, lesion margins became brown to black with slightly raised areas containing numerous acervuli. Unlike the classic symptom, the new symptom was characterized as leaf lesions that rarely caused defoliation; berries showed no lesions. The foliar disease incidence was up to 15%, but direct economic loss of berries was not noticed. This new symptom was similar to symptoms caused by C. dracaenophilum, a species identified as a pathogen on lucky bamboo (Dracaena sanderiana) (1). A fungus was isolated in pure culture from the pale green lesions and cultured on potato dextrose agar (PDA). At room temperature (28 ± 2°C), fungal growth on PDA was slow and mycelium appeared whitish at the margin with pale pink centers. A pinkish color was observed on the reverse side of the plate, reflecting profuse sporulation. The conidia were hyaline, broadly clavate to cylindrical, and measured 12.5 to 15 × 5 to 7.5 μm (average 14 × 7.5 μm). The internal transcribed spacer (ITS) region of the fungal DNA was amplified, sequenced, and submitted to NCBI GenBank (Accession No. EU744584). The specimen was deposited in the MTCC of IMTECH, Chandigarh, India (Accession No. MTCC9344). Pathogenicity was tested in five replications on 15- to 20-day-old pepper plants and repeated twice. A 1-ml conidial suspension (108 spores/ml) of the fungus was brushed on two intact leaves of each pepper plant and incubated for 2 weeks in a glasshouse at 28°C and 70% relative humidity with natural daylight conditions. Plants brushed with sterile water served as control. Similar pale green symptoms were observed only on treated leaves and the same organism was reisolated from lesions. BLAST searches of the GenBank using the ITS sequence revealed that this fungus was a member of the genus Colletotrichum, but a species level identification could not be made with these data. The fungus was most similar in sequence to unnamed endophytic strains of Colletotrichum (96% sequence identity) and phytopathogenic isolates of C. dracaenophilum (93% sequence similarity). Although the symptomatology and sequence data were most closely matched with those documented for C. dracaenophilum (1), the morphological and cultural characteristics of the black pepper anthracnose fungus differed from C. dracaenophilum and other known species of Colletotrichum (3). Together these morphological and molecular data suggest that this form of anthracnose disease on black pepper may be caused by a novel, undescribed species of Colletotrichum. Further investigations will be required to characterize this organism to the species level. References: (1) S. G. Bobev et al. Plant Dis. 92:173, 2008. (2) P. Santha Kumari and A. Sanker. J. Mycol. Plant Pathol. 33:329, 2003. (3) B. C. Sutton. In: Colletotrichum. Biology, Pathology and Control. CAB International, Wallingford, 1992.
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Slijkhuis, B., S. Konter, D. Liesker, A. Possel-Nicolai, E. Brouwer, R. Slart, A. Van Roon, B. Saleem, and D. J. Mulder. "AB1549 VALUE OF ULTRASOUND FOR THE EARLY DETECTION OF INFLAMMATORY ABDOMINAL AORTIC ANEURYSMS." Annals of the Rheumatic Diseases 82, Suppl 1 (May 30, 2023): 2008.1–2008. http://dx.doi.org/10.1136/annrheumdis-2023-eular.1972.
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BackgroundInflammatory abdominal aortic aneurysm (iAAA), a form of chronic periaortitis, is a frequently overlooked disease, occurring in patients with abdominal aneurysms (AAA). iAAA is strongly associated with underlying systemic inflammatory diseases such as IgG4-related disease (IgG4-RD),[1]potentially leading to retroperitoneal fibrosis (RPF). Ultrasound (US) is a widely available and low-cost imaging tool that may allow the detection of iAAA at an early-stage prior development of severe complications in patients with AAA.ObjectivesThis study aims to assess the feasibility of using US to detect iAAA in a small case series (exploratory cohort). And to structurally assess the diagnostic potential and overall incidence of iAAA using US in a larger retrospective cohort of patients in follow-up for AAA (validation cohort).MethodsIn the exploratory cohort, thirteen patients (median age 64 (61;72) years; 100 % male) with an established diagnosis of iAAA of whom US and CT findings were available were retrospectively included. The diagnosis of iAAA was based on a typical cuff surrounding the aneurysm on CT. Other potential causes such as infections and malignancies were ruled out by microbiological studies and when indicated by histology and/or FDG-PET scanning. Secondly, the validation cohort consisted of 191 patients (median age 74 (67;80) years; 73.3 % male) diagnosed with AAA who were in US follow-up for AAA without prior surgical intervention. In patients in whom a CT was (n=157) the diagnostic potential of US was explored using CT imaging as the golden standard. Perianeurysmal inflammation was assessed on US, as illustrated in Figure 1A, using a Siemens Acuson with 6 Mhz convex transducer in B-mode. In the validation cohort, US images were assessed by two independent observers blinded for the diagnosis.ResultsIn the exploratory cohort, 62% were smokers, 77% had hypertension, 31% and were diagnosed with IgG4-RD. CRP and BSE levels were 54.5 (±66.2) mg/L and 59.8 (±51,1) mm/h. All patients showed a typical hypoechogenic cuff surrounding the aortic wall eccentric to the calcified medial layer of the aneurysm, see figure 1B). The median anteroposterior diameter of the aneurysm itself was 5.7 cm (4.8; 6.1) and 0.64 cm (0.49; 0.84) of the cuff.In the validation cohort, 180 of 191 (94.2%) patients with AAA showed no evident signs of a hypoechogenic cuff on ultrasound. Of the remaining 11 patients, 8 (4.2%) showed the cuff surrounding the aortic wall and were identified as having iAAA. In 3 (1.6%) an iAAA could not be ruled out based on US. In 149 patients with both a negative US and available CT, all CT scans were negative as well. In the 8 patients with an evident cuff on US, the median age was 66 (65;79) years; and 100% were male, definite IgG4-RD was present in 25% (n=2) of the cases. This amounts to a sensitivity of 100% and a specificity of 98%.ConclusionThis retrospective study indicates that iAAA can be identified with US as a hypoechogenic cuff surrounding the aortic wall of the aneurysm. US could be used to rule out iAAA safely. However, in inconclusive cases, additional CT imaging is warranted. Besides a possible cost and radiation dose reduction, using US may facilitate earlier recognition and treatment of iAAA and underlying systemic inflammatory diseases such as IgG4-RD. Although this is the first study to structurally investigate US in iAAA, our results need validation in a prospective study.Reference[1]Kasashima F, Kawakami K, Matsumoto Y, Endo M, Kasashima S, Kawashima A. IgG4-Related Arterial Disease.Ann Vasc Dis. Published online 2018. doi:10.3400/AVD.RA.18-00012Figure 1.(a) lumen,(b) intima,(c) media,(d) adventitia,(e) thrombotic lesion,(f) inflammatory cuff,(1) The maximum anteroposterior diameter of the aorta including the hypo-echogenic cuff.(2) The anteroposterior diameter of the aorta excluding the hypo-echogenic cuff.(3) The diameter of the hypo-echogenic cuff.Acknowledgements:NIL.Disclosure of InterestsBerend Slijkhuis: None declared, Sherilyn Konter: None declared, David Liesker: None declared, Annet Possel-Nicolai: None declared, Elisabeth Brouwer Speakers bureau: Dr. E. Brouwer as an employee of the UMCG received speaker fees and consulting fees from Roche in 2017, 2018 which were paid to the UMCG., Riemer Slart Grant/research support from: Prof. dr. Slart received unrestricted research grants from Siemens Healthineers and Pfizer, Arie Van Roon: None declared, Ben Saleem: None declared, Douwe J Mulder Grant/research support from: Dr. DJ Mulder as an employee of the UMCG received research grants from Sanofi which were paid to the UMCG.
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Demircan, Caner, Neslihan Akdogan, and Leyla Elmas. "Nicolau Syndrome Secondary to Subcutaneous Glatiramer Acetate Injection." International Journal of Lower Extremity Wounds, December 1, 2020, 153473462097314. http://dx.doi.org/10.1177/1534734620973144.
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Nicolau syndrome, also known as embolia cutis medicamentosa, is a rare complication of injectable drugs. Patients present with pain at injection site, followed by swelling, erythema, purple, hemorrhagic patches and lastly ulcer formation. A variety of intramuscular agents have been implicated as responsible. We report a case of a 26-year-old woman with a history of a purple lesion on her thigh who was diagnosed with Nicolau syndrome due to subcutaneous administration of glatiramer acetate. The patient was followed up with topical mupirocin. On follow-up, although the patient stated that she continued using glatiramer acetate, no new lesions appeared and the existing lesion continued to shrink. Nicolau syndrome seems to have an unpredictable and unavoidable course. This case suggests that physicians should have a high index of suspicion for the presence of Nicolau syndrome in patients presenting with necrotic or ulcerative lesions with a history of using injectable drugs.
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Murdock, Joshua L., Marissa R. Duco, Subhash C. Sharma, and David J. Reeves. "Embolia Cutis Medicamentosa (Nicolau Syndrome) Secondary to Intramuscular Fulvestrant Injection: A Case Report." Journal of Pharmacy Practice, April 29, 2021, 089719002110122. http://dx.doi.org/10.1177/08971900211012263.
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Purpose: A case of embolia cutis medicamentosa (Nicolau syndrome) in a patient receiving monthly intramuscular fulvestrant injections is presented. Summary: An 85-year-old woman receiving monthly fulvestrant injections in the outpatient setting developed a necrotic lesion at the fulvestrant injection site on her right buttock. Her medical history is notable for metastatic breast cancer with bone metastases. Prior to developing the necrotic lesion, the patient was receiving monthly fulvestrant injections for 6 years. Other potential causes such as infection and pressure necrosis were ruled out clinically. After 185 days of wound care involving multiple surgical debridements, topical therapy, and frequent follow-up appointments, the patient’s wound resolved with 100% epithelialization. Nicolau syndrome has been reported with other non-vesicant, injectable medications such as antibiotics and corticosteroids; however, it has not been previously reported with fulvestrant. Conclusion: Nicolau syndrome developed in the right buttock of a patient with metastatic breast cancer following an intramuscular fulvestrant injection. Healthcare practitioners need to be cognizant of this adverse effect with intramuscular injections in order to recognize and refer patients for wound care evaluation early in the evolution of this syndrome. Proper injection technique is recommended to reduce the risk of this idiopathic adverse effect.
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Figueiredo, Priscilla da Silva. "A narradora descolonial: uma leitura de The Distant Marvels, de Chantel Acevedo." Revista Estudos Feministas 27, no. 1 (2019). http://dx.doi.org/10.1590/1806-9584-2019v27n159000.
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Resumo: Em “O narrador. Reflexões sobre a obra de Nicolai Leskov” (1987a), Walter Benjamin entende que a arte de narrar está em vias de extinção uma vez que o narrador, aquele que reúne em si mesmo o conhecimento do camponês sedentário e do marinheiro comerciante, parece não estar mais entre nós a partir da modernidade. Entretanto, se seguirmos a argumentação de Maria Lugones em “Rumo a um feminismo descolonial” (2014a), que coloca o [des]colonial dentro de uma categoria de não moderno, poderemos considerar que a presença do narrador é perene e se manifesta muitas vezes exatamente no romance, forma literária que Benjamin (1987a) aponta como um indicativo da evolução que vai culminar na morte da narrativa. Em The Distant Marvels (2015), a autora cubana-americana Chantel Acevedo constrói uma protagonista que é a representação literária de um narrador que reúne em si as características benjaminianas e que é, assim, capaz de transmitir experiência. A proposta do presente trabalho é verificar como uma leitura deste romance a partir do viés da descolonialidade pode contribuir para o debate acerca da potência que a intervenção estética feminista tem de contribuir para a construção de novas epistemologias.
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Oscar Deleprani, Felício, and João Cláudio Arendt. "O sentimento telúrico e a experiência (Erfahrung) em Nicolai Leskov e em Guimarães Rosa como condição de possibilidade para a (re)elaboração da memória." Antares: letras e humanidades 15, no. 35 (June 14, 2023). http://dx.doi.org/10.18226/19844921.v15.n35.18.
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Gal, Shaili, Paul E. Dart, and Kiya Movassaghi. "A Case Report of Nicolau Syndrome After Aesthetic Breast Surgery: A Review of the Literature and Introduction to a New Treatment Modality." Aesthetic Surgery Journal Open Forum 2, no. 3 (June 24, 2020). http://dx.doi.org/10.1093/asjof/ojaa027.
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Abstract Nicolau syndrome (NS) is a rare iatrogenic syndrome usually following intramuscular (IM) injection of various described medications. The typical presentation involves immediate injection site pain and development of a livedoid reticular patch, which can progress to muscle necrosis requiring surgical debridement. The pathophysiology is unclear, although vasoconstrictive etiologies have been implicated. Treatment ranges from supportive care to surgical debridement. The authors present a case report of this syndrome as well as a review of the literature and introduction to a new treatment modality. NS in a 52-year-old woman following IM injection of Demerol and Phenergan to address pain and nausea before discharge is reported. This occurred in the post-anesthesia care unit after aesthetic breast surgery in an ambulatory surgery center. Our patient had immediate injection site pain and a hemorrhagic patch was evident on her physical examination the following day. With local care and hyperbaric oxygen therapy, her lesion improved in appearance. However, she continued to have debilitating pain and was referred to a specialist for osteopathic manipulative therapy (OMT), which had the greatest impact on her pain level. After multi-modal therapy was initiated, the syndrome ultimately resolved without the need for surgical debridement. However, she continues to experience pain and ambulates with a limp due to muscle atrophy. NS is a rare diagnosis that can have devastating complications that can be averted by early recognition and initiation of treatment modalities. In this case, the authors introduced OMT as a new treatment modality, with the potential to improve the progression of this syndrome. Level of Evidence: 5
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Fostier, William, Akhtar Husain, and Neil Rajan. "CPC08 Cutaneous squamous cell carcinoma and MYH9-associated elastin aggregation (MALTA) syndrome." British Journal of Dermatology 188, Supplement_4 (June 2023). http://dx.doi.org/10.1093/bjd/ljad113.022.
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Abstract MYH9-associated elastin aggregation (MALTA) syndrome is a rare, inherited, irregular elastin aggregation and sweat duct proliferation syndrome caused by pathogenic variants in MYH9. MALTA syndrome was proposed in 2019, unifying Nicolau Balus and Rombo syndromes as phenotypes arising from pathogenic variants in the same gene, but it has not been associated with cutaneous squamous cell carcinoma (cSCC) [Fewings E, Ziemer M, Hörtnagel K et al. Malta (MYH9 associated elastin aggregation) syndrome: germline variants in MYH9 cause rare sweat duct proliferations and irregular elastin aggregations. J Invest Dermatol 2019; 139:2238–41]. Here, we report the clinical features of a family with a novel MYH9 c.1952A>C p.(Lys651Thr) pathogenic variant, providing evidence that cSCC may be an associated feature of MALTA syndrome. A 57-year-old woman presented with a longstanding skin lesion overlying her left infraorbital ridge, which had been present for 13 years. Lesion biopsy revealed a highly infiltrative tumour within the dermis that was composed of keratocysts with small islands of basaloid cells; immunostaining was positive for CK5/6, CK7, CK19, p63 and BerEP4. These histological features were consistent with a microcystic adnexal carcinoma (MAC)-like ductal proliferation, recognized in MALTA. In addition, she had previously developed one cSCC on her left shoulder and two basal cell carcinomas and had cutaneous milia. Her sister had a history of MAC-like ductal proliferation and cSCC, and her brother had two keratoacanthoma-like cSCCs. The copresentation of MAC-like ductal proliferations and early-onset cSCC in this family prompted targeted genetic testing of MYH9. This identified a heterozygous pathogenic variant in a highly conserved region of MYH9 [c.1952A>C p.(Lys651Thr)] that segregated with the phenotype in all three affected members. MYH9 has previously been identified as an important gene in the pathogenesis of cSCC in a genetic screen in transgenic mice, and our family adds novel clinical data, underscoring its importance in cSCC development (Schramek D, Sendoel A, Segal JP et al. Direct in vivo RNAi screen unveils myosin IIa as a tumor suppressor of squamous cell carcinomas. Science 2014; 343:309–13). Based on the recurrent presentation of early-onset cSCC in three members of this family, we propose the inclusion of cSCC in MALTA syndrome. This has implications for skin cancer surveillance of MYH9 pathogenic variant carriers, and the need to consider MALTA syndrome in patients presenting with multiple early-onset cSCC.
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Okomiko, Delphes Mathilde Otsasso, Zineb Hammoumi, Sarah Houti, Daghouj Ghizlane, Loubna El Maaloum, Bouchra Allali, and Asmaa El Kettani. "Ptosis revealing breast carcinoma about a case." Acta Ophthalmologica 102, S279 (January 2024). http://dx.doi.org/10.1111/aos.16091.
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Aims/Purpose: The purpose of our work is to describe the clinical and therapeutic aspects of a clinical case of ptosis revealing breast carcinoma.Methods: We report the case of a 61‐year‐old patient, with no pathological history, who presented to the ophthalmological emergency department for a unilateral left ptosis, of rapidly progressive onset.Results: This is a 61‐year‐old patient, with no pathological history, who presents to the ophthalmological emergency department for a unilateral left ptosis of rapidly progressive onset. Ophthalmological examination noted visual acuity at 10/10 in 2 eyes and Parinaud 2 in near vision in 2 eyes, complete ophthalmoplegia of oculomotor nerve (III) with severe ptosis on the left and relative left afferent pupillary deficit. The ophthalmological examination of the right eye was unremarkable. The general examination revealed a right breast mass. Cerebral angio‐MRI revealed four metastatic lesions on the left, above and under tentorial. A mammography showed a diffuse invasive lesion classified ACR 5 (American College of Radiology) on the right. A breast biopsy with histopathological study confirmed the diagnosis of poorly differentiated and invasive lobular carcinoma of the right breast. The patient is currently undergoing chemotherapy treatment.Conclusions: Acute ptosis is an emergency. Thus, a well‐conducted interrogation as well as a thorough general and ophthalmological examination make it possible to orient the etiological assessment and to take early and adequate management of a pathology that may be life‐threatening for the patient.References1. Barale PO, De Nicola R, Mann F, Miléa D, Tuil E. Ophtalmologie en Urgences. Elsevier Health 2018; 4e édition: p. 309.2. Audren F. Les paralysies de la IIIe paire crânienne: diagnostic. Pratiques en Ophtalmologie 2011; 5:119 A‐44.3. Birzu C, Royer‐Perron L, Hoang‐Xuan K. Tumeurs intracrâniennes. La Revue du Praticien 2020; 70(2): 39–46.
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PERUMAL, P., A. K. DE, D. BHATTACHARYA, and E. B. CHAKURKAR. "Macrocyclic lactone based tri-model therapy to treat humpsore in cattle under humid tropical island ecosystem." Indian Journal of Animal Sciences 93, no. 10 (October 6, 2023). http://dx.doi.org/10.56093/ijans.v93i10.133137.
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Humpsore is a chronic parasitic dermatitis in bovine species; induces severe economic losses to the dairy farmers. Various therapeutic methodologies were tried to treat humpsore in the past; however, they were partially effective against humpsore. Therefore, the present study was designed to assess the effect of tri-model therapy [macrocyclic lactone; Ivermectin, a piperazine derivative; diethylcarbamazine citrate (DECC) and an herbal ointment; Himax™] on treatment of humpsore in Andaman and Nicobar islands. Thirty‐six cattle (n=36 affected) were selected and divided into Gr 1: control (infected without treatment; n=18) and Gr 2: treatment group (infected with treatment; ivermectin, DECC and Himax, n=18) in South Andaman district. In Gr 2, treatment to the ailing animals was given for 45 days. Physiological profiles, hematological profiles, biochemical profiles [total protein, TP; albumin, AL; globulin, GL; creatinine, CR; glucose, GLU; total cholesterol, CHO and urea, URE], liver functional enzymes [aspartate aminotransferase, AST; alanine aminotransferase, ALT and alkaline phosphatase, ALP], mineral profiles, oxidative stress profiles [total antioxidant capacity, TAC; superoxide dismutase, SOD; catalase, CAT and malondialdehyde, MDA] and cortisol were estimated on day 30 of post treatment. Lesion was significantly reduced in day 15 of post‐treatment and completely healed on day 45 of post‐treatment in Gr 2. Physiological profiles, liver functional enzymes, urea, total white blood cell count, differential cell counts, MDA and cortisol were reduced significantly and blood profiles, biochemical profiles, mineral profiles and antioxidant profiles were increased significantly in tri-model therapy treated animals. Therefore, it can be concluded that tri‐model therapy is suitable to treat humpsore in dairy animals.