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Rogala, Sandra ; Ali, Tamer ; Melissari, Maria-Theodora ; Währisch, Sandra ; Schuster, Peggy ; Sarre, Alexandre ; Emídio, Rebeca Cordellini ; Böttger, Thomas ; Rogg, Eva-Maria Pia ; Kaur, Jaskiran ; Krishnan, Jaya ; Dumbović, Gabrijela ; Dimmeler, Stefanie ; Ounzain, Samir ; Pedrazzini, Thierry ; Herrmann, Bernhard ; Grote, Phillip
After myocardial infarction in the adult heart the remaining, non-infarcted tissue adapts to compensate the loss of functional tissue. This adaptation requires changes in gene expression networks, which are mostly controlled by transcription regulating proteins. Long non-coding transcripts (lncRNAs) are taking part in fine-tuning such gene programs. We describe and characterize the cardiomyocyte specific lncRNA Sweetheart RNA (Swhtr), an approximately 10 kb long transcript divergently expressed from the cardiac core transcription factor coding gene Nkx2-5. We show that Swhtr is dispensable for normal heart development and function but becomes essential for the tissue adaptation process after myocardial infarction in murine males. Re-expressing Swhtr from an exogenous locus rescues the Swhtr null phenotype. Genes that depend on Swhtr after cardiac stress are significantly occupied and therefore most likely regulated by NKX2-5. The Swhtr transcript interacts with NKX2-5 and disperses upon hypoxic stress in cardiomyocytes, indicating an auxiliary role of Swhtr for NKX2-5 function in tissue adaptation after myocardial injury.
Acharya, Shreyasi ; Adamová, Dagmar ; Agarwal, Apar ; Aglieri Rinella, Gianluca ; Aglietta, Luca ; Agnello, Michelangelo ; Agrawal, Neelima ; Ahammed, Zubayer ; Ahmad, Shakeel ; Ahn, Sang Un ; Ahuja, Ishaan ; Akindinov, Alexander ; Akishina, Valentina ; Al-Turany, Mohammad ; Aleksandrov, Dmitry ; Alessandro, Bruno ; Alfanda, Haidar Mas’ud ; Alfaro Molina, Jose Ruben ; Ali, Bushra ; Alici, Andrea ; Alizadehvandchali, Negin ; Alkin, Anton ; Alme, Johan ; Alocco, Giacomo ; Alt, Torsten ; Altamura, Anna Rita ; Altsybeev, Igor ; Alvarado Garcia, Jesús Ricardo ; Anaam, Mustafa Naji ; Andrei, Cristian ; Andreou, Nicodemos ; Andronic, Anton ; Andronov, Evgeny ; Anguelov, Venelin ; Antinori, Federico ; Antonioli, Pietro ; Apadula, Nicole ; Aphecetche, Laurent Bernard ; Appelshäuser, Harald ; Arata, Carolina ; Arcelli, Silvia ; Aresti, Mauro ; Arnaldi, Roberta ; Arneiro, Jhoao Gabriel Martins Campos Almeida ; Arsene, Ionut Cristian ; Arslandok, Mesut ; Augustinus, Andre ; Averbeck, Ralf Peter ; Azmi, Mohd Danish ; Baba, Hitoshi ; Badalà, Angela ; Bae, Joonsuk ; Baek, Yong Wook ; Bai, Xiaozhi ; Bailhache, Raphaëlle ; Bailung, Yoshini ; Bala, Renu ; Balbino, Alessandro ; Baldisseri, Alberto ; Balis, Bartosz ; Banerjee, Debjani ; Banoo, Zarina ; Barbasova, Veronika ; Barile, Francesco ; Barioglio, Luca ; Barlou, Maria ; Barman, Banajit ; Barnaföldi, Gergely Gábor ; Barnby, Lee Stuart ; Barreau, Emilie Martine ; Ramillien Barret, Valerie ; Barreto De Oliveira Campos, Leonardo ; Bartels, Clara ; Barth, Klaus ; Bartsch, Esther ; Bastid, Nicole ; Basu, Sumit ; Batigne, Guillaume ; Battistini, Daniel ; Batyunya, Boris ; Bauri, Dibakar ; Bazo Alba, José Luis ; Bearden, Ian Gardner ; Beattie, Caitlin ; Becht, Pascal ; Behera, Debadatta ; Belikov, Iouri ; Bell Hechavarria, Ailec de la Caridad ; Bellini, Francesca ; Bellwied, Rene ; Belokurova, Svetlana ; Espinoza Beltran, Lucina Gabriela ; Vasquez Beltran, Yael Antonio ; Bencédi, Gyula ; Bensaoula, Adel ; Beolè, Stefania ; Berdnikov, Yaroslav ; Berdnikova, Anastasia ; Bergmann, Luisa ; Besoiu, Mihaela Gabriela ; Betev, Latchezar ; Bhaduri, Partha Pratim ; Bhasin, Anju ; Bhat, Mohammad Asif ; Bhattacharjee, Buddhadeb ; Bianchi, Livio ; Bianchi, Nicola ; Bielčík, Jaroslav ; Bielčíková, Jana ; Bigot, Alexandre Patrick ; Bilandzic, Ante ; Biro, Gabor ; Biswas, Saikat ; Bize, Nicolas Luc ; Blair, Justin Thomas ; Blau, Dmitry S. ; Blidaru, Mihail-Bogdan ; Bluhme, Nora ; Blume, Christoph ; Boca, Gianluigi ; Bock, Friederike ; Bodova, Tea ; Bok, Jeongsu ; Boldizsar, Laszlo ; Bombara, Marek ; Bond, Peter Matthew ; Bonomi, Germano ; Borel, Herve ; Borissov, Alexander ; Borquez Carcamo, Andres Gerardo ; Bossi, Hannah ; Botta, Elena ; El Mard Bouziani, Youssef ; Bratrud, Lars ; Braun-Munzinger, Peter ; Bregant, Marco ; Broz, Michal ; Bruno, Giuseppe Eugenio ; Buckland, Matthew Daniel ; Budnikov, Dmitry ; Büsching, Henner ; Bufalino, Stefania ; Bühler, Paul ; Burmasov, Nazar ; Buthelezi, Edith Zinhle ; Bylinkin, Alexander ; Bysiak, Sebastian Adam ; 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Pachmayer, Yvonne C. ; Padhan, Sonali ; Pagano, Davide ; Paic, Guy ; Paisano Guzman, Sergio ; Palasciano, Antonio ; Panebianco, Stefano Matthias ; Park, Hanseo ; Park, Hyebin ; Parkkila, Jasper Elias ; Patley, Yash ; Paul, Biswarup ; Paulino, Maria Monalisa de Melo ; Pei, Hua ; Peitzmann, Thomas ; Peng, Xinye ; Pennisi, Michele ; Perciballi, Stefania ; Peresunko, Dmitry Yurevich ; Mesa Perez, Guillermo ; Pestov, Yury N. ; Petrov, Vitalii ; Petrovici, Mihai A. ; Piano, Stefano ; Pikna, Miroslav ; Pillot, Philippe ; Pinazza, Ombretta ; Pinsky, Lawrence ; Pinto, Chiara ; Pisano, Silvia ; Płoskoń, Mateusz ; Planinic, Mirko ; Pliquett, Fabian ; Poghosyan, Martin G. ; Polishchuk, Boris ; Politano, Stefano ; Poljak, Nikola ; Pop, Amalia ; Porteboeuf, Sarah Julie ; Pozdniakov, Valerii ; Yoval Pozos, Irandheny ; Pradhan, Kshitish Kumar ; Prasad, Sidharth Kumar ; Prasad, Suraj ; Preghenella, Roberto ; Prino, Francesco ; Pruneau, Claude A. ; Pshenichnov, Igor A. ; Puccio, Maximiliano ; Pucillo, Sara ; Qiu, Shi ; Quaglia, Luca ; Ragoni, Simone ; Rai, Ananya ; Rakotozafindrabe, Andry Malala ; Ramello, Luciano ; Rami, Fouad ; Rasa, Marika ; Räsänen, Sami Sakari ; Rath, Rutuparna ; Rauch, Max Philip ; Ravasenga, Ivan ; Read, Kenneth Francis ; Reckziegel, Christian ; Redelbach, Andreas Ralph ; Redlich, Krzysztof ; Reetz, Carolina Anna ; Regules Medel, Hector David ; Rehman, Attiq ur ; Reidt, Felix ; Reme-Ness, Haakon André ; Jakubcinova, Zuzana ; Reygers, Klaus ; Riabov, Andrei ; Riabov, Viktor ; Ricci, Riccardo ; Richter, Matthias ; Riedel, Anton Albert ; Riegler, Werner ; Riffero, Andrea Giovanni ; Ripoli, Cristina ; Ristea, Cătălin-Lucian ; Viqueira Rodriguez, Manuel ; Rodrı́guez Cahuantzi, Mario ; Rodríguez Ramírez, Saúl Aníbal ; Røed, Ketil ; Rogalev, Roman ; Rogochaya, Elena ; Rogoschinski, Tim Sebastian ; Rohr, David ; Röhrich, Dieter ; Rojas Torres, Solangel ; Rokita, Przemyslaw Stefan ; Romanenko, Gleb ; Ronchetti, Federico ; Dominguez Rosas, Edgar ; Rosłon, Krystian ; Rossi, Andrea ; Roy, Ankhi ; Roy, Subhadeep ; Rubini, Nicola ; Ruggiano, Daniela ; Rui, Rinaldo ; Russek, Paweł Grzegorz ; Russo, Roberto ; Rustamov, Anar ; Ryabinkin, Evgeny ; Ryabov, Yury ; Rybicki, Andrzej Krzysztof ; Ryu, Jaehyeok ; Rzęsa, Wioleta ; Sadhu, Samrangy ; Sadovskiy, Sergey ; Sætre, Jon-are ; Šafařík, Karel ; Saha, Sumit Kumar ; Saha, Swati ; Sahoo, Bhagyarathi ; Sahoo, Raghunath ; Sahoo, Sarita ; Sahu, Dushmanta ; Sahu, Pradip Kumar ; Saini, Jogender ; Tropp, Klaudia ; Sakai, Shingo ; Panikkassery Salvan, Malavika ; Sambyal, Sanjeev Singh ; Samitz, Daniel ; Sanna, Isabella ; Saramela, Thiago Badaró ; Sarkar, Debojit ; Sarma, Pranjal ; Sarritzu, Valerio ; Mantovani Sarti, Valentina ; Sas, Mike Henry Petrus ; Sawan, Sawan ; Scapparone, Eugenio ; Schambach, Johann Joachim ; Scheid, Horst Sebastian ; Schiaua, Claudiu Cornel ; Schicker, Rainer ; Schlepper, Felix ; Schmah, Alexander ; Schmidt, Christian Joachim ; Schmidt, Hans Rudolf ; Schmidt, Marten Ole ; Schmidt, Martin ; Schmidt, Nicolas ; Schmier, Austin Robert ; Schotter, Romain ; Wilhelmi, Alexander ; Schukraft, Jürgen ; Schweda, Kai ; Scioli, Gilda ; Scomparin, Enrico ; Seger, Janet Elizabeth ; Sekiguchi, Yuko ; Sekihata, Daiki ; Selina, Mariia ; Selyuzhenkov, Ilya ; Senyukov, Serhiy ; Seo, Jin Joo ; Serebryakov, Dmitry ; Serkin, Leonid ; Šerkšnytė, Laura ; Sevcenco, Adrian ; Shaba, Tebogo Joyce ; Shabetai, Alexandre ; Shahoyan, Ruben ; Shangaraev, Artem ; Sharma, Binti ; Sharma, Deependra ; Sharma, Himanshu ; Sharma, Meenakshi ; Sharma, Samarth ; Sharma, Sheetal ; Sharma, Upasana ; Shatat, Afnan ; Sheibani, Oveis ; Shigaki, Kenta ; Hachiya Shimomura, Maya ; Shin, Jaehyuck ; Shirinkin, Sergey ; Shou, Qiye ; Sibiryak, Yury ; Siddhanta, Sabyasachi ; Siemiarczuk, Teodor ; Silva, Tiago Fiorini da ; Silvermyr, David Olle Rickard ; Simantathammakul, Tawanchat ; Simeonov, Radoslav ; Singh, Balwan ; Singh, Bhawani ; Singh, Kamaljeet ; Singh, Ranbir ; Singh, Randhir ; Singh, Ravindra ; Singh, Sweta ; Singh, Vivek ; Singhal, Vikas ; Sarkar-Sinha, Tinku ; Sitar, Branislav ; Sitta, Mario ; Skaali, Toralf Bernhard ; Skorodumovs, Georgijs ; Smirnov, Nikolai ; Snellings, Raimond ; Solheim, Emilie ; Song, Jihye ; Sonnabend, Christian ; Sonneveld, Jorine Mirjam ; Soramel, Francesca ; Soto-Hernandez, Analyce Bella ; Spijkers, Rik ; Sputowska, Iwona Anna ; Staa, Joey ; Stachel, Johanna ; Stan, Ionel ; Steffanic, Patrick John ; Stiefelmaier, Stephan ; Stocco, Diego ; Storehaug, Ida ; Strangmann, Nicolas Justus ; Stratmann, Peter ; Strazzi, Sofia ; Sturniolo, Alessandro ; Pliatskas Stylianidis, Christos ; Suaide, Alexandre Alarcon do Passo ; Suire, Christophe Pierre ; Sukhanov, Mikhail ; Šuljić, Miljenko ; Sultanov, Rishat ; Sumberia, Vikash ; Sumowidagdo, Suharyo ; Szarka, Imrich ; Szymkowski, Maciej ; Taghavi, Seyed Farid ; Taillepied, Guillaume ; Takahashi, Jun ; Tambave, Ganesh ; Tang, Siyu ; Tang, Zebo ; Tapia Takaki, Jesus Daniel ; Țăpuş, Nicolae ; Tarasovičová, Lucia Anna ; Tarzila, Madalina-gabriela ; Tassielli, Giovanni Francesco ; Tauro, Arturo ; Tavira Garcia, Andrea ; Tejeda Muñoz, Guillermo ; Telesca, Adriana ; Terlizzi, Livia ; Terrevoli, Cristina ; Thakur, Sanchari ; Thomas, Deepa ; Tikhonov, Anatoly ; Tiltmann, Nicolas ; Timmins, Anthony Robert ; Tkacik, Milan ; Tkacik, Tomas ; Toia, Alberica ; Tokumoto, Ryoka ; Tomassini, Sofia ; Tomohiro, Keisuke ; Topilskaya, Nataliya ; Toppi, Marco ; Tork, Theraa M.A. ; Valencia Torres, Victor ; Torres Ramos, Arianna Grisel ; Trifiro, Antonio ; Triolo, Andrea Sofia ; Tripathy, Sushanta ; Tripathy, Tulika ; Trubnikov, Victor ; Trzaska, Wladyslaw Henryk ; Trzcinski, Tomasz Piotr ; Tumkin, Alexandr ; Turrisi, Rosario ; Tveter, Trine Spedstad ; Ullaland, Kjetil ; Ulukutlu, Berkin ; Uras, Antonio ; Urioni, Marta ; Usai, Gianluca ; Vala, Martin ; Valle, Nicolò ; Doremalen, Lennart Vincent Rogier van ; Leeuwen, Marco van ; Van Veen, Casper Arie ; Weelden, Roelof Jan Gijs van ; Vyvre, Pierre vande ; Varga, Dezsö ; Varga, Zoltán ; Vargas Torres, Paola ; Vasileiou, Maria ; Vasiliev, Andrey ; Vazquez Doce, Oton ; Vazquez Rueda, Omar ; Vechernin, Vladimir ; Vercellin, Ermanno ; Vergara Limon, Sergio ; Verma, Rahul ; Vermunt, Lucas Anne ; Vértesi, Róbert ; Verweij, Marta ; Vicković, Linda ; Vilakazi, Zabulon ; Villalobos Baillie, Orlando ; Villani, Anna ; Vinogradov, Alexander ; Virgili, Tiziano ; Virta, Maxim Mikael Olavi ; Vislavicius, Vytautas ; Vodopyanov, Alexander ; Völkel, Benedikt ; Völkl, Martin Andreas ; Voloshin, Sergei ; Volpe, Giacomo ; Haller, Barthélémy von ; Vorobyev, Ivan ; Vozniuk, Nikita ; Vrlakova, Janka ; Wan, Jie ; Wang, Chunzheng ; Wang, Dongfang ; Wang, Yuanzhe ; Wang, Yubiao ; Wegrzynek, Adami Tadeusz ; Weiglhofer, Felix Thomas ; Wenzel, Sandro Christian ; Wessels, Johannes P. ; Wiechula, Jens ; Wikne, Jon ; Wilk, Grzegorz Andrzej ; Wilkinson, Jeremy John ; Willems, Guido Alexander ; Windelband, Bernd ; Winn, Michael ; Wright, Josephina Rae ; Wu, Wenya ; Wu, Yitao ; Xiong, Zhenjun ; Xu, Ran ; Yadav, Ankur ; Yadav, Arun Kumar ; Yamaguchi, Yorito ; Yang, Shiming ; Yano, Satoshi ; Yeats, Emma Rose ; Yin, Zhongbao ; Yoo, In-Kwon ; Yoon, Jin Hee ; Yu, Hyeonjin ; Yuan, Shiming ; Yüncü, Alperen ; Zaccolo, Valentina ; Zampolli, Chiara ; Zhang, Mingyu ; Zanone, Federica ; Zardoshti, Nima ; Zarochentsev, Andrey ; Závada, Petr ; Zavyalov, Nikolay ; Zhalov, Mikhail ; Zhang, Biao ; Zhang, Chi ; Zhang, Liuyao ; Zhang, Maolin ; Zhang, Song ; Zhang, Xiaoming ; Zhang, Yifei ; Zhang, Zhen ; Zhao, Mingrui ; Zherebchevskii, Vladimir ; Yu, Zhi ; Zhong, Chen ; Zhou, Daicui ; Zhou, You ; Zhu, Jianhui ; Zhu, Senjie ; Zhu, Ya ; Zugravel, Stefan Cristi ; Zurlo, Nicola
The production of K∗(892)± meson resonance is measured at midrapidity (|y|<0.5) in Pb-Pb collisions at sNN−−−√=5.02 TeV using the ALICE detector at the LHC. The resonance is reconstructed via its hadronic decay channel K∗(892)±→K0Sπ±. The transverse momentum distributions are obtained for various centrality intervals in the pT range of 0.4-16 GeV/c. The reported measurements of integrated yields, mean transverse momenta, and particle yield ratios are consistent with previous ALICE measurements for K∗(892)0. The pT-integrated yield ratio 2K∗(892)±/(K++K−) in central Pb-Pb collisions shows a significant suppression (9.3σ) relative to pp collisions. Thermal model calculations overpredict the particle yield ratio. Although both simulations consider the hadronic phase, only HRG-PCE accurately represents the measurements, whereas MUSIC+SMASH tends to overpredict them. These observations, along with the kinetic freeze-out temperatures extracted from the yields of light-flavored hadrons using the HRG-PCE model, indicate a finite hadronic phase lifetime, which increases towards central collisions. The pT-differential yield ratios 2K∗(892)±/(K++K−) and 2K∗(892)±/(π++π−) are suppressed by up to a factor of five at pT<2 GeV/c in central Pb-Pb collisions compared to pp collisions at s√= 5.02 TeV. Both particle ratios and are qualitatively consistent with expectations for rescattering effects in the hadronic phase. The nuclear modification factor shows a smooth evolution with centrality and is below unity at pT>8 GeV/c, consistent with measurements for other light-flavored hadrons. The smallest values are observed in most central collisions, indicating larger energy loss of partons traversing the dense medium.
Background: Postoperative complication rates using 3D visualization are rarely reported. The primary aim of our study is to detect a possible advantage of using 3D on postoperative complication rates in a real-world setting.
Method: With a sample size calculation for a medium effect size difference that 3D reduces significantly postoperative complications, data of 287 patients with 3D visualization and 832 with 2D procedure were screened. The groups underwent an exact propensity score-matching to be comparable. Comprehensive complication index (CCI) for every procedure was calculated and Operation Time was determined.
Results: Including 1078 patients in the study, 213 exact propensity score-matched pairs could finally be established. Concerning overall CCI (3D: 5.70 ± 13.63 vs. 2D: 3.37 ± 9.89; p = 0.076) and operation time (3D: 103.98 ± 93.26 min vs. 2D: 88.60 ±6 9.32 min; p = 0.2569) there was no significant difference between the groups.
Conclusion: Our study shows no advantage of 3D over 2D laparoscopy regarding postoperative complications in a real-world setting, the second endpoint operation time, too, was not influenced by 3D overall.
Keywords: 3D laparoscopy; Comprehensive complication index; Propensity score matching
Kohmer, Niko ; Stein, Shivana ; Schenk, Barbara ; Grikscheit, Katharina ; Metzler, Melinda ; Rabenau, Holger ; Widera, Marek ; Herrmann, Eva ; Wicker, Sabine ; Ciesek, Sandra
Objectives: Regarding reactogenicity and immunogenicity, heterologous COVID-19 vaccination regimens are considered as an alternative to conventional immunization schemes.
Methods: Individuals receiving either heterologous (ChAdOx1-S [AstraZeneca, Cambridge, UK]/BNT162b2 [Pfizer-BioNTech, Mainz, Germany]; n = 306) or homologous (messenger RNA [mRNA]-1273 [Moderna, Cambridge, Massachusetts, USA]; n = 139) vaccination were asked to participate when receiving their second dose. Reactogenicity was assessed after 1 month, immunogenicity after 1, 3, and/or 6 months, including a third dose, through SARS-CoV-2 antispike immunoglobulin G, surrogate virus neutralization test, and a plaque reduction neutralization test against the Delta (B.1.167.2) and Omicron (B.1.1.529; BA.1) variants of concern.
Results: The overall reactogenicity was lower after heterologous vaccination. In both cohorts, SARS-CoV-2 antispike immunoglobulin G concentrations waned over time with the heterologous vaccination demonstrating higher neutralizing activity than homologous mRNA vaccination after 3 months to low neutralizing levels in the Delta plaque reduction neutralization test after 6 months. At this point, 3.2% of the heterologous and 11.4% of the homologous cohort yielded low neutralizing activity against Omicron. After a third dose of an mRNA vaccine, ≥99% of vaccinees demonstrated positive neutralizing activity against Delta. Depending on the vaccination scheme and against Omicron, 60% to 87.5% of vaccinees demonstrated positive neutralizing activity.
Conclusion: ChAdOx1-S/BNT162b2 vaccination demonstrated an acceptable reactogenicity and immunogenicity profile. A third dose of an mRNA vaccine is necessary to maintain neutralizing activity against SARS-CoV-2. However, variants of concern-adapted versions of the vaccines would be desirable.
Introduction Patients undergoing heart valve surgery are predominantly transferred postoperatively to the intensive care unit (ICU) under continuous sedation. Volatile anaesthetics are an increasingly used treatment alternative to intravenous substances in the ICU. As subject to inhalational uptake and elimination, the resulting pharmacological benefits have been repeatedly demonstrated. Therefore, volatile anaesthetics appear suitable to meet the growing demands of fast-track cardiac surgery. However, their use requires special preparation at the bedside and trained medical and nursing staff, which might limit the pharmacological benefits. The aim of our work is to assess whether the temporal advantages of recovery under volatile sedation outweigh the higher effort of special preparation.
Methods and analysis The study is designed to evaluate the differences between intravenous sedatives (n=48) and volatile sedatives (n=48) in continued intensive care sedation. This study will be conducted as a prospective, randomised, controlled, single-blinded, monocentre trial at a German university hospital in consenting adult patients undergoing heart valve surgery at a university hospital. This observational study will examine the necessary preparation time, staff consultation and overall feasibility of the chosen sedation method. For this purpose, the continuation of sedation in the ICU with volatile sedatives is considered as one study arm and with intravenous sedatives as the comparison group. Due to rapid elimination and quick awakening after the termination of sedation, closer consultation between the attending physician and the ICU nursing staff is required, in addition to a prolonged setup time. Study analysis will include the required setup time, time from admission to extubation as primary outcome and neurocognitive assessability. In addition, possible operation-specific (blood loss, complications), treatment parameters (catecholamine dosages, lung function) and laboratory results (acute kidney injury, acid base balance (lactataemia), liver failure) as influencing factors will be collected. The study-relevant data will be extracted from the continuous digital records of the patient data management system after the patient has been discharged from the ICU. For statistical evaluation, 95% CIs will be calculated for the median time to extubation and neurocognitive assessability, and the association will be assessed with a Cox regression model. In addition, secondary binary outcome measures will be evaluated using Fisher’s exact tests. Further descriptive and exploratory statistical analyses are also planned.
Ethics and dissemination The study was approved by the Institutional Ethics Board of the University of Frankfurt, Germany (#20-1050). Informed consent of all individual patients will be obtained before randomisation. Results will be disseminated via publication in peer-reviewed journals.
Association of mortality and early tracheostomy in patients with COVID-19: a retrospective analysis
(2022)
Flinspach, Armin Niklas ; Booke, Hendrik ; Zacharowski, Kai ; Balaban, Ümniye ; Herrmann, Eva ; Adam, Elisabeth
COVID-19 adds to the complexity of optimal timing for tracheostomy. Over the course of this pandemic, and expanded knowledge of the disease, many centers have changed their operating procedures and performed an early tracheostomy. We studied the data on early and delayed tracheostomy regarding patient outcome such as mortality. We performed a retrospective analysis of all tracheostomies at our institution in patients diagnosed with COVID-19 from March 2020 to June 2021. Time from intubation to tracheostomy and mortality of early (≤ 10 days) vs. late (> 10 days) tracheostomy were the primary objectives of this study. We used mixed cox-regression models to calculate the effect of distinct variables on events. We studied 117 tracheostomies. Intubation to tracheostomy shortened significantly (Spearman’s correlation coefficient; rho = − 0.44, p ≤ 0.001) during the course of this pandemic. Early tracheostomy was associated with a significant increase in mortality in uni- and multivariate analysis (Hazard ratio 1.83, 95% CI 1.07–3.17, p = 0.029). The timing of tracheostomy in COVID-19 patients has a potentially critical impact on mortality. The timing of tracheostomy has changed during this pandemic tending to be performed earlier. Future prospective research is necessary to substantiate these results.
Wilhelm, Alexander ; Widera, Marek ; Grikscheit, Katharina ; Toptan, Tuna ; Schenk, Barbara ; Pallas, Christiane ; Metzler, Melinda ; Kohmer, Niko ; Hoehl, Sebastian ; Marschalek, Rolf ; Herrmann, Eva ; Helfritz, Fabian Arnold ; Wolf, Timo ; Götsch, Udo ; Ciesek, Sandra
Background: In recent months, Omicron variants of SARS-CoV-2 have become dominant in many regions of the world, and case numbers with Omicron subvariants BA.1 and BA.2 continue to increase. Due to numerous mutations in the spike protein, the efficacy of currently available vaccines, which are based on Wuhan-Hu 1 isolate of SARS-CoV-2, is reduced, leading to breakthrough infections. Efficacy of monoclonal antibody therapy is also likely impaired.
Methods: In our in vitro study using A549-AT cells constitutively expressing ACE2 and TMPRSS2, we determined and compared the neutralizing capacity of vaccine-elicited sera, convalescent sera and monoclonal antibodies against authentic SARS-CoV-2 Omicron BA.1 and BA.2 compared with Delta.
Findings: Almost no neutralisation of Omicron BA.1 and BA.2 was observed using sera from individuals vaccinated with two doses 6 months earlier, regardless of the type of vaccine taken. Shortly after the booster dose, most sera from triple BNT162b2-vaccinated individuals were able to neutralise both Omicron variants. In line with waning antibody levels three months after the booster, only weak residual neutralisation was observed for BA.1 (26%, n = 34, 0 median NT50) and BA.2 (44%, n = 34, 0 median NT50). In addition, BA.1 but not BA.2 was resistant to the neutralising monoclonal antibodies casirivimab/imdevimab, while BA.2 exhibited almost a complete evasion from the neutralisation induced by sotrovimab.
Interpretation: Both SARS-CoV-2 Omicron subvariants BA.1 and BA.2 escape antibody-mediated neutralisation elicited by vaccination, previous infection with SARS-CoV-2, and monoclonal antibodies. Waning immunity renders the majority of tested sera obtained three months after booster vaccination negative in BA.1 and BA.2 neutralisation. Omicron subvariant specific resistance to the monoclonal antibodies casirivimab/imdevimab and sotrovimab emphasizes the importance of genotype-surveillance and guided application.
Funding: This study was supported in part by the Goethe-Corona-Fund of the Goethe University Frankfurt (M.W.) and the Federal Ministry of Education and Research (COVIDready; grant 02WRS1621C (M.W.).
Flinspach, Armin Niklas ; Booke, Hendrik ; Zacharowski, Kai ; Balaban, Ümniye ; Herrmann, Eva ; Adam, Elisabeth
The coronavirus pandemic continues to challenge global healthcare. Severely affected patients are often in need of high doses of analgesics and sedatives. The latter was studied in critically ill coronavirus disease 2019 (COVID-19) patients in this prospective monocentric analysis. COVID-19 acute respiratory distress syndrome (ARDS) patients admitted between 1 April and 1 December 2020 were enrolled in the study. A statistical analysis of impeded sedation using mixed-effect linear regression models was performed. Overall, 114 patients were enrolled, requiring unusual high levels of sedatives. During 67.9% of the observation period, a combination of sedatives was required in addition to continuous analgesia. During ARDS therapy, 85.1% (n = 97) underwent prone positioning. Veno-venous extracorporeal membrane oxygenation (vv-ECMO) was required in 20.2% (n = 23) of all patients. vv-ECMO patients showed significantly higher sedation needs (p < 0.001). Patients with hepatic (p = 0.01) or renal (p = 0.01) dysfunction showed significantly lower sedation requirements. Except for patient age (p = 0.01), we could not find any significant influence of pre-existing conditions. Age, vv-ECMO therapy and additional organ failure could be demonstrated as factors influencing sedation needs. Young patients and those receiving vv-ECMO usually require increased sedation for intensive care therapy. However, further studies are needed to elucidate the causes and mechanisms of impeded sedation.
Kinzler, Maximilian Nikolai ; Klasen, Christina ; Schulze, Falko ; Herrmann, Eva ; Schnitzbauer, Andreas ; Trojan, Jörg ; Zeuzem, Stefan ; Wild, Peter Johannes ; Walter, Dirk
Intrahepatic cholangiocarcinoma (iCCA) is the most frequent subtype of cholangiocarcinoma (CCA), and the incidence has globally increased in recent years. In contrast to surgically treated iCCA, data on the impact of fibrosis on survival in patients undergoing palliative chemotherapy are missing. We retrospectively analyzed the cases of 70 patients diagnosed with iCCA between 2007 and 2020 in our tertiary hospital. Histopathological assessment of fibrosis was performed by an expert hepatobiliary pathologist. Additionally, the fibrosis-4 score (FIB-4) was calculated as a non-invasive surrogate marker for liver fibrosis. For overall survival (OS) and progression-free survival (PFS), Kaplan–Meier curves and Cox-regression analyses were performed. Subgroup analyses revealed a median OS of 21 months (95% CI = 16.7–25.2 months) and 16 months (95% CI = 7.6–24.4 months) for low and high fibrosis, respectively (p = 0.152). In non-cirrhotic patients, the median OS was 21.8 months (95% CI = 17.1–26.4 months), compared with 9.5 months (95% CI = 4.6–14.3 months) in cirrhotic patients (p = 0.007). In conclusion, patients with iCCA and cirrhosis receiving palliative chemotherapy have decreased OS rates, while fibrosis has no significant impact on OS or PFS. These patients should not be prevented from state-of-the-art first-line chemotherapy.
Delbrück, Marla ; Hoehl, Sebastian ; Toptan, Tuna ; Schenk, Barbara ; Grikscheit, Katharina ; Metzler, Melinda ; Herrmann, Eva ; Ciesek, Sandra
The immune response is known to wane after vaccination with BNT162b2, but the role of age, morbidity and body composition is not well understood. We conducted a cross-sectional study in long-term care facilities (LTCFs) for the elderly. All study participants had completed two-dose vaccination with BNT162b2 five to 7 months before sample collection. In 298 residents (median age 86 years, range 75–101), anti-SARS-CoV-2 rector binding IgG antibody (anti-RBD-IgG) concentrations were low and inversely correlated with age (mean 51.60 BAU/ml). We compared the results to Health Care Workers (HCW) aged 18–70 years (n = 114, median age: 53 years), who had a higher mean anti-RBD-IgG concentration of 156.99 BAU/ml. Neutralization against the Delta variant was low in both groups (9.5% in LTCF residents and 31.6% in HCWs). The Charlson Comorbidity Index was inversely correlated with anti-RBD-IgG, but not the body mass index (BMI). A control group of 14 LTCF residents with known breakthrough infection had significant higher antibody concentrations (mean 3,199.65 BAU/ml), and 85.7% had detectable neutralization against the Delta variant. Our results demonstrate low but recoverable markers of immunity in LTCF residents five to 7 months after vaccination.