Influencing Factors on the Quality of Lymph Node Dissection for Stage IA Non-Small Cell Lung Cancer: A Retrospective Nationwide Cohort Study.

Lymphadenectomy is an essential part of complete surgical operation for non-small cell lung cancer (NSCLC). This retrospective, multicenter cohort study aimed to identify factors that influence the lymphadenectomy quality. Data were obtained from the Polish Lung Cancer Study Group Database. The primary endpoint was lobe-specific mediastinal lymph node dissection (L-SMLND). The study included 4271 patients who underwent VATS lobectomy for stage IA NSCLC, operated between 2007 and 2022. L-SMLND was performed in 1190 patients (27.9%). The remaining 3081 patients (72.1%) did not meet the L-SMLND criteria. Multivariate logistic regression analysis showed that patients with PET-CT (OR 3.238, 95% CI: 2.315 to 4.529; p < 0.001), with larger tumors (pT1a vs. pT1b vs. pT1c) (OR 1.292; 95% CI: 1.009 to 1.653; p = 0.042), and those operated on by experienced surgeons (OR 1.959, 95% CI: 1.432 to 2.679; p < 0.001) had a higher probability of undergoing L-SMLND. The quality of lymphadenectomy decreased over time (OR 0.647, 95% CI: 0.474 to 0.884; p = 0.006). An analysis of propensity-matched groups showed that more extensive lymph node dissection was not related to in-hospital mortality, complication rates, and hospitalization duration. Actions are needed to improve the quality of lymphadenectomy for NSCLC.

Combining bioengineered human skin with bioprinted cartilage for ear reconstruction.

Microtia is a congenital disorder that manifests as a malformation of the external ear leading to psychosocial problems in affected children. Here, we present a tissue-engineered treatment approach based on a bioprinted autologous auricular cartilage construct (EarCartilage) combined with a bioengineered human pigmented and prevascularized dermo-epidermal skin substitute (EarSkin) tested in immunocompromised rats. We confirmed that human-engineered blood capillaries of EarSkin connected to the recipient's vasculature within 1 week, enabling rapid blood perfusion and epidermal maturation. Bioengineered EarSkin displayed a stratified epidermis containing mature keratinocytes and melanocytes. The latter resided within the basal layer of the epidermis and efficiently restored the skin color. Further, in vivo tests demonstrated favorable mechanical stability of EarCartilage along with enhanced extracellular matrix deposition. In conclusion, EarCartilage combined with EarSkin represents a novel approach for the treatment of microtia with the potential to circumvent existing limitations and improve the aesthetic outcome of microtia reconstruction.

Characterization of Distinct Chondrogenic Cell Populations of Patients Suffering from Microtia Using Single-Cell Micro-Raman Spectroscopy.

Microtia is a congenital condition of abnormal development of the outer ear. Tissue engineering of the ear is an alternative treatment option for microtia patients. However, for this approach, the identification of high regenerative cartilage progenitor cells is of vital importance. Raman analysis provides a novel, non-invasive, label-free diagnostic tool to detect distinctive biochemical features of single cells or tissues. Using micro-Raman spectroscopy, we were able to distinguish and characterize the particular molecular fingerprints of differentiated chondrocytes and perichondrocytes and their respective progenitors isolated from healthy individuals and microtia patients. We found that microtia chondrocytes exhibited lower lipid concentrations in comparison to healthy cells, thus indicating the importance of fat storage. Moreover, we suggest that collagen is a useful biomarker for distinguishing between populations obtained from the cartilage and perichondrium because of the higher spectral contributions of collagen in the chondrocytes compared to perichondrocytes from healthy individuals and microtia patients. Our results represent a contribution to the identification of cell markers that may allow the selection of specific cell populations for cartilage tissue engineering. Moreover, the observed differences between microtia and healthy cells are essential for gaining better knowledge of the cause of microtia. It can be useful for designing novel treatment options based on further investigations of the discovered biochemical substrate alterations.

Identification of Factors Related to the Quality of Lymphadenectomy for Lung Cancer: Secondary Analysis of Prospective Randomized Trial Data.

The outcomes of non-small cell lung cancer surgery are influenced by the quality of lymphadenectomy. This study aimed to evaluate the impact of different energy devices on lymphadenectomy quality and identify additional influencing factors. This secondary analysis of the prospective randomized trial data (clinicaltrials.gov: NCT03125798) compared patients who underwent thoracoscopic lobectomy with the LigaSure device (study group, n = 96) and monopolar device (control group, n = 94). The primary endpoint was the lobe-specific mediastinal lymphadenectomy. Lobe-specific mediastinal lymphadenectomy criteria were met in 60.4% and 38.3% of patients in the study and control groups, respectively (p = 0.002). In addition, in the study group, the median number of mediastinal lymph node stations removed was higher (4 vs. 3, p = 0.017), and complete resection was more often achieved (91.7% vs. 80.9%, p = 0.030). Logistic regression analysis indicated that lymphadenectomy quality was positively associated with the use of the LigaSure device (OR, 2.729; 95% CI, 1.446 to 5.152; p = 0.002) and female sex (OR, 2.012; 95% CI, 1.058 to 3.829; p = 0.033), but negatively associated with a higher Charlson Comorbidity Index (OR, 0.781; 95% CI, 0.620 to 0.986; p = 0.037), left lower lobectomy (OR, 0.263; 95% CI, 0.096 to 0.726; p = 0.010) and middle lobectomy (OR, 0.136; 95% CI, 0.031 to 0.606, p = 0.009). This study found that using the LigaSure device can improve the quality of lymphadenectomy in lung cancer patients and also identified other factors that affect the quality of lymphadenectomy. These findings contribute to improving lung cancer surgical treatment outcomes and provide valuable insights for clinical practice.

Outcomes of lung cancer surgery in patients with COVID-19 history: a single center cohort study.

OBJECTIVES: Coronavirus disease 2019 (COVID-19) can irreversibly damage the lungs and could possibly increase the risk of surgical treatment of lung cancer. The study aimed to assess the relationship between preoperative COVID-19 and complications and early outcomes of lung cancer surgery. METHODS: This single-center cohort study included 444 patients who underwent lobectomy or segmentectomy for primary lung cancer from January 1, 2019 to December 31, 2021. The exclusion criteria were pneumonectomy, extended resection, and wedge resection. The groups of patients with (n = 72) and without (n = 372) the history of COVID-19 prior to surgery were compared. The groups were similar in terms of distribution of baseline, surgical and histopathological characteristics. The primary endpoint was the incidence of postoperative complications. Secondary endpoints were outcomes at discharge and at 90 days. RESULTS: The incidence of postoperative complications did not differ between the groups of patients with and without COVID-19 history (30.6% vs 29.3%, p = 0.831). Outcomes at discharge and at 90 days after surgery did not differ between the groups. Among the patients with and without prior COVID-19, 97.2 and 99.5% were alive at discharge (p = 0.125), and 97.2% and 98.1% ninety days after surgery (p = 0.644), respectively. Patients with COVID-19 history more often required re-drainage (6.9% v 2.2%, p = 0.044) and reoperation (5.6 v 1.3%, p = 0.042). CONCLUSIONS: COVID-19 history is not related to the general incidence of complications, outcomes at discharge from the hospital, and at 90-days after surgery.

The Role of CD200-CD200 Receptor in Human Blood and Lymphatic Endothelial Cells in the Regulation of Skin Tissue Inflammation.

CD200 is a cell membrane glycoprotein that interacts with its structurally related receptor (CD200R) expressed on immune cells. We characterized CD200-CD200R interactions in human adult/juvenile (j/a) and fetal (f) skin and in in vivo prevascularized skin substitutes (vascDESS) prepared by co-culturing human dermal microvascular endothelial cells (HDMEC), containing both blood (BEC) and lymphatic (LEC) EC. We detected the highest expression of CD200 on lymphatic capillaries in j/a and f skin as well as in vascDESS in vivo, whereas it was only weakly expressed on blood capillaries. Notably, the highest CD200 levels were detected on LEC with enhanced Podoplanin expression, while reduced expression was observed on Podoplanin-low LEC. Further, qRT-PCR analysis revealed upregulated expression of some chemokines, including CC-chemokine ligand 21 (CCL21) in j/aCD200+ LEC, as compared to j/aCD200- LEC. The expression of CD200R was mainly detected on myeloid cells such as granulocytes, monocytes/macrophages, T cells in human peripheral blood, and human and rat skin. Functional immunoassays demonstrated specific binding of skin-derived CD200+ HDMEC to myeloid CD200R+ cells in vitro. Importantly, we confirmed enhanced CD200-CD200R interaction in vascDESS in vivo. We concluded that the CD200-CD200R axis plays a crucial role in regulating tissue inflammation during skin wound healing.

Bio-engineering a prevascularized human tri-layered skin substitute containing a hypodermis.

Severe injuries to skin including hypodermis require full-thickness skin replacement. Here, we bioengineered a tri-layered human skin substitute (TLSS) containing the epidermis, dermis, and hypodermis. The hypodermal layer was generated by differentiation of human adipose stem cells (ASC) in a collagen type I hydrogel and combined with a prevascularized dermis consisting of human dermal microvascular endothelial cells and fibroblasts, which arranged into a dense vascular network. Subsequently, keratinocytes were seeded on top to generate the epidermal layer of the TLSS. The differentiation of ASC into adipocytes was confirmed in vitro on the mRNA level by the presence of adiponectin, as well as by the expression of perilipin and FABP-4 proteins. Moreover, functional characteristics of the hypodermis in vitro and in vivo were evaluated by Oil Red O, BODIPY, and AdipoRed stainings visualizing intracellular lipid droplets. Further, we demonstrated that both undifferentiated ASC and mature adipocytes present in the hypodermis influenced the keratinocyte maturation and homeostasis in the skin substitutes after transplantation. In particular, an enhanced secretion of TGF-ß1 by these cells affected the epidermal morphogenesis as assessed by the expression of key proteins involved in the epidermal differentiation including cytokeratin 1, 10, 19 and cornified envelope formation such as involucrin. Here, we propose a novel functional hypodermal-dermo-epidermal tri-layered skin substitute containing blood capillaries that efficiently promote regeneration of skin defects. STATEMENT OF SIGNIFICANCE: The main objective of this study was to develop and assess the usefulness of a tri-layered human prevascularized skin substitute (TLSS) containing an epidermis, dermis, and hypodermis. The bioengineered hypodermis was generated from human adipose mesenchymal stem cells (ASC) and combined with a prevascularized dermis and epidermis. The TLSS represents an exceptional model for studying the role of cell-cell and cell-matrix interactions in vitro and in vivo. In particular, we observed that enhanced secretion of TGF-ß1 in the hypodermis exerted a profound impact on fibroblast and keratinocyte differentiation, as well as epidermal barrier formation and homeostasis. Therefore, improved understanding of the cell-cell interactions in such a physiological skin model is essential to gain insights into different aspects of wound healing.

Artificial miRNAs targeting CAG repeat expansion in ORFs cause rapid deadenylation and translation inhibition of mutant transcripts.

Polyglutamine (polyQ) diseases are incurable neurological disorders caused by CAG repeat expansion in the open reading frames (ORFs) of specific genes. This type of mutation in the HTT gene is responsible for Huntington's disease (HD). CAG repeat-targeting artificial miRNAs (art-miRNAs) were shown as attractive therapeutic approach for polyQ disorders as they caused allele-selective decrease in the level of mutant proteins. Here, using polyQ disease models, we aimed to demonstrate how miRNA-based gene expression regulation is dependent on target sequence features. We show that the silencing efficiency and selectivity of art-miRNAs is influenced by the localization of the CAG repeat tract within transcript and the specific sequence context. Furthermore, we aimed to reveal the events leading to downregulation of mutant polyQ proteins and found very rapid activation of translational repression and HTT transcript deadenylation. Slicer-activity of AGO2 was dispensable in this process, as determined in AGO2 knockout cells generated with CRISPR-Cas9 technology. We also showed highly allele-selective downregulation of huntingtin in human HD neural progenitors (NPs). Taken together, art-miRNA activity may serve as a model of the cooperative activity and targeting of ORF regions by endogenous miRNAs.

Prognostic value of the six-minute walk test in heart failure patients undergoing cardiac surgery: a literature review.

Background. The prognostic value of cardiopulmonary exercise testing (CPET) is known, but the predictive value of 6MWT in patients with heart failure (HF) and patients undergoing coronary artery bypass grafting (CABG) is not established yet. Objective. We conducted a systematic review exploring the prognostic value of 6MWT in HF patients undergoing cardiac surgery. The aim was to find out whether the change in the distance walked during follow-up visits was associated with prognosis. Data Source. We searched "PubMed" from January 1990 to December 2012 for any review articles or experimental studies investigating the prognostic value of 6MWT in HF patients and patients undergoing cardiac surgery. Results. 53 studies were included in the review, and they explored the role of 6MWT in cardiology, cardiac surgery, and rehabilitation. The results did not show the relation between the six-minute walk distance and adverse events after CABG. The predictive power of the distance walked for death in HF patients undergoing cardiac surgery was not found. It is not yet proved if the change in the six-minute walk distance is associated with prognosis. The predictive power of the six-minute walk distance for death in HF patients undergoing cardiac surgery remains unclear.

The risk for syncope and presyncope during surgery in surgeons and nurses.

BACKGROUND: Surgeons and nurses are exposed to orthostatic stress. AIMS: To assess the lifetime incidence of syncopal and presyncopal events during surgery in operation room staff and reveal the predicting factors. METHODS AND RESULTS: The study included 317 subjects (161 F, 156 M) aged 43.9 ± 9.6; 216 surgeons and 101 instrumenters. The study included filling of an anonymous questionnaire on the syncope and presyncope history. RESULTS: At least one syncopal event during operation was reported by 4.7% and presyncope by 14.8% of the studied population. All but one subject reported prodromal symptoms before syncope. In the medical history, syncope outside the operating room was reported by 11% of the studied group. Syncope and presyncope during operation was related to syncope in the medical history outside the operation room, respectively: odds ratio (OR) 20.2 95% confidence interval (CI): 2.0-70.5 and OR 10.8; CI: 5.0-23.4 and to presyncope in the medical history, respectively: OR 23.5; CI: 7.4-74.4 OR 8.9; CI: 3.6-11.2 (P < 0.001). CONCLUSIONS: (1) Syncope and presyncope may occur during surgery in the staff of the operating room. (2) Syncope in the operating room is usually preceded by prodromal symptoms and has vasovagal origin. (3) Both lower then expected occurrence of syncope in the operating room staff and absence of any difference between genders in this regard indicate preselection in the process of choosing profession and specialization. (4) Syncope and presyncope outside the operating room in medical history increases the risk of syncope and presyncope inside the operation room.

Health-related quality of life in patients with coronary heart disease after residential vs ambulatory cardiac rehabilitation.

BACKGROUND: The aim of this study was to evaluate the influence of residential (RCR) vs ambulatory (ACR) cardiac rehabilitation (CR) on health-related quality of life (QOL) connected with changes in exercise capacity of patients with coronary heart disease (CHD). METHODS AND RESULTS: The 562 patients with CHD were studied: 313 participants in RCR and 249 participants in ACR. The examination was performed at the beginning of CR and after 8 weeks. QOL was assessed using the EuroQuol 5D (EQ-5D) and SF36 questionnaires. Exercise testing was performed with evaluation of workload during the last stage of the test and rate of perceived exertion intensity. In the first examination, patients from both groups did not differ significantly. After 8 weeks, a similar improvement in QOL was observed in both settings of CR according to EQ-5D and SF36 results. Health status was improved by 11.1% in the RCR group and by 10.4% in the ACR group. Last workload's intensity increased significantly by 32.1% in the RCR group and by 38.1% in the ACR group. The rate of perceived exertion intensity did not change despite the bigger workloads during the exercise test. CONCLUSIONS: Comprehensive CR improves health-related QOL and exercise capacity without differences between residential and ambulatory models.

The CAREGENE study: polymorphisms of the beta1-adrenoceptor gene and aerobic power in coronary artery disease.

AIMS: The heritability of aerobic power and of the response to physical training has been shown in healthy subjects. beta(1)-Adrenergic receptor (beta(1)AR) function affects exercise performance. This study aims to investigate whether the Ser49Gly and Gly389Arg polymorphisms of the beta(1)AR gene or their haplotypes are associated with aerobic power or its response to physical training in coronary artery disease (CAD). METHODS AND RESULTS: Nine hundred and thirty-five biologically unrelated Caucasian patients with CAD who had exercised until exhaustion during graded bicycle testing at baseline and after completion of 3 months of exercise training from 1990 to 2001 (n = 1095) were eligible for inclusion in the CAREGENE (CArdiac REhabilitation and GENetics of Exercise performance) study. Polymorphisms were detected using the invader assay (Third Wave Technologiestrade mark, Madison, Wisconsin, USA). Patients with the Gly49Gly genotype had significantly higher covariate-adjusted aerobic power at baseline than those with Ser49Ser and Ser49Gly (P < 0.05). Adjusted aerobic power at baseline was highest in the Ser49-Gly389/Gly49-Gly389 and Gly49-Arg389/Gly49-Arg389 haplotype combinations. Aerobic power increased significantly (P < 0.001) with physical training. There was no association with the effect of physical training. CONCLUSION: Ser49Gly and haplotype combinations of Ser49Gly and Gly389Arg of the beta(1)AR gene are associated with aerobic power, but not with the response to physical training in patients with CAD included in the CAREGENE study.

The caregene study: muscle-specific creatine kinase gene and aerobic power in coronary artery disease.

In 927 biologically unrelated Caucasian patients with coronary artery disease it was investigated whether the NcoI restriction fragment length polymorphism of the muscle-specific creatine kinase (CKMM) gene is associated with aerobic power and with the response to physical training. Physical training significantly (P<0.001) increased peak oxygen consumption in the GG, AG and AA NcoI genotypes. Covariate-adjusted peak oxygen consumption at baseline, after training and the response to training were not different across CKMM NcoI genotypes.