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Article ; Online: Angiotensin II Type I Receptor (AT1R): The Gate towards COVID-19-Associated Diseases.

El-Arif, George / Khazaal, Shaymaa / Farhat, Antonella / Harb, Julien / Annweiler, Cédric / Wu, Yingliang / Cao, Zhijian / Kovacic, Hervé / Abi Khattar, Ziad / Fajloun, Ziad / Sabatier, Jean-Marc

Molecules (Basel, Switzerland)

2022 Volume 27, Issue 7

Abstract: The binding of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein to its cellular receptor, the angiotensin-converting enzyme 2 (ACE2), causes its downregulation, which subsequently leads to the dysregulation of the renin- ...

Abstract	The binding of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein to its cellular receptor, the angiotensin-converting enzyme 2 (ACE2), causes its downregulation, which subsequently leads to the dysregulation of the renin-angiotensin system (RAS) in favor of the ACE-angiotensin II (Ang II)-angiotensin II type I receptor (AT1R) axis. AT1R has a major role in RAS by being involved in several physiological events including blood pressure control and electrolyte balance. Following SARS-CoV-2 infection, pathogenic episodes generated by the vasoconstriction, proinflammatory, profibrotic, and prooxidative consequences of the Ang II-AT1R axis activation are accompanied by a hyperinflammatory state (cytokine storm) and an acute respiratory distress syndrome (ARDS). AT1R, a member of the G protein-coupled receptor (GPCR) family, modulates Ang II deleterious effects through the activation of multiple downstream signaling pathways, among which are MAP kinases (ERK 1/2, JNK, p38MAPK), receptor tyrosine kinases (PDGF, EGFR, insulin receptor), and nonreceptor tyrosine kinases (Src, JAK/STAT, focal adhesion kinase (FAK)), and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. COVID-19 is well known for generating respiratory symptoms, but because ACE2 is expressed in various body tissues, several extrapulmonary pathologies are also manifested, including neurologic disorders, vasculature and myocardial complications, kidney injury, gastrointestinal symptoms, hepatic injury, hyperglycemia, and dermatologic complications. Therefore, the development of drugs based on RAS blockers, such as angiotensin II receptor blockers (ARBs), that inhibit the damaging axis of the RAS cascade may become one of the most promising approaches for the treatment of COVID-19 in the near future. We herein review the general features of AT1R, with a special focus on the receptor-mediated activation of the different downstream signaling pathways leading to specific cellular responses. In addition, we provide the latest insights into the roles of AT1R in COVID-19 outcomes in different systems of the human body, as well as the role of ARBs as tentative pharmacological agents to treat COVID-19.
MeSH term(s)	Angiotensin I ; Angiotensin II ; Angiotensin Receptor Antagonists/pharmacology ; Angiotensin-Converting Enzyme 2 ; Angiotensin-Converting Enzyme Inhibitors/pharmacology ; Humans ; Receptor, Angiotensin, Type 1/metabolism ; SARS-CoV-2 ; COVID-19 Drug Treatment
Chemical Substances	AGTR1 protein, human ; Angiotensin Receptor Antagonists ; Angiotensin-Converting Enzyme Inhibitors ; Receptor, Angiotensin, Type 1 ; Angiotensin II (11128-99-7) ; Angiotensin I (9041-90-1) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23)
Language	English
Publishing date	2022-03-22
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	1413402-0
ISSN	1420-3049 ; 1431-5165 ; 1420-3049
ISSN (online)	1420-3049
ISSN	1431-5165 ; 1420-3049
DOI	10.3390/molecules27072048
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Article ; Online: The Renin-Angiotensin System: A Key Role in SARS-CoV-2-Induced COVID-19.

El-Arif, George / Farhat, Antonella / Khazaal, Shaymaa / Annweiler, Cédric / Kovacic, Hervé / Wu, Yingliang / Cao, Zhijian / Fajloun, Ziad / Khattar, Ziad Abi / Sabatier, Jean Marc

Molecules (Basel, Switzerland)

2021 Volume 26, Issue 22

Abstract: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), was first identified in Eastern Asia (Wuhan, China) in December 2019. The virus then spread to Europe and across all ... ...

Abstract	The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), was first identified in Eastern Asia (Wuhan, China) in December 2019. The virus then spread to Europe and across all continents where it has led to higher mortality and morbidity, and was declared as a pandemic by the World Health Organization (WHO) in March 2020. Recently, different vaccines have been produced and seem to be more or less effective in protecting from COVID-19. The renin-angiotensin system (RAS), an essential enzymatic cascade involved in maintaining blood pressure and electrolyte balance, is involved in the pathogenicity of COVID-19, since the angiotensin-converting enzyme II (ACE2) acts as the cellular receptor for SARS-CoV-2 in many human tissues and organs. In fact, the viral entrance promotes a downregulation of ACE2 followed by RAS balance dysregulation and an overactivation of the angiotensin II (Ang II)-angiotensin II type I receptor (AT1R) axis, which is characterized by a strong vasoconstriction and the induction of the profibrotic, proapoptotic and proinflammatory signalizations in the lungs and other organs. This mechanism features a massive cytokine storm, hypercoagulation, an acute respiratory distress syndrome (ARDS) and subsequent multiple organ damage. While all individuals are vulnerable to SARS-CoV-2, the disease outcome and severity differ among people and countries and depend on a dual interaction between the virus and the affected host. Many studies have already pointed out the importance of host genetic polymorphisms (especially in the RAS) as well as other related factors such age, gender, lifestyle and habits and underlying pathologies or comorbidities (diabetes and cardiovascular diseases) that could render individuals at higher risk of infection and pathogenicity. In this review, we explore the correlation between all these risk factors as well as how and why they could account for severe post-COVID-19 complications.
MeSH term(s)	COVID-19/genetics ; COVID-19/virology ; Habits ; Humans ; Life Style ; Polymorphism, Genetic ; Renin-Angiotensin System/genetics ; SARS-CoV-2/physiology ; Sex Factors
Language	English
Publishing date	2021-11-17
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	1413402-0
ISSN	1420-3049 ; 1431-5165 ; 1420-3049
ISSN (online)	1420-3049
ISSN	1431-5165 ; 1420-3049
DOI	10.3390/molecules26226945
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Article ; Online: Angiotensin II Type I Receptor (AT1R)

George El-Arif / Shaymaa Khazaal / Antonella Farhat / Julien Harb / Cédric Annweiler / Yingliang Wu / Zhijian Cao / Hervé Kovacic / Ziad Abi Khattar / Ziad Fajloun / Jean-Marc Sabatier

Molecules, Vol 27, Iss 2048, p

The Gate towards COVID-19-Associated Diseases

2022 Volume 2048

Abstract	The binding of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein to its cellular receptor, the angiotensin-converting enzyme 2 (ACE2), causes its downregulation, which subsequently leads to the dysregulation of the renin–angiotensin system (RAS) in favor of the ACE–angiotensin II (Ang II)–angiotensin II type I receptor (AT1R) axis. AT1R has a major role in RAS by being involved in several physiological events including blood pressure control and electrolyte balance. Following SARS-CoV-2 infection, pathogenic episodes generated by the vasoconstriction, proinflammatory, profibrotic, and prooxidative consequences of the Ang II–AT1R axis activation are accompanied by a hyperinflammatory state (cytokine storm) and an acute respiratory distress syndrome (ARDS). AT1R, a member of the G protein-coupled receptor (GPCR) family, modulates Ang II deleterious effects through the activation of multiple downstream signaling pathways, among which are MAP kinases (ERK 1/2, JNK, p38MAPK), receptor tyrosine kinases (PDGF, EGFR, insulin receptor), and nonreceptor tyrosine kinases (Src, JAK/STAT, focal adhesion kinase (FAK)), and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. COVID-19 is well known for generating respiratory symptoms, but because ACE2 is expressed in various body tissues, several extrapulmonary pathologies are also manifested, including neurologic disorders, vasculature and myocardial complications, kidney injury, gastrointestinal symptoms, hepatic injury, hyperglycemia, and dermatologic complications. Therefore, the development of drugs based on RAS blockers, such as angiotensin II receptor blockers (ARBs), that inhibit the damaging axis of the RAS cascade may become one of the most promising approaches for the treatment of COVID-19 in the near future. We herein review the general features of AT1R, with a special focus on the receptor-mediated activation of the different downstream signaling pathways leading to specific cellular responses. In addition, we provide the ...
Keywords	SARS-CoV-2 ; COVID-19 ; Ang II–AT1R axis ; ACE2 ; AT1R downstream signaling pathways ; multiple system damages ; Organic chemistry ; QD241-441
Subject code	610
Language	English
Publishing date	2022-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The Renin-Angiotensin System

George El-Arif / Antonella Farhat / Shaymaa Khazaal / Cédric Annweiler / Hervé Kovacic / Yingliang Wu / Zhijian Cao / Ziad Fajloun / Ziad Abi Khattar / Jean Marc Sabatier

Molecules, Vol 26, Iss 6945, p

A Key Role in SARS-CoV-2-Induced COVID-19

2021 Volume 6945

Abstract	The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), was first identified in Eastern Asia (Wuhan, China) in December 2019. The virus then spread to Europe and across all continents where it has led to higher mortality and morbidity, and was declared as a pandemic by the World Health Organization (WHO) in March 2020. Recently, different vaccines have been produced and seem to be more or less effective in protecting from COVID-19. The renin–angiotensin system (RAS), an essential enzymatic cascade involved in maintaining blood pressure and electrolyte balance, is involved in the pathogenicity of COVID-19, since the angiotensin-converting enzyme II (ACE2) acts as the cellular receptor for SARS-CoV-2 in many human tissues and organs. In fact, the viral entrance promotes a downregulation of ACE2 followed by RAS balance dysregulation and an overactivation of the angiotensin II (Ang II)–angiotensin II type I receptor (AT1R) axis, which is characterized by a strong vasoconstriction and the induction of the profibrotic, proapoptotic and proinflammatory signalizations in the lungs and other organs. This mechanism features a massive cytokine storm, hypercoagulation, an acute respiratory distress syndrome (ARDS) and subsequent multiple organ damage. While all individuals are vulnerable to SARS-CoV-2, the disease outcome and severity differ among people and countries and depend on a dual interaction between the virus and the affected host. Many studies have already pointed out the importance of host genetic polymorphisms (especially in the RAS) as well as other related factors such age, gender, lifestyle and habits and underlying pathologies or comorbidities (diabetes and cardiovascular diseases) that could render individuals at higher risk of infection and pathogenicity. In this review, we explore the correlation between all these risk factors as well as how and why they could account for severe post-COVID-19 complications.
Keywords	SARS-CoV-2 ; COVID-19 ; ACE-2 ; Ang II/AT1R axis ; RAS imbalance ; cytokine storm ; Organic chemistry ; QD241-441
Subject code	610
Language	English
Publishing date	2021-11-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Inhibiting Interleukin 36 Receptor Signaling Reduces Fibrosis in Mice With Chronic Intestinal Inflammation.

Scheibe, Kristina / Kersten, Christina / Schmied, Anabel / Vieth, Michael / Primbs, Tatjana / Carlé, Birgitta / Knieling, Ferdinand / Claussen, Jing / Klimowicz, Alexander C / Zheng, Jie / Baum, Patrick / Meyer, Sebastian / Schürmann, Sebastian / Friedrich, Oliver / Waldner, Maximilian J / Rath, Timo / Wirtz, Stefan / Kollias, George / Ekici, Arif B /

Atreya, Raja / Raymond, Ernest L / Mbow, M Lamine / Neurath, Markus F / Neufert, Clemens

Gastroenterology

2018 Volume 156, Issue 4, Page(s) 1082–1097.e11

Abstract: Background & aims: Intestinal fibrosis is a long-term complication in inflammatory bowel diseases (IBD) that frequently results in functional damage, bowel obstruction, and surgery. Interleukin (IL) 36 is a group of cytokines in the IL1 family with ... ...

Abstract	Background & aims: Intestinal fibrosis is a long-term complication in inflammatory bowel diseases (IBD) that frequently results in functional damage, bowel obstruction, and surgery. Interleukin (IL) 36 is a group of cytokines in the IL1 family with inflammatory effects. We studied the expression of IL36 and its receptor, interleukin 1 receptor like 2 (IL1RL2 or IL36R) in the development of intestinal fibrosis in human tissues and mice. Methods: We obtained intestinal tissues from 92 patients with Crohn's disease (CD), 48 patients with ulcerative colitis, and 26 patients without inflammatory bowel diseases (control individuals). Tissues were analyzed by histology to detect fibrosis and by immunohistochemistry to determine the distribution of fibroblasts and levels of IL36R ligands. Human and mouse fibroblasts were incubated with IL36 or control medium, and transcriptome-wide RNA sequences were analyzed. Mice were given neutralizing antibodies against IL36R, and we studied intestinal tissues from Il1rl2 Results: Mucosal and submucosal tissue from patients with CD or ulcerative colitis had higher levels of collagens, including type VI collagen, compared with tissue from control individuals. In tissues from patients with fibrostenotic CD, significantly higher levels of IL36A were noted, which correlated with high numbers of activated fibroblasts that expressed α-smooth muscle actin. IL36R activation of mouse and human fibroblasts resulted in expression of genes that regulate fibrosis and tissue remodeling, as well as expression of collagen type VI. Il1rl2 Conclusion: We found higher levels of IL36A in fibrotic intestinal tissues from patients with IBD compared with control individuals. IL36 induced expression of genes that regulate fibrogenesis in fibroblasts. Inhibition or knockout of the IL36R gene in mice reduces chronic colitis and intestinal fibrosis. Agents designed to block IL36R signaling could be developed for prevention and treatment of intestinal fibrosis in patients with IBD.
MeSH term(s)	Actins/metabolism ; Animals ; Antibodies, Neutralizing/pharmacology ; Case-Control Studies ; Cells, Cultured ; Colitis/chemically induced ; Colitis/pathology ; Colitis, Ulcerative/metabolism ; Colitis, Ulcerative/pathology ; Collagen Type VI/metabolism ; Colon/pathology ; Crohn Disease/metabolism ; Crohn Disease/pathology ; Dextran Sulfate ; Fibroblasts/drug effects ; Fibrosis ; Gene Expression/drug effects ; Gene Expression Profiling ; Humans ; Interleukin-1/metabolism ; Interleukin-1/pharmacology ; Intestinal Mucosa/pathology ; Intestine, Small/pathology ; Ligands ; Mice ; Mice, Knockout ; Receptors, Interleukin-1/antagonists & inhibitors ; Receptors, Interleukin-1/genetics ; Receptors, Interleukin-1/metabolism ; Signal Transduction ; Transcriptome ; Trinitrobenzenesulfonic Acid
Chemical Substances	ACTA2 protein, human ; Actins ; Antibodies, Neutralizing ; Collagen Type VI ; IL1RL2 protein, human ; IL36A protein, human ; Interleukin-1 ; Ligands ; Receptors, Interleukin-1 ; alpha-smooth muscle actin, mouse ; interleukin 36, human ; interleukin-36 receptor, mouse ; interleukin-36, mouse ; Trinitrobenzenesulfonic Acid (8T3HQG2ZC4) ; Dextran Sulfate (9042-14-2)
Language	English
Publishing date	2018-11-16
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80112-4
ISSN	1528-0012 ; 0016-5085
ISSN (online)	1528-0012
ISSN	0016-5085
DOI	10.1053/j.gastro.2018.11.029
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Article ; Online: Pleiotropy-guided transcriptome imputation from normal and tumor tissues identifies candidate susceptibility genes for breast and ovarian cancer.

Kar, Siddhartha P / Considine, Daniel P C / Tyrer, Jonathan P / Plummer, Jasmine T / Chen, Stephanie / Dezem, Felipe S / Barbeira, Alvaro N / Rajagopal, Padma S / Rosenow, Will T / Moreno, Fernando / Bodelon, Clara / Chang-Claude, Jenny / Chenevix-Trench, Georgia / deFazio, Anna / Dörk, Thilo / Ekici, Arif B / Ewing, Ailith / Fountzilas, George / Goode, Ellen L /

Hartman, Mikael / Heitz, Florian / Hillemanns, Peter / Høgdall, Estrid / Høgdall, Claus K / Huzarski, Tomasz / Jensen, Allan / Karlan, Beth Y / Khusnutdinova, Elza / Kiemeney, Lambertus A / Kjaer, Susanne K / Klapdor, Rüdiger / Köbel, Martin / Li, Jingmei / Liebrich, Clemens / May, Taymaa / Olsson, Håkan / Permuth, Jennifer B / Peterlongo, Paolo / Radice, Paolo / Ramus, Susan J / Riggan, Marjorie J / Risch, Harvey A / Saloustros, Emmanouil / Simard, Jacques / Szafron, Lukasz M / Titus, Linda / Thompson, Cheryl L / Vierkant, Robert A / Winham, Stacey J / Zheng, Wei / Doherty, Jennifer A / Berchuck, Andrew / Lawrenson, Kate / Im, Hae Kyung / Manichaikul, Ani W / Pharoah, Paul D P / Gayther, Simon A / Schildkraut, Joellen M

HGG advances

2021 Volume 2, Issue 3

Abstract: Familial, sequencing, and genome-wide association studies (GWASs) and genetic correlation analyses have progressively unraveled the shared or pleiotropic germline genetics of breast and ovarian cancer. In this study, we aimed to leverage this shared ... ...

Abstract	Familial, sequencing, and genome-wide association studies (GWASs) and genetic correlation analyses have progressively unraveled the shared or pleiotropic germline genetics of breast and ovarian cancer. In this study, we aimed to leverage this shared germline genetics to improve the power of transcriptome-wide association studies (TWASs) to identify candidate breast cancer and ovarian cancer susceptibility genes. We built gene expression prediction models using the PrediXcan method in 681 breast and 295 ovarian tumors from The Cancer Genome Atlas and 211 breast and 99 ovarian normal tissue samples from the Genotype-Tissue Expression project and integrated these with GWAS meta-analysis data from the Breast Cancer Association Consortium (122,977 cases/105,974 controls) and the Ovarian Cancer Association Consortium (22,406 cases/40,941 controls). The integration was achieved through application of a pleiotropy-guided conditional/conjunction false discovery rate (FDR) approach in the setting of a TWASs. This identified 14 candidate breast cancer susceptibility genes spanning 11 genomic regions and 8 candidate ovarian cancer susceptibility genes spanning 5 genomic regions at conjunction FDR < 0.05 that were >1 Mb away from known breast and/or ovarian cancer susceptibility loci. We also identified 38 candidate breast cancer susceptibility genes and 17 candidate ovarian cancer susceptibility genes at conjunction FDR < 0.05 at known breast and/or ovarian susceptibility loci. The 22 genes identified by our cross-cancer analysis represent promising candidates that further elucidate the role of the transcriptome in mediating germline breast and ovarian cancer risk.
Language	English
Publishing date	2021-06-16
Publishing country	United States
Document type	Journal Article
ISSN	2666-2477
ISSN (online)	2666-2477
DOI	10.1016/j.xhgg.2021.100042
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Article: Global Practice Patterns and Variations in the Medical and Surgical Management of Non-Obstructive Azoospermia: Results of a World-Wide Survey, Guidelines and Expert Recommendations.

Rambhatla, Amarnath / Shah, Rupin / Ziouziou, Imad / Kothari, Priyank / Salvio, Gianmaria / Gul, Murat / Hamoda, Taha / Kavoussi, Parviz / Atmoko, Widi / Toprak, Tuncay / Birowo, Ponco / Ko, Edmund / Arafa, Mohamed / Ghayda, Ramy Abou / Karthikeyan, Vilvapathy Senguttuvan / Russo, Giorgio Ivan / Pinggera, Germar-Michael / Chung, Eric / Harraz, Ahmed M /

Martinez, Marlon / Phuoc, Nguyen Ho Vinh / Tadros, Nicholas / Saleh, Ramadan / Savira, Missy / Colpi, Giovanni M / Zohdy, Wael / Pescatori, Edoardo / Park, Hyun Jun / Fukuhara, Shinichiro / Tsujimura, Akira / Rojas-Cruz, Cesar / Marino, Angelo / Mak, Siu King / Amar, Edouard / Ibrahim, Wael / Sindhwani, Puneet / Alhathal, Naif / Busetto, Gian Maria / Al Hashimi, Manaf / El-Sakka, Ahmed / Ramazan, Asci / Dimitriadis, Fotios / Timpano, Massimiliano / Jezek, Davor / Altay, Baris / Zylbersztejn, Daniel Suslik / Wong, Michael Yc / Moon, Du Geon / Wyns, Christine / Gamidov, Safar / Akhavizadegan, Hamed / Franceschelli, Alessandro / Aydos, Kaan / Quang, Nguyen / Ashour, Shedeed / Al Dayel, Adel / Al-Marhoon, Mohammed S / Micic, Sava / Binsaleh, Saleh / Hussein, Alayman / Elbardisi, Haitham / Mostafa, Taymour / Ramsay, Jonathan / Zachariou, Athanasios / Abdelrahman, Islam Fathy Soliman / Rajmil, Osvaldo / Kalkanli, Arif / Molina, Juan Manuel Corral / Bocu, Kadir / Duarsa, Gede Wirya Kusuma / Çeker, Gökhan / Serefoglu, Ege Can / Bahar, Fahmi / Gherabi, Nazim / Kuroda, Shinnosuke / Bouzouita, Abderrazak / Gudeloglu, Ahmet / Ceyhan, Erman / Hasan, Mohamed Saeed Mohamed / Musa, Muhammad Ujudud / Motawi, Ahmad / Cho, Chak-Lam / Taniguchi, Hisanori / Ho, Christopher Chee Kong / Vazquez, Jesus Fernando Solorzano / Mutambirwa, Shingai / Gungor, Nur Dokuzeylul / Bendayan, Marion / Giulioni, Carlo / Baser, Aykut / Falcone, Marco / Boeri, Luca / Blecher, Gideon / Kheradmand, Alireza / Sethupathy, Tamilselvi / Adriansjah, Ricky / Narimani, Nima / Konstantinidis, Charalampos / Nguyen, Tuan Thanh / Japari, Andrian / Dolati, Parisa / Singh, Keerti / Ozer, Cevahir / Sarikaya, Selcuk / Sheibak, Nadia / Bosco, Ndagijimana Jean / Özkent, Mehmet Serkan / Le, Sang Thanh / Sokolakis, Ioannis / Katz, Darren / Smith, Ryan / Truong, Manh Nguyen / Le, Tan V / Huang, Zhongwei / Deger, Muslim Dogan / Arslan, Umut / Calik, Gokhan / Franco, Giorgio / Rashed, Ayman / Kahraman, Oguzhan / Andreadakis, Sotiris / Putra, Rosadi / Balercia, Giancarlo / Khalafalla, Kareim / Cannarella, Rossella / Tuân, Anh Ðăng / El Meliegy, Amr / Zilaitiene, Birute / Ramirez, Marlene Lizbeth Zamora / Giacone, Filippo / Calogero, Aldo E / Makarounis, Konstantinos / Jindal, Sunil / Hoai, Bac Nguyen / Banthia, Ravi / Peña, Marcelo Rodriguez / Moorthy, Dharani / Adamyan, Aram / Kulaksiz, Deniz / Kandil, Hussein / Sofikitis, Nikolaos / Salzano, Ciro / Jungwirth, Andreas / Banka, Surendra Reddy / Mierzwa, Tiago Cesar / Turunç, Tahsin / Jain, Divyanu / Avoyan, Armen / Salacone, Pietro / Kadıoğlu, Ateş / Gupta, Chirag / Lin, Haocheng / Shamohammadi, Iman / Mogharabian, Nasser / Barrett, Trenton / Danacıoğlu, Yavuz Onur / Crafa, Andrea / Daoud, Salima / Malhotra, Vineet / Almardawi, Abdulmalik / Selim, Osama Mohamed / Moussa, Mohamad / Haghdani, Saeid / Duran, Mesut Berkan / Kunz, Yannic / Preto, Mirko / Eugeni, Elena / Nguyen, Thang / Elshahid, Ahmed Rashad / Suyono, Seso Sulijaya / Parikesit, Dyandra / Nada, Essam / Orozco, Eduardo Gutiérrez / Boitrelle, Florence / Trang, Nguyen Thi Minh / Jamali, Mounir / Nair, Raju / Ruzaev, Mikhail / Gadda, Franco / Thomas, Charalampos / Ferreira, Raphael Henrique / Gul, Umit / Maruccia, Serena / Kanbur, Ajay / Kinzikeeva, Ella / Abumelha, Saad Mohammed / Kosgi, Raghavender / Gokalp, Fatih / Soebadi, Mohammad Ayodhia / Paul, Gustavo Marquesine / Sajadi, Hesamoddin / Gupte, Deepak / Ambar, Rafael F / Sogutdelen, Emrullah / Singla, Karun / Basukarno, Ari / Kim, Shannon Hee Kyung / Gilani, Mohammad Ali Sadighi / Nagao, Koichi / Brodjonegoro, Sakti Ronggowardhana / Rezano, Andri / Elkhouly, Mohamed / Mazzilli, Rossella / Farsi, Hasan M A / Ba, Hung Nguyen / Alali, Hamed / Kafetzis, Dimitrios / Long, Tran Quang Tien / Alsaid, Sami / Cuong, Hoang Bao Ngoc / Oleksandr, Knigavko / Mustafa, Akhmad / Acosta, Herik / Pai, Hrishikesh / Şahin, Bahadır / Arianto, Eko / Teo, Colin / Jayaprakash, Sanjay Prakash / Rachman, Rinaldo Indra / Yenice, Mustafa Gurkan / Sefrioui, Omar / Priyadarshi, Shivam / Tanic, Marko / Alfatlaw, Noor Kareem / Rizaldi, Fikri / Vishwakarma, Ranjit B / Kanakis, George / Cherian, Dinesh Thomas / Lee, Joe / Galstyan, Raisa / Keskin, Hakan / Wurzacher, Janan / Seno, Doddy Hami / Noegroho, Bambang S / Margiana, Ria / Javed, Qaisar / Castiglioni, Fabrizio / Tanwar, Raman / Puigvert, Ana / Kaya, Coşkun / Purnomo, Medianto / Yazbeck, Chadi / Amir, Azwar / Borges, Edson / Bellavia, Marina / Deswanto, Isaac Ardianson / Kv, Vinod / Liguori, Giovanni / Minh, Dang Hoang / Siddiqi, Kashif / Colombo, Fulvio / Zini, Armand / Patel, Niket / Çayan, Selahittin / Al-Kawaz, Ula / Ragab, Maged / Hebrard, Guadalupe Hernández / de la Rosette, Jean / Efesoy, Ozan / Hoffmann, Ivan / Teixeira, Thiago Afonso / Saylam, Barış / Delgadillo, Daniela / Agarwal, Ashok

The world journal of men's health

2024

Abstract: Purpose: Non-obstructive azoospermia (NOA) is a common, but complex problem, with multiple therapeutic options and a lack of clear guidelines. Hence, there is considerable controversy and marked variation in the management of NOA. This survey evaluates ... ...

Abstract	Purpose: Non-obstructive azoospermia (NOA) is a common, but complex problem, with multiple therapeutic options and a lack of clear guidelines. Hence, there is considerable controversy and marked variation in the management of NOA. This survey evaluates contemporary global practices related to medical and surgical management for patients with NOA. Materials and methods: A 56-question online survey covering various aspects of the evaluation and management of NOA was sent to specialists around the globe. This paper analyzes the results of the second half of the survey dealing with the management of NOA. Results have been compared to current guidelines, and expert recommendations have been provided using a Delphi process. Results: Participants from 49 countries submitted 336 valid responses. Hormonal therapy for 3 to 6 months was suggested before surgical sperm retrieval (SSR) by 29.6% and 23.6% of participants for normogonadotropic hypogonadism and hypergonadotropic hypogonadism respectively. The SSR rate was reported as 50.0% by 26.0% to 50.0% of participants. Interestingly, 46.0% reported successful SSR in <10% of men with Klinefelter syndrome and 41.3% routinely recommended preimplantation genetic testing. Varicocele repair prior to SSR is recommended by 57.7%. Half of the respondents (57.4%) reported using ultrasound to identify the most vascularized areas in the testis for SSR. One-third proceed directly to microdissection testicular sperm extraction (mTESE) in every case of NOA while others use a staged approach. After a failed conventional TESE, 23.8% wait for 3 months, while 33.1% wait for 6 months before proceeding to mTESE. The cut-off of follicle-stimulating hormone for positive SSR was reported to be 12-19 IU/mL by 22.5% of participants and 20-40 IU/mL by 27.8%, while 31.8% reported no upper limit. Conclusions: This is the largest survey to date on the real-world medical and surgical management of NOA by reproductive experts. It demonstrates a diverse practice pattern and highlights the need for evidence-based international consensus guidelines.
Language	English
Publishing date	2024-04-04
Publishing country	Korea (South)
Document type	Journal Article
ZDB-ID	2719786-4
ISSN	2287-4690 ; 2287-4208
ISSN (online)	2287-4690
ISSN	2287-4208
DOI	10.5534/wjmh.230339
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Article: Global Practice Patterns in the Evaluation of Non-Obstructive Azoospermia: Results of a World-Wide Survey and Expert Recommendations.

Shah, Rupin / Rambhatla, Amarnath / Atmoko, Widi / Martinez, Marlon / Ziouziou, Imad / Kothari, Priyank / Tadros, Nicholas / Phuoc, Nguyen Ho Vinh / Kavoussi, Parviz / Harraz, Ahmed / Salvio, Gianmaria / Gul, Murat / Hamoda, Taha / Toprak, Tuncay / Birowo, Ponco / Ko, Edmund / Arafa, Mohamed / Ghayda, Ramy Abou / Karthikeyan, Vilvapathy Senguttuvan /

Saleh, Ramadan / Russo, Giorgio Ivan / Pinggera, Germar-Michael / Chung, Eric / Savira, Missy / Colpi, Giovanni M / Zohdy, Wael / Pescatori, Edoardo / Park, Hyun Jun / Fukuhara, Shinichiro / Tsujimura, Akira / Rojas-Cruz, Cesar / Marino, Angelo / Mak, Siu King / Amar, Edouard / Ibrahim, Wael / Sindhwani, Puneet / Alhathal, Naif / Busetto, Gian Maria / Al Hashimi, Manaf / El-Sakka, Ahmed / Ramazan, Asci / Dimitriadis, Fotios / Timpano, Massimiliano / Jezek, Davor / Altay, Baris / Zylbersztejn, Daniel Suslik / Wong, Michael Yc / Moon, Du Geon / Wyns, Christine / Gamidov, Safar / Akhavizadegan, Hamed / Franceschelli, Alessandro / Aydos, Kaan / Quang, Vinh Nguyen / Ashour, Shedeed / Al Dayel, Adel / Al-Marhoon, Mohamed S / Micic, Sava / Binsaleh, Saleh / Hussein, Alayman / Elbardisi, Haitham / Mostafa, Taymour / Taha, Emad / Ramsay, Jonathan / Zachariou, Athanasios / Abdelrahman, Islam Fathy Soliman / Rajmil, Osvaldo / Kalkanli, Arif / Molina, Juan Manuel Corral / Bocu, Kadir / Duarsa, Gede Wirya Kusuma / Ceker, Gokhan / Serefoglu, Ege Can / Bahar, Fahmi / Gherabi, Nazim / Kuroda, Shinnosuke / Bouzouita, Abderrazak / Gudeloglu, Ahmet / Ceyhan, Erman / Hasan, Mohamed Saeed Mohamed / Musa, Muhammad Ujudud / Motawi, Ahmad / Chak-Lam, Cho / Taniguchi, Hisanori / Ho, Christopher Chee Kong / Vazquez, Jesus Fernando Solorzano / Mutambirwa, Shingai / Gungor, Nur Dokuzeylul / Bendayan, Marion / Giulioni, Carlo / Baser, Aykut / Falcone, Marco / Boeri, Luca / Blecher, Gideon / Kheradmand, Alireza / Sethupathy, Tamilselvi / Adriansjah, Ricky / Narimani, Nima / Konstantinidis, Charalampos / Nguyen, Tuan Thanh / Japari, Andrian / Dolati, Parisa / Singh, Keerti / Ozer, Cevahir / Sarikaya, Selcuk / Sheibak, Nadia / Bosco, Ndagijimana Jean / Özkent, Mehmet Serkan / Le, Sang Thanh / Sokolakis, Ioannis / Katz, Darren / Smith, Ryan / Truong, Manh Nguyen / Le, Tan V / Huang, Zhongwei / Deger, Muslim Dogan / Arslan, Umut / Calik, Gokhan / Franco, Giorgio / Rashed, Ayman / Kahraman, Oguzhan / Andreadakis, Sotiris / Putra, Rosadi / Balercia, Giancarlo / Khalafalla, Kareim / Cannarella, Rossella / Tuân, Anh Ðăng / El Meliegy, Amr / Zilaitiene, Birute / Ramirez, Marlene Lizbeth Zamora / Giacone, Filippo / Calogero, Aldo E / Makarounis, Konstantinos / Jindal, Sunil / Hoai, Bac Nguyen / Banthia, Ravi / Peña, Marcelo Rodriguez / Moorthy, Dharani / Adamyan, Aram / Kulaksiz, Deniz / Kandil, Hussein / Sofikitis, Nikolaos / Salzano, Ciro / Jungwirth, Andreas / Banka, Surendra Reddy / Mierzwa, Tiago Cesar / Turunç, Tahsin / Jain, Divyanu / Avoyan, Armen / Salacone, Pietro / Kadıoğlu, Ateş / Gupta, Chirag / Lin, Haocheng / Shamohammadi, Iman / Mogharabian, Nasser / Barrett, Trenton / Danacıoğlu, Yavuz Onur / Crafa, Andrea / Daoud, Salima / Malhotra, Vineet / Almardawi, Abdulmalik / Selim, Osama Mohamed / Moussa, Mohamad / Haghdani, Saeid / Duran, Mesut Berkan / Kunz, Yannic / Preto, Mirko / Eugeni, Elena / Nguyen, Thang / Elshahid, Ahmed Rashad / Suyono, Seso Sulijaya / Parikesit, Dyandra / Nada, Essam / Orozco, Eduardo Gutiérrez / Boitrelle, Florence / Trang, Nguyen Thi Minh / Jamali, Mounir / Nair, Raju / Ruzaev, Mikhail / Gadda, Franco / Thomas, Charalampos / Ferreira, Raphael Henrique / Gul, Umit / Maruccia, Serena / Kanbur, Ajay / Kinzikeeva, Ella / Abumelha, Saad / Quang, Nguyen / Kosgi, Raghavender / Gokalp, Fatih / Soebadi, Mohammad Ayodhia / Paul, Gustavo Marquesine / Sajadi, Hesamoddin / Gupte, Deepak / Ambar, Rafael F / Sogutdelen, Emrullah / Singla, Karun / Basurkano, Ari / Kim, Shannon Hee Kyung / Gilani, Mohammad Ali Sadighi / Nagao, Koichi / Brodjonegoro, Sakti Ronggowardhana / Rezano, Andri / Elkhouly, Mohamed / Mazzilli, Rossella / Farsi, Hasan M A / Ba, Hung Nguyen / Alali, Hamed / Kafetzis, Dimitrios / Long, Tran Quang Tien / Alsaid, Sami / Cuong, Hoang Bao Ngoc / Oleksandr, Knigavko / Mustafa, Akhmad / Acosta, Herik / Pai, Hrishikesh / Şahin, Bahadır / Arianto, Eko / Teo, Colin / Jayaprakash, Sanjay Prakash / Rachman, Rinaldo Indra / Yenice, Mustafa Gurkan / Sefrioui, Omar / Paghdar, Smit / Priyadarshi, Shivam / Tanic, Marko / Alfatlawy, Noor Kareem / Rizaldi, Fikri / Vishwakarma, Ranjit B / Kanakis, George / Cherian, Dinesh Thomas / Lee, Joe / Galstyan, Raisa / Keskin, Hakan / Wurzacher, Jana / Seno, Doddy Hami / Noegroho, Bambang S / Margiana, Ria / Javed, Qaisar / Castiglioni, Fabrizio / Tanwar, Raman / Puigvert, Ana / Kaya, Coşkun / Purnomo, Medianto / Yazbeck, Chadi / Amir, Azwar / Borges, Edson / Bellavia, Marina / Deswanto, Isaac Ardianson / V, Vinod K / Liguori, Giovanni / Minh, Dang Hoang / Siddiqi, Kashif / Colombo, Fulvio / Zini, Armand / Patel, Niket / Çayan, Selahittin / Al-Kawaz, Ula / Ragab, Maged / Hebrard, Guadalupe Hernández / Hoffmann, Ivan / Efesoy, Ozan / Saylam, Barış / Agarwal, Ashok

The world journal of men's health

2024

Abstract: Purpose: Non-obstructive azoospermia (NOA) represents the persistent absence of sperm in ejaculate without obstruction, stemming from diverse disease processes. This survey explores global practices in NOA diagnosis, comparing them with guidelines and ... ...

Abstract	Purpose: Non-obstructive azoospermia (NOA) represents the persistent absence of sperm in ejaculate without obstruction, stemming from diverse disease processes. This survey explores global practices in NOA diagnosis, comparing them with guidelines and offering expert recommendations. Materials and methods: A 56-item questionnaire survey on NOA diagnosis and management was conducted globally from July to September 2022. This paper focuses on part 1, evaluating NOA diagnosis. Data from 367 participants across 49 countries were analyzed descriptively, with a Delphi process used for expert recommendations. Results: Of 336 eligible responses, most participants were experienced attending physicians (70.93%). To diagnose azoospermia definitively, 81.7% requested two semen samples. Commonly ordered hormone tests included serum follicle-stimulating hormone (FSH) (97.0%), total testosterone (92.9%), and luteinizing hormone (86.9%). Genetic testing was requested by 66.6%, with karyotype analysis (86.2%) and Y chromosome microdeletions (88.3%) prevalent. Diagnostic testicular biopsy, distinguishing obstructive azoospermia (OA) from NOA, was not performed by 45.1%, while 34.6% did it selectively. Differentiation relied on physical examination (76.1%), serum hormone profiles (69.6%), and semen tests (68.1%). Expectations of finding sperm surgically were higher in men with normal FSH, larger testes, and a history of sperm in ejaculate. Conclusions: This expert survey, encompassing 367 participants from 49 countries, unveils congruence with recommended guidelines in NOA diagnosis. However, noteworthy disparities in practices suggest a need for evidence-based, international consensus guidelines to standardize NOA evaluation, addressing existing gaps in professional recommendations.
Language	English
Publishing date	2024-04-03
Publishing country	Korea (South)
Document type	Journal Article
ZDB-ID	2719786-4
ISSN	2287-4690 ; 2287-4208
ISSN (online)	2287-4690
ISSN	2287-4208
DOI	10.5534/wjmh.230333
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Article ; Online: Effect of the COVID-19 pandemic on surgery for indeterminate thyroid nodules (THYCOVID): a retrospective, international, multicentre, cross-sectional study.

Medas, Fabio / Dobrinja, Chiara / Al-Suhaimi, Ebtesam Abdullah / Altmeier, Julia / Anajar, Said / Arikan, Akif Enes / Azaryan, Irina / Bains, Lovenish / Basili, Giancarlo / Bolukbasi, Hakan / Bononi, Marco / Borumandi, Farzad / Bozan, Mehmet Buğra / Brenta, Gabriela / Brunaud, Laurent / Brunner, Maximilian / Buemi, Antoine / Canu, Gian Luigi / Cappellacci, Federico /

Cartwright, Sara Burchfield / Castells Fusté, Ignasi / Cavalheiro, Beatriz / Cavallaro, Giuseppe / Chala, Andres / Chan, Shun Yan Bryant / Chaplin, John / Cheema, Mustafa Sajjad / Chiapponi, Costanza / Chiofalo, Maria Grazia / Chrysos, Emmanuel / D'Amore, Annamaria / de Cillia, Michael / De Crea, Carmela / de Manzini, Nicolò / de Matos, Leandro Luongo / De Pasquale, Loredana / Del Rio, Paolo / Demarchi, Marco Stefano / Dhiwakar, Muthuswamy / Donatini, Gianluca / Dora, Jose Miguel / D'Orazi, Valerio / Doulatram Gamgaram, Viyey Kishore / Eismontas, Vitalijus / Kabiri, El Hassane / El Malki, Hadj Omar / Elzahaby, Islam / Enciu, Octavian / Eskander, Antoine / Feroci, Francesco / Figueroa-Bohorquez, David / Filis, Dimitrios / François, Gorostidi / Frías-Fernández, Pedro / Gamboa-Dominguez, Armando / Genc, Volkan / Giordano, Davide / Gómez-Pedraza, Antonio / Graceffa, Giuseppa / Griffin, James / Guerreiro, Sofia Cuco / Gupta, Karan / Gupta, Keshav Kumar / Gurrado, Angela / Hajiioannou, Jiannis / Hakala, Tommi / Harahap, Wirsma Arif / Hargitai, Lindsay / Hartl, Dana / Hellmann, Andrzej / Hlozek, Jiri / Hoang, Van Trung / Iacobone, Maurizio / Innaro, Nadia / Ioannidis, Orestis / Jang, J H Isabelle / Xavier-Junior, Jose Candido / Jovanovic, Milan / Kaderli, Reto Martin / Kakamad, Fahmi / Kaliszewski, Krzysztof / Karamanliev, Martin / Katoh, Hiroshi / Košec, Andro / Kovacevic, Bozidar / Kowalski, Luiz Paulo / Králik, Robert / Yadav, Sanjay Kumar / Kumorová, Adriána / Lampridis, Savvas / Lasithiotakis, Konstantinos / Leclere, Jean-Christophe / Leong, Eugene Kwong Fei / Leow, Melvin Khee-Shing / Lim, James Y / Lino-Silva, Leonardo S / Liu, Shirley Yuk Wah / Llorach, Núria Perucho / Lombardi, Celestino Pio / López-Gómez, Javier / Lori, Eleonora / Quintanilla-Dieck, Lourdes / Lucchini, Roberta / Madani, Amin / Manatakis, Dimitrios / Markovic, Ivan / Materazzi, Gabriele / Mazeh, Haggi / Mercante, Giuseppe / Meyer-Rochow, Goswin Yason / Mihaljevic, Olgica / Miller, Julie A / Minuto, Michele / Monacelli, Massimo / Mulita, Francesk / Mullineris, Barbara / Muñoz-de-Nova, José Luis / Muradás Girardi, Fábio / Nader, Saki / Napadon, Tangjaturonrasme / Nastos, Constantinos / Offi, Chiara / Ronen, Ohad / Oragano, Luigi / Orois, Aida / Pan, Yongqin / Panagiotidis, Emmanouil / Panchangam, Ramakanth Bhargav / Papavramidis, Theodosios / Parida, Pradipta Kumar / Paspala, Anna / Pérez, Òscar Vidal / Petrovic, Sabrina / Raffaelli, Marco / Ramacciotti, Constanza Fernanda / Ratia Gimenez, Tomas / Rivo Vázquez, Ángel / Roh, Jong-Lyel / Rossi, Leonardo / Sanabria, Alvaro / Santeerapharp, Alena / Semenov, Arseny / Seneviratne, Sanjeewa / Serdar, Altinay / Sheahan, Patrick / Sheppard, Sean C / Slotcavage, Rachel L / Smaxwil, Constantin / Kim, Soo Young / Sorrenti, Salvatore / Spartalis, Eleftherios / Sriphrapradang, Chutintorn / Testini, Mario / Turk, Yigit / Tzikos, George / Vabalayte, Kristina / Vargas-Osorio, Kelly / Vázquez Rentería, Rafael Sebastián / Velázquez-Fernández, David / Vithana, Sanura Malinda Pallegoda / Yücel, Levent / Yulian, Erwin Danil / Zahradnikova, Petra / Zarogoulidis, Paul / Ziablitskaia, Evgeniia / Zolotoukho, Anna / Calò, Pietro Giorgio

The lancet. Diabetes & endocrinology

2023 Volume 11, Issue 6, Page(s) 402–413

Abstract: Background: Since its outbreak in early 2020, the COVID-19 pandemic has diverted resources from non-urgent and elective procedures, leading to diagnosis and treatment delays, with an increased number of neoplasms at advanced stages worldwide. The aims ... ...

Abstract	Background: Since its outbreak in early 2020, the COVID-19 pandemic has diverted resources from non-urgent and elective procedures, leading to diagnosis and treatment delays, with an increased number of neoplasms at advanced stages worldwide. The aims of this study were to quantify the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic; and to evaluate whether delays in surgery led to an increased occurrence of aggressive tumours. Methods: In this retrospective, international, cross-sectional study, centres were invited to participate in June 22, 2022; each centre joining the study was asked to provide data from medical records on all surgical thyroidectomies consecutively performed from Jan 1, 2019, to Dec 31, 2021. Patients with indeterminate thyroid nodules were divided into three groups according to when they underwent surgery: from Jan 1, 2019, to Feb 29, 2020 (global prepandemic phase), from March 1, 2020, to May 31, 2021 (pandemic escalation phase), and from June 1 to Dec 31, 2021 (pandemic decrease phase). The main outcomes were, for each phase, the number of surgeries for indeterminate thyroid nodules, and in patients with a postoperative diagnosis of thyroid cancers, the occurrence of tumours larger than 10 mm, extrathyroidal extension, lymph node metastases, vascular invasion, distant metastases, and tumours at high risk of structural disease recurrence. Univariate analysis was used to compare the probability of aggressive thyroid features between the first and third study phases. The study was registered on ClinicalTrials.gov, NCT05178186. Findings: Data from 157 centres (n=49 countries) on 87 467 patients who underwent surgery for benign and malignant thyroid disease were collected, of whom 22 974 patients (18 052 [78·6%] female patients and 4922 [21·4%] male patients) received surgery for indeterminate thyroid nodules. We observed a significant reduction in surgery for indeterminate thyroid nodules during the pandemic escalation phase (median monthly surgeries per centre, 1·4 [IQR 0·6-3·4]) compared with the prepandemic phase (2·0 [0·9-3·7]; p<0·0001) and pandemic decrease phase (2·3 [1·0-5·0]; p<0·0001). Compared with the prepandemic phase, in the pandemic decrease phase we observed an increased occurrence of thyroid tumours larger than 10 mm (2554 [69·0%] of 3704 vs 1515 [71·5%] of 2119; OR 1·1 [95% CI 1·0-1·3]; p=0·042), lymph node metastases (343 [9·3%] vs 264 [12·5%]; OR 1·4 [1·2-1·7]; p=0·0001), and tumours at high risk of structural disease recurrence (203 [5·7%] of 3584 vs 155 [7·7%] of 2006; OR 1·4 [1·1-1·7]; p=0·0039). Interpretation: Our study suggests that the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic period could have led to an increased occurrence of aggressive thyroid tumours. However, other compelling hypotheses, including increased selection of patients with aggressive malignancies during this period, should be considered. We suggest that surgery for indeterminate thyroid nodules should no longer be postponed even in future instances of pandemic escalation. Funding: None.
MeSH term(s)	Humans ; Male ; Female ; Thyroid Nodule/epidemiology ; Thyroid Nodule/surgery ; Thyroid Nodule/diagnosis ; Cross-Sectional Studies ; Pandemics ; Retrospective Studies ; Lymphatic Metastasis ; COVID-19/epidemiology ; Thyroid Neoplasms/epidemiology ; Thyroid Neoplasms/surgery ; Thyroid Neoplasms/pathology
Language	English
Publishing date	2023-04-28
Publishing country	England
Document type	Multicenter Study ; Journal Article
ISSN	2213-8595
ISSN (online)	2213-8595
DOI	10.1016/S2213-8587(23)00094-3
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Article ; Online: Global Variations in Heart Failure Etiology, Management, and Outcomes.

Joseph, Philip / Roy, Ambuj / Lonn, Eva / Störk, Stefan / Floras, John / Mielniczuk, Lisa / Rouleau, Jean-Lucien / Zhu, Jun / Dzudie, Anastase / Balasubramanian, Kumar / Karaye, Kamilu / AlHabib, Khalid F / Gómez-Mesa, Juan Esteban / Branch, Kelley R / Makubi, Abel / Budaj, Andrzej / Avezum, Alvaro / Wittlinger, Thomas / Ertl, Georg /

Mondo, Charles / Pogosova, Nana / Maggioni, Aldo Pietro / Orlandini, Andres / Parkhomenko, Alexander / ElSayed, Ahmed / López-Jaramillo, Patricio / Grinvalds, Alex / Temizhan, Ahmet / Hage, Camilla / Lund, Lars H / Kazmi, Khawar / Lanas, Fernando / Sharma, Sanjib Kumar / Fox, Keith / McMurray, John J V / Leong, Darryl / Dokainish, Hisham / Khetan, Aditya / Yonga, Gerald / Kragholm, Kristian / Wagdy Shaker, Kerolos / Mwita, Julius Chacha / Al-Mulla, Arif Abdullatif / Alla, François / Damasceno, Albertino / Silva-Cardoso, José / Dans, Antonio L / Sliwa, Karen / O'Donnell, Martin / Bazargani, Nooshin / Bayés-Genís, Antoni / McCready, Tara / Probstfield, Jeffrey / Yusuf, Salim

JAMA

2023 Volume 329, Issue 19, Page(s) 1650–1661

Abstract: Importance: Most epidemiological studies of heart failure (HF) have been conducted in high-income countries with limited comparable data from middle- or low-income countries.: Objective: To examine differences in HF etiology, treatment, and outcomes ... ...

Abstract	Importance: Most epidemiological studies of heart failure (HF) have been conducted in high-income countries with limited comparable data from middle- or low-income countries. Objective: To examine differences in HF etiology, treatment, and outcomes between groups of countries at different levels of economic development. Design, setting, and participants: Multinational HF registry of 23 341 participants in 40 high-income, upper-middle-income, lower-middle-income, and low-income countries, followed up for a median period of 2.0 years. Main outcomes and measures: HF cause, HF medication use, hospitalization, and death. Results: Mean (SD) age of participants was 63.1 (14.9) years, and 9119 (39.1%) were female. The most common cause of HF was ischemic heart disease (38.1%) followed by hypertension (20.2%). The proportion of participants with HF with reduced ejection fraction taking the combination of a β-blocker, renin-angiotensin system inhibitor, and mineralocorticoid receptor antagonist was highest in upper-middle-income (61.9%) and high-income countries (51.1%), and it was lowest in low-income (45.7%) and lower-middle-income countries (39.5%) (P < .001). The age- and sex- standardized mortality rate per 100 person-years was lowest in high-income countries (7.8 [95% CI, 7.5-8.2]), 9.3 (95% CI, 8.8-9.9) in upper-middle-income countries, 15.7 (95% CI, 15.0-16.4) in lower-middle-income countries, and it was highest in low-income countries (19.1 [95% CI, 17.6-20.7]). Hospitalization rates were more frequent than death rates in high-income countries (ratio = 3.8) and in upper-middle-income countries (ratio = 2.4), similar in lower-middle-income countries (ratio = 1.1), and less frequent in low-income countries (ratio = 0.6). The 30-day case-fatality rate after first hospital admission was lowest in high-income countries (6.7%), followed by upper-middle-income countries (9.7%), then lower-middle-income countries (21.1%), and highest in low-income countries (31.6%). The proportional risk of death within 30 days of a first hospital admission was 3- to 5-fold higher in lower-middle-income countries and low-income countries compared with high-income countries after adjusting for patient characteristics and use of long-term HF therapies. Conclusions and relevance: This study of HF patients from 40 different countries and derived from 4 different economic levels demonstrated differences in HF etiologies, management, and outcomes. These data may be useful in planning approaches to improve HF prevention and treatment globally.
MeSH term(s)	Female ; Humans ; Male ; Middle Aged ; Causality ; Heart Failure/epidemiology ; Heart Failure/etiology ; Heart Failure/mortality ; Heart Failure/therapy ; Hospitalization/economics ; Hospitalization/statistics & numerical data ; Hypertension/complications ; Hypertension/epidemiology ; Income ; Stroke Volume ; Global Health/statistics & numerical data ; Registries/statistics & numerical data ; Developed Countries/economics ; Developed Countries/statistics & numerical data ; Developing Countries/economics ; Developing Countries/statistics & numerical data ; Aged
Language	English
Publishing date	2023-05-16
Publishing country	United States
Document type	Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
ZDB-ID	2958-0
ISSN	1538-3598 ; 0254-9077 ; 0002-9955 ; 0098-7484
ISSN (online)	1538-3598
ISSN	0254-9077 ; 0002-9955 ; 0098-7484
DOI	10.1001/jama.2023.5942
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