An Exceptional Response to Dostarlimab in Mismatch Repair Deficient, Microsatellite Instability-High and Platinum Refractory Endometrial Cancer

Until recently, effective therapies for advanced endometrial cancer progressing to a platinum-based combination were lacking. In this setting, immunotherapy with anti PD-1/PDL-1 monoclonal antibodies is rising as a new paradigm in particular for patients with microsatellites instability/mismatch repair deficiency. In this case report, we describe an exceptional and rapid response to dostarlimab in a platinum refractory endometrial cancer patient with high disease burden harboring a mismatch repair deficiency

Clinical validation of full HR-HPV genotyping HPV Selfy assay according to the international guidelines for HPV test requirements for cervical cancer screening on clinician-collected and self-collected samples

Background According to international guidelines, Human Papillomavirus (HPV) DNA tests represent a valid alternative to Pap Test for primary cervical cancer screening, provided that they guarantee balanced clinical sensitivity and specificity for cervical intraepithelial neoplasia grade 2 or more (CIN2+) lesions. The study aimed to assess whether HPV Selfy (Ulisse BioMed - Trieste, Italy), a full-genotyping HPV DNA test that detects and differentiates 14 high-risk HPV (HR-HPV) types, meets the criteria for primary cervical cancer screening described in the international guidelines, on clinician-collected as well as on self-collected samples. Methods For each participant woman, consecutively referring to Azienda Sanitaria Universitaria Giuliano Isontina (Trieste, Italy) and CRO-National Cancer Institute (Aviano, Italy) for the cervical cancer screening program, the following samples were tested: (a) a clinician-collected cervical specimen, analyzed with the reference test (Hybrid Capture (R) 2 test, HC2) and HPV Selfy; and (b) a self-collected vaginal sample, analyzed with HPV Selfy. Enrolled women were also asked to fulfill a questionnaire about self-sampling acceptability. As required by guidelines, a non-inferiority test was conducted to compare the clinical performance of the test under evaluation with its reference test. Results HPV Selfy clinical sensitivity and specificity resulted non-inferior to those of HC2. By analysis of a total of 889 cervical liquid-based cytology samples from a screening population, of which 98 were from women with CIN2+, HPV Selfy showed relative sensitivity and specificity for CIN2+ of 0.98 and 1.00 respectively (non-inferiority score test: P = 0.01747 and P = 0.00414, respectively); the test reached adequate intra- and inter-laboratory reproducibility. Moreover, we demonstrated that the performance of HPV Selfy on self-collected vaginal samples was non-inferior to the performance obtained on clinician-collected cervical specimen (0.92 relative sensitivity and 0.97 relative specificity). Finally, through HPV Selfy genotyping, we were able to describe HPV types prevalence in the study population. Conclusions HPV Selfy fulfills all the requirements of the international Meijer's guidelines and has been clinically validated for primary cervical cancer screening purposes. Moreover, HPV Selfy has also been validated for self-sampling according to VALHUDES guidelines. Therefore, at date, HPV Selfy is the only full-genotyping test validated both for screening purposes and for self-sampling. Trial registration ASUGI Trieste n. 16008/2018; CRO Aviano n.17149/201

High Risk of Secondary Infections Following Thrombotic Complications in Patients With COVID-19

Background. This study’s primary aim was to evaluate the impact of thrombotic complications on the development of secondary infections. The secondary aim was to compare the etiology of secondary infections in patients with and without thrombotic complications. Methods. This was a cohort study (NCT04318366) of coronavirus disease 2019 (COVID-19) patients hospitalized at IRCCS San Raffaele Hospital between February 25 and June 30, 2020. Incidence rates (IRs) were calculated by univariable Poisson regression as the number of cases per 1000 person-days of follow-up (PDFU) with 95% confidence intervals. The cumulative incidence functions of secondary infections according to thrombotic complications were compared with Gray’s method accounting for competing risk of death. A multivariable Fine-Gray model was applied to assess factors associated with risk of secondary infections. Results. Overall, 109/904 patients had 176 secondary infections (IR, 10.0; 95% CI, 8.8–11.5; per 1000-PDFU). The IRs of secondary infections among patients with or without thrombotic complications were 15.0 (95% CI, 10.7–21.0) and 9.3 (95% CI, 7.9–11.0) per 1000-PDFU, respectively (P = .017). At multivariable analysis, thrombotic complications were associated with the development of secondary infections (subdistribution hazard ratio, 1.788; 95% CI, 1.018–3.140; P = .043). The etiology of secondary infections was similar in patients with and without thrombotic complications. Conclusions. In patients with COVID-19, thrombotic complications were associated with a high risk of secondary infections

From Academia Armena Sancti Lazari to the Establishment of Armenian Studies at Ca’ Foscari

The Armenian Studies have a very long tradition in Italy. However, the establishment of the official teaching of Armenian at Ca’ Foscari is particularly significant. It is a direct continuation of many Armenian traces present in the lagoon city for centuries, such as the birth of the first Casa Armena in Europe in 1245, the prosperous diplomatic relations between the Republic of Serenissima and the Kingdom of Armenia, the printing of the first Armenian book in 1512, the arrival of Armenian merchants from Julfa, who highly contributed to the economy of Venice, and finally the institution of the Mekhitarist Congregation of the Armenian monks on the island of San Lazzaro, recognised by Napoleon as Academia Armena Sancti Lazari. After an historical excursus, the paper will go on to detail some significant periods of Armenian Studies at Ca’ Foscari

Geoambients of RPPN Serra do Caraça e features of quartzitic carste

A RPPN Serra do Caraça se enquadra na borda leste da província geológica do Quadrilátero Ferrífero, estado do Minas Gerais. A Reserva abrange refúgios ecológicos montanos e altimontanos em litologia predominantemente quartzítica, sendo portanto um forte fator de distribuição dos geoambientes locais. No local, diferentes patamares com vegetação principalmente endêmica formam um complexo entre campos cerrados e enclaves de mata atlântica. Além disso, a área em estudo contempla um dos mais complexos sistemas cársticos em quartzitos do Brasil. É notório a ocorrência de feições como dolinas e cavidades. Nesse contexto, procurou-se identificar, caracterizar e mapear os geoambientes para entender as dinâmicas e as relações ecológicas, para subsidiar as estratégias de manejo e visitação do parque. Para definir as unidades geoambientais utilizou-se uma metodologia pedogeomorfológica, identificando as principais características ecogeográficas. Utilizaram-se imagens satelitais ASTER de alta resolução e mapa 1: 50.000 planialtimétrico, para auxiliar as campanhas de estudo in loco. Foram abertos doze perfis de solos em diferentes níveis da paisagem, contemplando os topos, afloramentos, encostas, vales de acúmulo e diques. Cada perfil foi descrito e os horizontes coletado, identificação dos principais processos pedogenéticos e posteriormente submetidos às análises físicas, químicas e mineralógicas. As rochas de cavidades naturais foram analisadas por difratometria de raios-X (XRD) e microscopia eletrônica de varredura com microssonda EDS acoplada (MEV/EDS), procurando assim entender a gênese deste sistema cárstico quartzítico. Também foram identificadas as principais fitofisionomias vegetais, através da descrição em campo e coleta, quando necessário. Produziu-se o mapa das unidades geoambientais, sendo cada unidade caracterizada pormenorizadamente, procurando estabelecer as interações entre eles. Foram identificadas nove unidades: Campos rupestres, Campos cerrados, Brejos e turfeiras, Matas de encosta, Matas nebulares e Matas de candeias. Particular ênfase foi dada aos ambientes desenvolvidos sobre intrusões de rochas metabásicas, que proporcionaram solos distróficos porém texturalmente mais argilosos, com maior retenção hídrica e consequentemente desenvolveram fitofisionomias contrastantes, de maior porte. Todos os outros perfis se mostraram com texturas substancialmente arenosas, alumínicos e ácidos. Os dados levaram a entender que na RPPN, a taxa de pedogênese é menor que a morfogênese, sendo os ambientes definidos pelo controle morfoestrutural. As análises MEV/EDS das amostras de rochas mostraram mobilidade do Fe e Al intergranulares, podendo capear saprolitos e formar concreções nas paredes das grutas. A caracterização das unidades geoambientais permitiu esclarecer as relações entre os diferentes níveis da paisagem da Serra do Caraça, corroborada pelas análises físicas, químicas e mineralógicas dos solos, que em geral se mostraram gibbsiticos, com distrofismo e elevada saturação por alumínio. Assim, dado às condições extremas desses solos, as espécies vegetais ocorrentes indicam um alto grau de especialização e endemismo, que sujerem adaptações que otimizam a ciclagem biogeoquímica, tolerância à toxidez, e bioacumulação de alumínio.The RPPN Serra do Caraça falls on the eastern edge of the geologic province of the Iron Quadrangle, State of Minas Gerais. The Reserve covers ecological and montane highland refuges in lithology predominantly quartzite and is therefore a strong distribution factor of local Geoenvironments. On site, different levels with mostly endemic vegetation form a complex between savanna and niche of Atlantic forest. In addition the study area includes one of the most complex karst systems in quartzite from Brazil, it is clear the present features such as sinkholes and cavities. In this context we sought to identify, characterize and map the Geoenvironments to understand the dynamics and ecological relationships, to support management strategies and visiting the park. To define the environmental Units used a methodology pedogeomorphological identifying key characteristics ecogeographic. We used high-resolution ASTER satellite images and map 1: 50,000 planialtimetric to assist the on-site study of campaigns. Twelve soil profiles were opened at different levels of the landscape, covering the tops, outcrops, slopes, valleys and accumulation of dikes. Each profile was described and collected horizons, identifying key processes pedogenetic and subsequently subjected to physical, chemical and mineralogical. The rocks of natural cavities were analyzed by diffraction of X-ray (XRD) and scanning electron microscopy coupled with EDS microprobe (SEM / EDS), thus seeking to understand the genesis of this quartzite karst system. Also the main plant vegetation types were identified by describing the field and collect when needed. The map of the geo-environmental units was produced, each unit being characterized in detail, trying to establish the interactions between them. Nine units were identified: Outcrops, Savannas, Swamps and Bogs, Hillside Forest, Elfin Forest and Lamps. Particular emphasis was given to the developed environments on intrusion metabasic rocks, which provided dystrophic soils but texturally more clayey, with greater water retention and consequently developed contrasting vegetation types, of greater size. All other profiles have proven to substantially sandy textures, aluminic and acids. The data led to the understanding that the PRNP pedogenesis rate is less than the morphogenesis, the environments being defined by morphostructural control. Analyses SEM / EDS of rock samples showed the mobility of Fe and Al intergranular and can coat saprolite and form concretions on the walls of caves. Characterization of geoenvironmental units has clarified the relationships between the different levels of landscape Caraça, corroborated by physical, chemical and mineralogical soil, which generally showed gibbsitic, with dystrophic and high aluminum saturation. So, given the extreme conditions of these soils, the plant species occurring indicate a high degree of specialization and endemism, which suggest adaptations that optimize the biogeochemical cycling, tolerance toxicity, and aluminum bioaccumulation.Coordenação de Aperfeiçoamento de Pessoal de Nível Superio

Laparoscopic treatment of sclerosing stromal tumor of the ovary in a woman with Gorlin-Goltz Syndrome: a case report and review of the literature

Gorlin-Goltz syndrome is a rare hereditary multisystemic disease. Multiple basal cell carcinomas, odontogenic keratocysts and skeletal abnormalities are the main clinical manifestations of the syndrome, but several organs can be involved. Moreover this condition is associated with the development of various benign and malignant tumors, even in the genital tract. This report describes a rare association between Gorlin-Goltz syndrome and the sclerosing stromal tumor of the ovary. Since the ultrasounds and magnetic resonance pattern of this tumor can be similar to those of a malignant neoplasm, a prompt surgical intervention and histological confirmation of diagnosis is mandatory. However this is a benign lesion and thus can be approached with a laparoscopic fertility sparing surgery. Gynecologists should be aware of this possible association, in order to provide an appropriate counseling to these women, and to perform a fertility sparing laparoscopic approach, wherever possible

Thickness of preperitoneal fat as a predictor of malignancy in overweight and obese women with endometrial polyps

The aim of the present study was to determine the association between the thickness of preperitoneal fat (PFT), utilized as an indicator of visceral fat deposition, and the risk of premalignant and malignant changes of endometrial polyps (EPs) in overweight and obese women. Overweight and obese women who had undergone diagnostic outpatient hysteroscopy and subsequent endometrial polypectomy between January 2010 and May 2013 were analyzed. Each patient underwent a transabdominal ultrasound for the purpose of measuring the thickness of preperitoneal fat. A total of 146 overweight or obese women were analyzed. The overall incidence of malignant or premalignant lesions was 8.2%. Notably, 5 patients (3.4%) received a histopathological diagnosis of complex hyperplasia with atypia, while polyps harboring carcinoma were diagnosed in 7 cases (4.8%). A significantly increased PFT was observed in women exhibiting preneoplastic and neoplastic lesions, compared with women with benign EPs (mean ± SD, 23.2±3.7 vs. 15.9±8.3; P<0.01). Patient age of >60 years was significantly associated with malignant progression of EPs, while body mass index, menopausal status, arterial hypertension, diabetes, abnormal uterine bleeding, hormone replacement therapy and tamoxifen treatment demonstrated no significant association with the development of preneoplastic and neoplastic lesions of the endometrium. In a multivariate analysis, only PFT maintained a significant correlation with the diagnosis of preneoplastic and neoplastic lesions on EPs (odds ratio, 1.14; 95% confidence interval, 1.04–1.26). Ultrasound evaluation of PFT in overweight and obese women may be useful for the identification of a particularly high-risk subgroup of women. Therefore, regardless of symptoms or additional clinical variables, these particularly high-risk women require appropriate counseling and prompt surgical removal of EPs

Preperitoneal Fat Thicknesses, Lipid Profile, and Oxidative Status in Women With Uterine Fibroids

Purpose: There is growing evidence supporting a possible role for metabolic syndrome and its determinants, such as dyslipidemia, in uterine fibroid (UF) pathogenesis. The present study aims to investigate the association between UFs and visceral and subcutaneous fat thickness (SFT), lipid profile, and oxidative and antioxidative status. Methods: In this cross-sectional study, 35 patients diagnosed with UFs and 15 women without UFs were enrolled. Clinical history and anthropometric parameters were collected for every woman. Characteristics of UFs, preperitoneal fat thickness (PFT), and SFT were assessed ultrasonically. Lipid profile, glucose, thiobarbituric acid reactive substances (TBARs), and superoxide dismutase (SOD) activity were evaluated on plasma from participants. Results: Women with UFs showed a significantly increased PFT (11.63 ± 3.39 vs 7.01 ± 3.10 mm; P < .001), lower levels of high-density lipoprotein cholesterol (HDL-C; 45.4 ± 8.3 vs 57.2 ± 13.4 mg/dL; P = .017), higher levels of low-density lipoprotein cholesterol (LDL-C; 92.3 ± 21.5 vs 72.0 ± 14.6 mg/dL; P = .007), and oxidized LDL (65.2 ± 20.7 vs 43.0 ± 11.3 U/L; P = .002). In patients, TBARs concentration was significantly higher (9.41 ± 6.49 vs 2.92 ± 1.65 nmol malondialdehyde/100 μg prot; P < .001), whereas SOD activity was lower (1.09 ± 0.19 vs 1.37 ± 0.41 U/μL; P = .005). Preperitoneal fat thickness was positively associated with body mass index, oxidized LDL, and TBARs. At multivariate analysis, PFT and HDL-C maintained a significant correlation with the diagnosis of UFs. Conclusion: Chronic inflammation triggered and sustained by visceral fat could play a determinant role in cell differentiation and proliferation processes, necessary for the development of UFs. Alterations in cholesterol fractions may be explained as a consequence of the increased visceral fat deposits and can reflect an increased risk of subclinical atherosclerosis in patients with UF