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1,956 results on '"Basile A."'

1. The spectrum of kidney dysfunction requiring chronic dialysis therapy: Implications for clinical practice and future clinical trials

Author

Murea, Mariana, Deira, Javier, Kalantar‐Zadeh, Kamyar, Casino, Francesco G, and Basile, Carlo

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Kidney Disease, Renal and urogenital, Disease Progression, Female, Humans, Kidney, Kidney Failure, Chronic, Kidney Function Tests, Male, Renal Dialysis, Renal Replacement Therapy, Urology & Nephrology, Clinical sciences
Abstract

Staging to capture kidney function and pathophysiologic processes according to severity is widely used in chronic kidney disease or acute kidney injury not requiring dialysis. Yet the diagnosis of "end-stage kidney disease" (ESKD) considers patients as a single homogeneous group, with negligible kidney function, in need of kidney replacement therapy. Herein, we review the evidence behind the heterogeneous nature of ESKD and discuss potential benefits of recasting the terminology used to describe advanced kidney dysfunction from a monolithic entity to a disease with stages of ascending severity. We consider kidney assistance therapy in lieu of kidney replacement therapy to better reconcile all available types of therapy for advanced kidney failure including dietary intervention, kidney transplantation, and dialysis therapy at varied schedules. The lexicon "kidney dysfunction requiring dialysis" (KDRD) with stages of ascending severity based on levels of residual kidney function (RKF)-that is, renal urea clearance-and manifestations related to uremia, fluid status, and other abnormalities is discussed. Subtyping KDRD by levels of RKF could advance dialysis therapy as a form of kidney assistance therapy adjusted based on RKF and clinical symptoms. We focus on intermittent hemodialysis and underscore the need to personalize dialysis treatments and improve characterization of patients included in clinical trials.

Published
2022

2. Arginine Depletion Therapy with ADI-PEG20 Limits Tumor Growth in Argininosuccinate Synthase–Deficient Ovarian Cancer, Including Small-Cell Carcinoma of the Ovary, Hypercalcemic Type

Author

Ji, Jennifer X, Cochrane, Dawn R, Tessier-Cloutier, Basile, Chen, Shary Yutin, Ho, Germain, Pathak, Khyatiben V, Alcazar, Isabel N, Farnell, David, Leung, Samuel, Cheng, Angela, Chow, Christine, Colborne, Shane, Negri, Gian Luca, Kommoss, Friedrich, Karnezis, Anthony, Morin, Gregg B, McAlpine, Jessica N, Gilks, C Blake, Weissman, Bernard E, Trent, Jeffrey M, Hoang, Lynn, Pirrotte, Patrick, Wang, Yemin, and Huntsman, David G

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Genetics, Cancer, Cancer Genomics, Biotechnology, Ovarian Cancer, Orphan Drug, Rare Diseases, Human Genome, Women's Health, 5.1 Pharmaceuticals, 2.1 Biological and endogenous factors, Animals, Arginine, Argininosuccinate Synthase, Carcinoma, Small Cell, Cell Line, Tumor, Cell Proliferation, Female, Humans, Hydrolases, Mice, Ovarian Neoplasms, Ovary, Parathyroid Hormone-Related Protein, Polyethylene Glycols, Proteomics, Xenograft Model Antitumor Assays, Oncology & Carcinogenesis, Clinical sciences, Oncology and carcinogenesis
Abstract

PurposeMany rare ovarian cancer subtypes, such as small-cell carcinoma of the ovary, hypercalcemic type (SCCOHT), have poor prognosis due to their aggressive nature and resistance to standard platinum- and taxane-based chemotherapy. The development of effective therapeutics has been hindered by the rarity of such tumors. We sought to identify targetable vulnerabilities in rare ovarian cancer subtypes.Experimental designWe compared the global proteomic landscape of six cases each of endometrioid ovarian cancer (ENOC), clear cell ovarian cancer (CCOC), and SCCOHT to the most common subtype, high-grade serous ovarian cancer (HGSC), to identify potential therapeutic targets. IHC of tissue microarrays was used as validation of arginosuccinate synthase (ASS1) deficiency. The efficacy of arginine-depriving therapeutic ADI-PEG20 was assessed in vitro using cell lines and patient-derived xenograft mouse models representing SCCOHT.ResultsGlobal proteomic analysis identified low ASS1 expression in ENOC, CCOC, and SCCOHT compared with HGSC. Low ASS1 levels were validated through IHC in large patient cohorts. The lowest levels of ASS1 were observed in SCCOHT, where ASS1 was absent in 12 of 31 cases, and expressed in less than 5% of the tumor cells in 9 of 31 cases. ASS1-deficient ovarian cancer cells were sensitive to ADI-PEG20 treatment regardless of subtype in vitro. Furthermore, in two cell line mouse xenograft models and one patient-derived mouse xenograft model of SCCOHT, once-a-week treatment with ADI-PEG20 (30 mg/kg and 15 mg/kg) inhibited tumor growth in vivo.ConclusionsPreclinical in vitro and in vivo studies identified ADI-PEG20 as a potential therapy for patients with rare ovarian cancers, including SCCOHT.

Published
2020

3. Longitudinal cohort of HIV-negative transgender women of colour in New York City: protocol for the TURNNT (‘Trying to Understand Relationships, Networks and Neighbourhoods among Transgender women of colour’) study

Author

Callander, Denton, Schneider, John A, Radix, Asa, Chaix, Basile, Scheinmann, Roberta, Love, Gia, Smith, Jordyn, Regan, Seann D, Kawachi, Ichiro, St James, Kiara, Ransome, Yusuf, Herrera, Cristina, Reisner, Sari L, Doroshow, Ceyenne, Poteat, Tonia, Watson, Kim, Bluebond-Langner, Rachel, Toussaint, Nala, Garofalo, Robert, Sevelius, Jae, and Duncan, Dustin T

Subjects
Biomedical and Clinical Sciences, Public Health, Health Sciences, Prevention, Sexually Transmitted Infections, Sexual and Gender Minorities (SGM/LGBT*), HIV/AIDS, Behavioral and Social Science, Clinical Research, Social Determinants of Health, Women's Health, Health Disparities, Infectious Diseases, Infection, Good Health and Well Being, Adolescent, Adult, Black or African American, Asian, Asian People, Cross-Sectional Studies, Female, HIV Infections, HIV Seronegativity, Hispanic or Latino, Humans, Interpersonal Relations, Male, Middle Aged, Multivariate Analysis, Native Hawaiian or Other Pacific Islander, New York City, Prospective Studies, Residence Characteristics, Sexual Partners, Social Networking, Transgender Persons, Young Adult, HIV & AIDS, epidemiology, sexual medicine, Clinical Sciences, Public Health and Health Services, Other Medical and Health Sciences, Biomedical and clinical sciences, Health sciences, Psychology
Abstract

IntroductionIn the USA, transgender women are among the most vulnerable to HIV. In particular, transgender women of colour face high rates of infection and low uptake of important HIV prevention tools, including pre-exposure prophylaxis (PrEP). This paper describes the design, sampling methods, data collection and analyses of the TURNNT ('Trying to Understand Relationships, Networks and Neighbourhoods among Transgender women of colour') study. In collaboration with communities of transgender women of colour, TURNNT aims to explore the complex social and environmental (ie, neighbourhood) structures that affect HIV prevention and other aspects of health in order to identify avenues for intervention.Methods and analysesTURNNT is a prospective cohort study, which will recruit 300 transgender women of colour (150 Black/African American, 100 Latina and 50 Asian/Pacific Islander participants) in New York City. There will be three waves of data collection separated by 6 months. At each wave, participants will provide information on their relationships, social and sexual networks, and neighbourhoods. Global position system technology will be used to generate individual daily path areas in order to estimate neighbourhood-level exposures. Multivariate analyses will be conducted to assess cross-sectional and longitudinal, independent and synergistic associations of personal relationships (notably individual social capital), social and sexual networks, and neighbourhood factors (notably neighbourhood-level social cohesion) with PrEP uptake and discontinuation.Ethics and disseminationThe TURNNT protocol was approved by the Columbia University Institutional Review Board (reference no. AAAS8164). This study will provide novel insights into the relationship, network and neighbourhood factors that influence HIV prevention behaviours among transgender women of colour and facilitate exploration of this population's health and well-being more broadly. Through community-based dissemination events and consultation with policy makers, this foundational work will be used to guide the development and implementation of future interventions with and for transgender women of colour.

Published
2020

4. Delayed gastrointestinal-associated lymphoid tissue reconstitution in duodenum compared with rectum in HIV-infected patients initiating antiretroviral therapy.

Author

Sainz, Talia, Serrano-Villar, Sergio, Mann, Surinder, Ma, Zhong-Min, Utay, Netanya S, Thompson, Corbin G, Chun, Tae-Wook, Kashuba, Angela D, Siewe, Basile, Albanese, Anthony, Troia-Cancio, Paolo, Sinclair, Elizabeth, Somasunderam, Anoma, Yotter, Tammy, Moreno, Santiago, Pollard, Richard B, Landay, Alan, Miller, Christopher J, and Asmuth, David M

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Infectious Diseases, HIV/AIDS, Clinical Research, Sexually Transmitted Infections, Digestive Diseases, Infection, Adult, Antiretroviral Therapy, Highly Active, Biopsy, Blood, CD4-CD8 Ratio, CD4-Positive T-Lymphocytes, Duodenum, Female, HIV Infections, Humans, Immune Reconstitution, Immunophenotyping, Intestinal Mucosa, Linear Models, Lymphocyte Activation, Male, Rectum, duodenum, gastrointestinal-associated lymphoid tissue, HIV, immune reconstitution, lipoteichoic acid, rectum, small intestines, T regulatory cells, zonulin, gamma delta intestinal T cells, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Virology, Biomedical and clinical sciences, Health sciences
Abstract

BACKGROUND:We aimed to characterize the impact of ART initiation on GALT at various sites along the gastrointestinal site. METHODOLOGY:Peripheral blood and duodenal and rectal biopsies were obtained from 12 HIV and 33 treatment-naïve HIV subjects at baseline and after 9-months ART. Tissue was digested for immunophenotyping. Inflammatory, bacterial translocation and intestinal damage markers were measured in plasma. RESULTS:Twenty-six HIV subjects completed follow-up. The lowest reconstitution of CD4 T-cells and the lowest CD4/CD8 ratio during ART compared to blood were observed in the duodenum with the rectum being either intermediate or approaching blood levels. Regulatory T-cells (Treg) were in higher proportions in the duodenum than the rectum and neither declined significantly during ART. Several correlations with biomarkers of microbial translocation were observed including increases in LTA levels, which reflects gram-positive bacterial translocation, correlated with increases in %CD4 T-cells in duodenum (Rho 0.773, P = 0.033), and with decreases duodenal Treg populations (Rho -0.40, P = 0.045). CONCLUSIONS:HIV-mediated immunological disruption is greater in the duodenum than rectum and blood before and during ART. Small intestine damage may represent a unique environment for T-cell depletion, which might be attenuated by interaction with gram positive bacteria.

Published
2019

5. Tubo-Ovarian Transitional Cell Carcinoma and High-grade Serous Carcinoma Show Subtly Different Immunohistochemistry Profiles

Author

Magrill, Jamie, Karnezis, Anthony N, Tessier-Cloutier, Basile, Talhouk, Aline, Kommoss, Stefan, Cochrane, Dawn, Chow, Christine, Cheng, Angela, Soslow, Robert, Hauptmann, Steffen, du Bois, Andreas, Pfisterer, Jacobus, Gilks, C Blake, Huntsman, David G, and Kommoss, Friedrich

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Rare Diseases, Genetics, Cancer, Biomarkers, Tumor, Carcinoma, Transitional Cell, Cohort Studies, Female, Humans, Immunohistochemistry, Neoplasm Proteins, Ovarian Neoplasms, Proteomics, Tissue Array Analysis, Ovarian cancer, Transitional cell carcinoma, High-grade serous carcinoma, Biomarkers, Paediatrics and Reproductive Medicine, Pathology, Reproductive medicine
Abstract

Tubo-ovarian transitional cell carcinoma (TCC) is grouped with high-grade serous carcinoma (HGSC) in the current World Health Organization classification. TCC is associated with BRCA mutations and a better prognosis compared with HGSC. Previous papers examining the immunohistochemical features of TCC have studied limited numbers of samples. No marker reflecting the biological difference between TCC and HGSC is known. We collected a large cohort of TCC to determine whether TCC and HGSC could be distinguished by immunohistochemistry. A tissue microarray was built from 89 TCC and a control cohort of 232 conventional HGSC. Immunohistochemistry was performed, scored, and statistically analyzed for routine markers of HGSC and urothelial tumors: PAX8, WT1, p53, p16, ER, p63, and GATA3. Using scoring cutoffs commonly employed in clinical practice, the immunohistochemical profile of TCC was indistinguishable from HGSC for all markers. However, more detailed scoring criteria revealed statistically significant differences between the 2 groups of tumors with respect to ER, PAX8, and WT1. HGSC showed more diffuse and intense staining for PAX8 (P=0.004 and 0.001, respectively) and WT1 (P=0.002 and 0.002, respectively); conversely, TCC showed more intense staining for ER (P=0.007). TCC and HGSC therefore show subtle differences in their immunohistochemical profiles which might reflect underlying (epi)genetic differences. Further studies using proteomic analysis will focus on the identification of differentially expressed proteins that might serve as markers of TCC-like differentiation, which could help explain biologic differences between TCC and HGSC and might identify other cases of HGSC with a better prognosis.

Published
2019

6. Detection and genomic characterization of a mammary-like adenocarcinoma

Author

Grewal, Jasleen K, Eirew, Peter, Jones, Martin, Chiu, Kenrry, Tessier-Cloutier, Basile, Karnezis, Anthony N, Karsan, Aly, Mungall, Andy, Zhou, Chen, Yip, Stephen, Tinker, Anna V, Laskin, Janessa, Marra, Marco, and Jones, Steven JM

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Oncology and Carcinogenesis, Biotechnology, Cancer, Human Genome, Breast Cancer, Prevention, Rare Diseases, Good Health and Well Being, Adenocarcinoma, Breast, Breast Neoplasms, Diagnosis, Differential, Female, Gene Expression Profiling, Genomics, Humans, Immunohistochemistry, Middle Aged, Receptor, ErbB-2, Transcriptome, Vulva, Vulvar Neoplasms, Whole Genome Sequencing, Receptor, erbB-2, neoplasm of the breast, neoplasm of the genitourinary tract, Pharmacology and pharmaceutical sciences
Abstract

Whole-genome and transcriptome sequencing were performed to identify potential therapeutic strategies in the absence of viable treatment options for a patient initially diagnosed with vulvar adenocarcinoma. Genomic events were prioritized by comparison against variant distributions in the TCGA pan-cancer data set and complemented with detailed transcriptome sequencing and copy-number analysis. These findings were considered against published scientific literature in order to evaluate the functional effects of potentially relevant genomic events. Analysis of the transcriptome against a background of 27 TCGA cancer types led to reclassification of the tumor as a primary HER2+ mammary-like adenocarcinoma of the vulva. This revised diagnosis was subsequently confirmed by follow-up immunohistochemistry for a mammary-like adenocarcinoma. The patient was treated with chemotherapy and targeted therapies for HER2+ breast cancer. The detailed pathology and genomic findings of this case are presented herein.

Published
2017

7. Immunophenotypic features of dedifferentiated endometrial carcinoma – insights from BRG1/INI1‐deficient tumours

Author

Hoang, Lien N, Lee, Yow‐Shan, Karnezis, Anthony N, Tessier‐Cloutier, Basile, Almandani, Noorah, Coatham, Mackenzie, Gilks, C Blake, Soslow, Robert A, Stewart, Colin JR, Köbel, Martin, and Lee, Cheng‐Han

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Cancer, Adult, Aged, Aged, 80 and over, Biomarkers, Tumor, Carcinoma, Endometrioid, Cell Dedifferentiation, DNA Helicases, Endometrial Neoplasms, Female, Humans, Immunohistochemistry, Immunophenotyping, Middle Aged, Nuclear Proteins, PAX8 Transcription Factor, Receptors, Estrogen, SMARCB1 Protein, Transcription Factors, Tumor Suppressor Protein p53, BRG1, dedifferentiated carcinoma, endometrial cancer, INI1, PAX8, SMARCA4, SMARCB1, undifferentiated carcinoma, Clinical Sciences, Pathology, Clinical sciences, Oncology and carcinogenesis
Abstract

AimsDedifferentiated endometrial carcinoma (DDEC) is defined by the presence of an undifferentiated carcinoma together with an endometrioid carcinoma. Inactivation of SMARCA4 (BRG1) and inactivation of SMARCB1 (INI1) were recently described as potential mechanisms underlying the histological dedifferentiation. The aim of this study was to characterize the immunophenotypic features of DDECs, particularly in cases with prototypical histological and molecular features (BRG1/INI1 deficiency).Methods and resultsWe evaluated PAX8, oestrogen receptor (ER) and p53 immunostaining in the endometrioid and the undifferentiated components of 20 BRG1/INI1-deficient DDECs and 15 BRG1/INI1-intact DDECs, and compared the results with those of 23 grade 3 endometrioid carcinomas. The differentiated endometrioid component was positive for PAX8 and/or ER in 19 of 20 BRG1/INI1-deficient DDECs, whereas the corresponding undifferentiated component of all 20 tumours showed a complete absence of PAX8 and ER staining. All except one of the BRG1/INI1-deficient tumours showed a wild-type p53 staining pattern. PAX8 and ER expression in the undifferentiated component was absent in 67% and 80% of BRG1/INI1-intact DDECs, respectively, whereas 47% of the BRG1/INI1-intact DDECs showed a mutated p53 staining pattern. In comparison, absent PAX8 expression and absent ER expression were each observed in the more solid area of 48% and 48% of grade 3 endometrioid carcinomas.ConclusionsThe consistent absence of PAX8 and ER expression in molecularly defined (BRG1/INI1-deficient) DDECs suggests that the loss of PAX8 and ER expression is a fundamental feature of dedifferentiation. The frequent findings of a mutated p53 staining pattern in BRG1/INI1-intact DDECs indicate that BRG1/INI1-intact DDECs may be biologically different from BRG1/INI1-deficient tumours.

Published
2016

8. Loss of switch/sucrose non-fermenting complex protein expression is associated with dedifferentiation in endometrial carcinomas

Author

Karnezis, Anthony N, Hoang, Lien N, Coatham, Mackenzie, Ravn, Sarah, Almadani, Noorah, Tessier-Cloutier, Basile, Irving, Julie, Meng, Bo, Li, Xiaodong, Chow, Christine, McAlpine, Jessica, Kuo, Kuan-Ting, Mao, Tsui-Lien, Djordjevic, Bojana, Soslow, Robert A, Huntsman, David G, Gilks, C Blake, Köbel, Martin, and Lee, Cheng-Han

Subjects
Cancer, Aged, Cell Dedifferentiation, Chromosomal Proteins, Non-Histone, DNA Mutational Analysis, Endometrial Neoplasms, Female, Humans, Immunohistochemistry, Kaplan-Meier Estimate, Middle Aged, Oligonucleotide Array Sequence Analysis, Tissue Array Analysis, Transcription Factors, Medical and Health Sciences, Pathology
Abstract

Dedifferentiated endometrial carcinoma is an aggressive type of endometrial cancer that contains a mix of low-grade endometrioid and undifferentiated carcinoma components. We performed targeted sequencing of eight dedifferentiated carcinomas and identified somatic frameshift/nonsense mutations in SMARCA4, a core ATPase of the switch/sucrose non-fermenting (SWI/SNF) complex, in the undifferentiated components of four tumors. Immunohistochemical analysis confirmed the loss of SMARCA4 in the undifferentiated component of these four SMARCA4-mutated cases, whereas the corresponding low-grade endometrioid component showed retained SMARCA4 expression. An expanded survey of other members of the SWI/SNF complex showed SMARCB1 loss in the undifferentiated component of two SMARCA4-intact tumors, and all SMARCA4- or SMARCB1-deficient tumors showed concomitant loss of expression of SMARCA2. We subsequently examined the expression of SMARCA2, SMARCA4, and SMARCB1 in an additional set of 22 centrally reviewed dedifferentiated carcinomas and 31 grade 3 endometrioid carcinomas. Combining the results from the index and the expansion set, 15 of 30 (50%) of the dedifferentiated carcinomas examined showed either concurrent SMARCA4 and SMARCA2 loss (37%) or concurrent SMARCB1 and SMARCA2 loss (13%) in the undifferentiated component. The loss of SMARCA4 or SMARCB1 was mutually exclusive. All 31 grade 3 endometrioid carcinomas showed intact expression of these core SWI/SNF proteins. The majority (73%) of the SMARCA4/SMARCA2-deficient and half of SMARCB1/SMARCA2-deficient undifferentiated component developed in a mismatch repair-deficient molecular context. The observed spatial association between SWI/SNF protein loss and histologic dedifferentiation suggests that inactivation of these core SWI/SNF proteins may contribute to the development of dedifferentiated endometrial carcinoma.

Published
2016

9. Effects of Combined CCR5/Integrase Inhibitors-Based Regimen on Mucosal Immunity in HIV-Infected Patients Naïve to Antiretroviral Therapy: A Pilot Randomized Trial.

Author

Serrano-Villar, Sergio, Sainz, Talia, Ma, Zhong-Min, Utay, Netanya S, Chun, Tae-Wook, Mann, Surinder, Kashuba, Angela D, Siewe, Basile, Albanese, Anthony, Troia-Cancio, Paolo, Sinclair, Elizabeth, Somasunderam, Anoma, Yotter, Tammy, Deeks, Steven G, Landay, Alan, Pollard, Richard B, Miller, Christopher J, Moreno, Santiago, and Asmuth, David M

Subjects
T-Lymphocyte Subsets, Humans, HIV Infections, Alkynes, Cyclohexanes, Cyclopropanes, Triazoles, Benzoxazines, Drug Combinations, HIV Integrase Inhibitors, Anti-HIV Agents, Enzyme-Linked Immunosorbent Assay, Chromatography, High Pressure Liquid, Flow Cytometry, Pilot Projects, Lymphocyte Activation, Immunity, Mucosal, Adult, Female, Male, CCR5 Receptor Antagonists, Raltegravir Potassium, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination, Maraviroc, Chromatography, High Pressure Liquid, Immunity, Mucosal, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination, Infectious Diseases, HIV/AIDS, Clinical Research, Clinical Trials and Supportive Activities, 5.1 Pharmaceuticals, 6.1 Pharmaceuticals, Infection, Inflammatory and Immune System, Virology, Microbiology, Immunology, Medical Microbiology
Abstract

Whether initiation of antiretroviral therapy (ART) regimens aimed at achieving greater concentrations within gut associated lymphoid tissue (GALT) impacts the level of mucosal immune reconstitution, inflammatory markers and the viral reservoir remains unknown. We included 12 HIV- controls and 32 ART-naïve HIV patients who were randomized to efavirenz, maraviroc or maraviroc+raltegravir, each with fixed-dose tenofovir disoproxil fumarate/emtricitabine. Rectal and duodenal biopsies were obtained at baseline and at 9 months of ART. We performed a comprehensive assay of T-cell subsets by flow cytometry, T-cell density in intestinal biopsies, plasma and tissue concentrations of antiretroviral drugs by high-performance liquid chromatography/mass spectroscopy, and plasma interleukin-6 (IL-6), lipoteichoic acid (LTA), soluble CD14 (sCD14) and zonulin-1 each measured by ELISA. Total cell-associated HIV DNA was measured in PBMC and rectal and duodenal mononuclear cells. Twenty-six HIV-infected patients completed the follow-up. In the duodenum, the quadruple regimen resulted in greater CD8+ T-cell density decline, greater normalization of mucosal CCR5+CD4+ T-cells and increase of the naïve/memory CD8+ T-cell ratio, and a greater decline of sCD14 levels and duodenal HIV DNA levels (P = 0.004 and P = 0.067, respectively), with no changes in HIV RNA in plasma or tissue. Maraviroc showed the highest drug distribution to the gut tissue, and duodenal concentrations correlated well with other T-cell markers in duodenum, i.e., the CD4/CD8 ratio, %CD4+ and %CD8+ HLA-DR+CD38+ T-cells. Maraviroc use elicited greater activation of the mucosal naïve CD8+ T-cell subset, ameliorated the distribution of the CD8+ T-cell maturational subsets and induced higher improvement of zonulin-1 levels. These data suggest that combined CCR5 and integrase inhibitor based combination therapy in ART treatment naïve patients might more effectively reconstitute duodenal immunity, decrease inflammatory markers and impact on HIV persistence by cell-dependent mechanisms, and show unique effects of MVC in duodenal immunity driven by higher drug tissue penetration and possibly by class-dependent effects.

Published
2016

10. Examining explanations for the link between bullying perpetration and physical dating violence perpetration: Do they vary by bullying victimization?

Author

Foshee, Vangie A, Benefield, Thad S, McNaughton Reyes, Heath Luz, Eastman, Meridith, Vivolo-Kantor, Alana M, Basile, Kathleen C, Ennett, Susan T, and Faris, Robert

Subjects
Biological Psychology, Social and Personality Psychology, Psychology, Applied and Developmental Psychology, Mental Health, Youth Violence, Pediatric, Youth Violence Prevention, Childhood Injury, Clinical Research, Behavioral and Social Science, Violence Against Women, Prevention, Physical Injury - Accidents and Adverse Effects, Violence Research, Depression, 2.3 Psychological, social and economic factors, Aetiology, Mental health, Peace, Justice and Strong Institutions, Adolescent, Adolescent Behavior, Bullying, Crime Victims, Female, Humans, Interpersonal Relations, Intimate Partner Violence, Longitudinal Studies, Male, Models, Psychological, Social Environment, Surveys and Questionnaires, bullying involvement, dating abuse, dating violence, conditional indirect effects, Criminology, Developmental & Child Psychology, Applied and developmental psychology, Biological psychology, Social and personality psychology
Abstract

This short-term longitudinal study examined whether the association between bullying perpetration and later physical dating violence perpetration and mediators of that association (via anger, depression, anxiety, and social status), varied depending on level of bullying victimization. Differences have been noted between those who bully but are not victims of bullying, and those who are both bullies and victims. These differences may influence dating violence risk and the explanations for why bullying leads to dating violence. Data were from dating adolescents in three rural counties who completed self-administered questionnaires in the fall semester of grades 8-10 and again in the spring semester. The sample (N = 2,414) was 44.08% male and 61.31% white. Bullying perpetration in the fall semester predicted physical dating violence perpetration in the spring semester when there was no bullying victimization, but not when there was any bullying victimization. Bullying perpetration was positively associated with anger at all levels of bullying victimization and with social status when there was no or low amounts of victimization; it was negatively associated with social status at high levels of victimization. Bullying victimization was positively associated with anger, depression, and anxiety at all levels of bullying perpetration. Anger mediated the association between bullying perpetration and dating violence, regardless of level of victimization; depression, anxiety, and social status did not mediate the association at any level of bullying victimization. The findings have implications for dating violence prevention efforts and for future research on the link between bullying and dating violence.

Published
2016

11. Semaphorin 4D Promotes Skeletal Metastasis in Breast Cancer.

Author

Yang, Ying-Hua, Buhamrah, Asma, Schneider, Abraham, Lin, Yi-Ling, Zhou, Hua, Bugshan, Amr, and Basile, John R

Subjects
Cell Line, Tumor, Animals, Humans, Mice, Bone Neoplasms, Breast Neoplasms, Neoplasm Metastasis, Semaphorins, Neoplasm Proteins, Interleukin-8, Antigens, CD, Neoplasm Transplantation, Calcification, Physiologic, Female, Heterografts, Antigens, CD, Calcification, Physiologic, Cell Line, Tumor, General Science & Technology
Abstract

Bone density is controlled by interactions between osteoclasts, which resorb bone, and osteoblasts, which deposit it. The semaphorins and their receptors, the plexins, originally shown to function in the immune system and to provide chemotactic cues for axon guidance, are now known to play a role in this process as well. Emerging data have identified Semaphorin 4D (Sema4D) as a product of osteoclasts acting through its receptor Plexin-B1 on osteoblasts to inhibit their function, tipping the balance of bone homeostasis in favor of resorption. Breast cancers and other epithelial malignancies overexpress Sema4D, so we theorized that tumor cells could be exploiting this pathway to establish lytic skeletal metastases. Here, we use measurements of osteoblast and osteoclast differentiation and function in vitro and a mouse model of skeletal metastasis to demonstrate that both soluble Sema4D and protein produced by the breast cancer cell line MDA-MB-231 inhibits differentiation of MC3T3 cells, an osteoblast cell line, and their ability to form mineralized tissues, while Sema4D-mediated induction of IL-8 and LIX/CXCL5, the murine homologue of IL-8, increases osteoclast numbers and activity. We also observe a decrease in the number of bone metastases in mice injected with MDA-MB-231 cells when Sema4D is silenced by RNA interference. These results are significant because treatments directed at suppression of skeletal metastases in bone-homing malignancies usually work by arresting bone remodeling, potentially leading to skeletal fragility, a significant problem in patient management. Targeting Sema4D in these cancers would not affect bone remodeling and therefore could elicit an improved therapeutic result without the debilitating side effects.

Published
2016

12. BAG3 promotes pancreatic ductal adenocarcinoma growth by activating stromal macrophages.

Author

Rosati, Alessandra, Basile, Anna, D'Auria, Raffaella, d'Avenia, Morena, De Marco, Margot, Falco, Antonia, Festa, Michelina, Guerriero, Luana, Iorio, Vittoria, Parente, Roberto, Pascale, Maria, Marzullo, Liberato, Franco, Renato, Arra, Claudio, Barbieri, Antonio, Rea, Domenica, Menichini, Giulio, Hahne, Michael, Bijlsma, Maarten, Barcaroli, Daniela, Sala, Gianluca, di Mola, Fabio Francesco, di Sebastiano, Pierluigi, Todoric, Jelena, Antonucci, Laura, Corvest, Vincent, Jawhari, Anass, Firpo, Matthew A, Tuveson, David A, Capunzo, Mario, Karin, Michael, De Laurenzi, Vincenzo, and Turco, Maria Caterina

Subjects
Macrophages, Stromal Cells, Animals, Mice, Inbred C57BL, Humans, Mice, Carcinoma, Pancreatic Ductal, Pancreatic Neoplasms, Adaptor Proteins, Signal Transducing, Membrane Proteins, Cell Proliferation, Female, Apoptosis Regulatory Proteins, Phosphatidylinositol 3-Kinases, Inbred C57BL, Carcinoma, Pancreatic Ductal, Adaptor Proteins, Signal Transducing
Abstract

The incidence and death rate of pancreatic ductal adenocarcinoma (PDAC) have increased in recent years, therefore the identification of novel targets for treatment is extremely important. Interactions between cancer and stromal cells are critically involved in tumour formation and development of metastasis. Here we report that PDAC cells secrete BAG3, which binds and activates macrophages, inducing their activation and the secretion of PDAC supporting factors. We also identify IFITM-2 as a BAG3 receptor and show that it signals through PI3K and the p38 MAPK pathways. Finally, we show that the use of an anti-BAG3 antibody results in reduced tumour growth and prevents metastasis formation in three different mouse models. In conclusion, we identify a paracrine loop involved in PDAC growth and metastatic spreading, and show that an anti-BAG3 antibody has therapeutic potential.

Published
2015

13. Dysregulated B-cell TLR2 expression and elevated regulatory B-cell frequency precede the diagnosis of AIDS-related non-Hodgkin lymphoma

Author

Siewe, Basile, Pham, Joey T, Cohen, Mardge, Hessol, Nancy A, Levine, Alexandra, Martinez-Maza, Otoniel, and Landay, Alan

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Clinical Research, Cancer, Lymphoma, Sexually Transmitted Infections, Hematology, Genetics, Rare Diseases, Lymphatic Research, HIV/AIDS, Infectious Diseases, 2.1 Biological and endogenous factors, Infection, Acquired Immunodeficiency Syndrome, Adult, B-Lymphocyte Subsets, Bacterial Translocation, Case-Control Studies, Cohort Studies, Female, Gene Expression Profiling, Humans, Immunophenotyping, Lymphoma, Non-Hodgkin, MicroRNAs, Toll-Like Receptor 2, HIV, microbial translocation, microRNA, non-Hodgkin lymphoma, regulatory B cells, Toll-like receptor, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Virology, Biomedical and clinical sciences, Health sciences
Abstract

ObjectivesIn antiretroviral therapy (ART)-treated patients, to determine if AIDS-related non-Hodgkin lymphoma (AIDS-NHL) is preceded by: elevated frequency of potentially malignant abnormal activated/germinal center-like B cells, elevated serum prevalence of B-cell stimulatory Toll-like receptor (TLR) ligands resulting from HIV infection-associated microbial translocation, dysregulated B-cell TLR expression/signaling, and perturbations in the frequency of immunoregulatory cells.DesignA case-control study nested with a cohort study of HIV-infected women.MethodsPrediagnostic AIDS-NHL cases (n = 12, collected 1-12 months before diagnosis) and controls (n = 42) from the Women's Interagency HIV Study cohort, were matched for HIV and ART status, age, race, and CD4 lymphocyte count. Serum levels of TLR ligands, the prevalence of malignancy-associated abnormal activated/germinal center-like (CD19CD10CD71CD86AID) B cells, TLR2 expression on B cells, expression of TLR2-modulating micro-RNA, and the frequency of regulatory T and B cells were assessed.ResultsDiagnosis of AIDS-NHL was preceded by a significantly elevated frequency of activated/germinal center-like CD19CD10CD71CD86AID B cells (P = 0.0072), elevated serum prevalence of the TLR2 ligand, and significantly elevated B-cell TLR2 expression (P = 0.0015), positively correlating with the frequency of activated/germinal center-like B cells (rho = 0.7273, P = 0.0144). In cases, a purified subset of activated/germinal center-like B cells exhibited decreased expression of microRNAs that modulate TLR2 signaling, including miR-21, 146a, 146b, and 155. Finally, cases also exhibited significantly elevated frequencies of antitumor immunity inhibitory regulatory B cells (P = 0.0024), but not regulatory T cells.ConclusionsOur findings suggest that increased microbial translocation and dysregulated TLR expression/signaling, coupled with an elevated frequency of regulatory B cells, precede the diagnosis of AIDS-NHL in HIV-infected ART-treated patients.

Published
2015

14. Bullying as a Longitudinal Predictor of Adolescent Dating Violence

Author

Foshee, Vangie A, Reyes, Heath Luz McNaughton, Vivolo-Kantor, Alana M, Basile, Kathleen C, Chang, Ling-Yin, Faris, Robert, and Ennett, Susan T

Subjects
Violence Against Women, Mental Health, Physical Injury - Accidents and Adverse Effects, Behavioral and Social Science, Youth Violence Prevention, Prevention, Childhood Injury, Violence Research, Clinical Research, Youth Violence, Pediatric, Peace, Justice and Strong Institutions, Adolescent, Adolescent Behavior, Bullying, Crime Victims, Female, Humans, Interpersonal Relations, Longitudinal Studies, Male, North Carolina, Rural Population, Sexual Behavior, Violence, Adolescent dating abuse, Dating violence, Dating violence prevention, Medical and Health Sciences, Education, Psychology and Cognitive Sciences, Public Health
Abstract

Purpose: One suggested approach to preventing adolescent dating violence is to prevent behavioral precursors to dating violence, such as bullying. However, no longitudinal study has examined bullying as a behavioral precursor to dating violence. In this study, longitudinal data were used to examine (1) whether direct and indirect bullying perpetration in the sixth grade predicted the onset of physical dating violence perpetration by the eighth grade and (2) whether the associations varied by sex and race/ethnicity of the adolescent. Methods: Data were collected in school from sixth graders in three primarily rural counties and then again when students were in the eighth grade. Analyses were conducted with 1,154 adolescents who had not perpetrated dating violence at the sixth-grade assessment. The sample was 47% male, 29% black, and 10% of another race/ethnicity than black or white. Results: Direct bullying, defined as hitting, slapping, or picking on another kid in the sixth grade, predicted the onset of physical dating violence perpetration by the eighth grade, controlling for indirect bullying and potential confounders. Although indirect bullying, defined as spreading false rumors and excluding students from friendship groups, was associated with the onset of physical dating violence perpetration in bivariate analyses, it did not predict the onset of physical dating violence when controlling for direct bullying. None of the associations examined varied by sex or race/ethnicity of the adolescents. Conclusions: Our findings suggest that efforts targeted at preventing direct bullying may also prevent the onset of physical dating violence. © 2014 Society for Adolescent Health and Medicine.

Published
2014

15. A role for p38 MAPK in head and neck cancer cell growth and tumor-induced angiogenesis and lymphangiogenesis.

Author

Leelahavanichkul, Kantima, Amornphimoltham, Panomwat, Molinolo, Alfredo, Basile, John, Koontongkaew, Sittichai, and Gutkind, J

Subjects
Angiogenesis, Head and neck cancer, JNK, Lymphangiogenesis, MAPK, p38 Inhibitor, p38 MAPK, Animals, Carcinoma, Squamous Cell, Cell Line, Tumor, Cell Proliferation, Cytokines, Enzyme Activation, Female, Head and Neck Neoplasms, Humans, Lymphangiogenesis, Mice, Mice, Nude, Neovascularization, Pathologic, Squamous Cell Carcinoma of Head and Neck, Tumor Microenvironment, p38 Mitogen-Activated Protein Kinases
Abstract

We have recently gained a remarkable understanding of the mutational landscape of head and neck squamous cell carcinoma (HNSCC). However, the nature of the dysregulated signaling networks contributing to HNSCC progression is still poorly defined. Here, we have focused on the role of the family of mitogen activated kinases (MAPKs), extracellular regulated kinase (ERK), c-Jun terminal kinase (JNK) and p38 MAPK in HNSCC. Immunohistochemical analysis of a large collection of human HNSCC tissues revealed that the levels of the phosphorylated active form of ERK1/2 and JNK were elevated in less than 33% and 16% of the cases, respectively. Strikingly, however, high levels of active phospho-p38 were observed in most (79%) of hundreds of tissues analyzed. We explored the biological role of p38 in HNSCC cell lines using three independent approaches: treatment with a specific p38 inhibitor, SB203580; a retro-inhibition strategy consisting in the use of SB203580 combined with the expression of an inhibitor-insensitive mutant form of p38α; and short-hairpin RNAs (shRNAs) targeting p38α. We found that specific blockade of p38 signaling significantly inhibited the proliferation of HNSCC cells both in vitro and in vivo. Indeed, we observed that p38 inhibition in HNSCC cancer cells reduces cancer growth in tumor xenografts and a remarkable decrease in intratumoral blood and lymphatic vessels. We conclude that p38α functions as a positive regulator of HNSCC in the context of the tumor microenvironment, controlling cancer cell growth as well as tumor-induced angiogenesis and lymphangiogenesis.

Published
2014

16. TLR2-Activated B Cells are Phenotypically Similar to the Abnormal Circulating B Cells Seen Preceding the Diagnosis of AIDS-Related NHL Diagnosis

Author

Guo, Yu, Siewe, Basile, Epeldegui, Marta, Detels, Roger, Landay, Alan L, and Martínez-Maza, Otoniel

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Sexually Transmitted Infections, Hematology, Infectious Diseases, Cancer, Health Disparities, Clinical Research, Minority Health, Rare Diseases, HIV/AIDS, Lymphoma, Genetics, Lymphatic Research, 2.1 Biological and endogenous factors, Infection, Good Health and Well Being, Adult, B-Lymphocytes, Case-Control Studies, Cytidine Deaminase, Female, Flow Cytometry, HIV Infections, Humans, Lymphocyte Activation, Lymphoma, AIDS-Related, Lymphoma, Non-Hodgkin, Male, Middle Aged, Phenotype, Toll-Like Receptor 2, phenotype, HIV, AIDS lymphoma, non-Hodgkin lymphoma, activation-induced cytidine deaminase, toll-like receptor, Clinical Sciences, Public Health and Health Services, Virology, Clinical sciences, Epidemiology, Public health
Abstract

BackgroundAIDS-related non-Hodgkin lymphoma (AIDS-NHL) is a common AIDS-defining cancer. Prior studies suggest that chronic B-cell activation precedes AIDS-NHL diagnosis. Activation of B cells by multiple factors, including Toll-like receptor (TLR) signaling, leads to the expression of activation-induced cytidine deaminase (AID), a DNA mutating molecule that can contribute to oncogene translocations/mutations, leading to NHL. The goal of this study was to determine whether surface markers expressed on activated and/or germinal center B cells, and AID expression, were elevated on circulating B cells preceding AIDS-NHL and to determine if TLR signaling contributes to this activated B-cell phenotype.MethodsStored viable peripheral blood mononuclear cell specimens, obtained before AIDS-NHL diagnosis, were assessed by multicolor flow cytometry. Additionally, B cells isolated from peripheral blood mononuclear cell were exposed to TLR ligands in vitro, after which B-cell phenotype was assessed by flow cytometry.ResultsAn elevated fraction of B cells expressing CD10, CD71, or CD86 was seen in those who went on to develop AIDS-NHL. AID expression was detected in some who developed AIDS-NHL, but not in HIV+ or HIV- controls. TLR2-stimulated purified B cells exhibited the activated B-cell phenotype observed in HIV+ subjects before AIDS-NHL diagnosis.ConclusionsThese results indicate that an elevated fraction of B cells display an activated/germinal center phenotype in those HIV+ subjects who go on to develop AIDS-NHL and suggest that TLR2-mediated activation may play a role in HIV infection-associated B-cell activation, potentially contributing to the genesis of AIDS-NHL.

Published
2013

17. Air Pollution and Coronary Vasomotor Disorders in Patients With Myocardial Ischemia and Unobstructed Coronary Arteries

Author

Massimiliano Camilli, Michele Russo, Riccardo Rinaldi, Andrea Caffè, Giulia La Vecchia, Alice Bonanni, Giulia Iannaccone, Mattia Basile, Rocco Vergallo, Cristina Aurigemma, Carlo Trani, Giampaolo Niccoli, Filippo Crea, and Rocco A. Montone

Subjects
Male, Spasm, myocardial infarction with nonobstructive coronary arteries, Myocardial Ischemia, Coronary Vasospasm, Coronary Artery Disease, Middle Aged, Coronary Angiography, Coronary Vessels, acetylcholine, coronary spasm, myocardial ischemia and nonobstructive coronary arteries, Air Pollution, Settore MED/11 - MALATTIE DELL'APPARATO CARDIOVASCOLARE, Humans, Female, Particulate Matter, Cardiology and Cardiovascular Medicine
Abstract

Coronary vasomotor abnormalities are important causes of myocardial ischemia in patients with nonobstructive coronary artery disease (NOCAD). However, the role of air pollution in determining coronary vasomotor disorders has never been investigated.We aimed to evaluate the association between long-term exposure to particulate matter 2.5 (PM2.5) and 10 (PM10), and coronary vasomotor disorders in NOCAD patients.Patients with myocardial ischemia and NOCAD undergoing coronary angiography and intracoronary provocation test with acetylcholine were prospectively studied. Both patients with chronic myocardial ischemia and nonobstructive coronary arteries and myocardial infarction with nonobstructive coronary arteries (MINOCA) were enrolled. Based on each case's home address, exposure to PM2.5 and PM10 was assessed.We included 287 patients (median age, 62.0 years [IQR: 52.0-70.0 years], 149 [51.9%] males); there were 161 (56.1%) myocardial ischemia and nonobstructive coronary arteries and 126 (43.9%) MINOCA cases. One hundred seventy-six patients (61.3%) had positive provocation test. Exposure to PM2.5 and PM10 was higher in patients with a positive provocation test (P 0.001). At multivariate logistic regression analysis, PM2.5 and PM10 were independent predictors of a positive provocation test (P = 0.001 and P = 0.029, respectively). Interestingly, among these patients, PM2.5 and PM10 were both independent predictors of MINOCA (P 0.001 and P = 0.001, respectively) as clinical presentation, whereas PM2.5 was independently associated with the occurrence of epicardial spasm as opposed to microvascular spasm (P = 0.001).Higher exposure to PM2.5 and PM10 in patients with myocardial ischemia and NOCAD is associated with coronary vasomotor abnormalities. In particular, PM2.5 is an independent risk factor for the occurrence of epicardial spasm and MINOCA as clinical presentation.

Published
2022
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19. Molecular analysis suggests oligoclonality and metastasis of endometriosis lesions across anatomically defined subtypes

Author

Teresa H. Praetorius, Anna Leonova, Vivian Lac, Janine Senz, Basile Tessier-Cloutier, Tayyebeh M. Nazeran, Martin Köbel, Marcel Grube, Bernhard Kraemer, Paul J. Yong, Stefan Kommoss, and Michael S. Anglesio

Subjects
Endometrium, Reproductive Medicine, Neoplasms, Mutation, Endometriosis, Humans, Obstetrics and Gynecology, Female, Retrospective Studies
Abstract

To investigate the heterogeneity of somatic cancer-driver mutations within patients and across endometriosis types.A single-center cohort, retrospective study.Tertiary specialist-care center at a university hospital.Patients with surgically and histologically confirmed endometriosis of at least 2 anatomically distinct types (ovarian, deep infiltrating, and superficial).None.Specimens were analyzed for the presence or absence of somatic cancer-driver mutations using targeted panel sequencing with orthogonal validation using droplet digital polymerase chain reaction and mutation-surrogate immunohistochemistry.It was found that 13 of 27 patients had informative somatic driver mutations in endometriosis lesions; of these 13 patients, 9 had identical mutations across distinct lesions. Endometriomas showed a higher mutational complexity, with functionally redundant driver mutations in the same gene and within the same lesions.Our data are consistent with clonality across endometriosis lesions, regardless of subtype. Further, the finding of redundancy in mutations within the same gene and lesions is consistent with endometriosis representing an oligoclonal disease with dissemination likely to consist of multiple epithelial clones traveling together. This suggests that the current anatomically defined classification of endometriosis does not fully recognize the etiology of the disease. A novel classification should consider genomic and other molecular features to promote personalized endometriosis diagnosis and care.

Published
2022
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20. Hyperglycemia at admission, comorbidities, and in-hospital mortality in elderly patients hospitalized in internal medicine wards: data from the RePoSI Registry

Author

Salvatore, Corrao, Alessandro, Nobili, Giuseppe, Natoli, Pier Mannuccio Mannucci, Francesco, Perticone, Antonello, Pietrangelo, Christiano, Argano, Giuseppe, Licata, Francesco, Violi, Gino Roberto Corazza, Alessandra, Marengoni, Francesco, Salerno, Matteo, Cesari, Mauro, Tettamanti, Luca, Pasina, Carlotta, Franchi, Laura, Cortesi, Gabriella, Miglio, Ilaria, Ardoino, Alessio, Novella, Domenico, Prisco, Elena, Silvestri, Giacomo, Emmi, Alessandra, Bettiol, Cenci, Caterina, Gianni, Biolo, Michela, Zanetti, Martina, Guadagni, Michele, Zaccari, Massimiliano, Chiuch, Massimo, Vanoli, Giulia, Grignani, Edoardo Alessandro Pulixi, Mauro, Bernardi, Silvia Li Bassi, Luca, Santi, Giacomo, Zaccherini, Graziana, Lupattelli, Elmo, Mannarino, Vanessa, Bianconi, Francesco, Paciullo, Riccardo, Alcidi, Ranuccio, Nuti, Roberto, Valenti, Martina, Ruvio, Silvia, Cappelli, Alberto, Palazzuoli, Domenico, Girelli, Fabiana, Busti, Giacomo, Marchi, Mario, Barbagallo, Ligia, Dominguez, Floriana, Cocita, Vincenza, Beneduce, Lidia, Plances, Salvatore, Mularo, Massimo, Raspanti, Marco, Zoli, Ilaria, Lazzari, Mattia, Brunori, Elisa, Fabbri, Donatella, Magalotti, Raffaella, Arnò, Franco Laghi Pasini, Pier Leopoldo Capecchi, Giuseppe, Palasciano, Maria Ester Modeo, Carla Di Gennaro, Maria Domenica Cappellini, Diletta, Maira, Valeria Di Stefano, Giovanna, Fabio, Sonia, Seghezzi, Marta, Mancarella, Margherita Migone De Amicis, Giacomo De Luca, Natalia, Scaramellini, Paolo Dionigi Rossi, Sarah, Damanti, Marta, Clerici, Federica, Conti, Giulia, Bonini, Barbara Brignolo Ottolini, Antonio Di Sabatino, Emanuela, Miceli, Marco Vincenzo Lenti, Martina, Pisati, Costanza Caccia Dominioni, Giovanni, Murialdo, Alessio, Marra, Federico, Cattaneo, Roberto, Pontremoli, Valentina, Beccati, Giulia, Nobili, Maria Beatrice Secchi, Davide, Ghelfi, Luigi, Anastasio, Lucia, Sofia, Maria, Carbone, Francesco, Cipollone, Maria Teresa Guagnano, Emanuele, Valeriani, Ilaria, Rossi, Gerardo, Mancuso, Daniela, Calipari, Mosè, Bartone, Giuseppe, Delitala, Maria, Berria, Chiara, Pes, Alessandro, Delitala, Maurizio, Muscaritoli, Alessio, Molfino, Enrico, Petrillo, Giuseppe, Zuccalà, Gabriella, D'Aurizio, Giuseppe, Romanelli, Alberto, Zucchelli, Francesca, Manzoni, Andrea, Volpini, Antonio, Picardi, Umberto Vespasiani Gentilucci, Paolo, Gallo, Chiara, Dell'Unto, Giorgio, Annoni, Maurizio, Corsi, Giuseppe, Bellelli, Sara, Zazzetta, Paolo, Mazzola, Hajnalka, Szabo, Alessandra, Bonfanti, Franco, Arturi, Elena, Succurro, Mariangela, Rubino, Bruno, Tassone, Giorgio, Sesti, Maria Grazia Serra, Maria Antonietta Bleve, Laura, Gasbarrone, Maria Rosaria Sajeva, Antonio, Brucato, Silvia, Ghidoni, Fabrizio, Fabris, Irene, Bertozzi, Giulia, Bogoni, Maria Victoria Rabuini, Elisabetta, Cosi, Paolo, Scarinzi, Annalisa, Amabile, Elisabetta, Omenetto, Tancredi, Prandini, Manfredini, Roberto, Fabbian, Fabio, Boari, Benedetta, DE GIORGI, Alfredo, Tiseo, Ruana, DE GIORGIO, Roberto, Giuseppe, Paolisso, Maria Rosaria Rizzo, Claudio, Borghi, Enrico, Strocchi, Eugenia, Ianniello, Mario, Soldati, Carlo, Sabbà, Francesco Saverio Vella, Patrizia, Suppressa, Andrea, Schilardi, Francesca, Loparco, Giovanni Michele De Vincenzo, Alessio, Comitangelo, Emanuele, Amoruso, Luigi, Fenoglio, Andrea, Falcetta, Christian, Bracco, Anna, L Fracanzani Silvia Fargion, Silvia, Tiraboschi, Annalisa, Cespiati, Giovanna, Oberti, Giordano, Sigon, Flora, Peyvandi, Raffaella, Rossio, Barbara, Ferrari, Giulia, Colombo, Pasquale, Agosti, Valter, Monzani, Valeria, Savojardo, Christian, Folli, Giuliana, Ceriani, Giada, Pallini, Franco, Dallegri, Luciano, Ottonello, Luca, Liberale, Lara, Caserza, Kassem, Salam, Nicola Lucio Liberato, Tiziana, Tognin, Giovanni Battista Bianchi, Sabrina, Giaquinto, Francesco, Purrello, Antonino Di Pino, Salvatore, Piro, Renzo, Rozzini, Lina, Falanga, Elena, Spazzini, Camillo, Ferrandina, Giuseppe, Montrucchio, Paolo, Petitti, Paolo, Peasso, Edoardo, Favale, Cesare, Poletto, Raffaella, Salmi, Piergiorgio, Gaudenzi, Ludovica, Perri, Raffaele, Landolfi, Massimo, Montalto, Antonio, Mirijello, Luigina, Guasti, Luana, Castiglioni, Andrea, Maresca, Alessandro, Squizzato, Leonardo, Campiotti, Alessandra, Grossi, Marco, Bertolotti, Chiara, Mussi, Giulia, Lancellotti, Maria Vittoria Libbra, Giulia, Dondi, Elisa, Pellegrini, Lucia, Carulli, Matteo, Galassi, Yasmine, Grassi, Maria, Perticone, Rosa, Battaglia, Marco, Filice, Raffaele, Maio, Vincenzo, Stanghellini, Eugenio, Ruggeri, Sara Del Vecchio, Andrea, Salvi, Roberto, Leonardi, Giampaolo, Damiani, William, Capeci, Armando, Gabrielli, Massimo, Mattioli, Giuseppe Pio Martino, Lorenzo, Biondi, Pietro, Pettinari, Riccardo, Ghio, Anna Dal Col, Salvatore, Minisola, Luciano, Colangelo, Mirella, Cilli, Giancarlo, Labbadia, Antonella, Afeltra, Benedetta, Marigliano, Maria Elena Pipita, Pietro, Castellino, Luca, Zanoli, Samuele, Pignataro, Alfio, Gennaro, Julien, Blanco, Valter, Saracco, Marisa, Fogliati, Carlo, Bussolino, Francesca, Mete, Miriam, Gino, Antonio, Cittadini, Carlo, Vigorito, Michele, Arcopinto, Andrea, Salzano, Emanuele, Bobbio, Alberto Maria Marra, Domenico, Sirico, Guido, Moreo, Francesca, Gasparini, Silvia, Prolo, Gloria, Pina, Alberto, Ballestrero, Fabio, Ferrando, Sergio, Berra, Simonetta, Dassi, Maria Cristina Nava, Bruno, Graziella, Stefano, Baldassarre, Salvatore, Fragapani, Gabriella, Gruden, Giorgio, Galanti, Gabriele, Mascherini, Cristian, Petri, Laura, Stefani, Margherita, Girino, Valeria, Piccinelli, Francesco, Nasso, Vincenza, Gioffrè, Maria, Pasquale, Giuseppe, Scattolin, Sergio, Martinelli, Mauro, Turrin, Leonardo, Sechi, Cristina, Catena, Gianluca, Colussi, Nicola, Passariello, Luca, Rinaldi, Franco, Berti, Giuseppe, Famularo, Patrizia, Tarsitani, Roberto, Castello, Michela, Pasino, Gian Paolo Ceda, Marcello Giuseppe Maggio, Simonetta, Morganti, Andrea, Artoni, Stefano Del Giacco, Davide, Firinu, Francesca, Losa, Giovanni, Paoletti, Giulia, Costanzo, Giuseppe, Montalto, Anna, Licata, Valentina, Malerba, Filippo Alessandro Montalto, Antonino, Lasco, Giorgio, Basile, Antonino, Catalano, Lorenzo, Malatino, Benedetta, Stancanelli, Valentina, Terranova, Salvatore Di Marca, Rosario Di Quattro, Lara La Malfa, Rossella, Caruso, Patrizia, Mecocci, Carmelinda, Ruggiero, Virginia, Boccardi, Tiziana, Meschi, Fulvio, Lauretani, Andrea, Ticinesi, Antonio, Nouvenne, Pietro, Minuz, Luigi, Fondrieschi, Mario, Pirisi, Gian Paolo Fra, Daniele, Sola, Massimo, Porta, Piero, Riva, Roberto, Quadri, Erica, Larovere, Marco, Novelli, Giorgio, Scanzi, Caterina, Mengoli, Stella, Provini, Laura, Ricevuti, Emilio, Simeone, Rosa, Scurti, Fabio, Tolloso, Roberto, Tarquini, Alice, Valoriani, Silvia, Dolenti, Giulia, Vannini, Alberto, Tedeschi, Lucia, Trotta, Riccardo, Volpi, Pietro, Bocchi, Alessandro, Vignali, Sergio, Harari, Chiara, Lonati, Mara, Cattaneo, Federico, Napoli., Corrao S, Nobili A, Natoli G, Mannucci PM, Perticone F, Pietrangelo A, Argano C, REPOSI Investigator, Borghi C, Corrao S., Nobili A., Natoli G., Mannucci P.M., Perticone F., Pietrangelo A., Argano C., Licata G., Violi F., Corazza G.R., Marengoni A., Salerno F., Cesari M., Tettamanti M., Pasina L., Franchi C., Cortesi L., Miglio G., Ardoino I., Novella A., Prisco D., Silvestri E., Emmi G., Bettiol A., Caterina C., Biolo G., Zanetti M., Guadagni M., Zaccari M., Chiuch M., Vanoli M., Grignani G., Pulixi E.A., Bernardi M., Bassi S.L., Santi L., Zaccherini G., Lupattelli G., Mannarino E., Bianconi V., Paciullo F., Alcidi R., Nuti R., Valenti R., Ruvio M., Cappelli S., Palazzuoli A., Girelli D., Busti F., Marchi G., Barbagallo M., Dominguez L., Cocita F., Beneduce V., Plances L., Mularo S., Raspanti M., Zoli M., Lazzari I., Brunori M., Fabbri E., Magalotti D., Arno R., Pasini F.L., Capecchi P.L., Palasciano G., Modeo M.E., Di Gennaro C., Cappellini M.D., Maira D., Di Stefano V., Fabio G., Seghezzi S., Mancarella M., De Amicis M.M., De Luca G., Scaramellini N., Rossi P.D., Damanti S., Clerici M., Conti F., Bonini G., Ottolini B.B., Di Sabatino A., Miceli E., Lenti M.V., Pisati M., Dominioni C.C., Murialdo G., Marra A., Cattaneo F., Pontremoli R., Beccati V., Nobili G., Secchi M.B., Ghelfi D., Anastasio L., Sofia L., Carbone M., Cipollone F., Guagnano M.T., Valeriani E., Rossi I., Mancuso G., Calipari D., Bartone M., Delitala G., Berria M., Pes C., Delitala A., Muscaritoli M., Molfino A., Petrillo E., Zuccala G., D'Aurizio G., Romanelli G., Zucchelli A., Manzoni F., Volpini A., Picardi A., Gentilucci U.V., Gallo P., Dell'Unto C., Annoni G., Corsi M., Bellelli G., Zazzetta S., Mazzola P., Szabo H., Bonfanti A., Arturi F., Succurro E., Rubino M., Tassone B., Sesti G., Serra M.G., Bleve M.A., Gasbarrone L., Sajeva M.R., Brucato A., Ghidoni S., Fabris F., Bertozzi I., Bogoni G., Rabuini M.V., Cosi E., Scarinzi P., Amabile A., Omenetto E., Prandini T., Manfredini R., Fabbian F., Boari B., De Giorgi A., Tiseo R., De Giorgio R., Paolisso G., Rizzo M.R., Borghi C., Strocchi E., Ianniello E., Soldati M., Sabba C., Vella F.S., Suppressa P., Schilardi A., Loparco F., De Vincenzo G.M., Comitangelo A., Amoruso E., Fenoglio L., Falcetta A., Bracco C., Fargion A.L.F.S., Tiraboschi S., Cespiati A., Oberti G., Sigon G., Peyvandi F., Rossio R., Ferrari B., Colombo G., Agosti P., Monzani V., Savojardo V., Folli C., Ceriani G., Pallini G., Dallegri F., Ottonello L., Liberale L., Caserza L., Salam K., Liberato N.L., Tognin T., Bianchi G.B., Giaquinto S., Purrello F., Di Pino A., Piro S., Rozzini R., Falanga L., Spazzini E., Ferrandina C., Montrucchio G., Petitti P., Peasso P., Favale E., Poletto C., Salmi R., Gaudenzi P., Perri L., Landolfi R., Montalto M., Mirijello A., Guasti L., Castiglioni L., Maresca A., Squizzato A., Campiotti L., Grossi A., Bertolotti M., Mussi C., Lancellotti G., Libbra M.V., Dondi G., Pellegrini E., Carulli L., Galassi M., Grassi Y., Perticone M., Battaglia R., FIlice M., Maio R., Stanghellini V., Ruggeri E., del Vecchio S., Salvi A., Leonardi R., Damiani G., Capeci W., Gabrielli A., Mattioli M., Martino G.P., Biondi L., Pettinari P., Ghio R., Col A.D., Minisola S., Colangelo L., Cilli M., Labbadia G., Afeltra A., Marigliano B., Pipita M.E., Castellino P., Zanoli L., Pignataro S., Gennaro A., Blanco J., Saracco V., Fogliati M., Bussolino C., Mete F., Gino M., Cittadini A., Vigorito C., Arcopinto M., Salzano A., Bobbio E., Marra A.M., Sirico D., Moreo G., Gasparini F., Prolo S., Pina G., Ballestrero A., Ferrando F., Berra S., Dassi S., Nava M.C., Graziella B., Baldassarre S., Fragapani S., Gruden G., Galanti G., Mascherini G., Petri C., Stefani L., Girino M., Piccinelli V., Nasso F., Gioffre V., Pasquale M., Scattolin G., Martinelli S., Turrin M., Sechi L., Catena C., Colussi G., Passariello N., Rinaldi L., Berti F., Famularo G., Tarsitani P., Castello R., Pasino M., Ceda G.P., Maggio M.G., Morganti S., Artoni A., Del Giacco S., Firinu D., Losa F., Paoletti G., Costanzo G., Montalto G., Licata A., Malerba V., Montalto F.A., Lasco A., Basile G., Catalano A., Malatino L., Stancanelli B., Terranova V., Di Marca S., Di Quattro R., La Malfa L., Caruso R., Mecocci P., Ruggiero C., Boccardi V., Meschi T., Lauretani F., Ticinesi A., Nouvenne A., Minuz P., Fondrieschi L., Pirisi M., Fra G.P., Sola D., Porta M., Riva P., Quadri R., Larovere E., Novelli M., Scanzi G., Mengoli C., Provini S., Ricevuti L., Simeone E., Scurti R., Tolloso F., Tarquini R., Valoriani A., Dolenti S., Vannini G., Tedeschi A., Trotta L., Volpi R., Bocchi P., Vignali A., Harari S., Lonati C., Cattaneo M., Napoli F., Corrao, S., Nobili, A., Natoli, G., Mannucci, P. M., Perticone, F., Pietrangelo, A., Argano, C., Licata, G., Violi, F., Corazza, G. R., Marengoni, A., Salerno, F., Cesari, M., Tettamanti, M., Pasina, L., Franchi, C., Cortesi, L., Miglio, G., Ardoino, I., Novella, A., Prisco, D., Silvestri, E., Emmi, G., Bettiol, A., Caterina, C., Biolo, G., Zanetti, M., Guadagni, M., Zaccari, M., Chiuch, M., Vanoli, M., Grignani, G., Pulixi, E. A., Bernardi, M., Bassi, S. L., Santi, L., Zaccherini, G., Lupattelli, G., Mannarino, E., Bianconi, V., Paciullo, F., Alcidi, R., Nuti, R., Valenti, R., Ruvio, M., Cappelli, S., Palazzuoli, A., Girelli, D., Busti, F., Marchi, G., Barbagallo, M., Dominguez, L., Cocita, F., Beneduce, V., Plances, L., Mularo, S., Raspanti, M., Zoli, M., Lazzari, I., Brunori, M., Fabbri, E., Magalotti, D., Arno, R., Pasini, F. L., Capecchi, P. L., Palasciano, G., Modeo, M. E., Di Gennaro, C., Cappellini, M. D., Maira, D., Di Stefano, V., Fabio, G., Seghezzi, S., Mancarella, M., De Amicis, M. M., De Luca, G., Scaramellini, N., Rossi, P. D., Damanti, S., Clerici, M., Conti, F., Bonini, G., Ottolini, B. B., Di Sabatino, A., Miceli, E., Lenti, M. V., Pisati, M., Dominioni, C. C., Murialdo, G., Marra, A., Cattaneo, F., Pontremoli, R., Beccati, V., Nobili, G., Secchi, M. B., Ghelfi, D., Anastasio, L., Sofia, L., Carbone, M., Cipollone, F., Guagnano, M. T., Valeriani, E., Rossi, I., Mancuso, G., Calipari, D., Bartone, M., Delitala, G., Berria, M., Pes, C., Delitala, A., Muscaritoli, M., Molfino, A., Petrillo, E., Zuccala, G., D'Aurizio, G., Romanelli, G., Zucchelli, A., Manzoni, F., Volpini, A., Picardi, A., Gentilucci, U. V., Gallo, P., Dell'Unto, C., Annoni, G., Corsi, M., Bellelli, G., Zazzetta, S., Mazzola, P., Szabo, H., Bonfanti, A., Arturi, F., Succurro, E., Rubino, M., Tassone, B., Sesti, G., Serra, M. G., Bleve, M. A., Gasbarrone, L., Sajeva, M. R., Brucato, A., Ghidoni, S., Fabris, F., Bertozzi, I., Bogoni, G., Rabuini, M. V., Cosi, E., Scarinzi, P., Amabile, A., Omenetto, E., Prandini, T., Manfredini, R., Fabbian, F., Boari, B., De Giorgi, A., Tiseo, R., De Giorgio, R., Paolisso, G., Rizzo, M. R., Borghi, C., Strocchi, E., Ianniello, E., Soldati, M., Sabba, C., Vella, F. S., Suppressa, P., Schilardi, A., Loparco, F., De Vincenzo, G. M., Comitangelo, A., Amoruso, E., Fenoglio, L., Falcetta, A., Bracco, C., Fargion, A. L. F. S., Tiraboschi, S., Cespiati, A., Oberti, G., Sigon, G., Peyvandi, F., Rossio, R., Ferrari, B., Colombo, G., Agosti, P., Monzani, V., Savojardo, V., Folli, C., Ceriani, G., Pallini, G., Dallegri, F., Ottonello, L., Liberale, L., Caserza, L., Salam, K., Liberato, N. L., Tognin, T., Bianchi, G. B., Giaquinto, S., Purrello, F., Di Pino, A., Piro, S., Rozzini, R., Falanga, L., Spazzini, E., Ferrandina, C., Montrucchio, G., Petitti, P., Peasso, P., Favale, E., Poletto, C., Salmi, R., Gaudenzi, P., Perri, L., Landolfi, R., Montalto, M., Mirijello, A., Guasti, L., Castiglioni, L., Maresca, A., Squizzato, A., Campiotti, L., Grossi, A., Bertolotti, M., Mussi, C., Lancellotti, G., Libbra, M. V., Dondi, G., Pellegrini, E., Carulli, L., Galassi, M., Grassi, Y., Perticone, M., Battaglia, R., Filice, M., Maio, R., Stanghellini, V., Ruggeri, E., del Vecchio, S., Salvi, A., Leonardi, R., Damiani, G., Capeci, W., Gabrielli, A., Mattioli, M., Martino, G. P., Biondi, L., Pettinari, P., Ghio, R., Col, A. D., Minisola, S., Colangelo, L., Cilli, M., Labbadia, G., Afeltra, A., Marigliano, B., Pipita, M. E., Castellino, P., Zanoli, L., Pignataro, S., Gennaro, A., Blanco, J., Saracco, V., Fogliati, M., Bussolino, C., Mete, F., Gino, M., Cittadini, A., Vigorito, C., Arcopinto, M., Salzano, A., Bobbio, E., Marra, A. M., Sirico, D., Moreo, G., Gasparini, F., Prolo, S., Pina, G., Ballestrero, A., Ferrando, F., Berra, S., Dassi, S., Nava, M. C., Graziella, B., Baldassarre, S., Fragapani, S., Gruden, G., Galanti, G., Mascherini, G., Petri, C., Stefani, L., Girino, M., Piccinelli, V., Nasso, F., Gioffre, V., Pasquale, M., Scattolin, G., Martinelli, S., Turrin, M., Sechi, L., Catena, C., Colussi, G., Passariello, N., Rinaldi, L., Berti, F., Famularo, G., Tarsitani, P., Castello, R., Pasino, M., Ceda, G. P., Maggio, M. G., Morganti, S., Artoni, A., Del Giacco, S., Firinu, D., Losa, F., Paoletti, G., Costanzo, G., Montalto, G., Licata, A., Malerba, V., Montalto, F. A., Lasco, A., Basile, G., Catalano, A., Malatino, L., Stancanelli, B., Terranova, V., Di Marca, S., Di Quattro, R., La Malfa, L., Caruso, R., Mecocci, P., Ruggiero, C., Boccardi, V., Meschi, T., Lauretani, F., Ticinesi, A., Nouvenne, A., Minuz, P., Fondrieschi, L., Pirisi, M., Fra, G. P., Sola, D., Porta, M., Riva, P., Quadri, R., Larovere, E., Novelli, M., Scanzi, G., Mengoli, C., Provini, S., Ricevuti, L., Simeone, E., Scurti, R., Tolloso, F., Tarquini, R., Valoriani, A., Dolenti, S., Vannini, G., Tedeschi, A., Trotta, L., Volpi, R., Bocchi, P., Vignali, A., Harari, S., Lonati, C., Cattaneo, M., Napoli, F., Corrao, S, Nobili, A, Natoli, G, Mannucci, P, Perticone, F, Pietrangelo, A, Argano, C, Licata, G, Violi, F, Corazza, G, Marengoni, A, Salerno, F, Cesari, M, Tettamanti, M, Pasina, L, Franchi, C, Cortesi, L, Miglio, G, Ardoino, I, Novella, A, Prisco, D, Silvestri, E, Emmi, G, Bettiol, A, Caterina, C, Biolo, G, Zanetti, M, Guadagni, M, Zaccari, M, Chiuch, M, Vanoli, M, Grignani, G, Pulixi, E, Bernardi, M, Bassi, S, Santi, L, Zaccherini, G, Lupattelli, G, Mannarino, E, Bianconi, V, Paciullo, F, Alcidi, R, Nuti, R, Valenti, R, Ruvio, M, Cappelli, S, Palazzuoli, A, Girelli, D, Busti, F, Marchi, G, Barbagallo, M, Dominguez, L, Cocita, F, Beneduce, V, Plances, L, Mularo, S, Raspanti, M, Zoli, M, Lazzari, I, Brunori, M, Fabbri, E, Magalotti, D, Arno, R, Pasini, F, Capecchi, P, Palasciano, G, Modeo, M, Di Gennaro, C, Cappellini, M, Maira, D, Di Stefano, V, Fabio, G, Seghezzi, S, Mancarella, M, De Amicis, M, De Luca, G, Scaramellini, N, Rossi, P, Damanti, S, Clerici, M, Conti, F, Bonini, G, Ottolini, B, Di Sabatino, A, Miceli, E, Lenti, M, Pisati, M, Dominioni, C, Murialdo, G, Marra, A, Cattaneo, F, Pontremoli, R, Beccati, V, Nobili, G, Secchi, M, Ghelfi, D, Anastasio, L, Sofia, L, Carbone, M, Cipollone, F, Guagnano, M, Valeriani, E, Rossi, I, Mancuso, G, Calipari, D, Bartone, M, Delitala, G, Berria, M, Pes, C, Delitala, A, Muscaritoli, M, Molfino, A, Petrillo, E, Zuccala, G, D'Aurizio, G, Romanelli, G, Zucchelli, A, Manzoni, F, Volpini, A, Picardi, A, Gentilucci, U, Gallo, P, Dell'Unto, C, Annoni, G, Corsi, M, Bellelli, G, Zazzetta, S, Mazzola, P, Szabo, H, Bonfanti, A, Arturi, F, Succurro, E, Rubino, M, Tassone, B, Sesti, G, Serra, M, Bleve, M, Gasbarrone, L, Sajeva, M, Brucato, A, Ghidoni, S, Fabris, F, Bertozzi, I, Bogoni, G, Rabuini, M, Cosi, E, Scarinzi, P, Amabile, A, Omenetto, E, Prandini, T, Manfredini, R, Fabbian, F, Boari, B, De Giorgi, A, Tiseo, R, De Giorgio, R, Paolisso, G, Rizzo, M, Borghi, C, Strocchi, E, Ianniello, E, Soldati, M, Sabba, C, Vella, F, Suppressa, P, Schilardi, A, Loparco, F, De Vincenzo, G, Comitangelo, A, Amoruso, E, Fenoglio, L, Falcetta, A, Bracco, C, Fargion, A, Tiraboschi, S, Cespiati, A, Oberti, G, Sigon, G, Peyvandi, F, Rossio, R, Ferrari, B, Colombo, G, Agosti, P, Monzani, V, Savojardo, V, Folli, C, Ceriani, G, Pallini, G, Dallegri, F, Ottonello, L, Liberale, L, Caserza, L, Salam, K, Liberato, N, Tognin, T, Bianchi, G, Giaquinto, S, Purrello, F, Di Pino, A, Piro, S, Rozzini, R, Falanga, L, Spazzini, E, Ferrandina, C, Montrucchio, G, Petitti, P, Peasso, P, Favale, E, Poletto, C, Salmi, R, Gaudenzi, P, Perri, L, Landolfi, R, Montalto, M, Mirijello, A, Guasti, L, Castiglioni, L, Maresca, A, Squizzato, A, Campiotti, L, Grossi, A, Bertolotti, M, Mussi, C, Lancellotti, G, Libbra, M, Dondi, G, Pellegrini, E, Carulli, L, Galassi, M, Grassi, Y, Perticone, M, Battaglia, R, Filice, M, Maio, R, Stanghellini, V, Ruggeri, E, del Vecchio, S, Salvi, A, Leonardi, R, Damiani, G, Capeci, W, Gabrielli, A, Mattioli, M, Martino, G, Biondi, L, Pettinari, P, Ghio, R, Col, A, Minisola, S, Colangelo, L, Cilli, M, Labbadia, G, Afeltra, A, Marigliano, B, Pipita, M, Castellino, P, Zanoli, L, Pignataro, S, Gennaro, A, Blanco, J, Saracco, V, Fogliati, M, Bussolino, C, Mete, F, Gino, M, Cittadini, A, Vigorito, C, Arcopinto, M, Salzano, A, Bobbio, E, Sirico, D, Moreo, G, Gasparini, F, Prolo, S, Pina, G, Ballestrero, A, Ferrando, F, Berra, S, Dassi, S, Nava, M, Graziella, B, Baldassarre, S, Fragapani, S, Gruden, G, Galanti, G, Mascherini, G, Petri, C, Stefani, L, Girino, M, Piccinelli, V, Nasso, F, Gioffre, V, Pasquale, M, Scattolin, G, Martinelli, S, Turrin, M, Sechi, L, Catena, C, Colussi, G, Passariello, N, Rinaldi, L, Berti, F, Famularo, G, Tarsitani, P, Castello, R, Pasino, M, Ceda, G, Maggio, M, Morganti, S, Artoni, A, Del Giacco, S, Firinu, D, Losa, F, Paoletti, G, Costanzo, G, Montalto, G, Licata, A, Malerba, V, Montalto, F, Lasco, A, Basile, G, Catalano, A, Malatino, L, Stancanelli, B, Terranova, V, Di Marca, S, Di Quattro, R, La Malfa, L, Caruso, R, Mecocci, P, Ruggiero, C, Boccardi, V, Meschi, T, Lauretani, F, Ticinesi, A, Nouvenne, A, Minuz, P, Fondrieschi, L, Pirisi, M, Fra, G, Sola, D, Porta, M, Riva, P, Quadri, R, Larovere, E, Novelli, M, Scanzi, G, Mengoli, C, Provini, S, Ricevuti, L, Simeone, E, Scurti, R, Tolloso, F, Tarquini, R, Valoriani, A, Dolenti, S, Vannini, G, Tedeschi, A, Trotta, L, Volpi, R, Bocchi, P, Vignali, A, Harari, S, Lonati, C, Cattaneo, M, and Napoli, F

Subjects
Registrie, Male, Comorbidity, Diabetes, Disability, Elderly, Hyperglycemia, Mortality, Aged, Aged, 80 and over, Female, Hospital Mortality, Hospitals, Humans, Internal Medicine, Registries, Hospitalization, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Socio-culturale, Renal function, 030204 cardiovascular system & hematology, Diabete, Hospital, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Rating scale, Internal medicine, Diabetes mellitus, 80 and over, medicine, LS4_4, 030212 general & internal medicine, Class III obesity, business.industry, Mortality rate, Comorbidity, Diabetes, Disability, Elderly, Hyperglycemia, Mortality, General Medicine, medicine.disease, Mood disorders, Geriatric Depression Scale, Original Article, business, Human
Abstract

Aims The association between hyperglycemia at hospital admission and relevant short- and long-term outcomes in elderly population is known. We assessed the effects on mortality of hyperglycemia, disability, and multimorbidity at admission in internal medicine ward in patients aged ≥ 65 years. Methods Data were collected from an active register of 102 internal medicine and geriatric wards in Italy (RePoSi project). Patients were recruited during four index weeks of a year. Socio-demographic data, reason for hospitalization, diagnoses, treatment, severity and comorbidity indexes (Cumulative Illness rating Scale CIRS-SI and CIRS-CI), renal function, functional (Barthel Index), and cognitive status (Short Blessed Test) and mood disorders (Geriatric Depression Scale) were recorded. Mortality rates were assessed in hospital 3 and 12 months after discharge. Results Of the 4714 elderly patients hospitalized, 361 had a glycemia level ≥ 250 mg/dL at admission. Compared to subjects with lower glycemia level, patients with glycemia ≥ 250 mg/dL showed higher rates of male sex, smoke and class III obesity. These patients had a significantly lower Barthel Index (p = 0.0249), higher CIRS-SI and CIRS-CI scores (p = 0.0025 and p = 0.0013, respectively), and took more drugs. In-hospital mortality rate was 9.2% and 5.1% in subjects with glycemia ≥ 250 and p = 0.0010). Regression analysis showed a strong association between in-hospital death and glycemia ≥ 250 mg/dL (OR 2.07; [95% CI 1.34–3.19]), Barthel Index ≤ 40 (3.28[2.44–4.42]), CIRS-SI (1.87[1.27–2.77]), and male sex (1.54[1.16–2.03]). Conclusions The stronger predictors of in-hospital mortality for older patients admitted in general wards were glycemia level ≥ 250 mg/dL, Barthel Index ≤ 40, CIRS-SI, and male sex.

Published
2021

21. Ovarian tissue cryopreservation and transplantation in menopause: new perspective of therapy in postmenopausal women and the importance of ethical and legal frameworks

Author

G, Gullo, A, Etrusco, G, Cucinella, G, Basile, M, Fabio, A, Perino, O, De Tommasi, G, Buzzaccarini, C, Morreale, L, Marchi, A S, Laganà, V, Chiantera, S, Zaami, Gullo, G, Etrusco, A, Cucinella, G, Basile, G, Fabio, M, Perino, A, De Tommasi, O, Buzzaccarini, G, Morreale, C, Marchi, L, Laganà, A S, Chiantera, V, and Zaami, S

Subjects
Cryopreservation, Counseling, Transplantation, Estrogen Replacement Therapy, Estrogens, Guidelines, Hormone replacement therapy (HRT), Settore MED/40 - Ginecologia E Ostetricia, Postmenopause, Ovarian tissue cryopreservation (OTC), Medicolegal viability, Quality of Life, Humans, Osteoporosis, Female, Menopause
Abstract

Menopausal transition entails a progressive decrease in hormone production by the ovaries that lead to important physical and psychological changes that could significantly affect quality of life. Hormone replacement therapy (HRT) administered from the onset of menopausal symptoms usually improves quality of life and life expectancy. Nevertheless, it is not risk-free. Ovarian tissue cryopreservation (OTC) has been investigated as a potential new strategy for delaying menopause and/or to avoid HRT. This review analyzes the critical points of HRT to assess whether OTC and subsequent reimplantation can affect postmenopausal management. We assessed available randomized clinical trials in PubMed, Cochrane Library, ISI web of science, and Scopus from August 2021 to November 2022, including studies and trials evaluating the efficacy of OTC in both cancer and menopausal patients, the efficacy of freezing techniques and the possible clinical scenarios that OTC can open, even from the standpoint of legal and ethical issues arising as such innovative techniques become mainstream. Lower duration of the graft and efficacy on estrogen secretions at a physiological and safer concentration of estrogen than conventional HRT based on hormonal supplements. OTC can reportedly trigger estrogen secretions at a lower and safer physiological concentration than conventional HRT. OTC and subsequent reimplantation remain a valid fertility-sparing approach in patients undergoing gonadotoxic treatments. Further studies are needed to better evaluate its safety and efficacy within postmenopausal therapy management and in order to lay out widely shared and evidence-based guidelines and best practices and perform such novel and innovative techniques in a legally and ethically safe fashion, in the best interest of patients and healthcare professionals.

Published
2022

22. Advanced Squamous Cell Carcinomas of the Pelvic and Perineal Region: A Comprehensive Genomic Profiling Study

Author

Andrea Necchi, Philippe E Spiess, Marco Bandini, Giuseppe Basile, Petros Grivas, Gennady Bratslavsky, Joseph Jacob, Natalie Danziger, Douglas Lin, Brennan Decker, Ethan S Sokol, Richard S P Huang, Sanjay B Kulkarni, and Jeffrey S Ross

Subjects
Male, Human papillomavirus 16, Cancer Research, Human papillomavirus 18, Oncology, Carcinoma, Squamous Cell, Humans, Female, Genomics, B7-H1 Antigen
Abstract

Background Advanced pelvic squamous cell carcinoma (pSCC) is a broad category of cancers affecting different pelvic organs and usually featuring unfavorable clinical outcomes. Thus, we aimed to assess genomic differences among pSCC cases and learn whether pSCC could potentially benefit from targeted therapies and/or immunotherapy. Materials and Methods A total of 1917 advanced pSCCs, including penile (penSCC), male urethral (murthSCC), male anal (manSCC), female urethral (furthSCC), vulvar (vulSCC), cervical (crvSCC), female anal (fanSCC), and vaginal (vagSCC), underwent comprehensive genomic profiling (CGP). We used hybrid capture-based CGP to evaluate recurrent genomic alterations (GAs). Tumor mutational burden (TMB) was determined on up to 1.1 Mb of sequenced DNA and microsatellite instability (MSI) was determined on up to 95 loci. Programmed cell-death-ligand-1 (PD-L1) expression was determined by immunohistochemistry (IHC; Dako 22C3). Results PIK3CA was the most frequently identified potentially “actionable” GA (22%-43%), followed by mTOR pathway [PTEN (0%-18%), FBXW7 (7%-29%)], and cell-cycle GAs. DNA-damage response (DDR) GAs and receptor-tyrosine kinase (RTK) targeted options were uncommon. NOTCH1 GAs were present in >15% of penSCC and vulvSCC. TMB ≥10 mut/Mb was >15% in manSCC, fanSCC, crvSCC, and vagSCC. PD-L1 high expression was >18% in all pSCC except urthSCC, manSCC, and vagSCC. HPV-16/18 detection was highest in manSCC, fanSCC, and crvSCC. Conclusion Despite similar histology, pSCCs can differ in GAs and HPV status. Overall, PIK3CA is the most frequent potentially “targetable” GA followed by mTOR and cell cycle pathway. RTK and DDR GAs are rare in pSCC. Immunotherapy could be considered for pSCC management based on TMB and PD-L1 expression.

Published
2022
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23. Assessment of olfactory fluctuations in a clinical context

Author

Anna Kristina Hernandez, Lena Juratli, Antje Haehner, Julien W. Hsieh, Basile N. Landis, and Thomas Hummel

Subjects
Male, Smell, Olfaction Disorders, Otorhinolaryngology, Taste, Surveys and Questionnaires, Humans, Female, General Medicine, Retrospective Studies
Abstract

Purpose The aim of the study was to investigate whether olfactory fluctuations (OF) are pronounced in patients with sinonasal olfactory dysfunction (OD). Methods The retrospective investigation included patients aged 18 years or older, who consulted a tertiary referral center for olfactory loss. Patients with normal smell function were excluded. Patients answered a structured questionnaire about their olfactory symptoms, with specific questions related to the presence of OF and its average frequency, amplitude, duration, time since most recent OF, and associated symptoms of self-reported OF. Patients also underwent clinical evaluation including a structured medical history and physical examination including nasal endoscopy. In addition, we assessed orthonasal olfactory function using Sniffin’ Sticks, and gustatory function using “taste sprays”. Results Participants included 131 men and 205 women (n = 336), aged 18 to 86 years (mean 50, SD 16). Patient-reported fluctuations occurred most frequently in sinonasal (38%), idiopathic (29%), and postviral (29%) OD. Amplitude of OF was highest in postviral OD (p = 0.009). Average frequency, duration, and the time since the most recent fluctuation were not significantly different between groups (all p’s > 0.42). Odor discrimination (p = 0.002) and identification (p = 0.017) scores were higher among those individuals with OF. Conclusion Amplitude of OF may help distinguish postviral from other causes of OD, especially in patients presenting with equivocal symptoms of sinonasal disease.

Published
2022
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24. Associations between posttraumatic stress symptoms and abuse experiences in child and adolescent girls from a Central African country

Author

Kakungu Assani Wa Mwenda Jonas, Kalema Kisungu Basile, Kakoma N'dusu Jean Baptiste, Hala Ayaman Alyousef, and Heng Meng

Subjects
Stress Disorders, Post-Traumatic, Psychiatry and Mental health, Clinical Psychology, Cross-Sectional Studies, Adolescent, Democratic Republic of the Congo, Prevalence, Humans, Female, Child Abuse, Survivors, Child
Abstract

Posttraumatic stress disorder (PTSD) is frequently reported among survivors of abuse. However, there is a paucity of research examining the association between PTSD and abuse, including polyvictimization, in nonconflict areas of the Democratic Republic of Congo (DRC). We aimed to investigate the prevalence and correlates of PTSD among girls in nonconflict zones who experienced at least one type of abuse. Participants in this cross-sectional study were 3,011 middle-school girls, aged 11-18 years, who attended randomly selected schools and completed questionnaires. The probable PTSD prevalence was 67.5%. The rate of probable PTSD increased with the number of experienced abuse types over a 12-month period. The findings demonstrated associations between probable PTSD and exposure to five (86.9%), four (63.9%), and three types of abuse (60.1%). The strongest association was observed between probable PTSD and experiencing five types of abuse, OR = 26.806, 95% CI [19.303, 37.225]; associations were also found between PTSD and abuse with a weapon, OR = 4.341, 95% CI [3.519, 5.354]; rape with penetration, OR = 4.728, 95% CI [3.447, 6.484]; and experiencing three, OR = 6.625, 95% CI [4.325, 10.148], or four types of abuse, OR = 7.114, 95% CI [5.025,10.070]. The findings of this study underscore the importance of the need for psychological and physical health care for girls who have been exposed to abuse, regardless of the number of abuse experiences or abuse types she has experienced.

Published
2022
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25. Cellular context determines <scp>DNA</scp> methylation profiles in <scp>SWI</scp> / <scp>SNF</scp> ‐deficient cancers of the gynecologic tract

Author

Felix KF Kommoss, Basile Tessier‐Cloutier, Leora Witkowski, Erna Forgo, Christian Koelsche, Martin Köbel, William D Foulkes, Cheng‐Han Lee, David L Kolin, Andreas Deimling, and Brooke E Howitt

Subjects
Lung Neoplasms, DNA Helicases, Nuclear Proteins, DNA Methylation, Small Cell Lung Carcinoma, United Kingdom, Endometrial Neoplasms, Pathology and Forensic Medicine, Hypercalcemia, Humans, Female, Carcinoma, Small Cell, Carcinoma, Endometrioid, Rhabdoid Tumor, Transcription Factors
Abstract

SWI/SNF (SWItch/Sucrose Non-Fermentable) complex deficiency has been reported in a wide variety of cancers and is often associated with an undifferentiated phenotype. In the gynecologic tract SWI/SNF-deficient cancers are diagnostically challenging and little is known about their cellular origins. Here we show that undifferentiated endometrial carcinoma (UDEC), SMARCA4-deficient uterine sarcoma (SDUS), and ovarian small cell carcinoma, hypercalcemic type (SCCOHT) harbor distinct DNA methylation signatures despite shared morphology and SWI/SNF inactivation. Our results indicate that the cellular context is an important determinant of the epigenetic landscape, even in the setting of core SWI/SNF deficiency, and therefore methylation profiling may represent a useful diagnostic tool in undifferentiated, SWI/SNF-deficient cancers. Furthermore, applying copy number analyses and group-wise differential methylation analyses including endometrioid endometrial carcinomas and extracranial malignant rhabdoid tumors, we uncover analogous molecular features in SDUS and SCCOHT in contrast to UDEC. These results suggest that SDUS and SCCOHT represent chromosomally stable SWI/SNF-deficient cancers of the gynecologic tract, which are within the broader spectrum of malignant rhabdoid tumors. © 2022 The Authors. The Journal of Pathology published by John WileySons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Published
2022
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26. Racial Discrimination, Mental Health, and Parenting Among African American Mothers of Preschool-Aged Children

Author

Cindy A. Crusto, Eileen M. Condon, Bridget Basile Ibrahim, Jacquelyn Y. Taylor, and Veronica Barcelona

Subjects
Mediation (statistics), Coping (psychology), media_common.quotation_subject, Psychological intervention, Mothers, Racism, Article, Developmental and Educational Psychology, Parenting styles, Humans, 0501 psychology and cognitive sciences, Parent-Child Relations, Child, Pandemics, media_common, Parenting, SARS-CoV-2, 05 social sciences, Beck Depression Inventory, COVID-19, Moderation, Mental health, United States, Black or African American, Psychiatry and Mental health, Mental Health, Child, Preschool, Female, Psychology, 050104 developmental & child psychology, Clinical psychology
Abstract

Objective Indirect exposure to racism experienced by a caregiver (ie, vicarious racism) is associated with poor outcomes for children, but mechanisms of vicarious racism transmission are poorly understood. The purpose of this study was to examine the relationship between experiences of racial discrimination and parenting among African American mothers and to identify psychological mediators and moderators of this relationship. Method African American mothers (N = 250) with young children (mean age = 3.7 years old) reported on perceived racial discrimination (Race-Related Events Scale), parenting (Parenting Stress Index, Parenting Styles and Dimensions Questionnaire), coping (Coping Strategies Index), and mental health (Stress Overload Scale, Beck Depression Inventory). Multivariable linear regression was used to examine associations between perceived racial discrimination and parenting and to test coping as a moderator of these relationships. Ordinary least-squares regression-based path analysis with bootstrapping was used to examine mediation by stress overload and depressive symptoms. Results At least one experience of racial discrimination was reported by 57% of women. Experiences of racial discrimination were associated with increased parenting stress (β = 0.69, p = .02), and this relationship was mediated by stress overload (95% CI [0.35, 1.09]) and depressive symptoms (95% CI [0.27, 1.18]). Racial discrimination was not associated with parenting styles, and coping strategies largely did not moderate the relationships examined. Conclusion Racial discrimination has harmful intergenerational effects on African American children and families. Systemic-level interventions are needed, including adoption of policies to promote racial justice and eliminate structural racism in the United States. Future research on coping strategies specific to racism-related stress is needed to inform approaches to intervention.

Published
2022
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27. Treatment and prevention of viral hepatitis in pregnancy

Author

Gabriella D. Cozzi, Basile Njei, Alan T.N. Tita, Ricardo A. Franco, and Jodie Dionne-Odom

Subjects
Hepatitis B virus, Pediatrics, medicine.medical_specialty, Sexual transmission, Antiviral Agents, Article, Hepatitis B, Chronic, Pregnancy, medicine, Humans, Lactation, Hepatitis B Vaccines, Pregnancy Complications, Infectious, Transmission (medicine), business.industry, Infant, Newborn, Obstetrics and Gynecology, Hepatitis A, Hepatitis C, Viral Load, Jaundice, Hepatitis B, medicine.disease, Infectious Disease Transmission, Vertical, Immunoglobulin G, Female, medicine.symptom, Viral hepatitis, business, Viral load
Abstract

Viral hepatitis in pregnancy may be caused by many types of viruses that cause systemic infection or target hepatocytes in their pathogenesis. Because viral hepatitis during pregnancy may represent acute or chronic infection or the reactivation of a prior infection, a high clinical suspicion, medical history review, and awareness of risk factors for the acquisition of infection are important management principles. The route of infection varies widely and ranges from fecal-oral transmission for the hepatitis A and E viruses to vertical transmission for hepatitis B, blood-borne transmission for hepatitis C, and sexual transmission for the herpes simplex virus. For this reason, the exposure details about travel, food preferences, drug use, and sexual contacts are important to elicit. Although routine prenatal screening is recommended for chronic viral hepatitis caused by hepatitis B and C, most other causes of viral hepatitis in pregnancy are detected in the setting of compatible signs and symptoms (fatigue, abdominal discomfort, jaundice, scleral icterus) or incidentally noted transaminitis on routine labs. Serologic testing is helpful for diagnosis with molecular testing as indicated to guide the management of hepatitis B and C. Preventive vaccines for hepatitis A and B with established safety of use in pregnancy are recommended for women who are at risk of acquisition. Postexposure prophylaxis for hepatitis A is a single dose of immunoglobulin and vaccination can be used if immunoglobulin G is not available. Antiviral therapy with tenofovir disoproxil fumarate is recommended as prophylaxis in pregnant women with active hepatitis B and an elevated viral load (>200,000 IU/mL) during the third trimester to prevent vertical transmission. The neonate exposed to hepatitis B at birth should receive immunoglobulin G and a monovalent birth dose vaccine within 12 hours, followed by completion of the 3-dosage vaccine series. The prevalence of hepatitis C in women of reproductive age has increased in the United States, and the role of antiviral therapy during pregnancy is of great interest. Cesarean delivery is not currently recommended for the sole purpose of reducing vertical transmission risk in pregnant women with viral hepatitis. Breastfeeding is recommended in women with hepatitis A, B, and C. New and promising prevention and treatment options for hepatitis B and C are under investigation. Investigators and regulatory authorities should ensure that these clinical trials for promising antivirals and vaccines are designed to include pregnant and lactating women.

Published
2022
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28. Birth during the Covid‐19 pandemic: What childbearing people in the United States needed to achieve a positive birth experience

Author

Joan L. Combellick, Bridget Basile Ibrahim, Tamika Julien, Kirsten Scharer, Kierra Jackson, and HP Kennedy

Subjects
Cross-Sectional Studies, Pregnancy, Infant, Newborn, Parturition, COVID-19, Humans, Obstetrics and Gynecology, Female, Maternal Health Services, Midwifery, Pandemics, Qualitative Research, United States
Abstract

The COVID pandemic exposed many inadequacies in the maternity care system in the United States. Maternity care protocols put in place during this crisis often did not include input from childbearing people or follow prepandemic guidelines for high-quality care. Departure from standard maternity care practices led to unfavorable and traumatic experiences for childbearing people. This study aimed to identify what childbearing people needed to achieve a positive birth experience during the pandemic.This mixed-methods, cross-sectional study was conducted among individuals who gave birth during the COVID pandemic from 3/1/2020 to 11/1/2020. Participants were sampled via a Web-based questionnaire that was distributed nationally. Descriptive and bivariate statistics were analyzed. Thematic and content analyses of qualitative data were based on narrative information provided by participants. Qualitative and convergent quantitative data were reported.Participants (n = 707) from 46 states and the District of Columbia completed the questionnaire with 394 contributing qualitative data about their experiences. Qualitative findings reflected women's priorities for (a) the option of community birth, (b) access to midwives, (c) the right to an advocate at birth, and (d) the need for transparent and affirming communication. Quantitative data reinforced these findings. Participants with a midwife provider felt significantly better informed. Those who gave birth in a community setting (at home or in a freestanding birth center) also reported significantly higher satisfaction and felt better informed. Participants of color (BIPOC) were significantly less satisfied and more stressed while pregnant and giving birth during the pandemic.High-quality maternity care places childbearing people at the center of care. Prioritizing the needs of childbearing people, in COVID times or otherwise, is critical for improving their experiences and delivering efficacious and safe care.

Published
2022
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29. The association between low skeletal muscle mass and delirium: results from the nationwide multi-centre Italian Delirium Day 2017

Author

Zucchelli, A, Manzoni, F, Morandi, A, Di Santo, S, Rossi, E, Valsecchi, Mg, Inzitari, M, Cherubini, A, Bo, M, Mossello, E, Marengoni, A, Bellelli, G, Tarasconi, A, Sella, M, Auriemma, S, Paternò, G, Faggian, G, Lucarelli, C, De Grazia, N, Alberto, C, Margola, A, Porcella, L, Nardiello, I, Chimenti, E, Zeni, M, Giani, A, Famularo, S, Romairone, E, Minaglia, C, Ceccotti, C, Guerra, G, Mantovani, G, Monacelli, F, Candiani, T, Ballestrero, A, Santolini, F, Rosso, M, Bono, V, Sibilla, S, Dal Santo, P, Ceci, M, Barone, P, Schirinzi, T, Formenti, A, Nastasi, G, Isaia, G, Gonella, D, Battuello, A, Casson, S, Calvani, D, Boni, F, Ciaccio, A, Rosa, R, Sanna, G, Manfredini, S, Cortese, L, Rizzo, M, Prestano, R, Greco, A, Lauriola, M, Gelosa, G, Piras, V, Arena, M, Cosenza, D, Bellomo, A, Lamontagna, M, Gabbani, L, Lambertucci, L, Perego, S, Parati, G, Basile, G, Gallina, V, Pilone, G, Giudice, C, De, F, Pietrogrande, L, De, B, Mosca, M, Corazzin, I, Rossi, P, Nunziata, V, D'Amico, F, Grippa, A, Giardini, S, Barucci, R, Cossu, A, Fiorin, L, Distefano, M, Lunardelli, M, Brunori, M, Ruffini, I, Abraham, E, Varutti, A, Fabbro, E, Catalano, A, Martino, G, Leotta, D, Marchet, A, Dell'Aquila, G, Scrimieri, A, Davoli, M, Casella, M, Cartei, A, Polidori, G, Brischetto, D, Motta, S, Saponara, R, Perrone, P, Russo, G, Del, D, Car, C, Pirina, T, Franzoni, S, Cotroneo, A, Ghiggia, F, Volpi, G, Menichetti, C, Panico, A, Calogero, P, Corvalli, G, Mauri, M, Lupia, E, Manfredini, R, Fabbian, F, March, A, Pedrotti, M, Veronesi, M, Strocchi, E, Bianchetti, A, Crucitti, A, Di Francesco, V, Fontana, G, Bonanni, L, Barbone, F, Serrati, C, Ballardini, G, Simoncelli, M, Ceschia, G, Scarpa, C, Brugiolo, R, Fusco, S, Ciarambino, T, Biagini, C, Tonon, E, Porta, M, Venuti, D, Delsette, M, Poeta, M, Barbagallo, G, Trovato, G, Delitala, A, Arosio, P, Reggiani, F, Zuliani, G, Ortolani, B, Mussio, E, Girardi, A, Coin, A, Ruotolo, G, Castagna, A, Masina, M, Cimino, R, Pinciaroli, A, Tripodi, G, Cannistrà, U, Cassadonte, F, Vatrano, M, Scaglione, L, Fogliacco, P, Muzzuilini, C, Romano, F, Padovani, A, Rozzini, L, Cagnin, A, Fragiacomo, F, Desideri, G, Liberatore, E, Bruni, A, Orsitto, G, Franco, M, Bonfrate, L, Bonetto, M, Pizio, N, Magnani, G, Cecchetti, G, Longo, A, Bubba, V, Marinan, L, Cotelli, M, Turla, M, Sessa, M, Abruzzi, L, Castoldi, G, Lovetere, D, Musacchio, C, Novello, M, Cavarape, A, Bini, A, Leonardi, A, Seneci, F, Grimaldi, W, Fimognari, F, Bambara, V, Saitta, A, Corica, F, Braga, M, Ettorre, E, Camellini, C, Crescenzo, A, Noro, G, Turco, R, Ponzetto, M, Giuseppe, L, Mazzei, B, Maiuri, G, Costaggiu, D, Damato, R, Formilan, M, Patrizia, G, Santuari, L, Gallucci, M, Paragona, M, Bini, P, Modica, D, Abati, C, Clerici, M, Barbera, I, Nigroimperiale, F, Manni, A, Votino, C, Castiglioni, C, Di, M, Degl'Innocenti, M, Moscatelli, G, Guerini, S, Casini, C, Dini, D, D'Imporzano, E, Denotariis, S, Bonometti, F, Paolillo, C, Riccardi, A, Tiozzo, A, Samy Salama Fahmy, A, Dibari, M, Vanni, S, Scarpa, A, Zara, D, Ranieri, P, Pezzoni, D, Gentile, S, Platto, C, D'Ambrosio, V, Faraci, B, Brambilla, C, Ivaldi, C, Milia, P, Desalvo, F, Solaro, C, Strazzacappa, M, Cazzadori, M, Confente, S, Grasso, M, Troisi, E, Guerini, V, Bernardini, B, C Boffelli S, Corsini, Filippi, A, Delpin, K, Bertoletti, E, Vannucci, M, Tesi, F, Crippa, P, Malighetti, A, Caltagirone, C, Disant, S, Bettini, D, Maltese, F, Abruzzese, G, Cosimo, D, Azzini, M, Colombo, M, Procino, G, Fascendini, S, Barocco, F, Del, P, Mazzone, A, Riva, E, Dell'Acqua, D, Cottino, M, Vezzadini, G, Avanzi, S, Orini, S, Sgrilli, F, Mello, A, Lombardi, L, Muti, E, Dijk, B, Fenu, S, Pes, C, Gareri, P, Passamonte, M, Rigo, R, Locusta, L, Caser, L, Rosso, G, Cesarini, S, Cozzi, R, Santini, C, Carbone, P, Cazzaniga, I, Lovati, R, Cantoni, A, Ranzani, P, Barra, D, Pompilio, G, Dimori, S, Cernesi, S, Riccò, C, Piazzolla, F, Capittini, E, Rota, C, Gottardi, F, Merla, L, A Millul A, Barelli, De, G, Morrone, G, Bigolari, M, Macchi, M, Zambon, F, Pizzorni, C, Dicasaleto, G, Menculini, G, Marcacci, M, Catanese, G, Sprini, D, Dicasalet, T, Bocci, M, Borga, S, Caironi, P, Cat, C, Cingolani, E, Avalli, L, Greco, G, Citerio, G, Gandini, L, Cornara, G, Lerda, R, Brazzi, L, Simeone, F, Caciorgna, M, Alampi, D, Francesconi, S, Beck, E, Antonini, B, Vettoretto, K, Meggiolaro, M, Garofalo, E, Notaro, S, Varutti, R, Bassi, F, Mistraletti, G, Marino, A, Rona, R, Rondelli, E, Riva, I, Scapigliati, A, Cortegiani, A, Vitale, F, Pistidda, L, D'Andrea, R, Querci, L, Gnesin, P, Todeschini, M, Lugano, M, Castelli, G, Ortolani, M, Cotoia, A, Maggiore, S, Ditizio, L, Graziani, R, Testa, I, Ferretti, E, Castioni, C, Lombardi, F, Caserta, R, Pasqua, M, Simoncini, S, Baccarini, F, Rispoli, M, Grossi, F, Cancelliere, L, Carnelli, M, Puccini, F, Biancofiore, G, Siniscalchi, A, Laici, C, Torrini, M, Pasetti, G, Palmese, S, Oggioni, R, Mangani, V, Pini, S, Martelli, M, Rigo, E, Zuccalà, F, Cherri, A, Spina, R, Calamai, I, Petrucci, N, Caicedo, A, Ferri, F, Gritti, P, Brienza, N, Fonnesu, R, Dessena, M, Fullin, G, Saggioro, D., Zucchelli, A, Manzoni, F, Morandi, A, Di Santo, S, Rossi, E, Valsecchi, M, Inzitari, M, Cherubini, A, Bo, M, Mossello, E, Marengoni, A, Bellelli, G, Citerio, G, Zucchelli, Alberto, Valsecchi, M G, and A Tarasconi, M Sella, S Auriemma, G Paternò, G Faggian, C Lucarelli, N De Grazia, C Alberto, A Margola, L Porcella, I Nardiello, E Chimenti, M Zeni, A Giani, S Famularo, E Romairone, C Minaglia, C Ceccotti, G Guerra, G Mantovani, F Monacelli, C Minaglia, T Candiani, A Ballestrero, C Minaglia, F Santolini, C Minaglia, M Rosso, V Bono, S Sibilla, P Dal Santo, M Ceci, P Barone, T Schirinzi, A Formenti, G Nastasi, G Isaia, D Gonella, A Battuello, S Casson, D Calvani, F Boni, A Ciaccio, R Rosa, G Sanna, S Manfredini, L Cortese, M Rizzo, R Prestano, A Greco, M Lauriola, G Gelosa, V Piras, M Arena, D Cosenza, A Bellomo, M LaMontagna, L Gabbani, L Lambertucci, S Perego, G Parati, G Basile, V Gallina, G Pilone, C Giudice, F De, L Pietrogrande, B De, M Mosca, I Corazzin, P Rossi, V Nunziata, F D'Amico, A Grippa, S Giardini, R Barucci, A Cossu, L Fiorin, M Arena, M Distefano, M Lunardelli, M Brunori, I Ruffini, E Abraham, A Varutti, E Fabbro, A Catalano, G Martino, D Leotta, A Marchet, G Dell'Aquila, A Scrimieri, M Davoli, M Casella, A Cartei, G Polidori, G Basile, D Brischetto, S Motta, R Saponara, P Perrone, G Russo, D Del, C Car, T Pirina, S Franzoni, A Cotroneo, F Ghiggia, G Volpi, C Menichetti, M Bo, A Panico, P Calogero, G Corvalli, M Mauri, E Lupia, R Manfredini, F Fabbian, A March, M Pedrotti, M Veronesi, E Strocchi, A Bianchetti, A Crucitti, V Di Francesco, G Fontana, L Bonanni, F Barbone, C Serrati, G Ballardini, M Simoncelli, G Ceschia, C Scarpa, R Brugiolo, S Fusco, T Ciarambino, C Biagini, E Tonon, M Porta, D Venuti, M DelSette, M Poeta, G Barbagallo, G Trovato, A Delitala, P Arosio, F Reggiani, G Zuliani, B Ortolani, E Mussio, A Girardi, A Coin, G Ruotolo, A Castagna, M Masina, R Cimino, A Pinciaroli, G Tripodi, U Cannistrà, F Cassadonte, M Vatrano, F Cassandonte, L Scaglione, P Fogliacco, C Muzzuilini, F Romano, A Padovani, L Rozzini, A Cagnin, F Fragiacomo, G Desideri, E Liberatore, A Bruni, G Orsitto, M Franco, L Bonfrate, M Bonetto, N Pizio, G Magnani, G Cecchetti, A Longo, V Bubba, L Marinan, M Cotelli, M Turla, M Brunori, M Sessa, L Abruzzi, G Castoldi, D LoVetere, C Musacchio, M Novello, A Cavarape, A Bini, A Leonardi, F Seneci, W Grimaldi, F Fimognari, V Bambara, A Saitta, F Corica, M Braga, E Ettorre, C Camellini, A Marengoni, A Bruni, A Crescenzo, G Noro, R Turco, M Ponzetto, L Giuseppe, B Mazzei, G Maiuri, D Costaggiu, R Damato, E Fabbro, G Patrizia, L Santuari, M Gallucci, C Minaglia, M Paragona, P Bini, D Modica, C Abati, M Clerici, I Barbera, F NigroImperiale, A Manni, C Votino, C Castiglioni, M Di, M Degl'Innocenti, G Moscatelli, S Guerini, C Casini, D Dini, S DeNotariis, F Bonometti, C Paolillo, A Riccardi, A Tiozzo, A SamySalamaFahmy, A Riccardi, C Paolillo, M DiBari, S Vanni, A Scarpa, D Zara, P Ranieri, P Calogero, G Corvalli, D Pezzoni, S Gentile, A Morandi, C Platto, V D'Ambrosio, B Faraci, C Ivaldi, P Milia, F DeSalvo, C Solaro, M Strazzacappa, M Bo, A Panico, M Cazzadori, S Confente, M Bonetto, G Magnani, G Cecchetti, V Guerini, B Bernardini, C Corsini, S Boffelli, A Filippi, K Delpin, E Bertoletti, M Vannucci, F Tesi, P Crippa, A Malighetti, C Caltagirone, S DiSant, D Bettini, F Maltese, M Formilan, G Abruzzese, C Minaglia, D Cosimo, M Azzini, M Cazzadori, M Colombo, G Procino, S Fascendini, F Barocco, P Del, F D'Amico, A Grippa, A Mazzone, E Riva, D Dell'Acqua, M Cottino, G Vezzadini, S Avanzi, S Orini, F Sgrilli, A Mello, L Lombardi, E Muti, B Dijk, S Fenu, C Pes, P Gareri, A Castagna, M Passamonte, F De, R Rigo, L Locusta, L Caser, G Rosso, S Cesarini, R Cozzi, C Santini, P Carbone, I Cazzaniga, R Lovati, A Cantoni, P Ranzani, D Barra, G Pompilio, S Dimori, S Cernesi, C Riccò, F Piazzolla, E Capittini, C Rota, F Gottardi, L Merla, A Barelli, A Millul, G De, G Morrone, M Bigolari, C Minaglia, M Macchi, F Zambon, F D'Amico, F D'Amico, C Pizzorni, G DiCasaleto, G Menculini, M Marcacci, G Catanese, D Sprini, T DiCasalet, M Bocci, S Borga, P Caironi, C Cat, E Cingolani, L Avalli, G Greco, G Citerio, L Gandini, G Cornara, R Lerda, L Brazzi, F Simeone, M Caciorgna, D Alampi, S Francesconi, E Beck, B Antonini, K Vettoretto, M Meggiolaro, E Garofalo, A Bruni, S Notaro, R Varutti, F Bassi, G Mistraletti, A Marino, R Rona, E Rondelli, I Riva, A Scapigliati, A Cortegiani, F Vitale, L Pistidda, R D'Andrea, L Querci, P Gnesin, M Todeschini, M Lugano, G Castelli, M Ortolani, A Cotoia, S Maggiore, L DiTizio, R Graziani, I Testa, E Ferretti, C Castioni, F Lombardi, R Caserta, M Pasqua, S Simoncini, F Baccarini, M Rispoli, F Grossi, L Cancelliere, M Carnelli, F Puccini, G Biancofiore, A Siniscalchi, C Laici, E Mossello, M Torrini, G Pasetti, S Palmese, R Oggioni, V Mangani, S Pini, M Martelli, E Rigo, F Zuccalà, A Cherri, R Spina, I Calamai, N Petrucci, A Caicedo, F Ferri, P Gritti, N Brienza, R Fonnesu, M Dessena, G Fullin, D Saggioro

Subjects
Male, Aging, medicine.medical_specialty, Sarcopenia, medicine.medical_treatment, Socio-culturale, Older person, Logistic regression, Delirium, Older persons, Sarcopenia, Internal medicine, mental disorders, Delirium, Older persons, medicine, Dementia, Humans, LS4_4, Muscle, Skeletal, Pathological, Aged, Rehabilitation, business.industry, Area under the curve, Settore MED/23 - Chirurgia Cardiaca, Skeletal, medicine.disease, Skeletal muscle mass, Cross-Sectional Studies, Italy, Muscle, Female, Geriatrics and Gerontology, medicine.symptom, business
Abstract

Introduction Delirium and sarcopenia are common, although underdiagnosed, geriatric syndromes. Several pathological mechanisms can link delirium and low skeletal muscle mass, but few studies have investigated their association. We aimed to investigate (1) the association between delirium and low skeletal muscle mass and (2) the possible role of calf circumference mass in finding cases with delirium. Methods The analyses were conducted employing the cross-sectional “Delirium Day” initiative, on patient 65 years and older admitted to acute hospital medical wards, emergency departments, rehabilitation wards, nursing homes and hospices in Italy in 2017. Delirium was diagnosed as a 4 + score at the 4-AT scale. Low skeletal muscle mass was operationally defined as calf circumference ≤ 34 cm in males and ≤ 33 cm in females. Logistic regression models were used to investigate the association between low skeletal muscle mass and delirium. The discriminative ability of calf circumference was evaluated using non-parametric ROC analyses. Results A sample of 1675 patients was analyzed. In total, 73.6% of participants had low skeletal muscle mass and 24.1% exhibited delirium. Low skeletal muscle mass and delirium showed an independent association (OR: 1.50; 95% CI 1.09–2.08). In the subsample of patients without a diagnosis of dementia, the inclusion of calf circumference in a model based on age and sex significantly improved its discriminative accuracy [area under the curve (AUC) 0.69 vs 0.57, p Discussion and conclusion Low muscle mass is independently associated with delirium. In patients without a previous diagnosis of dementia, calf circumference may help to better identify those who develop delirium.

Published
2022

30. Removal of the influence of plasma volume fluctuations for the athlete biological passport and stability of haematological variables in active women taking oral contraception

Author

Basile Moreillon, Tristan Equey, Tiffany Astolfi, Olivier Salamin, and Raphael Faiss

Subjects
Doping in Sports, Contraception, Athletes, Humans, Pharmaceutical Science, Environmental Chemistry, Female, Plasma Volume, Biomarkers, Spectroscopy, Analytical Chemistry
Abstract

The haematological module of the athlete biological passport (ABP) monitors longitudinal haematological variations that could be indicative of blood manipulation. This study applied a multi-parametric model previously validated in elite cyclists to compare inferred and actual PV variations, whereas the potential influence of the oral contraceptive pill (OCP) cycle on the ABP blood biomarkers and plasma volume (PV) in 14 physically active women taking OCPs was also investigated. Blood and serum samples were collected each week for 8 weeks, and the ABP haematological variables were determined according to the World Anti-Doping Agency guidelines. Transferrin (sTFN), ferritin (FERR), albumin (ALB), calcium (Ca), creatinine (CRE), total protein (TP) and low-density lipoprotein (LDL) were additionally computed as 'volume-sensitive' variables in a multivariate analysis to determine individual estimations of PV variations. Actual PV variations were indirectly measured using a validated carbon monoxide rebreathing method. We hypothesised ABP markers to be stable during a standard OCP cycle and estimated PV variations similar to measured PV variations. Measured PV variations were in good agreement with the predictions and allowed to explain an atypical passport finding (ATPF). The ABP biomarkers, Hbmass and PV were stable over 8 weeks. Significant differences occurred only between Week 7 and Week 1, with lower levels of haemoglobin concentration ([Hb]), haematocrit (HCT) and red blood cell count (RBC)(-4.4%, p 0.01; -5.1%, p 0.01; -5.2%, p 0.01) and higher levels of PV at week 7 (+9%, p = 0.05). We thus concluded that estimating PV variations may help interpret individual ABP haematological profiles in women.

Published
2022
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31. Symptoms of Survivors of Pediatric Hematopoietic Stem Cell Transplant by Age, Sex, and Transplant Type

Author

Caroline F. Morrison, Sarah Drake, Nathan L. Basile, Mary Jane Horn, Joshua Lambert, Kasiani C. Myers, and Ahna L.H. Pai

Subjects
Male, Research, Hematopoietic Stem Cell Transplantation, Pain, Pilot Projects, humanities, Cross-Sectional Studies, Child, Preschool, Quality of Life, Humans, Female, Survivors, Child, Fatigue
Abstract

Purpose: The purpose of this study was to describe symptoms experienced by survivors of pediatric hematopoietic stem cell transplant (HSCT), and demographic and treatment-factors associated with ongoing symptomology. Methods: Fifty pediatric survivors completed a cross-sectional pilot study. Questionnaires were administered online via REDCap to assess symptoms experienced in the last week. Survivors also consented to a medical record chart review. Results: Survivors were on average 5.4 years post-HSCT (range 1.1 to 9 years), male (58%), and Caucasian (80%) who received an allogeneic HSCT (92%). The most commonly reported symptoms were difficulty concentrating (42.5%), pain (38%), worry (38%), nervousness (37.5%), and lack of energy/fatigue (34%). Survivors reported up to 14 symptoms, with 90% of the sample experiencing at least one symptom in the previous week. Average number of symptoms varied by age group between 2.1 (8–9 years) and 6.8 (18 and older). Age and female gender were associated with higher levels of fatigue. Conclusions: The majority of survivors experienced at least one symptom in the previous week. Neuropsychological symptoms and pain endure well into survivorship that can influence outcomes such as function and health-related quality of life (HRQOL). Research is needed on biological mechanisms of ongoing symptomology, effective interventions to prevent or mitigate symptoms, and the impact of symptoms on patient outcomes including daily functioning and HRQOL. Implications Survivors of pediatric HSCT continued to experience symptoms for up to nine years. Survivors should be frequently screened for symptoms, as symptoms may affect function, learning/employment outcomes, and HRQOL.

Published
2022
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32. Arterial Spin Labeling for the Etiological Workup of Intracerebral Hemorrhage in Children

Author

Francis Brunelle, Gregoire Boulouis, Vincent Vidal, Nadine Girard, Olivier Naggara, Philippe Meyer, Thomas Blauwblomme, Basile Kerleroux, Florent Gariel, Manoelle Kossorotoff, Sarah Stricker, Nathalie Boddaert, Lorenzo Garzelli, Jean François Hak, Volodia Dangouloff Ros, and Sandro Benichi

Subjects
Intracranial Arteriovenous Malformations, Male, medicine.medical_specialty, Adolescent, Fistula, Computed tomography, Lesion, medicine, Humans, Prospective Studies, Registries, Child, Stroke, Cerebral Hemorrhage, Retrospective Studies, Advanced and Specialized Nursing, Intracerebral hemorrhage, medicine.diagnostic_test, business.industry, Angiography, Digital Subtraction, Magnetic resonance imaging, medicine.disease, Cerebrovascular Circulation, Child, Preschool, Arteriovenous Fistula, Arterial spin labeling, Etiology, Female, Spin Labels, Neurology (clinical), Radiology, medicine.symptom, Tomography, X-Ray Computed, Cardiology and Cardiovascular Medicine, business
Abstract

Background and Purpose: Pediatric nontraumatic intracerebral hemorrhage accounts for half of stroke in children. Early diagnostic of the causative underlying lesion is the first step toward prevention of hemorrhagic recurrence. We aimed to investigate the performance of arterial spin labeling sequence (ASL) in the acute phase etiological workup for the detection of an arteriovenous shunt (AVS: including malformation and fistula), the most frequent cause of pediatric nontraumatic intracerebral hemorrhage. Methods: Children with a pediatric nontraumatic intracerebral hemorrhage between 2011 and 2019 enrolled in a prospective registry were retrospectively included if they had undergone ASL-magnetic resonance imaging before any etiological treatment. ASL sequences were reviewed using cerebral blood flow maps by 2 raters for the presence of an AVS. The diagnostic performance of ASL was compared with admission computed tomography angiography, other magnetic resonance imaging sequences including contrast-enhanced sequences and subsequent digital subtraction angiography. Results: A total of 121 patients with pediatric nontraumatic intracerebral hemorrhage were included (median age, 9.9 [interquartile range, 5.8–13]; male sex 48.8%) of whom 76 (63%) had a final diagnosis of AVS. Using digital subtraction angiography as an intermediate reference, visual ASL inspection had a sensitivity and a specificity of, respectively, 95.9% (95% CI, 88.5%–99.1%) and 79.0% (95% CI, 54.4%–94.0%). ASL had a sensitivity, specificity, and accuracy of 90.2%, 97.2%, and 92.5%, respectively for the detection of the presence of an AVS, with near perfect interrater agreement (κ=0.963 [95% CI, 0.912–1.0]). The performance of ASL alone was higher than that of other magnetic resonance imaging sequences, individually or combined, and higher than that of computed tomography angiography. Conclusions: ASL has strong diagnostic performance for the detection of AVS in the initial workup of intracerebral hemorrhage in children. If our findings are confirmed in other settings, ASL may be a helpful diagnostic imaging modality for patients with pediatric nontraumatic intracerebral hemorrhage. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifiers: 3618210420, 2217698.

Published
2022
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33. Long-term (180-day) outcomes in critically ill patients with COVID-19 in the REMAP-CAP randomized clinical trial

Author

Florescu, S, Stanciu, D, Zaharia, M, Kosa, A, Codreanu, D, Kidwai, A, Masood, S, Kaye, C, Coutts, A, MacKay, L, Summers, C, Polgarova, P, Farahi, N, Fox, E, McWilliam, S, Hawcutt, D, Rad, L, O’Malley, L, Whitbread, J, Jones, D, Dore, R, Saunderson, P, Kelsall, O, Cowley, N, Wild, L, Thrush, J, Wood, H, Austin, K, Bélteczki, J, Magyar, I, Fazekas, Á, Kovács, S, Szőke, V, Donnelly, A, Kelly, M, Smyth, N, O’Kane, S, McClintock, D, Warnock, M, Campbell, R, McCallion, E, Azaiz, A, Charron, C, Godement, M, Geri, G, Vieillard-Baron, A, Johnson, P, McKenna, S, Hanley, J, Currie, A, Allen, B, McGoldrick, C, McMaster, M, Mani, A, Mathew, M, Kandeepan, R, Vignesh, C, TV, B, Ramakrishnan, N, James, A, Elvira, E, Jayakumar, D, Pratheema, R, Babu, S, Ebenezer, R, Krishnaoorthy, S, Ranganathan, L, Ganesan, M, Shree, M, Guilder, E, Butler, M, Cowdrey, K-A, Robertson, M, Ali, F, McMahon, E, Duffy, E, Chen, Y, Simmonds, C, McConnochie, R, O’Connor, C, El-Khawas, K, Richardson, A, Hill, D, Commons, R, Abdelkharim, H, Saxena, M, Muteithia, M, Dobell-Brown, K, Jha, R, Kalogirou, M, Ellis, C, Krishnamurthy, V, O’Connor, A, Thurairatnam, S, Mukherjee, D, Kaliappan, A, Vertue, M, Nicholson, A, Riches, J, Maloney, G, Kittridge, L, Solesbury, A, Ramos, A, Collins, D, Brickell, K, Reid, L, Smyth, M, Breen, P, Spain, S, Curley, G, McEvoy, N, Geoghegan, P, Clarke, J, Silversides, J, McGuigan, P, Ward, K, O’Neill, A, Finn, S, Wright, C, Green, J, Collins, É, Knott, C, Smith, J, Boschert, C, Slieker, K, Ewalds, E, Sanders, A, Wittenberg, W, Geurts, H, Poojara, L, Sara, T, Nand, K, Reeve, B, Dechert, W, Phillips, B, Oritz-Ruiz de Gordoa, L, Affleck, J, Shaikh, A, Murray, A, Ramanan, M, Frakking, T, Pinnell, J, Robinson, M, Gledhill, L, Wood, T, Sanghavi, R, Bhonagiri, D, Ford, M, Parikh, HG, Avard, B, Nourse, M, McDonald, B, Edmunds, N, Hoiting, O, Peters, M, Rengers, E, Evers, M, Prinssen, A, Morgan, M, Cole, J, Hill, H, Davies, M, Williams, A, Thomas, E, Davies, R, Wise, M, Grimm, P, Soukup, J, Wetzold, R, Löbel, M, Starke, L, Lellouche, F, Lizotte, P, Declerq, P, Antoine, M, Stephanie, G, Jean-Pierre, E, François, B, Marion, B, Philippe, R, Pourcine, F, Monchi, M, Luis, D, Mercier, R, Sagnier, A, Verrier, N, Caplin, C, Richecoeu, J, Combaux, D, Siami, S, Aparicio, C, Vautier, S, Jeblaoui, A, Lemaire-Brunel, D, D'Aragon, F, Carbonneau, E, Leblond, J, Plantefeve, G, Leparco, C, Contou, D, Fartoukh, M, Courtin, L, Labbe, V, Voiriot, G, Salhi, S, Chassé, M, Carrier, F, Boumahni, D, Benettaib, F, Ghamraoui, A, Sement, A, Gachet, A, Hanisch, A, Haffiane, A, Boivin, A-H, Barreau, A, Guerineau, E, Poupblanc, S, Egreteau, P, Lefevre, M, Bocher, S, Le Loup, G, Le Guen, L, Carn, V, Bertel, M, Antcliffe, D, Templeton, M, Rojo, R, Coghlan, P, Smee, J, Barker, G, Finn, A, Kreb, G, Hoff, U, Hinrichs, C, Nee, J, Mackay, E, Cort, J, Whileman, A, Spencer, T, Spittle, N, Beavis, S, Padmakumar, A, Dale, K, Hawes, J, Moakes, E, Gascoyne, R, Pritchard, K, Stevenson, L, Cooke, J, Nemeth-Roszpopa, K, Gauli, B, Bastola, S, Muller, G, Nay, M-A, Kamel, T, Benzekri, D, Jacquier, S, Runge, I, Mathonnet, A, Barbier, F, Bretagnol, A, Carter, J, Van Der Heyden, K, Mehrtens, J, Morris, A, Morgan, S, Burke, T, Mercier, E, Chartier, D, Salmon, C, Dequin, P-F, Garot, D, Bellemare, D, Cloutier, È, Daher, R, Costerousse, O, Boulanger, M-C, Couillard-Chénard, É, Lauzier, F, Francoeur, C, Francois, B, Gay, A, Anne-Laure, F, Ramali, M, HC, O, Ghosh, A, Osagie, R, Arachchige, M, Hartley, M, Cheung, W, Wong, H, Seigne, P, Eustace, J, O'Callaghan, A-M, O'Brien, F, Bamford, P, Reid, A, Cawley, K, Faulkner, M, Pickering, C, Raj, A, Tsinaslanidis, G, Khade, R, Agha, G, Sekiwala, R, Smith, T, Brewer, C, Gregory, J, Limb, J, Cowton, A, O’Brien, J, Postlethwaite, K, Malakouti, S, Music, E, Ricketts, D, King, A, Clermont, G, Bart, R, Mayr, F, Schoenling, A, Andreae, M, Shetty, V, Brant, E, Malley, B, Donadee, C, Sackrowitz, R, Weissman, A, Yealy, D, Barton, D, Talia, N, Nikitas, N, Wells, C, Lankester, L, McMillan, H, Van den Oever, H, Kruisdijk-Gerritsen, A, Haidar, G, Bain, W, Barbash, I, Fitzpatrick, M, Franz, C, Kitsios, G, Moghbeli, K, Rosborough, B, Shah, F, Suber, T, Pulletz, M, Williams, P, Birch, J, Wiseman, S, Horton, S, Alegria, A, Turki, S, Elsefi, T, Crisp, N, Allen, L, Truman, N, Smith, M, Chukkambotla, S, Goddard, W, Duberley, S, Khan, M, Kazi, A, Simpson, J, Duke, G, Chan, P, Carter, B, Hunter, S, Voigt, I, Schueler, R, Blank, E, Hüning, V, Steffen, M, Goralski, P, Litton, E, Regli, A, Pellicano, S, Palermo, A, Eroglu, E, Bihari, S, Laver, RD, Jin, X, Brown, J, McIntyre, J, French, C, Bates, S, Towns, M, Yang, Y, McGain, F, McCullagh, I, Cairns, T, Hanson, H, Patel, B, Clement, I, Evetts, G, Touma, O, Holland, S, Hodge, C, Taylor, H, Alderman, M, Barnes, N, Da Rocha, J, Smith, C, Brooks, N, Weerasinghe, T, Sinclair, J-A, Abusamra, Y, Doherty, R, Cudlipp, J, Singh, R, Yu, H, Daebis, A, Ng, C, Kendrick, S, Saran, A, Makky, A, Greener, D, Rowe-Leete, L, Edwards, A, Bland, Y, Dolman, R, Foster, T, Laffey, J, McNicholas, B, Scully, M, Casey, S, Kernan, M, Brennan, A, Rangan, R, Tully, R, Corbett, S, McCarthy, A, Duffy, O, Burke, D, Linnett, V, Sanderson, A, Ritzema, J, Wild, H, Lucas, R, Marriott, Y, Andric, Z, Cviljevic, S, Br, R, Zapalac, M, Mirković, G, Khare, D, Pinder, M, Gopinath, A, Kannan, T, Dean, S, Vanmali, P, Depuydt, P, De Waele, J, De Bus, L, Fierens, J, Bracke, S, Vermassen, J, Vermeiren, D, Pugh, R, Lean, R, Qiu, X, Scanlan, J, Evans, A, Davies, G, Lewis, J, Plesnikova, Y, Khoud, A, Coetzee, S, Puxty, K, Cathcart, S, Rimmer, D, Bagot, C, Scott, K, Martin, L, Yusuff, H, Isgro, G, Brightling, C, Bourne, M, Craner, M, Boyles, R, Alexander, B, Roberts, T, Nelli, A, Rosenstein-Sisson, R, Speyer, R, Pech, Y, McCullough, J, Tallott, M, Vazquez-Grande, G, Marten, N, Liu, T, Siddiqui, A, Khanal, S, Amatya, S, Szakmany, T, Cherian, S, Williams, G, James, C, Waters, A, Prout, R, Stedman, R, Davies, L, Pegler, S, Kyeremeh, L, Moorhouse, L, Arbane, G, Marotti, M, Bociek, A, Campos, S, Van Nieuwkoop, K, Ottens, T, Visser, Y, Van den Berg, L, Van der Kraan-Donker, A, Brett, S, Arias, S, Hall, R, Paneru, H, Koirala, S, Paudel, P, Wilson, M, Vaara, S, Pettilä, L, Heinonen, J, Pettilä, V, Jain, S, Gupta, A, Holbrook, C, Antoine, P, Meziani, F, Allam, H, Cattelan, J, Clere-Jehl, R, Helms, J, Kummerlen, C, Merdji, H, Monnier, A, Rahmani, H, Studer, A, Schneider, F, Castelain, V, Morel, G, L’Hotellier, S, Ochin, E, Vanjak, C, Rouge, P, Bendjemar, L, Albert, M, Serri, K, Cavayas, A, Duplaix, M, Williams, V, Catorze, NJTADS, Pereira, TNAL, Ferreira, RMC, Bastos, JMPS, Batista, TMO, Badie, J, Berdaguer, F, Malfroy, S, Mezher, C, Bourgoin, C, Moneger, G, Bouvier, E, Muñoz-Bermúdez, R, Marin-Corral, J, Degracia, A, Gómez, F, López, M, Aceto, R, Aghemo, A, Badalamenti, S, Brunetta, E, Cecconi, M, Ciccarelli, M, Constantini, E, Greco, M, Folci, M, Selmi, C, Voza, A, Henning, J, Bonner, S, Hugill, K, Cirstea, E, Wilkinson, D, Jones, J, Altomy, M, Karlikowski, M, Sutherland, H, Wilhelmsen, E, Woods, J, North, J, Pletz, M, Hagel, S, Ankert, J, Kolanos, S, Bloos, F, Simons, K, Van Zuylen, T, Bouman, A, Kumar, N, Panwar, R, Poulter, A-L, Sunkara, K, Szigligeti, G, Leszkoven, J, Rochwerg, B, Karachi, T, Oczkowski, S, Centofanti, J, Millen, T, Sundaran, D, Hollos, L, Turns, M, Walsh, J, Al Qasim, E, Alswaidan, L, Hegazy, M, Arishi, H, Al Amri, A, AlQahtani, S, Naidu, B, Tlayjeh, H, Hussain, S, Al Enezi, F, Abdukahil, SA, Hopkins, P, Noble, H, O’Reilly, K, Mehta, R, Wong, O, Makanju, E, Rao, D, Sikondari, N, Saha, S, Corcoran, E, Pappa, E, Cockrell, M, Donegan, C, Balaie, M, Nickoleit-Bitzenberger, D, Schaaf, B, Meermeier, W, Prebeg, K, Azzaui, H, Hower, M, Brieger, K-G, Elender, C, Sabelhaus, T, Riepe, A, Akamp, C, Kremling, J, Klein, D, Landsiedel-Mechenbier, E, Laha, S, Verlander, M, Jha, A, Megarbane, B, Voicu, S, Deye, N, Malissin, I, Sutterlin, L, Mrad, A, Lehalleur, A, Naim, G, Nguyen, P, Ekhérian, J-M, Boué, Y, Sidéris, G, Vodovar, D, Guérin, E, Grant, C, Brain, M, Mineall, S, Paramasivam, E, Wilby, E, Ogg, B, Howcroft, C, Aspinwall, A, Charlton, S, Gould, R, Mistry, D, Awan, S, Bedford, C, Carr-Wilkinson, J, Hall, A, Gardiner-Hill, C, Maloney, C, Brunskill, N, Watchorn, O, Hardy, C, Qureshi, H, Flint, N, Nicholson, S, Southin, S, Ghattaoraya, A, Harding, D, O’Halloran, S, Collins, A, Smith, E, Trues, E, Borgatta, B, Turner-Bone, I, Reddy, A, Wilding, L, Wilson, C, Surti, Z, Aneman, A, Miller, J, White, H, Estensen, K, Morrison, L, Sutton, J, Cooper, M, Warnapura, L, Agno, R, Sathianathan, P, Shaw, D, Ijaz, N, Spong, A, Sabaretnam, S, Burns, D, Lang, E, Tate, M, Fischer, R, Biradar, V, Soar, N, Golden, D, Davey, M, Seaman, R, Osborne, A, Bannard-Smith, J, Clark, R, Birchall, K, Henry, J, Pomeroy, F, Quayle, R, Wylie, K, Sukuraman, A, John, M, Sibin, S, Leditschke, A, Finnis, M, Jongebloed, K, Khwaja, K, Campisi, J, Van Vonderen, M, Pietersma, M, Vrolijk, L, Kampschreur, L, Van Gulik, 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J, Wrey Brown, C, Arias, A-M, Bevan, E, Westlake, S, Craven, T, Hope, D, Singleton, J, Clark, S, McCulloch, C, Biddie, S, Welters, I, Hamilton, D, Williams, K, Waugh, V, Mulla, S, Waite, A, Roman, J, Martinez, M, Johnston, B, Puthucheary, Z, Martin, T, Santos, F, Uddin, R, Fernandez, M, Seidu, F, Somerville, A, Pakats, M-L, Begum, S, Shahid, T, Presneill, J, Barge, D, Byrne, K, Janin, P, Yarad, E, Bass, F, Hammond, N, Vuylsteke, A, Chan, C, Victor, S, Waterson, S, McNamara, R, Boardman, M, Gattas, D, Buhr, H, Coles, J, Matsa, R, Gellamucho, M, Creagh-Brown, B, Marriot, C, Salberg, A, Zouita, L, Stone, S, Michalak, N, Donlon, S, Mtuwa, S, Mayangao, I, Verula, J, Burda, D, Harris, C, Jones, E, Bradley, P, Tarr, E, Harden, L, Piercy, C, Nolan, J, Kerslake, I, Cook, T, Simpson, T, Dalton, J, Demetriou, C, Mitchard, S, Ramos, L, White, K, Johnson, T, Headdon, W, Spencer, S, White, A, Howie, L, Reay, M, Watts, A, Traverse, E, Jennings, S, Anumakonda, V, Tuckwell, C, Harrow, K, Matthews, J, McGarry, K, Moore, V, Smith, L, Summerfield, A, Dark, P, Harvey, A, Doonan, R, McMorrow, L, Knowles, K, Pendlebury, J, Perez, J, Marsden, T, Taylor, M, Michael, A, Collis, M, Claxton, A, Habeichi, W, Horner, D, Slaughter, M, Thomas, V, Proudfoot, N, Keatley, C, Donnison, P, Casey, R, Irving, B, Matimba-Mupaya, W, Reed, C, Anthony, A, Trim, F, Cambalova, L, Robertson, D, Wilson, A, Hulme, J, Kannan, S, Kinney, F, Senya, H, Ratnam, V, Gill, M, Kirk, J, Shelton, S, Schweikert, S, Wibrow, B, Anstey, M, Rauniyar, R, Khoso, N, Asif, N, Taqdees, H, Frey, C, Scano, R, McKee, M, Murphy, P, Thomas, M, Worner, R, Faulkner, B, Gendall, E, Hayes, K, Blakemore, H, Borislavova, B, Deshpande, K, Van Haren, F, Konecny, P, Inskip, D, Tung, R, Hayes, L, Murphy, L, Neill, A, Reidy, B, O’Dwyer, M, Ryan, D, Ainscough, K, Hamilton-Davies, C, Mfuko, C, Abbass, H, Mandadapu, V, Leaver, S, Patel, K, Farnell-Ward, S, Saluzzio, R, Rawlins, S, Sicat, C, De Keulenaer, B, Ferrier, J, Fysh, E, Davda, A, Mevavala, B, Cook, D, Clarke, F, Banach, D, Fernández de Pinedo Artaraz, Z, Cabreros, L, Latham, V, Kruisselbrink, R, Brochard, L, Burns, K, Sandhu, G, Khalid, I, White, I, Croft, M, Holland, N, Pereira, R, Nair, P, Buscher, H, Reynolds, C, Newman, S, Santamaria, J, Barbazza, L, Homes, J, Smith, R, Zaki, A, Johnson, D, Garrard, H, Juhaz, V, Brown, L, Pemberton, A, Roy, A, Rostron, A, Woods, L, Cornell, S, Fowler, R, Adhikari, N, Kamra, M, Marinoff, N, Garrett, P, Murray, L, Brailsford, J, Fennessy, G, Mulder, J, Morgan, R, Pillai, S, Harford, R, Ivatt, H, Evans, D, Richards, S, Roberts, E, Bowen, J, Ainsworth, J, Kuitunen, A, Karlsson, S, Vahtera, A, Kiiski, H, Ristimäki, S, Albrett, J, Jackson, C, Kirkham, S, Tamme, K, Reinhard, V, Ellervee, A, Põldots, L, Rennit, P, Svitškar, N, Browne, T, Grimwade, K, Goodson, J, Keet, O, Callender, O, Udy, A, McCracken, P, Young, M, Board, J, Martin, E, Kasipandian, V, Patel, A, Allibone, S, Mary-Genetu, R, English, S, Watpool, I, Porteous, R, Miezitis, S, McIntyre, L, Brady, K, Vale, C, Shekar, K, Lavana, J, Parmar, D, Peake, S, Kurenda, C, Hormis, A, Walker, R, Collier, D, Kimpton, S, Oakley, S, Bhagani, S, De Neef, M, Garcia, S, Maharajh, A, Nandani, A, Dobson, J, Fernando, G, Eastgate, C, Gomez, K, Abdi, Z, Tatham, K, Jhanji, S, Black, E, Dela Rosa, A, Howle, R, Baikady, R, Drummond, A, Dearden, J, Philbin, J, Munt, S, Gopal, S, Pooni, J-S, Ganguly, S, Smallwood, A, Metherell, S, Naeem, A, Fagan, L, Ryan, E, Mariappa, V, Foulds, A, Revill, A, Bhattarai, B, De Jonge, E, Wigbers, J, Del Prado, M, Cremer, O, Mulier, J, Peters, A, Romberg, B, Schutgens, R, Troeman, D, Van Opdorp, M, Besten, H, Brakké, K, Barber, R, Hilldrith, A, Kluge, S, Nierhaus, A, Jarczak, D, Roedl, K, Kochanek, M, Rueß-Paterno, G, Mc-Kenzie, J, Eichenauer, D, Shimabukuro-Vornhagen, A, Wilcox, E, Del Sorbo, L, Abdelhady, H, Romagnuolo, T, Simpson, S, Maiden, M, Horton, M, Trickey, J, Krajinovic, V, Kutleša, M, Kotarski, V, Brohi, F, Jagannathan, V, Clark, M, Purvis, S, Wetherill, B, Brajković, A, Babel, J, Sever, H, Dragija, L, Kušan, I, Dushianthan, A, Cusack, R, De Courcy-Golder, K, Salmon, K, Burnish, R, Smith, S, Ruiz, W, Duke, Z, Johns, M, Male, M, Gladas, K, Virdee, S, Swabe, J, Tomlinson, H, Rohde, G, Grünewaldt, A, Bojunga, J, Petros, S, Kunz, K, Schütze, B, Weismann, D, Frey, A, Drayss, M, Goebeler, ME, Flor, T, Fragner, G, Wahl, N, Totzke, J, Sayehli, C, Hakak, S, Altaf, W, O'Sullivan, M, Murphy, A, Walsh, L, Rega La Valle, A, Bewley, J, Sweet, K, Grimmer, L, Johnson, R, Wyatt, R, Morgan, K, Varghese, S, Willis, J, Stratton, E, Kyle, L, Putensen, D, Drury, K, Skorko, A, Bremmer, P, Ward, G, Bassford, C, Sligl, W, Baig, N, Rewa, O, Bagshaw, S, Basile, K, Stavor, D, Burbee, D, McNamara, A, Wunderley, R, Bensen, N, Adams, P, Vita, T, Buhay, M, Scholl, D, Gilliam, M, Winters, J, Doherty, K, Berryman, E, Ghaffari, M, Marroquin, O, Quinn, K, Garrard, W, Kalchthaler, K, Beard, G, Skrtich, A, Bagavathy, K, Drapola, D, Bryan-Morris, K, Arnold, J, Reynolds, B, Hussain, M, Dunsavage, J, Saiyed, S, Hernandez, E, Goldman, J, Brown, C, Comp, S, Raczek, J, Morris, J, Vargas Jr., J, Weiss, D, Hensley, J, Kochert, E, Wnuk, C, Nemeth, C, Mowery, B, Hutchinson, C, Winters, L, McAdams, D, Walker, G, Minnier, T, Wisniewski, M, Mayak, K, McCreary, E, Bariola, R, Viehman, A, Daley, J, Lopus, A, Schmidhofer, M, Ambrosino, R, Keen, S, Toffalo, S, Stambaugh, M, Trimmer, K, Perri, R, Casali, S, Medva, R, Massar, B, Beyerl, A, Burkey, J, Keeler, S, Lowery, M, Oncea, L, Daugherty, J, Sevilla, C, Woelke, A, Dice, J, Weber, L, Roth, J, Ferringer, C, Beer, D, Fesz, J, Carpio, L, Colin, G, Zinzoni, V, Maquigneau, N, Henri-Lagarrigue, M, Pouplet, C, Reill, L, Distler, M, Maselli, A, Martynoga, R, Trask, K, Butler, A, Attwood, B, Parsons, P, Campbell, B, Smith, A, Page, V, Zhao, X, Oza, D, Abrahamson, G, Sheath, B, Young, P, Young, C, Lesona, E, Navarra, L, Cruz, R, Delaney, K, Aguilar-Dano, A, Gojanovic, M, Rhodes, J, Anderson, T, Morris, S, Nayyar, V, Bowen, D, Kong, J, Joy, J, Fuchs, R, Lambert, B, Tai, C, Thomas, A, Keen, A, Tierney, C, Omer, N, Bacon, G, Tridente, A, Shuker, K, Anders, J, Greer, S, Scott, P, Millington, A, Buchanan, P, Binnie, A, Powell, E, McMillan, A, Luk, T, Aref, N, Denmade, C, Sadera, G, Jacob, R, Hughes, D, Sterba, M, Geng, W, Digby, S, Southern, D, Reddy, H, Hulse, S, Campbell, A, Garton, M, Watkins, C, Smuts, S, Quinn, A, Simpson, B, McMillan, C, Finch, C, Hill, C, Cooper, J, Budd, J, Small, C, O’Leary, R, Collins, E, Holland, A, Alexander, P, Felton, T, Ferguson, S, Sellers, K, Ward, L, Yates, D, Birkinshaw, I, Kell, K, Scott, Z, Pearson, H, Hashmi, M, Hassan, N, Panjwani, A, Umrani, Z, Shaikh, M, Ain, Q, Kanwal, D, Van Bree, S, Bouw-Ruiter, M, Osinga, M, Van Zanten, A, McEldrew, R, Rashan, S, Singh, V, Azergui, N, Bari, S, Beltran, M, Brugman, C, Groeneveld, E, Jafarzadeh, M, Keijzer-Timmers, N, Kester, E, Koelink, M, Kwakkenbos-Craanen, M, Okundaye, C, Parker, L, Peters, S, Post, S, Rietveld, I, Scheepstra-Beukers, I, Schreuder, G, Smit, A, Brillinger, N, Markgraf, R, Eichinger, F, Doran, P, Anjum, A, Best-Lane, J, Barton, F, Miller, L, Richards-Belle, A, Saull, M, Sprinckmoller, S, Wiley, D, Darnell, R, Au, C, Lindstrum, K, Cheng, A, Forbes, A, Heritier, S, Trapani, T, Cuthbertson, B, Manoharan, V, Dondrop, A, Tolppa, T, Ehrmann, S, Hullegie, S, Povoa, P, Beasley, R, Daneman, N, McGloughlin, S, Paterson, D, Venkatesh, B, De Jong, M, Uyeki, T, Baillie, K, Netea, M, Orr, K, Patanwala, A, Tong, S, Cooper, N, Galea, J, Leavis, H, Ogungbenro, K, Patawala, A, Rademaker, E, Youngstein, T, Carrier, M, Fergusson, D, Hunt, B, Kumar, A, Laffan, M, Lother, S, Middeldorp, S, Stanworth, S, De Man, A, Masse, M-H, Abraham, J, Arnold, D, Begin, P, Charlewood, R, Chasse, M, Coyne, M, Daly, J, Gosbell, I, Harvala-Simmonds, H, MacLennan, S, McDyer, J, Menon, D, Pridee, N, Roberts, D, Thomas, H, Tinmouth, A, Triulzi, D, Walsh, T, Wood, E, Calfee, C, O’Kane, C, Shyamsundar, M, Sinha, P, Thompson, T, Young, I, Burrell, A, Ferguson, N, Hodgson, C, Orford, N, Phua, J, Baron, R, Epelman, S, Frankfurter, C, Gommans, F, Kim, E, Leaf, D, Vaduganathan, M, Van Kimmenade, R, Sanil, A, Van Beurden, M, Effelaar, E, Schotsman, J, Boyd, C, Harland, C, Shearer, A, Wren, J, Attanayaka, U, Darshana, S, Ishani, P, Udayanga, I, Higgins, AM, Berry, LR, Lorenzi, E, Murthy, S, McQuilten, Z, Mouncey, PR, Al-Beidh, F, Annane, D, Arabi, YM, Beane, A, Van Bentum-Puijk, W, Bhimani, Z, Bonten, MJM, Bradbury, CA, Brunkhorst, FM, Buzgau, A, Buxton, M, Charles, WN, Cove, M, Detry, MA, Estcourt, LJ, Fagbodun, EO, Fitzgerald, M, Girard, TD, Goligher, EC, Goossens, H, Haniffa, R, Hills, T, Horvat, CM, Huang, DT, Ichihara, N, Lamontagne, F, Marshall, JC, McAuley, DF, McGlothlin, A, McGuinness, SP, McVerry, BJ, Neal, MD, Nichol, AD, Parke, RL, Parker, JC, Parry-Billings, K, Peters, SEC, Reyes, LF, Rowan, KM, Saito, H, Santos, MS, Saunders, CT, Serpa-Neto, A, Seymour, CW, Shankar-Hari, M, Stronach, LM, Turgeon, AF, Turner, AM, Van de Veerdonk, FL, Zarychanski, R, Green, C, Lewis, RJ, Angus, DC, McArthur, CJ, Berry, S, Derde, LPG, Gordon, AC, Webb, SA, Lawler, PR, Comm REMAP-CAP Investigators, Apollo - University of Cambridge Repository, Intensive Care Medicine, Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Hôpital Raymond Poincaré [Garches], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Pittsburgh Foundation, PF, Amgen, Health Research Board, HRB: CTN 2014-012, Horizon 2020 Framework Programme, H2020: 101003589, Translational Breast Cancer Research Consortium, TBCRC, Canadian Institutes of Health Research, IRSC: 158584, Heart and Stroke Foundation of Canada, HSF, National Institute for Health and Care Research, NIHR, European Commission, EC, National Health and Medical Research Council, NHMRC: 1101719, APP194811, CS-2016-16-011, GNT2008447, RP-2015-06-18, Office of Health and Medical Research, OHMR, Health Research Council of New Zealand, HRC: 16/631, Eisai, Ministère des Affaires Sociales et de la Santé: PHRC-20-0147, Université Pierre et Marie Curie, UPMC, NIHR Imperial Biomedical Research Centre, BRC, Minderoo Foundation, Funding/Support : The Platform for European Preparedness Against (Re-) emerging Epidemics (PREPARE) consortium by the European Union, FP7-HEALTH-2013-INNOVATION-1 (#602525), the Rapid European COVID-19 Emergency Research response (RECOVER) consortium by the European Union’s Horizon 2020 research and innovation programme (#101003589), the Australian National Health and Medical Research Council (#APP1101719), the Australian Medical Research Future Fund (#APP2002132), the Health Research Council of New Zealand (#16/631), the Canadian Institutes of Health Research Strategy for Patient-Oriented Research Innovative Clinical Trials Program Grant (#158584) and the Canadian Institute of Health Research COVID-19 Rapid Research Funding (#447335), the UK National Institute for Health Research (NIHR) and the NIHR Imperial Biomedical Research Centre, the Health Research Board of Ireland (CTN 2014-012), the UPMC Learning While Doing Program, the Translational Breast Cancer Research Consortium, the French Ministry of Health (PHRC-20-0147), the Wellcome Trust Innovations Project (215522), the Minderoo Foundation, the EU Programme Emergency Support Instrument, the NHS Blood and Transplant Research and Development Programme, the Translational Breast Cancer Research Consortium, the NSW Office of Health and Medical Research, Amgen, Eisai, and the Pittsburgh Foundation. Dr Higgins is funded by an NHMRC Emerging Leadership Fellowship (GNT2008447). Dr McQuilten is funded by an NHMRC Emerging Leadership Fellowship (APP194811). Dr Gordon is funded by an NIHR Research Professorship (RP-2015-06-18) and Dr Shankar-Hari by an NIHR Clinician Scientist Fellowship (CS-2016-16-011). Dr Turgeon is the Chairholder of the Canada Research Chair in Critical Care Neurology and Trauma. Dr Lawler is supported by a career award from the Heart and Stroke Foundation of Canada., and European Project: 602525,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-1,PREPARE(2014)

Subjects
Adult, Male, corticosteroid, [SDV]Life Sciences [q-bio], Critical Illness, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], antiplatelet, Lopinavir, Adaptive platform trial randomized controlled trial intensive care, pneumonia COVID-19 antiplatelet immunoglobulin antiviral corticosteroid immune modulation anticoagulation, All institutes and research themes of the Radboud University Medical Center, Adrenal Cortex Hormones, Humans, anticoagulation, intensive care, pneumonia, COVID-19 Serotherapy, Original Investigation, Medicine(all), immune modulation, Ritonavir, SARS-CoV-2, COVID-19, Anticoagulants, Bayes Theorem, General Medicine, Middle Aged, antiviral, Receptors, Interleukin-6, Adaptive platform trial, randomized controlled trial, Female, Human medicine, immunoglobulin, Follow-Up Studies, Hydroxychloroquine
Abstract

ImportanceThe longer-term effects of therapies for the treatment of critically ill patients with COVID-19 are unknown.ObjectiveTo determine the effect of multiple interventions for critically ill adults with COVID-19 on longer-term outcomes.Design, Setting, and ParticipantsPrespecified secondary analysis of an ongoing adaptive platform trial (REMAP-CAP) testing interventions within multiple therapeutic domains in which 4869 critically ill adult patients with COVID-19 were enrolled between March 9, 2020, and June 22, 2021, from 197 sites in 14 countries. The final 180-day follow-up was completed on March 2, 2022.InterventionsPatients were randomized to receive 1 or more interventions within 6 treatment domains: immune modulators (n = 2274), convalescent plasma (n = 2011), antiplatelet therapy (n = 1557), anticoagulation (n = 1033), antivirals (n = 726), and corticosteroids (n = 401).Main Outcomes and MeasuresThe main outcome was survival through day 180, analyzed using a bayesian piecewise exponential model. A hazard ratio (HR) less than 1 represented improved survival (superiority), while an HR greater than 1 represented worsened survival (harm); futility was represented by a relative improvement less than 20% in outcome, shown by an HR greater than 0.83.ResultsAmong 4869 randomized patients (mean age, 59.3 years; 1537 [32.1%] women), 4107 (84.3%) had known vital status and 2590 (63.1%) were alive at day 180. IL-6 receptor antagonists had a greater than 99.9% probability of improving 6-month survival (adjusted HR, 0.74 [95% credible interval {CrI}, 0.61-0.90]) and antiplatelet agents had a 95% probability of improving 6-month survival (adjusted HR, 0.85 [95% CrI, 0.71-1.03]) compared with the control, while the probability of trial-defined statistical futility (HR >0.83) was high for therapeutic anticoagulation (99.9%; HR, 1.13 [95% CrI, 0.93-1.42]), convalescent plasma (99.2%; HR, 0.99 [95% CrI, 0.86-1.14]), and lopinavir-ritonavir (96.6%; HR, 1.06 [95% CrI, 0.82-1.38]) and the probabilities of harm from hydroxychloroquine (96.9%; HR, 1.51 [95% CrI, 0.98-2.29]) and the combination of lopinavir-ritonavir and hydroxychloroquine (96.8%; HR, 1.61 [95% CrI, 0.97-2.67]) were high. The corticosteroid domain was stopped early prior to reaching a predefined statistical trigger; there was a 57.1% to 61.6% probability of improving 6-month survival across varying hydrocortisone dosing strategies.Conclusions and RelevanceAmong critically ill patients with COVID-19 randomized to receive 1 or more therapeutic interventions, treatment with an IL-6 receptor antagonist had a greater than 99.9% probability of improved 180-day mortality compared with patients randomized to the control, and treatment with an antiplatelet had a 95.0% probability of improved 180-day mortality compared with patients randomized to the control. Overall, when considered with previously reported short-term results, the findings indicate that initial in-hospital treatment effects were consistent for most therapies through 6 months.

Published
2023
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34. Laparoscopic atypical resection of subcardial gastric GIST guided by intraoperative endoscopy. A single-center study and a review of the literature

Author

Marianna, Capuano, Giuseppe, Palomba, Giuseppe, Sorrentino, Raffaele, Basile, Alessia, Chini, Rosa, Maione, Francesco, Maione, Giovanni Domenico, De Palma, and Giovanni, Aprea

Subjects
Male, Surgeons, Gastrointestinal Stromal Tumors, Stomach Neoplasms, Humans, Female, Laparoscopy
Abstract

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. They are 1% of all gastrointestinal cancer and 60% of them affects the stomach. Up to 10% to 30% of GISTs are malignant. They occur in people over the age of 50 in both sexes. The most common symptoms of gastric GIST are bleeding, dyspepsia, vague abdominal pain or discomfort, and mass palpation. Some are asymptomatic and diagnosed incidentally. The first choice of treatment for primary localized gastric GISTs is surgery. The most suitable type of resection is not yet clear and it depends on size and location of tumor, especially for difficult localizations, such as subcardial, posterior wall and less curvature GISTs.We report a rare case of a patient with subcardial gastric GIST treated with laparoscopic atypical quadrangular resection guided by intraoperative endoscopy. Furthermore, we performed a review of the literature about this topic.Despite the difficult localization an atypical resection of the gastric GIST was performed without breaking the lesion but preserving the lumen of the esofagogastrich junction.An atypical quadrangular resection for subcardial gastric GISTs, located along the posterior wall and lesser curvature, can be a safe and reliable alternative technique. However, we believe that it should be performed by an experienced surgeon and endoscopist to decrease the risk of mass's break and the narrowing of the cardial region's lumen. In our literature's knowledge there aren't cases treated with this technique.Gastric GIST, Gastrointestinal stromal tumors, Intraoperative endoscopy, Laparoscopic resection, Minimally invasive surgery.I tumori stromali gastrointestinali (GIST) sono i tumori mesenchimali più comuni del tratto gastrointestinale, il 60% dei GIST interessa lo stomaco. La prima scelta di trattamento per i GIST gastrici primari localizzati è la chirurgia. La resezione laparoscopica del GIST gastrico rispetto alla chirurgia a cielo aperto ha migliorato i risultati a breve termine con risultati simili a lungo termine. Tuttavia, non ci sono indicazioni assolute sul tipo di resezione in base alle dimensioni e alla posizione del tumore. Riportiamo un raro caso di un paziente di 53 anni con un GIST gastrico localizzato in una posizione sfavorevole (sottocardiale, lungo la parete posteriore della piccola curvatura dello stomaco) trattato con resezione laparoscopica atipica supportata da un’endoscopia intraoperatoria. La TC addominale nel giugno 2021 mostrava una grossa massa (59x35x39 mm) che occupava parte del lume, il fondo e il corpo gastrico a partenza dalla componente muscolare della piccola curvatura. La gastroscopia, tuttavia non era diagnostica per GIST ma rilevava solo papule erose in sede antrale e prepilorica, come da gastrite cronica. Ad agosto un’acoendoscopia (US) con biopsia ha diagnosticato un GIST gastrico sottocardiale lungo la piccola curva di circa 5 cm di diametro. Dopo una valutazione multidisciplinare il paziente è stato sottoposto ad intervento chirurgico di resezione laparoscopica del GIST gastrico. La visione laparoscopica iniziale non è stata in grado di identificare la massa tranne che per una leggera impronta sulla parete anteriore dello stomaco nella regione sottocardiale, che si estendeva lungo la piccola curva. Pertanto, è stata eseguita una gastroscopia intraoperatoria che ha mostrato inaspettatamente una massa di circa 5cm ulcerata, sulla parete posteriore dello stomaco, sotto il cardias, lungo la piccola curva. La lesione è stata visualizzata endoscopicamente grazie alla compressione ab-estrinseco laparoscopica sulla parete posteriore dello stomaco e la crescita intraluminale probabilmente era dovuta al tempo intercorso tra la gastroscopia preoperatoria e quella intraoperatoria. Grazie alla visione laparoscopica ed endoscopica combinata mediante l’utilizzo di due monitor, il chirurgo è stato in grado di comprendere i margini superiore, inferiore e laterale della lesione. È stata eseguita una resezione atipica che ha consentito l’asportazione della lesione nonostante la difficile localizzazione. È stata realizzata un’asportazione quadrangolare utilizzando una suturatrice lineare su tre lati: la prima sutura sul margine caudale della lesione, la seconda sul margine laterale verso l’alto. Le prime due suture hanno consentito una maggiore mobilizzazione dello stomaco recuperando il range di movimento per l’ultima sutura, che è stata eseguita sul margine prossimale della massa con l’endoscopio posizionato in modo tale da preservare il lume della giunzione esofagogastrica. La visione endoscopica ha permesso di rimuovere la parte di stomaco che conteneva l’intera lesione senza romperla e contemporaneamente di preservare il lume della giunzione esofagogastrica lasciando libero il passaggio tra esofago e stomaco. Nonostante la differenza tra le indagini preoperatorie e la reale visione intraoperatoria del GIST, la difficile localizzazione del tumore e l’utilizzo di una tecnica non standardizzata, l’intervento non ha avuto complicanze ed è durato 120 minuti. La resezione quadrangolare atipica laparoscopica per GIST gastrici sottocardiali, situata lungo la parete posteriore e la piccola curvatura, può essere considerata una tecnica sicura, fattibile e riproducibile. Questo approccio potrebbe essere considerato una scelta chirurgica alternativa alla gastrectomia totale o parziale per questo tipo di tumori. Tuttavia, esso richiede sale operatorie integrate con attività endoscopica e dovrebbe essere eseguita da chirurgo ed endoscopista esperti per ridurre il rischio di rottura della massa e il restringimento del lume della regione cardiaca. In base alle nostre conoscenze non ci sono in letteratura casi trattati con questa tecnica. Pertanto, questo ne rappresenta il primo caso.

Published
2022

35. COVID-19 vaccines associated with vasovagal malaise: A retrospective study in two mass vaccination centers and analysis of the WHO pharmacovigilance database

Author

Basile Chrétien, Rhéda Stroiazzo, Leila Troussier, Pierre-Yves Le Houssel, Magali Jacquet, Cécile Lheureux, Sandy Voyen, Philippe Court, Charles Dolladille, Joachim Alexandre, Sophie Fedrizzi, and Xavier Humbert

Subjects
Pharmacology, Adult, Vaccines, COVID-19 Vaccines, Adolescent, Immunology, Vaccination, COVID-19, World Health Organization, Mass Vaccination, Young Adult, Immunology and Allergy, Humans, Adverse Drug Reaction Reporting Systems, Female, Retrospective Studies
Abstract

The association between COVID-19 vaccines and vasovagal malaise (VVM) has recently been reported in the literature. Our study aimed to describe COVID-19 vaccines associated VVM cases and to identify risk factors of COVID-19 vaccines associated VVM. To this end, we performed a descriptive study of VVM reports associated with COVID-19 vaccines from two French mass COVID-19 vaccination centers. We also extracted reports of VVM associated with all-COVID-19 vaccines in VigiBase®, the World Health Organization (WHO) pharmacovigilance database to analyze demographic data. In the two French mass vaccination center database, 408 entries reported VVM after the standard administration of tozinameran - Pfizer® (1.63/1,000 vaccinated persons). Of these cases, 213 (52.2%) occurred in women, and 193 (47.3%) occurred in the 18-29 year-old (yo) age group. In 232 cases (56.8%), patients had a history of anxiety related to needles or medical visits, 213 (52.2%) reported a fear of COVID-19 vaccination in particular, and 233 (57.1%) had a history of VVM. In VigiBase®, 336,291 notifications of COVID-19 vaccines associated with VVM were identified in the adult population during the period of analysis. The most reported age class was 18-44 years (52.4%), and women represented 71.7% of the reports. Reporting widely differed depending on the country. This study, performed in real-life conditions, highlights that VVM is associated with all-COVID-19 vaccines. Young age and history of anxiety related in young adults could be a triggering factor of vaccines-associated VVM. Further studies are needed to confirm our results.

Published
2022

36. The spectrum of kidney dysfunction requiring chronic dialysis therapy: Implications for clinical practice and future clinical trials

Author

Javier Deira, Kamyar Kalantar-Zadeh, Francesco G. Casino, Carlo Basile, and Mariana Murea

Subjects
Male, medicine.medical_specialty, medicine.medical_treatment, Renal function, Kidney, Kidney Function Tests, Renal Dialysis, medicine, Humans, Intensive care medicine, Kidney transplantation, Dialysis, urogenital system, business.industry, Acute kidney injury, medicine.disease, Uremia, Renal Replacement Therapy, Clinical trial, medicine.anatomical_structure, Nephrology, Disease Progression, Kidney Failure, Chronic, Female, business, Kidney disease
Abstract

Staging to capture kidney function and pathophysiologic processes according to severity is widely used in chronic kidney disease or acute kidney injury not requiring dialysis. Yet the diagnosis of "end-stage kidney disease" (ESKD) considers patients as a single homogeneous group, with negligible kidney function, in need of kidney replacement therapy. Herein, we review the evidence behind the heterogeneous nature of ESKD and discuss potential benefits of recasting the terminology used to describe advanced kidney dysfunction from a monolithic entity to a disease with stages of ascending severity. We consider kidney assistance therapy in lieu of kidney replacement therapy to better reconcile all available types of therapy for advanced kidney failure including dietary intervention, kidney transplantation, and dialysis therapy at varied schedules. The lexicon "kidney dysfunction requiring dialysis" (KDRD) with stages of ascending severity based on levels of residual kidney function (RKF)-that is, renal urea clearance-and manifestations related to uremia, fluid status, and other abnormalities is discussed. Subtyping KDRD by levels of RKF could advance dialysis therapy as a form of kidney assistance therapy adjusted based on RKF and clinical symptoms. We focus on intermittent hemodialysis and underscore the need to personalize dialysis treatments and improve characterization of patients included in clinical trials.

Published
2021
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37. Ovarian arteries embolization in women with persistent symptoms following uterine arteries embolization for uterus fibroids

Author

Denis Herbreteau, Basile Kerleroux, Thomas Perus, Jonathan Ifergan, Kevin Janot, R. Bibi, Henri Azaïs, Héloïse Ifergan, Gregoire Boulouis, and Henri Marret

Subjects
Adult, medicine.medical_specialty, Uterine fibroids, Urology, medicine.medical_treatment, Uterus, Internal medicine, medicine, Humans, Radiology, Nuclear Medicine and imaging, Embolization, Retrospective Studies, Hysterectomy, Leiomyoma, Radiological and Ultrasound Technology, business.industry, Gastroenterology, Retrospective cohort study, Middle Aged, Uterine Artery Embolization, Hepatology, medicine.disease, Embolization, Therapeutic, Surgery, Uterine Artery, Treatment Outcome, medicine.anatomical_structure, Uterine Neoplasms, Cohort, Quality of Life, Female, business
Abstract

In patients with persisting symptoms after uterine arteries embolization (UAE), ovarian arteries embolization (OAE) may play a role to improve symptoms and decrease subsequent surgery rates. In a retrospective cohort, we aimed to investigate the efficacy and safety of OAE in females with recurrent or persistent symptoms following UAE. We performed a retrospective analysis of prospectively collected cases at a single reference academic hospital; we identified patients who benefited from OAE for persisting symptoms following UAE from 2008 to 2021. Outcome variables included the rates of subsequent surgery, a quality-of-life questionnaire with the UFS-QOL tool, the MRI reduction in uterine and fibroids volumes and the fibroid devascularization rate. Among 1300 women treated with UAE during the study period, 18 eventually received OAE and were included (mean age 44 ± 4.3 SD). There was no OAE procedural complication. There was a decrease in uterine volume and a complete devascularization of the dominant fibroid in 10/11 (90.9%) patients who underwent 12 months MRI. Three women underwent subsequent hysterectomy. Among 10/18 patients who answered the quality-of-life questionnaire after a mean follow-up of 70 months, eight reported an improvement or stability of symptoms. OAE for persisting symptoms after UAE was associated with improvement or stability of quality-of-life in most study subjects and less than a fifth of the cohort underwent hysterectomy after OAE. This study highlights the role of OAE as an adjunct to UAE.

Published
2021
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38. Experiences of Quality Perinatal Care During the US COVID‐19 Pandemic

Author

Holly Powell Kennedy, Joan Combellick, and Bridget Basile Ibrahim

Subjects
medicine.medical_specialty, media_common.quotation_subject, Computer-assisted web interviewing, community birth, Indigenous, COVID‐19, Pregnancy, Maternity and Midwifery, Health care, Pandemic, medicine, Humans, autonomy, Child, Pandemics, midwifery, Original Research, health equity, media_common, home birth, SARS-CoV-2, business.industry, Public health, structural racism, Infant, Newborn, Parturition, COVID-19, Obstetrics and Gynecology, United States, Health equity, respectful maternity care, Perinatal Care, birth setting, Family medicine, Female, business, Home birth, Autonomy
Abstract

Introduction Quality perinatal care is recognized as an important birth process and outcome. During the coronavirus disease 2019 (COVID-19) pandemic, quality of perinatal care was compromised as the health care system grappled with adapting to an ever-changing, uncertain, and unprecedented public health crisis. Methods The aim of this study was to explore the quality of perinatal care received during the COVID-19 pandemic in the United States. Data were collected via an online questionnaire completed by people who gave birth in the United States after March 15, 2020. The questionnaire included the Mothers on Respect Index and the Mothers Autonomy in Decision Making validated measures. Low-quality perinatal care was defined as decreased respect and/or autonomy in the perinatal care received. Responses were geocoded by zip code to determine COVID-19 case-load in the county on the date of birth. Multivariate regression analyses described associations between respect and autonomy in decision-making for perinatal care and levels of COVID-19 outbreak across the United States. Results Participants (N = 707) from 46 states and the District of Columbia completed the questionnaire. As COVID-19 cases increased, participants' experiences of autonomy in decision-making for perinatal care decreased significantly (P = .04). Participants who identified as Black, Indigenous, and people of color, those who had an obstetrician provider, and those who gave birth in a hospital were more likely to experience low-quality perinatal care. Those with a midwife provider or who had a home birth were more likely to experience high-quality perinatal care in adjusted models. Discussion Variability in experiences of high-quality perinatal care by sociodemographic characteristics, birth setting, and provider type may relate to implicit bias, structural racism, and inequities in maternal health and COVID-19 outcomes for birthing people from marginalized communities.

Published
2021
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39. [Human Papillomavirus: screening of cervical and anal cancers]

Author

Basile, Pache, Martine, Jacot-Guillarmod, Martin, Hübner, and Patrice, Mathevet

Subjects
Papillomavirus Infections, Humans, Uterine Cervical Neoplasms, Female, Cervix Uteri, Papillomavirus Vaccines, Alphapapillomavirus, Anus Neoplasms, Papillomaviridae, Early Detection of Cancer
Abstract

Cervical cancer is preventable through primary and secondary prevention. Vaccination against the human papillomavirus (HPV), the virus necessary for the development of precancerous lesions, can prevent most of them. Screening by cytology for these precancerous (or cancerous) lesions can be replaced by screening for certain types of HPV, high risk (HR-HPV), causing cervical cancer. The presence of HR-HPV on the cervix should raise suspicion of concomitant infection in the anus, as both epithelia are highly susceptible. This attitude is dictated by the increase incidence in anal cancer in the population, which is also HPV-dependent and therefore also potentially preventable through vaccination and screening.Le cancer du col utérin est évitable, au travers d’une politique de prévention primaire et secondaire. Une vaccination contre le papillomavirus humain (HPV), et plus particulièrement contre les HPV dits à haut risque (HR-HPV) qui induisent le développement des états précancéreux, permet ainsi d’éviter une majeure partie de ceux-ci. Un dépistage par cytologie à la recherche de ces lésions précancéreuses (ou cancéreuses) peut être supplanté par la recherche de la présence des HR-HPV. La présence de HR-HPV sur le col doit faire suspecter une infection concomitante au niveau de l’anus car les deux épithéliums y sont très sensibles. Cette attitude est dictée par l’augmentation des cancers de l’anus dans la population, cancer lui aussi dépendant du HPV, et donc aussi potentiellement évitable au travers de la vaccination et du dépistage.

Published
2022

40. [Vaginal microbiota and vaginosis]

Author

Anna, Surbone, Basile, Pache, and Patrice, Mathevet

Subjects
Lactobacillus, Bacteria, Microbiota, Vagina, Humans, Dysbiosis, Female, Vaginosis, Bacterial
Abstract

The vaginal microbiota is essentially composed of bacteria of the Lactobacillus genus. These bacteria, by their presence, prevent vaginal contamination by other potentially aggressive germs. Disturbances of the microbiota lead to a pathological state called dysbiosis, one of the most frequent pathogenic aspects of which is bacterial vaginosis. This vaginal state results in nauseating leucorrhoea induced by the proliferation of aero-anaerobic bacteria. Bacterial vaginosis is a source of different clinical impacts: increased risk of genital infection with many pathogens, loss of chance in medically assisted procreation, increased risk of premature delivery. The treatment of bacterial vaginosis must take into account the restitution of a normal microbiota.Le microbiote vaginal est composé de bactéries du genre

Published
2022

41. Long-Term Influence of Locus of Control and Quality of Life on Metabolic Profile in Elderly Subjects with Type 2 Diabetes

Author

Annalisa Giandalia, Marta Ragonese, Eugenio Alessi, Maria C. Ruffo, Alberto Sardella, Alessandro Cuttone, Maria A. Aragona, Antonio G. Versace, Giorgio Basile, Domenico Cucinotta, Giovanni Squadrito, and Giuseppina T. Russo

Subjects
Male, Glucose, Diabetes Mellitus, Type 2, Health, Toxicology and Mutagenesis, Surveys and Questionnaires, Public Health, Environmental and Occupational Health, Quality of Life, Metabolome, type 2 diabetes, Locus of Control, elderly, quality of life, gender differences, Humans, Female, Internal-External Control, Aged
Abstract

Background: The Locus of Control (LOC) is a mental disposition indicating the individuals’ belief that disease-related outcomes are under their own control (Internal), dependent on others (External), or dependent on chance (Chance). Quality of Life (QoL) and LOC may have complex effects on self-care activities and diabetes management in subjects with type 2 diabetes (T2D). The aim of the present study was to evaluate the predictive role of LOC and QoL scores on metabolic control in elderly T2D outpatients, secondly evaluating potential gender differences. Methods: An extensive set of questionnaires was administered to a group of consecutive elderly T2D outpatients on oral glucose-lowering drugs attending a single diabetes center. Personal and clinical variables were analyzed at baseline (between 1 February and 31 March 2015) and after 6 years of follow-up. Results: At baseline, study participants showed an overall good metabolic control. Diabetes Specific Quality of Life (DSQoL) scores indicated an overall good QoL in both genders, with a higher DSQoL satisfaction score in women. Both genders presented higher scores in the LOC-Internal domain, with men reaching higher scores in the LOC-External domain than women. At the 6-years follow-up, subjects with baseline higher LOC-External score presented better metabolic outcome. In the regression analysis, LOC-External score was an independent predictor of good metabolic control maintenance, but this result was only statistically significant in men. Conclusions: LOC scores may influence long-term glycemic control in elderly T2D patients on oral glucose-lowering drugs.

Published
2022
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42. The proteome of clear cell ovarian carcinoma

Author

Jennifer X Ji, Dawn R Cochrane, Gian Luca Negri, Shane Colborne, Sandra E Spencer Miko, Lynn N Hoang, David Farnell, Basile Tessier‐Cloutier, Jutta Huvila, Emily Thompson, Samuel Leung, Derek Chiu, Christine Chow, Monica Ta, Martin Köbel, Lucas Feil, Michael Anglesio, Ellen L Goode, Kelly Bolton, Gregg B Morin, and David G Huntsman

Subjects
Proteomics, Ovarian Neoplasms, Proteome, Humans, Female, Carcinoma, Ovarian Epithelial, Article, Pathology and Forensic Medicine, Adenocarcinoma, Clear Cell
Abstract

Clear cell ovarian carcinoma (CCOC) is the second most common subtype of epithelial ovarian carcinoma. Late-stage CCOC is not responsive to gold-standard chemotherapy and results in suboptimal outcomes for patients. In-depth molecular insight is urgently needed to stratify the disease and drive therapeutic development. We conducted global proteomics for 192 cases of CCOC and compared these with other epithelial ovarian carcinoma subtypes. Our results showed distinct proteomic differences in CCOC compared with other epithelial ovarian cancer subtypes including alterations in lipid and purine metabolism pathways. Furthermore, we report potential clinically significant proteomic subgroups within CCOC, suggesting the biologic plausibility of stratified treatment for this cancer. Taken together, our results provide a comprehensive understanding of the CCOC proteomic landscape to facilitate future understanding and research of this disease. © 2022 The Pathological Society of Great Britain and Ireland.

Published
2022

43. COVID-19 and female fertility: the flaws of Italian Law 40/2004 on assisted procreation in pandemic times

Author

Susanna, Marinelli, Gaspare, Cucinella, and Giuseppe, Basile

Subjects
Fertility, SARS-CoV-2, Humans, COVID-19, Reproducibility of Results, Female, Angiotensin-Converting Enzyme 2, Pandemics
Abstract

SARS-CoV-2 has infected over 614 million people worldwide, killing more than 6.5 million. COVID-19 impact on fertility may have far-reaching ramifications, considering that only in Italy, over 20 million people have been infected, many more considering unconfirmed cases.The authors aimed to outline the repercussions of COVID-19 on female reproductive capabilities, through an analysis of underlying mechanisms and dynamics liable to cause long-term COVID-19 complications and sequelae, including direct virus-induced tissue damage.The entry receptor for SARS-CoV-2, Angiotensin-converting enzyme 2 (ACE2) can be found in several tissues and organs within the human body, including ovaries, oocytes and placenta. In order to assess the fertility-damaging potential of the disease, it is necessary to clarify highly complex mechanisms such as the ovarian renin-angiotensin system (OVRAS) affecting ovarian physiology and dysfunction. COVID-19 and its potential to undermine the fertility prospects of millions cannot be underestimated. It is therefore essential for lawmakers to solve inconsistencies such as those in Italy's Law 40/2004, which has been all but dismantled by Constitutional Court and European Court of Human Rights rulings, and cannot therefore offer a sufficient degree of certainty and reliability.When crafting novel, updated standards, norms and regulations to govern access to medically-assisted procreation, national leaders need to take into account the grave threat to fertility in a country such as Italy, which already has one of the world's lowest birth rates, posed by COVID-19 in light of currently available research findings outlining its impact on reproductive capacity.

Published
2022

45. The armed conflict in Ukraine and the risks of inter-country surrogacy: the unsolved dilemma

Author

Marinelli, S., Del Rio, A., Straccamore, M., Negro, F., and Basile, G.

Subjects
Research, ukraine war, Armed Conflicts, ethics, Pregnancy, cild status, liability, Humans, Family, Female, Child, Ukraine, Surrogate Mothers
Abstract

Commercial surrogacy in Ukraine has been legal since 2002, and although no official figures are released, estimates point to several thousand births occurring yearly. The country has long been regarded as one of the surrogacy capitals of the world, due to relatively affordable costs and effective targeted legislation making the surrogacy contracts enforceable. Would-be parents come from countries where surrogacy is banned or heavily restricted to start a family despite their infertility, a practice known as inter-country surrogacy. When a child is born through surrogacy, the surrogate mother forfeits her rights over the child, thus allowing the so-called "intended" or "commissioning" parents to be recognized as such on the Ukrainian birth certificate. Inter-country surrogacy has long been a highly controversial practice from an ethical and legal perspective, but the brutally destructive armed conflict erupted in the country over three months ago has laid bare all the pitfalls and deep flaws of such a system. Children born through surrogacy cannot be handed over to their intended parents, and surrogates risk legal issues and see their rights jeopardized by their choices even in a war setting, for instance if they decide to seek refuge abroad. The horrors of war thus risk victimizing the most vulnerable to an irreparable degree. An international effort is now more urgent than ever to seek a tenable balance between the desires of couples to achieve parenthood and the rights and freedom of often vulnerable women who risk exploitation and abuse and their children.

Published
2022

46. Single-nucleus RNA-Seq reveals singular gene signatures of human ductal cells during adaptation to insulin resistance

Author

Ercument Dirice, Giorgio Basile, Sevim Kahraman, Danielle Diegisser, Jiang Hu, and Rohit N. Kulkarni

Subjects
Adult, Homeodomain Proteins, Infant, Newborn, Mice, Nude, Mice, SCID, General Medicine, Mice, Mice, Inbred NOD, Pregnancy, Animals, Humans, Insulin, Female, RNA-Seq, Insulin Resistance, Transcription Factors
Abstract

Adaptation to increased insulin demand is mediated by β cell proliferation and neogenesis, among other mechanisms. Although it is known that pancreatic β cells can arise from ductal progenitors, these observations have been limited mostly to the neonatal period. We have recently reported that the duct is a source of insulin-secreting cells in adult insulin-resistant states. To further explore the signaling pathways underlying the dynamic β cell reserve during insulin resistance, we undertook human islet and duct transplantations under the kidney capsule of immunodeficient NOD/SCID-γ (NSG) mouse models that were pregnant, were insulin-resistant, or had insulin resistance superimposed upon pregnancy (insulin resistance + pregnancy), followed by single-nucleus RNA-Seq (snRNA-Seq) on snap-frozen graft samples. We observed an upregulation of proliferation markers (e.g., NEAT1) and expression of islet endocrine cell markers (e.g., GCG and PPY), as well as mature β cell markers (e.g., INS), in transplanted human duct grafts in response to high insulin demand. We also noted downregulation of ductal cell identity genes (e.g., KRT19 and ONECUT2) coupled with upregulation of β cell development and insulin signaling pathways. These results indicate that subsets of ductal cells are able to gain β cell identity and reflect a form of compensation during the adaptation to insulin resistance in both physiological and pathological states.

Published
2022
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47. Temporary cervical sling and uterine twist before B-Lynch for massive uterine bleeding after delivery

Author

Basile Pache, Vincent Balaya, and David Desseauve

Subjects
Postpartum Hemorrhage, Suture Techniques, Uterus, Obstetrics and Gynecology, Humans, Female, Cervix Uteri, Uterine Inertia
Abstract

Massive uterine bleeding occurring after delivery is in most cases unpredictable and can have fatal consequences. This article presents the technique of combining the twisting of uterus on a 90° rotation on its axis and positioning a sling around the cervix, allowing to decrease incoming blood flow from uterine and ovarian arteries. The aim of this easy-to-use procedure is to enable surgeons and anaesthesiologists to respectively ensure the presence of an experienced surgeon and to stabilise the haemodynamic of the patient. It is

Published
2022

48. A toddler with an unusually severe polyarticular arthritis and a lung involvement: a case report

Author

Pietro Basile, Giulia Gortani, Andrea Taddio, Serena Pastore, Federica Corona, Alessandra Tesser, Egidio Barbi, Alberto Tommasini, Basile, Pietro, Gortani, Giulia, Taddio, Andrea, Pastore, Serena, Corona, Federica, Tesser, Alessandra, Barbi, Egidio, and Tommasini, Alberto

Subjects
Interferonopathy, COPA Syndrome, Case report, Interstitial pneumopathy, Polyarticular arthritis, Arthralgia, Arthritis, Juvenile, Rheumatoid Factor, Child, Preschool, Pediatrics, Perinatology and Child Health, Humans, Female, Lung Diseases, Interstitial, Lung
Abstract

Background COPA syndrome is a rare hereditary inflammatory disease caused by mutations in the gene encoding the coatomer protein subunit alpha, causing excessive production of type I interferon. This case is a reminder for the general paediatrician, highlighting the relevance of the association between arthritis and lung involvement in toddlers. Case presentation We report the case of a 2-year-old girl with intermittent limping and joint pain. Her family history was relevant for a Still disease with lung involvement in the mother. Physical examination showed moderate wrist swelling. Laboratory findings on admission showed an increase in inflammatory markers, positive rheumatoid factor, antibodies antinuclear antibody (ANA) and cyclic citrullinated peptide (anti-CCP). Wrists’ ultrasound documented synovial thickening, and chest X-rays showed an unexpected severe interstitial pneumopathy. Genetic testing confirmed the diagnosis of a heterozygous mutation of the COPA gene in c.841C > T (p.R281W). Janus kinase treatment was started (baricitinib, 4 mg daily per os) with a remarkable improvement in limping and joint pain after two weeks. Conclusions In cases of recurrent arthritis with family history and multiple involvement organs, a genetic disorder should be suspected and genetic testing should be performed. Furthermore, this case suggests that therapy with jak inhibitors may be effective and safe in interferonopathies.

Published
2022

49. Association Between Disease-Modifying Therapies Prescribed to Persons with Multiple Sclerosis and Cancer: a WHO Pharmacovigilance Database Analysis

Author

Joachim Alexandre, Basile Chrétien, Olivier Dejardin, Charles Dolladille, Sophie Fedrizzi, Gilles Defer, and Laure Peyro-Saint-Paul

Subjects
Adult, Data Analysis, Male, medicine.medical_specialty, Multiple Sclerosis, Databases, Factual, World Health Organization, Cohort Studies, Pharmacovigilance, chemistry.chemical_compound, Antineoplastic Agents, Immunological, Natalizumab, Neoplasms, Internal medicine, Teriflunomide, Cancer screening, medicine, Humans, Immunologic Factors, Pharmacology (medical), Glatiramer acetate, Adverse effect, Aged, Retrospective Studies, Pharmacology, business.industry, Multiple sclerosis, Middle Aged, medicine.disease, Fingolimod, Cross-Sectional Studies, chemistry, Female, Original Article, Ocrelizumab, Neurology (clinical), business, Immunosuppressive Agents, medicine.drug
Abstract

The risk of cancer associated with persons with multiple sclerosis (pwMS) prescribed with disease modifying therapies (DMTs) is not well established. This observational, cross-sectional, pharmacovigilance cohort study examined individual case safety reports from the World Health Organization database: VigiBase®. All consecutive reports of DMTs prescribed to pwMS (alemtuzumab, dimethyl fumarate, fingolimod, glatiramer acetate, interferon-β, natalizumab, ocrelizumab, and teriflunomide), and their serious adverse event cases were eligible, excluding those reporting immunosuppressant DMTs used as anticancer therapies. The primary outcome was the multivariate odds ratio of cancer reporting (r-OR) for DMTs prescribed to pwMS after imputation of missing data. There were 5966 cancer cases from 240,993 reports of DMTs prescribed to pwMS. After adjustments on age, sex, and geographical region, natalizumab (r-OR 1.74, 95% CI 1.63–1.87), interferon-β (r-OR 1.39, 95% CI 1.30–1.49), dimethyl fumarate (r-OR 1.35, 95% CI 1.25–1.46), and fingolimod (r-OR 1.15, 95% CI 1.06–1.24) were significantly associated with a greater cancer reporting, whereas alemtuzumab, glatiramer acetate, ocrelizumab, and teriflunomide were not, in the disproportionality analysis. As exploratory analyses, upper aerodigestive tract, breast, urinary including the male genitourinary tract, and nervous system cancers were associated with natalizumab, interferon-β, and dimethyl fumarate. Fingolimod was only associated with skin cancer types. Cancer cases reporting these four DMTs prescribed to pwMS were younger in age than for non-pwMS drugs in the VigiBase® (p

Published
2021
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50. Prehospital hemodynamic optimisation is associated with a 30-day mortality decrease in patients with septic shock

Author

Vincent Bounes, Benoît Vivien, Papa-Ngalgou Gueye, Patrick Ecollan, Josiane Boularan, Basile Gilbert, Jean Pierre Tourtier, Romain Jouffroy, and Emmanuel Bloch-Laine

Subjects
Male, Emergency Medical Services, Mean arterial pressure, Resuscitation, Organ Dysfunction Scores, Urinary system, Hemodynamics, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Humans, Medicine, Aged, Retrospective Studies, business.industry, Septic shock, Proportional hazards model, Mortality rate, Hemodynamic Monitoring, 030208 emergency & critical care medicine, General Medicine, Length of Stay, medicine.disease, Shock, Septic, Blood pressure, Anesthesia, Emergency Medicine, Female, France, business
Abstract

Introduction Septic shock (SS) is characterized by low blood pressure resulting in organ failure and poor prognosis. Among SS treatments, in hospital studies reported a beneficial effect of early hemodynamic resuscitation on mortality rate. This study aims to investigate the relationship between prehospital hemodynamic optimisation and 30-day mortality in patients with SS. Methods From April 6th, 2016 to December 31th, 2019, patients with SS requiring prehospital Mobile Intensive Care Unit intervention (mICU) were included. Prehospital hemodynamic optimisation was defined as a arterial blood pressure of >65 mmHg, or >75 mmHg if previous hypertension history, at the end of the prehospital stage. Results Three hundred thirty-seven patients were retrospectively analysed. The mean age was 69 ± 15 years, and 226 patients (67%) were male. One hundred and thirty-six patients (40%) had previous hypertension history. Pulmonary, digestive and urinary infections were the suspected cause of the SS in respectively 46%, 23% and 15% of the cases. 30-day overall mortality was 30%. Prehospital hemodynamic optimisation was complete for 204 patients (61%). Cox regression analysis reports a significant association between prehospital hemodynamic optimisation and 30-day mortality (HRa = 0.52 95%CI [0.31–0.86], p = 0.01). Conclusion In this study, we report that prehospital hemodynamic optimisation is associated with a decrease in 30-day mortality in patients with SS cared for by a mICU in the prehospital setting. An individualized mean arterial pressure target, based on previous hypertension history, may be considered from the prehospital stage of SS resuscitation.

Published
2021
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