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  • 1
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    Online Resource
    Neuroendocrine Differentiation in Conventional Colorectal Adenocarcinomas: Incidental Finding or Prognostic Biomarker?
    MDPI AG ; 2021
    In:  Cancers Vol. 13, No. 20 ( 2021-10-12), p. 5111-
    Details
    In: Cancers, MDPI AG, Vol. 13, No. 20 ( 2021-10-12), p. 5111-
    Abstract: Background: Colorectal mixed adenoneuroendocrine carcinomas (MANECs) are clinically highly aggressive neoplasms. MANECs are composed of variable adenocarcinoma components combined with morphologically distinct neuroendocrine carcinoma components, which are confirmed by synaptophysin immunohistochemistry, the gold standard marker of a neuroendocrine differentiation. However, the biological behavior of adenocarcinomas that express synaptophysin but do not show a typical neuroendocrine morphology remains unclear. Methods: We investigated synaptophysin expression in 1002 conventional colorectal adenocarcinomas and correlated the results with clinicopathological characteristics and patient survival and compared the survival characteristics of synaptophysin expression groups to MANECs. Results: Synaptophysin expression in conventional colorectal adenocarcinomas was associated with a shortened disease-free survival (p = 0.037), but not with overall survival or disease-specific survival (DSS) in univariate analyses and without any survival impact in multivariate analyses. Patients with “true” MANECs, on the other hand, showed a significantly shorter survival than all conventional adenocarcinomas with or without synaptophysin expression in uni- and multivariate analyses (e.g., multivariate DSS: p 〈 0.001, HR: 5.20). Conclusions: Our study demonstrates that synaptophysin expression in conventional colorectal adenocarcinomas, in contrast to MANECs, is not associated with a significantly poorer clinical outcome when compared to adenocarcinomas without synaptophysin expression. Furthermore, our data suggest that conventional adenocarcinomas with a diffuse synaptophysin expression should not be classified as MANECs, also strongly arguing that synaptophysin testing should be reserved for carcinomas with an H & E morphology suggestive of a neuroendocrine differentiation.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers13205111
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2527080-1
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  • 2
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    Prediction of the Postoperative Outcome in Liver Resection Using Perioperative Serum Lactate Levels
    MDPI AG ; 2023
    In:  Journal of Clinical Medicine Vol. 12, No. 6 ( 2023-03-07), p. 2100-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 12, No. 6 ( 2023-03-07), p. 2100-
    Abstract: Background: The aim of our study was to analyze perioperative lactate levels and their predictive value for postoperative mortality and morbidity after liver resection. Methods: The clinicopathological characteristics and outcomes of 152 patients who underwent liver resection for benign and malign diagnoses were analyzed retrospectively. Lactate concentrations at three different time points, (1) before liver resection (LAC-PRE), (2) after liver resection on day 0 (LAC-POST), and (3) on day one after the operation (LAC-POD1) were assessed regarding the prognostic value in predicting postoperative complications and mortality according to the Clavien–Dindo (CD) classification. Results: The rates of postoperative complications (CD ≥ IIIb) and mortality rates were 19.7% (N = 30) and 4.6% (N = 7), respectively. The LAC-PRE levels showed no correlation with the postoperative outcome. The ROC curve analysis showed that LCT-POST and LCT-POD1 values were moderately strong in predicting postoperative morbidity (0.681 and 0.768, respectively) and had strong predictive accuracies regarding postoperative mortality (0.800 and 0.838, respectively). The multivariate analysis revealed LAC-POST as a significant predictor of postoperative complications (CD ≥ IIIb: OR 9.28; 95% CI: 2.88–29.9; p 〈 0.001) and mortality (OR 11.69; 95% CI: 1.76–77.7; p = 0.011). Conclusion: Early postoperative lactate levels are a useful and easily practicable predictor of postoperative morbidity and mortality in patients after liver resection.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm12062100
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2662592-1
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  • 3
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    Effect of Fish Stock Density on Hormone Genes Expression from Brain and Gastrointestinal Tract of Salmo salar
    MDPI AG ; 2022
    In:  Animals Vol. 12, No. 9 ( 2022-05-04), p. 1174-
    Details
    In: Animals, MDPI AG, Vol. 12, No. 9 ( 2022-05-04), p. 1174-
    Abstract: A variety of long-term stress conditions may exist in fish cultivation, some of which are so severe that fish can no longer reestablish homeostasis. In teleost fish, the brain and gastrointestinal tract integrate signals that include the perception of stress factors regulating physiological responses, such as social stress by fish population density, where peripheral and central signals, such as peptide hormones, are the main regulators. Therefore, we proposed in this study to analyze the effect of different stock densities (SD) in the gene expression of brain neuropeptide Y (NPY) and calcitonin gene-related peptide (CGRP), together with the gastrointestinal peptide hormones leptin (Lep), vasointestinal peptide (VIP), and protachykinin-1 (Prk-1) in Salmo salar post-smolt. The coding sequence of S. salar VIP and Prk-1 precursors were firstly cloned and characterized. Then, the mRNA expression of these genes, together with the NPY, Lep, and CGRP genes, were evaluated in post-smolts kept at 11 Kg/m3, 20 Kg/m3, and 40 Kg/m3. At 14 days of culture, the brain CGRP and liver leptin mRNA levels increased three and tenfold in the post-smolt salmons kept at the highest SD, respectively. The high levels of leptin were kept during all the fish culture experiments. In addition, the highest expression of intestine VIP mRNA was obtained on Day 21 in the group of 40 Kg/m3 returning to baseline on Day 40. In terms of stress biochemical parameters, cortisol levels were increased in the 20 Kg/m3 and 40 Kg/m3 groups on Day 40 and were the highest in the 20 Kg/m3 group on Day 14. This study provides new insight into the gastrointestinal signals that could be affected by chronic stress induced by high stock density in fish farming. Thus, the expression of these peptide hormones could be used as molecular markers to improve production practices in fish aquaculture.
    Type of Medium: Online Resource
    ISSN: 2076-2615
    URL: Article
    DOI: 10.3390/ani12091174
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2606558-7
    SSG: 23
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  • 4
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    Autoantibodies to Vasoregulative G-Protein-Coupled Receptors Correlate with Symptom Severity, Autonomic Dysfunction and Disability in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
    MDPI AG ; 2021
    In:  Journal of Clinical Medicine Vol. 10, No. 16 ( 2021-08-19), p. 3675-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 10, No. 16 ( 2021-08-19), p. 3675-
    Abstract: Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is an acquired complex disease with patients suffering from the cardinal symptoms of fatigue, post-exertional malaise (PEM), cognitive impairment, pain and autonomous dysfunction. ME/CFS is triggered by an infection in the majority of patients. Initial evidence for a potential role of natural regulatory autoantibodies (AAB) to beta-adrenergic (AdR) and muscarinic acetylcholine receptors (M-AChR) in ME/CFS patients comes from a few studies. Methods: Here, we analyzed the correlations of symptom severity with levels of AAB to vasoregulative AdR, AChR and Endothelin-1 type A and B (ETA/B) and Angiotensin II type 1 (AT1) receptor in a Berlin cohort of ME/CFS patients (n = 116) by ELISA. The severity of disease, symptoms and autonomic dysfunction were assessed by questionnaires. Results: We found levels of most AABs significantly correlated with key symptoms of fatigue and muscle pain in patients with infection-triggered onset. The severity of cognitive impairment correlated with AT1-R- and ETA-R-AAB and severity of gastrointestinal symptoms with alpha1/2-AdR-AAB. In contrast, the patients with non-infection-triggered ME/CFS showed fewer and other correlations. Conclusion: Correlations of specific AAB against G-protein-coupled receptors (GPCR) with symptoms provide evidence for a role of these AAB or respective receptor pathways in disease pathomechanism.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm10163675
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
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  • 5
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    Carbapenem-Resistant Klebsiella pneumoniae Infections in ICU COVID-19 Patients—A Scoping Review
    MDPI AG ; 2021
    In:  Journal of Clinical Medicine Vol. 10, No. 10 ( 2021-05-12), p. 2067-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 10, No. 10 ( 2021-05-12), p. 2067-
    Abstract: Introduction: The spread of multidrug-resistant pathogens is a serious problem and challenge for the whole medical community. Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections in immunocompromised patients have a severe course and may be fatal. Increasingly, these bacteria are exhibiting resistance to carbapenem antibiotics, which have been used as so-called drugs of last resort. The emergence of the new coronavirus and the pandemic that it has caused require changes to protect against the spread of the new SARS-CoV-2. These changes paradoxically may contribute to the spread of other infections. Methods: PubMed, Cochrane Library databases were searched using relevant keywords. A literature review of carbapenem-resistant Klebsiella pneumoniae infection in patients hospitalized for COVID-19 was conducted according to PRISMA recommendations. A written review protocol was not prepared. Results: 1016 studies in scientific databases were searched. After rejecting duplicate studies, 964 results were obtained. Inclusion and exclusion criteria were then applied, and studies were qualitatively analyzed. Finally, 11 studies were included in the review. The results of infected patients were from six countries. The prevalence of CRKP in Covid-19 patients ranged from 0.35–53%. The majority of CRKP infected patients were male (85%), with a mean age of 61 years. Among isolates, the predominant genes were KPC, OXY-48, CTX-M, TEM, NDM and SHV. Conclusion: The results presented in our review indicate the necessity of paying attention to carbapenem-resistant Klebsiella pneumoniae infections in patients with COVID-19. In order to prevent the increase of bacterial resistance, rational antibiotic therapy should be used, as well as continuous control and surveillance of hospital infections caused by multidrug-resistant organisms.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm10102067
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2662592-1
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  • 6
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    Risk Factors of Proximal Junctional Kyphosis in Adolescent Idiopathic Scoliosis—The Spinous Processes and Proximal Rod Contouring
    MDPI AG ; 2022
    In:  Journal of Clinical Medicine Vol. 11, No. 20 ( 2022-10-16), p. 6098-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 11, No. 20 ( 2022-10-16), p. 6098-
    Abstract: Proximal junctional kyphosis (PJK), as one of the most discussed problems after corrective surgery in adolescent idiopathic scoliosis (AIS), is still not fully clarified and seems to be multifactorial. Biomechanical and a few clinical studies have shown the influence of destruction of posterior ligaments by resection of spinous processes and some parameters concerning rod contouring as risk factors for PJK. To verify these results, 192 patients with AIS and corrective surgery via a posterior approach between 2009 and 2017 were included. Radiographic parameters were analyzed preoperatively (preOP), postoperatively (postOP), and with a mean follow up (FU) of 27 months. The participants were divided into two groups (PJK group and non-PJK group). The incidence of PJK was 15.6%. Contrary to the results of biomechanical studies, we could not find any significant influence of the spinous process resection. However, the PJK group had significantly larger preOP T4–T12 kyphosis (31.1° ± 13.93° vs. 23.3° ± 14.93°, p = 0.016). Furthermore, the PJK group showed a significantly larger rod contour angle (RCA) (8.0° ± 4.44° vs. 5.9° ± 3.28°, p = 0.003) and mismatch of postOP proximal junctional angle (PJA) and RCA (3.5° ± 5.72° vs. 0.9° ± 4.86°, p = 0.010) compared to the non-PJK group. An increase in the mismatch of postOP PJA and RCA (OR = 1.14, p = 0.008) and a high RCA are risk factors for PJK and need to be focused on by surgeons.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm11206098
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
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  • 7
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    Left Atrial Posterior Wall Isolation with Pulsed Field Ablation in Persistent Atrial Fibrillation
    MDPI AG ; 2023
    In:  Journal of Clinical Medicine Vol. 12, No. 19 ( 2023-09-29), p. 6304-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 12, No. 19 ( 2023-09-29), p. 6304-
    Abstract: Background: Left atrial posterior wall isolation (LAPWI) may improve rhythm control in addition to pulmonary vein isolation (PVI) in persistent atrial fibrillation (persAF) patients undergoing catheter ablation (CA). However, LAPWI may be challenging when using thermal energy sources. Objective: This study aimed to investigate the efficacy and safety of LAPWI performed by non-thermal pulsed field ablation (PFA) in CA for persAF. Methods: Consecutive persAF patients from two German centers were prospectively enrolled. There were two study cohorts: (1) the LAPWI cohort, which included PFA-guided (re-)PVI with LAPWI for first-time and/or repeat ablation procedures; and (2) a comparative persAF cohort with a PFA PVI-only approach without LAPWI for first-time ablation within the same timeframe. Patients were followed up by routine Holter ECGs. Results: In total, 79 persistent AF patients were included in the study: 59/79 patients were enrolled in the LAPWI cohort, including 16/59 index (27%) and 43/59 repeat ablation procedures (73%). Sixteen patients (16/79; 21%) were in the PVI-only cohort without LAPWI. Of the patients treated with LAPWI, procedure time and fluoroscopy time was 91 ± 30 min and 15 ± 7 min, respectively. The acute PVI rate was 100% in all first-time ablation patients (32 patients (16 PVI only, 16 PVI plus LAPWI), 196/196 PVs). Of the 43 re-do patients in the LAPWI cohort, re-PVI was necessary in 33% (14/43) of patients (27 PVs; 1.9 PV per-patient); in 67% (29/43), all PVs were isolated, and antral ablation of the PV ostia was performed in 48% (14/29). LAPWI was performed successfully in all 59 (100%) patients of the LAPWI cohort. Two minor complications occurred. No esophageal lesion was detected in the LAPWI cohort (n = 33/59 (56%) patients underwent endoscopy). After 354 ± 197 days of follow-up, freedom from atrial arrhythmias was 79.3% (95-CI: 62–95%) in the complete LAPWI cohort (n = 14/59 (24%) on AAD: class Ic n = 9, class III n = 5). There was no difference regarding acute procedural and clinical outcome compared to the PVI-only cohort. Conclusion: LAPWI guided by PFA is feasible and safe in patients undergoing CA for persAF and shows favorable outcomes. In the context of durable PVI, PFA-guided LAPWI may be an effective adjunctive treatment option.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm12196304
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
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  • 8
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    Behavioural Fever Promotes an Inflammatory Reflex Circuit in Ectotherms
    MDPI AG ; 2021
    In:  International Journal of Molecular Sciences Vol. 22, No. 16 ( 2021-08-17), p. 8860-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 22, No. 16 ( 2021-08-17), p. 8860-
    Abstract: Background: The communication between the brain and the immune system is a cornerstone in animal physiology. This interaction is mediated by immune factors acting in both health and pathogenesis, but it is unclear how these systems molecularly and mechanistically communicate under changing environmental conditions. Behavioural fever is a well-conserved immune response that promotes dramatic changes in gene expression patterns during ectotherms’ thermoregulatory adaptation, including those orchestrating inflammation. However, the molecular regulators activating the inflammatory reflex in ectotherms remain unidentified. Methods: We revisited behavioural fever by providing groups of fish a thermal gradient environment during infection. Our novel experimental setup created temperature ranges in which fish freely moved between different thermal gradients: (1) wide thermoregulatory range; T° = 6.4 °C; and (2) restricted thermoregulatory range; T° = 1.4 °C. The fish behaviour was investigated during 5-days post-viral infection. Blood, spleen, and brain samples were collected to determine plasmatic pro- and anti-inflammatory cytokine levels. To characterize genes’ functioning during behavioural fever, we performed a transcriptomic profiling of the fish spleen. We also measured the activity of neurotransmitters such as norepinephrine and acetylcholine in brain and peripheral tissues. Results: We describe the first set of the neural components that control inflammatory modulation during behavioural fever. We identified a neuro-immune crosstalk as a potential mechanism promoting the fine regulation of inflammation. The development of behavioural fever upon viral infection triggers a robust inflammatory response in vivo, establishing an activation threshold after infection in several organs, including the brain. Thus, temperature shifts strongly impact on neural tissue, specifically on the inflammatory reflex network activation. At the molecular level, behavioural fever causes a significant increase in cholinergic neurotransmitters and their receptors’ activity and key anti-inflammatory factors such as cytokine Il10 and Tgfβ in target tissues. Conclusion: These results reveal a cholinergic neuronal-based mechanism underlying anti-inflammatory responses under induced fever. We performed the first molecular characterization of the behavioural fever response and inflammatory reflex activation in mobile ectotherms, identifying the role of key regulators of these processes. These findings provide genetic entry points for functional studies of the neural–immune adaptation to infection and its protective relevance in ectotherm organisms.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms22168860
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 9
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    Significant Tumor Regression after Neoadjuvant Chemotherapy in Gastric Cancer, but Poor Survival of the Patient? Role of MHC Class I Alterations
    MDPI AG ; 2023
    In:  Cancers Vol. 15, No. 3 ( 2023-01-26), p. 771-
    Details
    In: Cancers, MDPI AG, Vol. 15, No. 3 ( 2023-01-26), p. 771-
    Abstract: We aimed to determine the clinical and prognostic relevance of allelic imbalance (AI) of the major histocompatibility complex (MHC) class I genes, encompassing the human leukocyte antigen (HLA) class I and beta-2 microglobulin (B2M) genes, in the context of neoadjuvant platinum/fluoropyrimidine chemotherapy (CTx). Biopsies before CTx were studied in 158 patients with adenocarcinoma of the stomach or gastroesophageal junction. The response was histopathologically evaluated. AI was detected by multiplex PCRs analysis of four or five microsatellite markers in HLA and B2M regions, respectively. AI with no marker was significantly associated with response or survival. However, subgroup analysis revealed differences. AI at marker D6S265, close to the HLA-A gene, was associated with an obvious increased risk in responding (HR, 3.62; 95% CI, 0.96–13.68, p = 0.058) but not in non-responding patients (HR, 0.92; 95% CI, 0.51–1.65, p = 0.773). Markers D6S273 and D6S2872 showed similar results. The interaction between AI at D6S265 and response to CTx was significant in a multivariable analysis (p = 0.010). No associations were observed for B2M markers. Our results underline the importance of intact neoantigen presentation specifically for responding patients and may help explain an unexpectedly poor survival of a patient despite significant tumor regression after neoadjuvant platinum/fluoropyrimidine CTx.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers15030771
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2527080-1
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  • 10
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    Evaluation of a Developed MRI-Guided Focused Ultrasound System in 7 T Small Animal MRI and Proof-of-Concept in a Prostate Cancer Xenograft Model to Improve Radiation Therapy
    MDPI AG ; 2023
    In:  Cells Vol. 12, No. 3 ( 2023-02-02), p. 481-
    Details
    In: Cells, MDPI AG, Vol. 12, No. 3 ( 2023-02-02), p. 481-
    Abstract: Focused ultrasound (FUS) can be used to physiologically change or destroy tissue in a non-invasive way. A few commercial systems have clinical approval for the thermal ablation of solid tumors for the treatment of neurological diseases and palliative pain management of bone metastases. However, the thermal effects of FUS are known to lead to various biological effects, such as inhibition of repair of DNA damage, reduction in tumor hypoxia, and induction of apoptosis. Here, we studied radiosensitization as a combination therapy of FUS and RT in a xenograft mouse model using newly developed MRI-compatible FUS equipment. Xenograft tumor-bearing mice were produced by subcutaneous injection of the human prostate cancer cell line PC-3. Animals were treated with FUS in 7 T MRI at 4.8 W/cm2 to reach ~45 °C and held for 30 min. The temperature was controlled via fiber optics and proton resonance frequency shift (PRF) MR thermometry in parallel. In the combination group, animals were treated with FUS followed by X-ray at a single dose of 10 Gy. The effects of FUS and RT were assessed via hematoxylin-eosin (H & E) staining. Tumor proliferation was detected by the immunohistochemistry of Ki67 and apoptosis was measured by a TUNEL assay. At 40 days follow-up, the impact of RT on cancer cells was significantly improved by FUS as demonstrated by a reduction in cell nucleoli from 189 to 237 compared to RT alone. Inhibition of tumor growth by 4.6 times was observed in vivo in the FUS + RT group (85.3%) in contrast to the tumor volume of 393% in the untreated control. Our results demonstrated the feasibility of combined MRI-guided FUS and RT for the treatment of prostate cancer in a xenograft mouse model and may provide a chance for less invasive cancer therapy through radiosensitization.
    Type of Medium: Online Resource
    ISSN: 2073-4409
    URL: Article
    DOI: 10.3390/cells12030481
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2661518-6
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