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  • 1
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 18, No. 10 ( 2017-09-28), p. 2066-
    Type of Medium: Online Resource
    ISSN: 1422-0067
    Language: English
    Publisher: MDPI AG
    Publication Date: 2017
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 2
    In: Journal of Clinical Medicine, MDPI AG, Vol. 10, No. 8 ( 2021-04-12), p. 1643-
    Abstract: Background: Acute type A aortic dissection (AAAD) is considered a fatal disease which requires an emergent surgical intervention. This study focuses onthe neurological outcome after surgical repair in cases of AAAD in comparison between elderly and young patients. Methods: a retrospective analysis of 368 consecutive patients who underwent emergency surgery of ascending aorta in moderate hypothermic circulatory arrest (MHCA) (20–24 °C) and antegrade cerebral perfusion after AAAD between 2001 and 2016. Patients were divided into two groups: those aged 75 years and older (68 (18.5%)) and those younger than 75 years (300 (81.5%)). Results: Comparing both groups, average age was 79.0 ± 3.2 vs. 59.2 ± 10.7 years (p 〈 0.001); female gender represents 58.8% of elderly patients vs. 28.7% in younger patients (p 〈 0.001). Intraoperatively, cardiopulmonary bypass time (155 min (131; 187) vs. 171 min (137; 220); p = 0.012), cross-clamping time (79 min (60; 105) vs. 93 min (71; 134); p = 0.001] and circulatory arrest time (29 min (22; 40) vs. 33 min (26; 49); p = 0.011) were significantly shorter in elderly than younger group. Postoperatively, there was no significant difference in delirium (11.8% vs. 20.5%; p = 0.0968) or stroke (11.8% vs. 16.1%; p = 0.369). The 30-day mortality was satisfactory for both groups but significantly higher in the elderly group (27.9% vs. 14.3%; p = 0.007). Conclusion: The current study concluded that surgical treatment of AAAD in elderly patients can be applied safely without increasing risk of neurological complication. However, minimizing operation time may help limit the occurrence of postoperative neurological complication.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2662592-1
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  • 3
    In: Journal of Fungi, MDPI AG, Vol. 8, No. 3 ( 2022-02-23), p. 220-
    Abstract: In recent years, we have moved from the sporadic description of terbinafine-resistant (TerR) Trichophyton spp. isolates to the Indian outbreak due to T. indotineae. Population flows have spread TerR worldwide, altering local epidemiology. We conducted a prospective multicentric study to determine the relative frequency of TerR isolates in France (Paris area) and of the newly introduced T. indotineae species. TerR isolates were screened by the terbinafine-containing-agar-medium (TCAM) method and confirmed by EUCAST. Sequencing methods were used to identify isolates to the species/genotype level and to analyze substitutions in the squalene epoxidase gene (SQLE). In total, 3 isolates out of 580 (T. rubrumn = 1; T. interdigitalen = 1; T. indotineaen = 1) grew on TCAM, showed terbinafine resistance by EUCAST and harbored the Phe397Leu (n = 2) or Leu393Ser (n = 1) substitution in the SQLE. ITS-sequencing of isolates of the T. mentagrophytes/interdigitale complex (n = 125) revealed a relative frequency of 4.8% for T. indotineae and the presence of T. mentagrophytes genotype VII. Despite the detection of terbinafine resistance, isolates from this complex remained susceptible to itraconazole, voriconazole and amorolfine. Terbinafine resistance is present in France and the dermatophyte epidemiology is changing. Efficient systems must be implemented to survey the evolution of newly introduced species and to identify TerR isolates.
    Type of Medium: Online Resource
    ISSN: 2309-608X
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2784229-0
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  • 4
    In: Journal of Fungi, MDPI AG, Vol. 8, No. 10 ( 2022-10-19), p. 1103-
    Abstract: Trichophyton indotineae is an emerging pathogen which recently spread from India to Europe and that is more prone than other species of the Trichophyton mentagrophytes complex to show resistance to terbinafine, resulting in the necessity of rapid identification. Here, we improved the online MSI-2 MALDI-TOF identification tool in order to identify T. indotineae. By multiplying the culture conditions (2 culture media and 6 stages of growth) prior to protein extractions for both test isolates and reference strains, we added 142 references corresponding to 12 strains inside the T. mentagrophytes complex in the online MSI-2 database, of which 3 are T. indotineae strains. The resulting database was tested with 1566 spectra of 67 isolates from the T. mentagrophytes complex, including 16 T. indotineae isolates. Using the newly improved MSI-2 database, we increased the identification rate of T. indotineae from 5% to 96%, with a sensitivity of 99.6%. We also identified specific peaks (6834/6845 daltons and 10,634/10,680 daltons) allowing for the distinction of T. indotineae from the other species of the complex. Our improved version of the MSI-2 application allows for the identification of T. indotineae. This will improve the epidemiological knowledge of the spread of this species throughout the world and will help to improve patient care.
    Type of Medium: Online Resource
    ISSN: 2309-608X
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2784229-0
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  • 5
    In: Journal of Clinical Medicine, MDPI AG, Vol. 10, No. 22 ( 2021-11-18), p. 5370-
    Abstract: Background: Acute type A aortic dissection (AAAD) has high mortality. Improvements in surgical technique have lowered mortality but postoperative functional status and decreased quality of life due to debilitating deficits remain of concern. Our study aims to identify preoperative conditions predictive of undesirable outcome to help guide perioperative management. Methods: We performed retrospective analysis of 394 cases of AAAD who underwent repair in our institution between 2001 and 2018. A combined endpoint of parameters was defined as (1) 30-day versus hospital mortality, (2) new neurological deficit, (3) new acute renal insufficiency requiring postoperative renal replacement, and (4) prolonged mechanical ventilation with need for tracheostomy. Results: Total survival/ follow-up time averaged 3.2 years with follow-up completeness of 94%. Endpoint was reached by 52.8%. Those had higher EuroSCORE II (7.5 versus 5.5), higher incidence of coronary artery disease (CAD) (9.2% versus 3.2%), neurological deficit (ND) upon presentation (26.4% versus 11.8%), cardiopulmonary resuscitation (CPR) (14.4% versus 1.6%) and intubation (RF) before surgery (16.9% versus 4.8%). 7-day mortality was 21.6% versus 0%. Hospital mortality 30.8% versus 0%. Conclusions: This 15-year follow up shows, that unfavorable postoperative clinical outcome is related to ND, CAD, CPR and RF on arrival.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2662592-1
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  • 6
    In: Journal of Clinical Medicine, MDPI AG, Vol. 10, No. 11 ( 2021-05-29), p. 2411-
    Abstract: The study was approved by the institutional review board (IRB) at the University Medical Center Campus Kiel, Kiel, Germany (reference number: AZ D 559/18) and registered at the German Clinical Trials Register (reference number: DRKS00022222). Objective. Unilateral pulmonary edema (UPE) is a complication after minimally invasive mitral valve surgery (MIMVS). We analyzed the impact of this complication on the short- and long-term outcome over a 10-year period. Methods. We retrospectively observed 393 MIMVS patients between 01/2009 and 12/2019. The primary endpoint was a radiographically and clinically defined UPE within the first postoperative 24 h, secondary endpoints were 30-day and long-term mortality and the percentage of patients requiring ECLS. Risk factors for UPE incidence were evaluated by logistic regression, and risk factors for mortality in the follow-up period were assessed by Cox regression. Results. Median EuroSCORE II reached 0.98% in the complete MIMVS group. Combined 30-day and in-hospital mortality after MIMVS was 2.0% with a 95, 93 and 77% survival rate after 1, 3 and 10 years. Seventy-two (18.3%) of 393 patients developed a UPE 24 h after surgery. Six patients (8.3%) with UPE required an extracorporeal life-support system. Logistic regression analysis identified a higher creatinine level, a worse LV function, pulmonary hypertension, intraoperative transfusion and a longer aortic clamp time as predictors for UPE. Combined in hospital mortality and 30-day mortality was slightly but not significantly higher in the UPE group (4.2 vs. 1.6%; p = 0.17). Predictors for mortality during follow-up were age ≥ 70 years, impaired RVF, COPD, drainage loss ≥ 800 mL and length of ventilation ≥ 48 h. During a median follow-up of 4.6 years, comparable survival between UPE and non-UPE patients was seen in our analysis after 5 years (89 vs. 88%; p = 0.98). Conclusions. In-hospital outcome with UPE after MIMVS was not significantly worse compared to non-UPE patients, and no differences were observed in the long-term follow-up. However, prolonged aortic clamp time, worse renal and left ventricular function, pulmonary hypertension and transfusion are associated with UPE.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2662592-1
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  • 7
    In: Biomedicines, MDPI AG, Vol. 8, No. 8 ( 2020-08-06), p. 276-
    Abstract: Vivostat Platelet-Rich Fibrin® (PRF) is an autologous platelet concentrate used for the local treatment of chronic or complicated wounds. Still, its application for this indication is not evidence-based. Therefore, we performed this monocentric retrospective pilot study investigating the clinical outcome of a local treatment of chronic or complicated wounds in 35 patients (23 male, 12 female, mean age 68.7 years) treated with Vivostat PRF®. This study population is the largest among published studies analyzing the clinical efficacy of Vivostat PRF® on chronic wounds so far. Using the perpendicular method we divided the wounds into three sizes ( 〈 10, 10–30, and 〉 30 cm2). The clinical efficacy of the Vivostat PRF treatment was the primary endpoint and was divided into three groups of increasing degrees of wound improvement: (1) no improvement of the wound (wound area was not reduced 〉 10% under Vivostat PRF® treatment), (2) improvement of the wound (reduced area 〉 10% under Vivostat PRF® treatment) and (3) complete epithelialization (wounds that were completely re-epithelialized after Vivostat PRF® treatment). We included patients’ diagnosis and concomitant diseases (peripheral arterial occlusive disease (PAOD)), chronic venous insufficiency (CVI)), diabetic foot syndrome (DFS)) in our data analysis in order to investigate their potential impact on the wound healing capacity of Vivostat PRF®. Our results show that in the entire study population, 13 out of 35 (37.1%) patients experienced wound improvement and 14 out of 35 (40%) patients showed complete epithelialization of their wound under Vivostat PRF® treatment. In summary, 77.1% of the treated patients benefited from the Vivostat PRF® therapy. These positive wound healing effects were all observed within the first three to six Vivostat PRF® applications. Subgroup analyses showed that Vivostat PRF® appeared to be more efficient in patients without CVI in comparison to patients with CVI (p = 0.02). Moreover, Vivostat PRF® treatment seems to be particularly efficient in PAOD-related wounds with a reduced crural arterial blood supply (p = 0.01). Additionally, we performed an experimental human in vivo study on ten male students where we artificially generated bilateral gluteal wounds and analyzed the influence of the Vivostat PRF® treatment on the expression of two genes (human beta Defensin-2, ((hBD-2) and human beta-Defensin-3 (hBD-3)) in keratinocytes of resected wound specimens that are induced during wound healing. Interestingly, this analysis revealed that only seven of out ten individuals showed a relevant hBD-2 and hBD-3 gene induction after Vivostat PRF® treatment. This led to the novel “key-lock-hypothesis”. With the goal of an individualized precision medicine approach with optimized wound treatment strategies in the future, this is an important observation that demands further experimental and clinical studies.
    Type of Medium: Online Resource
    ISSN: 2227-9059
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2720867-9
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  • 8
    In: Life, MDPI AG, Vol. 12, No. 9 ( 2022-09-10), p. 1413-
    Abstract: Cardiovascular risk factors, biomarkers, and diseases are associated with poor prognosis in COVID-19 infections. Significant progress in artificial intelligence (AI) applied to cardiac imaging has recently been made. We assessed the utility of AI analytic software EchoGo in COVID-19 inpatients. Fifty consecutive COVID-19+ inpatients (age 66 ± 13 years, 22 women) who had echocardiography in 4/17/2020–8/5/2020 were analyzed with EchoGo software, with output correlated against standard echocardiography measurements. After adjustment for the APACHE-4 score, associations with clinical outcomes were assessed. Mean EchoGo outputs were left ventricular end-diastolic volume (LVEDV) 121 ± 42 mL, end-systolic volume (LVESV) 53 ± 30 mL, ejection fraction (LVEF) 58 ± 11%, and global longitudinal strain (GLS) −16.1 ± 5.1%. Pearson correlation coefficients (p-value) with standard measurements were 0.810 ( 〈 0.001), 0.873 ( 〈 0.001), 0.528 ( 〈 0.001), and 0.690 ( 〈 0.001). The primary endpoint occurred in 26 (52%) patients. Adjusting for APACHE-4 score, EchoGo LVEF and LVGLS were associated with the primary endpoint, odds ratios (95% confidence intervals) of 0.92 (0.85–0.99) and 1.22 (1.03–1.45) per 1% increase, respectively. Automated AI software is a new clinical tool that may assist with patient care. EchoGo LVEF and LVGLS were associated with adverse outcomes in hospitalized COVID-19 patients and can play a role in their risk stratification.
    Type of Medium: Online Resource
    ISSN: 2075-1729
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2662250-6
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  • 9
    In: Children, MDPI AG, Vol. 8, No. 6 ( 2021-06-14), p. 503-
    Abstract: Tufting enteropathy (TE) is caused by recessive EPCAM mutations, and is characterized by intractable diarrhea of congenital onset and disorganization of enterocytes. TE generally requires parenteral nutrition (PN) during childhood or intestinal bowel transplantation. We report three unrelated families with six children with TE. We highlight the high rate of disease-related mortality. We observe adequate weight gain with PN, but low to normal and stunted body length, supporting the recent notion that a short stature might be intrinsic to TE. The diagnosis of TE in the index patients from each family was delayed for months to years, even when clinical data, duodenal biopsies, or exome sequencing data were obtained early on. We identified three novel pathogenic EPCAM variants: a deletion of exon 1 that removes the ATG initiation codon, a missense variant c.326A 〉 G (p.Gln109Arg), and nonsense mutation c.429G 〉 A (p.Trp143*) in a compound heterozygous state with the Mediterranean splice site variant c.556-14A 〉 G (Tyr186Phefs*6). Homozygosity for p.Gln109Arg was associated with absent EPCAM staining, and compound heterozygosity for p.Trp143*/Tyr186Phefs*6 was associated with reduced EPCAM staining in duodenal biopsies; such observations might contribute to a genotype–phenotype correlation in larger cohorts of TE patients. This study extends the clinical and molecular spectrum of TE.
    Type of Medium: Online Resource
    ISSN: 2227-9067
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2732685-8
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  • 10
    In: Molecules, MDPI AG, Vol. 28, No. 7 ( 2023-03-30), p. 3103-
    Abstract: Human immunodeficiency virus type I (HIV-1) is a retrovirus that infects cells of the host’s immune system leading to acquired immunodeficiency syndrome and potentially death. Although treatments are available to prevent its progression, HIV-1 remains a major burden on health resources worldwide. Continued emergence of drug-resistance mutations drives the need for novel drugs that can inhibit HIV-1 replication through new pathways. The viral protein reverse transcriptase (RT) plays a fundamental role in the HIV-1 replication cycle, and multiple approved medications target this enzyme. In this study, fragment-based drug discovery was used to optimize a previously identified hit fragment (compound B-1), which bound RT at a novel site. Three series of compounds were synthesized and evaluated for their HIV-1 RT binding and inhibition. These series were designed to investigate different vectors around the initial hit in an attempt to improve inhibitory activity against RT. Our results show that the 4-position of the core scaffold is important for binding of the fragment to RT, and a lead compound with a cyclopropyl substitution was selected and further investigated. Requirements for binding to the NNRTI-binding pocket (NNIBP) and a novel adjacent site were investigated, with lead compound 27—a minimal but efficient NNRTI—offering a starting site for the development of novel dual NNIBP-Adjacent site inhibitors.
    Type of Medium: Online Resource
    ISSN: 1420-3049
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2008644-1
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