NGS Nominated CELA1, HSPG2, and KCNK5 as Candidate Genes for Predisposition to Balkan Endemic Nephropathy

Balkan endemic nephropathy (BEN) is a familial chronic tubulointerstitial disease with insidious onset and slow progression leading to terminal renal failure. The results of molecular biological investigations propose that BEN is a multifactorial disease with genetic predisposition to environmental risk agents. Exome sequencing of 22 000 genes with Illumina Nextera Exome Enrichment Kit was performed on 22 DNA samples (11 Bulgarian patients and 11 Serbian patients). Software analysis was performed via NextGene, Provean, and PolyPhen. The frequency of all annotated genetic variants with deleterious/damaging effect was compared with those of European populations. Then we focused on nonannotated variants (with no data available about them and not found in healthy Bulgarian controls). There is no statistically significant difference between annotated variants in BEN patients and European populations. From nonannotated variants with more than 40% frequency in both patients' groups, we nominated 3 genes with possible deleterious/damaging variants-CELA1, HSPG2, and KCNK5. Mutant genes (CELA1, HSPG2, and KCNK5) in BEN patients encode proteins involved in basement membrane/extracellular matrix and vascular tone, tightly connected to process of angiogenesis. We suggest that an abnormal process of angiogenesis plays a key role in the molecular pathogenesis of BEN

MUC2 polymorphisms are associated with endometriosis development and infertility: a case-control study

<p>Abstract</p> <p>Background</p> <p>Mucins are highly glycosylated proteins protecting and lubricating epithelial surface of respiratory, gastrointestinal and reproductive tracts. Members of the mucin protein family have been suggested to play an important role in development of endometriosis and infertility. This study investigates genetic association of mucin2 (<it>MUC2</it>) with the risk of endometriosis and endometriosis-related infertility.</p> <p>Methods</p> <p>This case-control study was conducted at China Medical University Hospital, with 195 endometriosis patients and 196 healthy controls enrolled. Genotyping of six SNPs (rs2856111, rs11245936, rs10794288, rs10902088, rs7103978 and rs11245954) within <it>MUC2 </it>gene were performed by using <it>Taqman </it>genotyping assay; individual SNP and haplotype associations with endometriosis and endometriosis-related infertility were assessed by <it>χ</it>²test.</p> <p>Results</p> <p>Endometriosis patients exhibit significantly lower frequency of the rs10794288 C allele, the rs10902088 T allele and the rs7103978 G allele (<it>P </it>= 0.030, 0.013 and 0.040, respectively). In addition, the rs10794288 C allele and the rs10902088 T allele were also less abundant in patients with infertility versus fertile ones (<it>P </it>= 0.015 and 0.024, respectively). Haplotype analysis of the endometriosis associated SNPs in <it>MUC2 </it>also showed significantly association between the most common haplotypes and endometriosis or endometriosis-related infertility.</p> <p>Conclusions</p> <p><it>MUC2 </it>polymorphisms, especially rs10794288 and rs10902088, are associated with endometriosis as well as endometriosis-related infertility. Our data present MUC2 as a new candidate involved in development of endometriosis and related infertility in Taiwanese Han women.</p

Epidemiology of intra-abdominal infection and sepsis in critically ill patients: “AbSeS”, a multinational observational cohort study and ESICM Trials Group Project

Purpose: To describe the epidemiology of intra-abdominal infection in an international cohort of ICU patients according to a new system that classifies cases according to setting of infection acquisition (community-acquired, early onset hospital-acquired, and late-onset hospital-acquired), anatomical disruption (absent or present with localized or diffuse peritonitis), and severity of disease expression (infection, sepsis, and septic shock). Methods: We performed a multicenter (n = 309), observational, epidemiological study including adult ICU patients diagnosed with intra-abdominal infection. Risk factors for mortality were assessed by logistic regression analysis. Results: The cohort included 2621 patients. Setting of infection acquisition was community-acquired in 31.6%, early onset hospital-acquired in 25%, and late-onset hospital-acquired in 43.4% of patients. Overall prevalence of antimicrobial resistance was 26.3% and difficult-to-treat resistant Gram-negative bacteria 4.3%, with great variation according to geographic region. No difference in prevalence of antimicrobial resistance was observed according to setting of infection acquisition. Overall mortality was 29.1%. Independent risk factors for mortality included late-onset hospital-acquired infection, diffuse peritonitis, sepsis, septic shock, older age, malnutrition, liver failure, congestive heart failure, antimicrobial resistance (either methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, extended-spectrum beta-lactamase-producing Gram-negative bacteria, or carbapenem-resistant Gram-negative bacteria) and source control failure evidenced by either the need for surgical revision or persistent inflammation. Conclusion: This multinational, heterogeneous cohort of ICU patients with intra-abdominal infection revealed that setting of infection acquisition, anatomical disruption, and severity of disease expression are disease-specific phenotypic characteristics associated with outcome, irrespective of the type of infection. Antimicrobial resistance is equally common in community-acquired as in hospital-acquired infection

Antimicrobial Lessons From a Large Observational Cohort on Intra-abdominal Infections in Intensive Care Units

Severe intra-abdominal infection commonly requires intensive care. Mortality is high and is mainly determined by disease-specific characteristics, i.e. setting of infection onset, anatomical barrier disruption, and severity of disease expression. Recent observations revealed that antimicrobial resistance appears equally common in community-acquired and late-onset hospital-acquired infection. This challenges basic principles in anti-infective therapy guidelines, including the paradigm that pathogens involved in community-acquired infection are covered by standard empiric antimicrobial regimens, and second, the concept of nosocomial acquisition as the main driver for resistance involvement. In this study, we report on resistance profiles of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterococcus faecalis and Enterococcus faecium in distinct European geographic regions based on an observational cohort study on intra-abdominal infections in intensive care unit (ICU) patients. Resistance against aminopenicillins, fluoroquinolones, and third-generation cephalosporins in E. coli, K. pneumoniae and P. aeruginosa is problematic, as is carbapenem-resistance in the latter pathogen. For E. coli and K. pneumoniae, resistance is mainly an issue in Central Europe, Eastern and South-East Europe, and Southern Europe, while resistance in P. aeruginosa is additionally problematic in Western Europe. Vancomycin-resistance in E. faecalis is of lesser concern but requires vigilance in E. faecium in Central and Eastern and South-East Europe. In the subcohort of patients with secondary peritonitis presenting with either sepsis or septic shock, the appropriateness of empiric antimicrobial therapy was not associated with mortality. In contrast, failure of source control was strongly associated with mortality. The relevance of these new insights for future recommendations regarding empiric antimicrobial therapy in intra-abdominal infections is discussed

Epidemiology of intra-abdominal infection and sepsis in critically ill patients: “AbSeS”, a multinational observational cohort study and ESICM Trials Group Project

Purpose: To describe the epidemiology of intra-abdominal infection in an international cohort of ICU patients according to a new system that classifies cases according to setting of infection acquisition (community-acquired, early onset hospital-acquired, and late-onset hospital-acquired), anatomical disruption (absent or present with localized or diffuse peritonitis), and severity of disease expression (infection, sepsis, and septic shock). Methods: We performed a multicenter (n = 309), observational, epidemiological study including adult ICU patients diagnosed with intra-abdominal infection. Risk factors for mortality were assessed by logistic regression analysis. Results: The cohort included 2621 patients. Setting of infection acquisition was community-acquired in 31.6%, early onset hospital-acquired in 25%, and late-onset hospital-acquired in 43.4% of patients. Overall prevalence of antimicrobial resistance was 26.3% and difficult-to-treat resistant Gram-negative bacteria 4.3%, with great variation according to geographic region. No difference in prevalence of antimicrobial resistance was observed according to setting of infection acquisition. Overall mortality was 29.1%. Independent risk factors for mortality included late-onset hospital-acquired infection, diffuse peritonitis, sepsis, septic shock, older age, malnutrition, liver failure, congestive heart failure, antimicrobial resistance (either methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, extended-spectrum beta-lactamase-producing Gram-negative bacteria, or carbapenem-resistant Gram-negative bacteria) and source control failure evidenced by either the need for surgical revision or persistent inflammation. Conclusion: This multinational, heterogeneous cohort of ICU patients with intra-abdominal infection revealed that setting of infection acquisition, anatomical disruption, and severity of disease expression are disease-specific phenotypic characteristics associated with outcome, irrespective of the type of infection. Antimicrobial resistance is equally common in community-acquired as in hospital-acquired infection. © 2019, The Author(s)

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study (Intensive Care Medicine, (2021), 47, 2, (160-169), 10.1007/s00134-020-06234-9)

1832The original version of this article unfortunately contained a mistake. The members of the ESICM Trials Group Collaborators were not shown in the article but only in the ESM. The full list of collaborators is shown below. 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Villafuerte M.V.E.; Herrera M.O.G.; Belii A.; Naranpurev M.; Baasanjav B.; Hachimi A.; Elkhayari M.; Abidi K.; Dendane T.; Subedi N.B.; Pathak S.D.; Gautam P.; Manandhar M.; Van Gulik L.; Van Den Brink M.; Van Vliet P.; Gerretsen B.; Van Den Berg L.; De Haan M.; Tuinstra B.; Kuijpers P.; Reijntjens J.; Vermeijden J.W.; Rinket M.; Vanroest M.; Reidinga A.; Loef B.; Dieperink W.; Onrust M.; Dormans T.; Bormans L.; Koopmans M.; Gerritsen R.T.; Van Den Elst A.; Evers M.; Oiting O.; Wilting R.; Ramaker B.; van der Kuil M.; Fijen J.-W.; Haas L.; De Lange D.; Haringman J.; Newby L.; Parke R.; Gilder E.; Hacking D.; Dagooc R.; Song R.; Waibel H.; Dawn F.; Rapley J.; Chadwick L.; Chapman C.; Crone P.; Albrett J.; Marko P.; Goodson J.; Browne T.; Whitticase R.; Davidson C.; Judd H.; Owens D.; Onyeka T.; Ugwu I.; Ilesanmi R.; Adejumo P.O.; Owojuyigbe A.; Adenekan A.; Uba S.; Chime C.; Jibrin D.; Sankey B.J.; Adekola O.; Olanipekun S.; Olanipekun S.; Adekola O.; Shosolcheva M.; Gievski V.; Kartalov A.; Naumovski F.; Kuzmanovska B.; Trposak A.; Bogoevska-Miteva Z.; Rosalia R.; Olsen B.F.; Sjobo B.; Jensen K.D.; Sykehus D.; Johansen B.F.; Straede E.; Johansen E.; Finnstrom I.J.; Toellefsen A.; Ostenjo H.; Bjorgen H.; Bratsberg B.; Kristoffersen E.; Skorstad E.M.; Hansen S.; Vullum S.; Lunde G.A.; Arntsen W.; Lund M.; Akselsen G.R.; Monstad K.R.; Stenset A.; Haugom H.; Monsen B.; Hogvall L.; Trudvang S.; Galaaen B.; Malmin S.K.; Andersen M.H.; Hargott R.F.; Andersen Y.; Steffenak E.; Nyhus M.; Meland B.; Hashmi M.; Rivas N.; Maidana E.; de Jesus Ortiz A.; Cabral D.M.B.; Simi M.; Aponte C.; Rivas J.C.; Gill S.; Garcia A.; Alvarenga G.; Cespedes L.; Perez H.; Moreira M.L.; Canete F.; Gonzalez R.; Monges N.; Garcia A.; Coman M.; Pederzani M.; Franco N.; Aganon F.; Martinez R.; Noblezada-Uy D.; Ellazar C.G.; Cerezo F.D.; Hernandez A.M.; Palo J.E.; Aperocho C.A.J.; Isanan M.; Tubacka M.; Jasiewicz P.; Czuczwar M.; Borys M.; Gutysz-Wojnicka A.; Glinka L.; Gawda R.; Mikaszewska-Sokolewicz M.; Bilawicz J.; Cabrita P.; Vieira J.; Figueiredo M.F.; Pinheiro C.M.; Antunes N.; Pedro L.; Ferreira F.; Parente I.; Varela M.; Fernandes F.; Martins C.; Viveiros A.; Cavaco R.; Rita C.S.; Dias S.; Feranandes A.M.; Silva P.; Nunes C.; Cabral J.; Sousa B.; Pires F.; Ferreira H.; Santos J.; Pinto V.M.V.; Bispo B.M.; Ferreira A.; Molinos E.; Lafuente E.; Gregorio R.; Costa H.; Lima A.; Ferreira S.; Seromenho V.; Luis E.; Valerio I.; Cesar H.; Tavares A.; Alsheikhly A.S.; Mahmood S.; Guran C.T.; Moise A.; Filipescu D.C.; Luchian M.; Tomescu D.; Popescu M.; Scutariu M.A.; Petrisor C.; Hagau N.; Grigoras I.; Patrichi T.; Gusarev V.; Pivkina A.; Kulakov V.; Ignatenko O.; Kovaleva J.; Zhivotneva T.; Zhedaeva M.; Matiushkov N.; Ershova O.; Egorova N.; Khoronenko V.; Baskakov D.; Sergeev D.; Piradov M.; Grishina L.; Magomedov M.; Zuev E.; Gorokhovatsky U.; Leonova A.; Fadeeva L.; Belskiy V.; Galishevskiy D.; Zubareva N.; Tribulev M.; Zueva O.; Kiselev A.; Kamenshchikov N.; Tokareva E.; Petrushin M.; Starchenko I.; Twagirumugabe T.; Nshimyumuremyi I.; Muhizi J.; Buregeya E.; Nzarora J.; Assiri A.; Ebaid M.S.; Almekhlafi G.; Mandourah Y.; Velickovic J.; Velickovic D.; Jovanovic B.; Hadzibegovic A.; Stefanovic B.; Misic V.; Bumbasirevic V.; Rajkovic M.; Stojanovic M.; Gavrilovic S.; Stanojevic M.; Martonova A.; Yaghi A.; Turcan A.; Firment P.; Slobodianiuk G.; Rabarova D.; Lancaricova D.; Vlaovic J.; Groznik M.; Lukic M.; Perme J.; Sostaric M.; Umek N.; Mirkovic T.; Dolenc S.; Knafelj R.; Fister M.; Zorko N.; Markota A.; Yeni N.P.; Jali P.; Schmollgruber S.; Syed M.R.; Parag N.; Wise R.; Galiana M.; Navarro J.A.; De Pablo A.M.; Albert P.; Martinez P.; Mendiara Y.; Garcia B.; Llinas A.A.; Riveiro M.; Gallart E.; Riera A.; Sanz M.; Salo S.; Lajara M.A.G.; Nieto M.V.; Garcia R.; Pena J.M.G.; Gorgolas M.C.; Isasi M.A.; Sierra R.; Gordo F.; Conejo I.; Salva-Costa V.; Garzon-Tovar C.; Lospitao S.; Gonzalez R.; Gutierrez P.; Girona M.; Adamuz J.; Olivares P.G.; de Ceballos J.P.G.; Tirado C.; De Wit I.; Polo A.B.C.; del Mar Diaz Salcedo M.; Ripolles-Melchor J.; Martinez-Hurtado E.; Alvarez J.D.; Arcas M.L.B.; Gonzalez J.I.T.; de la Ventana A.B.S.; Calleja P.L.-A.; Alvarez R.G.; Zamora P.S.; Guerrero A.O.; Cosano R.; Perez-Vacas J.; Campos-Perez M.; Barreiro E.M.; Sanchez L.C.; Diaz M.G.; Jimenez R.; Del Rio Cabajo L.; Muriel D.S.; Alonso H.F.; Fernandez A.W.; Pinan I.S.; Albaiceta G.M.; Fernandez M.C.I.; Abos F.J.S.; Monedero P.; Chueca R.M.; Aguirre L.G.; Manosa S.C.; Luque C.P.; Calpe N.; Losilla M.R.; Fores M.T.; Farre O.; Fernandez O.; del Rosario Villar Redondo M.; Arteta Arteta D.S.; Sanchez M.A.H.; Espinosa C.P.; Reyes L.M.; Domenech L.C.; Guillen C.V.; Alvarez J.T.; del Cotillo M.; Barrueco-Francioni J.E.; Conde B.B.; Blanco M.P.S.; Blasco M.L.; Clement A.I.; Hurtado C.; Sanz L.C.; Perez-Torres D.; Prol-Silva E.; Pereira J.; Gonzalez I.A.; Cano A.E.; Nunez C.R.; Fernadez I.L.; Fernandez A.A.M.; Del Bosque Diez R.; Hilario B.; Zalba-Etayo B.; Pascual-Bielsa A.; Panka B.; Banwarie P.; Nahar D.; van Axel A.; Boedjawan N.N.; Jansson E.B.; Malvemyr A.-S.; Johansson L.; Sandberg U.; Tingsvik C.; Mattsson G.; Lof G.; Spangfors M.; Ringdal M.; Geijer S.; Orvelius L.; Hylen M.; Lagerhall C.; Joelsson-Alm E.; Akerman E.; Hellkvist V.H.; Mickelsson U.; Akerman E.; Wahlbom E.; Larsson I.-M.; Wallin E.; Boroli F.; Ory S.; Jong M.L.; Dullenkopf A.; Lang M.; Fleury Y.; Maus M.; Ben-Hamouda N.; Fishman A.; Hsu M.Y.; Chang S.C.; Trongtratul K.; Sawawiboon C.; Morakul S.; Khwannimit B.; Merritt-Charles L.; Singh K.; Ventour D.; Figaro-Barclay D.; Sankar-Maharaj S.; Mebazaa M.S.; Kamoun S.; Elatrous S.; Besbes L.; Abroug F.; Naija W.; Elhechmi Y.Z.; Sellami W.; Hajjej Z.; Merhabene T.; Talik I.; Kuscu O.O.; Dilek O.; Zerman A.; Dal H.C.; Turan S.; Aydemir S.; Yilmaz H.; Calili D.K.; Izdes S.; Cengiz M.; Gumus A.; Tasdemir B.; Kagnici A.; Ay M.; Ay S.A.; Caliskan G.; Akbas T.; Balbay A.O.; Efe S.; Inal V.; Elay G.; Karabacak P.; Ozserezli B.; Senturk E.; Demirkiran O.; Bozbay S.; Dikmen Y.; Erdogan E.; Akker M.; Peker N.; Ozgultekin A.; Serin S.O.; Turan C.; Karaoren G.; Goksu S.; Karakurt S.; Arikan H.; Gul F.; Cinel I.; Kara I.; Undar H.N.; Bayraktar Y.S.; Celik J.B.; Tokur M.E.; Aydin D.T.; Yildiz I.; Ozcan B.; Erdivanli B.; Erdivanli B.; Ozcan B.; Eroglu A.; Akdag D.; Unlu N.; Fielding M.; Dungca A.; Ali A.; Thankamma B.; Reyes P.E.; John S.; Rajendran A.; Ahmad F.K.E.; Smiley K.A.; Hojden S.; Miller M.T.; Das Sasidharan Nair V.; Antonio M.G.S.; Qawasmeh K.A.; Shawish S.A.; Twiggs H.; Rosado I.; Babych V.; Morren F.; Young C.; Vaughan-Jones N.; Harris S.; Burns K.; Georgiev C.; Shayamano R.; Kerslake I.; Creber P.; Vochin A.; O'Brien C.; Caddell P.; Hagan S.; Hughes M.; Torlinski T.; Sherwin J.; Kannan S.; Markham A.; Lebon R.; Cupitt J.; Cranshaw J.; White N.; Marriott V.; Milner W.; Groba C.B.; Azoia J.; Polgarova P.; George S.; Kapoor R.; Lynch C.; Fox N.; Cranmer K.; Fox N.; Llewellym T.; Matthews K.; Maltby L.; Ibao J.; Boulton K.; Jarman R.; Baxter K.; Raj A.S.; Moghal A.; White J.; Barrowcliffe S.; Pulletz M.; Ganeshalingam V.; Baruah R.; Baker H.; Woods J.; Ei P.P.; Ogbeide V.; Hayden P.; Matthews K.; Hughes J.; Balasubramanian M.; Salberg A.; Saha R.; Holmquist D.; Young C.; Derbyshire C.; Smith N.; Stones E.; Ademokun J.; Popescu M.; Legorburo M.S.; North S.; Brett C.; Jaundoo H.; Craig J.; Whiteley S.; Howcroft C.; Wilby L.; Delve P.; Shaw D.; Williams K.; Welters I.D.; McMullen J.; Brett S.; Flores L.; Trueman-Dawkins T.; Templeton M.; Adams J.; Smith C.; Prowle J.; Byers H.; McDonnell A.; Rose B.O.; Reece-Anthony R.; Mendes L.; Vizcaychipi M.; Bull R.; Lacaden G.; Santiago E.; Delgado C.C.; Farnell-Ward S.; Thorpe E.; Somerville J.; Williams A.; Cummings D.; Derrick H.; Brumwell S.; Randell C.; McCann N.; Aves E.; Berry G.; Szakmany T.; Gunter U.; Pulak P.; Sarkar N.; Wright K.; Gomes V.; Jones J.; Palfrey R.; Camsooksai J.; Lewis A.; Eneas A.; Tridente A.; Barr L.; Jovaisa T.; Thomas B.; Parkin E.; Horner D.; Frey C.; Bench S.; Baumber R.; Broadhurst P.; Jackson M.; Williams L.; Clark M.; Paddle J.; Bean S.; Buckley S.; Palfreeman C.; Liu S.; Allison N.; Attwood B.; Parsons P.; Houghton V.; Turner S.J.; Higgins D.; Bielskute E.; Horrigan N.; Jacob R.; Habgood K.; Zaki A.; Collins A.; Lord J.; Ramiro C.; Kubisz-Pudelko A.; Kotze M.; Williams H.; Iovenko I.; Tsarev A.; Zgrzheblovska L.; Briva A.; Mendez G.; Napolitano L.; Teig M.; Lee J.; Rodriguez G.E.; Ben-Jacob T.; Potestio C.; Eng T.; Mahanes D.; Khanna A.; Duggal A.;

Epidemiology of intra-abdominal infection and sepsis in critically ill patients: "AbSeS", a multinational observational cohort study and ESICM Trials Group Project

PurposeTo describe the epidemiology of intra-abdominal infection in an international cohort of ICU patients according to a new system that classifies cases according to setting of infection acquisition (community-acquired, early onset hospital-acquired, and late-onset hospital-acquired), anatomical disruption (absent or present with localized or diffuse peritonitis), and severity of disease expression (infection, sepsis, and septic shock).MethodsWe performed a multicenter (n=309), observational, epidemiological study including adult ICU patients diagnosed with intra-abdominal infection. Risk factors for mortality were assessed by logistic regression analysis.ResultsThe cohort included 2621 patients. Setting of infection acquisition was community-acquired in 31.6%, early onset hospital-acquired in 25%, and late-onset hospital-acquired in 43.4% of patients. Overall prevalence of antimicrobial resistance was 26.3% and difficult-to-treat resistant Gram-negative bacteria 4.3%, with great variation according to geographic region. No difference in prevalence of antimicrobial resistance was observed according to setting of infection acquisition. Overall mortality was 29.1%. Independent risk factors for mortality included late-onset hospital-acquired infection, diffuse peritonitis, sepsis, septic shock, older age, malnutrition, liver failure, congestive heart failure, antimicrobial resistance (either methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, extended-spectrum beta-lactamase-producing Gram-negative bacteria, or carbapenem-resistant Gram-negative bacteria) and source control failure evidenced by either the need for surgical revision or persistent inflammation.ConclusionThis multinational, heterogeneous cohort of ICU patients with intra-abdominal infection revealed that setting of infection acquisition, anatomical disruption, and severity of disease expression are disease-specific phenotypic characteristics associated with outcome, irrespective of the type of infection. Antimicrobial resistance is equally common in community-acquired as in hospital-acquired infection