Development of a transcriptome-based determination of innate immune suppressor (TDIS) assay as an in vitro test for immunotoxicity.

Immunotoxicity has been an important topic in toxicology since inadvertent exposures to xenobiotics were found to alter immune functions in humans. While rodent toxicity tests can reveal some levels of immunotoxicity, alternative methods must be developed to identify the detailed mechanisms. In this study, a method of in vitro prediction of innate immune suppression by substances was developed using a genomics approach. The primary selection of immune suppressors was based on their ability to downregulate MCP-1, CCL3, TNF, IL-8, and IL-12p40 expression levels in lipopolysaccharide (LPS)-stimulated THP-1 cells. Among 11 substances classified as potent immune suppressors, six including dexamethasone, tacrolimus, tofacitinib, prednisolone, sodium lauryl sulfate, and benzoic acid were used to create a dataset by transcriptomics of chemical-treated THP-1 cells using bulk RNA sequencing. We selected genes that were significantly upregulated by suppressor treatment while filtering out genes also upregulated in LPS-treated THP-1 cells. We identified a 226-gene immunosuppressive gene set (ISG). Innate immune suppressor signature scores were calculated as the median expression of the ISG. In a validation dataset, the signature score predicted acyclovir, cyclosporine, and mercuric chloride as immune suppressors, while selecting genistein as a non-immune suppressor. Although more dataset integration is needed in the future, our results demonstrated the possibility and utility of a novel genomics-based approach, the transcriptome-based determination of innate immune suppressor (TDIS) assay, to evaluate innate immune suppression by different substances. This provides insight into the development of future alternative testing methods because it reflects a comprehensive genetic signature derived from multiple substances rather than one cytokine.

Use of a pectus bar for surgical stabilization of cardiopulmonary resuscitation induced flail chest.

A flail chest can occur when cardiopulmonary resuscitation causes extensive rib fractures. Despite successful cardiopulmonary resuscitation, if the flail chest is not treated, the patient may not survive regardless of the correction of the primary condition that caused the cardiac arrest. Therefore, if flail chest persists despite the appropriate conservative management to correct the flail chest, active surgical management is essential. We present a successful surgical treatment with a pectus bar for a patient with flail chest, caused by extensive segmental rib fractures sustained during cardiopulmonary resuscitation for a massive pulmonary thromboembolism.

Incidence of Postoperative Chylothorax Following Congenital Heart Surgery in Pediatric Patients: A Single-Center Experience.

BACKGROUND: Although postoperative chylothorax following congenital heart surgery occurs rarely, it is associated with substantial morbidity and mortality. The incidence of postoperative chylothorax has been reported as 2% to 5%. Therefore, we aimed to evaluate the incidence of postoperative chylothorax at our center and compared our results with those of other studies. METHODS: Between January 2009 and December 2018, there were 2,515 congenital heart repair surgeries performed at our center. Thirty-six patients with postoperative chylothorax were enrolled in this study, and their medical records retrospectively were reviewed. We calculated the overall and surgery-specific incidences. We compared the data of the medical management group with those of the surgical management group. RESULTS: The overall incidence of postoperative chylothorax was 1.4%. The incidence was highest for patients who underwent vascular ring repair (3/32). Moreover, the incidence was higher for single ventricle-related procedure than bi-ventricle-related procedures (5.6% versus 1.0%, P < .0001). Chylothorax was predominantly found on the left side (20/36). Among these cases, six patients died; three of these six were in the surgical management group. CONCLUSIONS: The postoperative chylothorax incidence at our center was comparable to those of other centers. However, a reasonable protocol for postoperative chylothorax management to improve outcomes is necessary.

PAK1 as a Potential Therapeutic Target in Male Smokers with EGFR-Mutant Non-Small Cell Lung Cancer.

P21-activated kinases (PAKs) are serine/threonine protein kinases that contribute to several cellular processes. Here, we aimed to determine the prognostic value of PAK1 and its correlation with the clinicopathological characteristics and five-year survival rates in patients with non-small cell lung cancer (NSCLC). We evaluated PAK1 mRNA and protein expression in NSCLC cells and resected tumor specimens, as well as in healthy human bronchial epithelial cells and adjacent healthy lung tissues, respectively, for effective comparison. Immunohistochemical tissue microarray analysis of 201 NSCLC specimens showed the correlation of PAK1 expression with clinicopathological characteristics. The mRNA and protein expression of PAK1 were 2.9- and 4.3-fold higher in six of seven NSCLC cell types and human tumors (both, p < 0.001) than in healthy human bronchial epithelial BEAS-2B cells and adjacent healthy lung tissues, respectively. Decreased survival was significantly associated with PAK1 overexpression in the entire cohort (χ2 = 8.48, p = 0.0036), men (χ2 = 17.1, p < 0.0001), and current and former smokers (χ2 = 19.2, p < 0.0001). Notably, epidermal growth factor receptor (EGFR) mutation-positive lung cancer patients with high PAK1 expression showed higher mortality rates than those with low PAK1 expression (91.3% vs. 62.5%, p = 0.02). Therefore, PAK1 overexpression could serve as a molecular target for the treatment of EGFR mutation-positive lung cancer, especially among male patients and current/former smokers.

Early results of modified aortic-valve sparing partial root replacement in acute type A aortic dissection with an intimal tear in the aortic sinuses.

We describe a modified aortic valve-sparing partial root replacement (AVSPRR) technique for acute type A aortic dissection with an intimal tear (IT) in the aortic sinus. This procedure consists of selective replacement of the sinus containing an IT with a rectangular patch. If an IT exists in any coronary sinus, the coronary button was reimplanted to the neo-sinus and an external wrapping of the noncoronary sinus was added. Modified AVSPRR may be considered a feasible short-term outcome, and may be considered as an option in selected patients.

Impact of Respiratory Phase during Pleural Puncture on Complications in CT-Guided Percutaneous Lung Biopsy.

Purpose: This study investigated whether the respiratory phase during pleural puncture in CT-guided percutaneous transthoracic needle biopsy (PTNB) affects complications. Materials and Methods: We conducted a retrospective review of 477 lung biopsy CT scans performed during free breathing. The respiratory phases during pleural puncture were determined based on the table position of the targeted nodule using CT scans obtained during free breathing. We compared the rates of complications among the inspiratory, mid-, and expiratory respiratory phases. Logistic regression analysis was performed to control confounding factors associated with pneumothorax. Results: Among the 477 procedures, pleural puncture was performed during the expiratory phase in 227 (47.6%), during the mid-phase in 108 (22.6%), and during the inspiratory phase in 142 (29.8%). The incidence of pneumothorax was significantly lower in the expiratory puncture group (40/227, 17.6%; p = 0.035) and significantly higher in the mid-phase puncture group (31/108, 28.7%; p = 0.048). After controlling for confounding factors, expiratory-phase puncture was found to be an independent protective factor against pneumothorax (odds ratio = 0.571; 95% confidence interval = 0.360-0.906; p = 0.017). Conclusion: Our findings suggest that pleural puncture during the expiratory phase may reduce the risk of pneumothorax during image guided PTNB.

New Heteroleptic Germanium Precursors for GeO2 Thin Films by Atomic Layer Deposition.

This study describes the synthesis of 12 new germanium complexes containing ß-diketonate and/or N-alkoxy carboxamidate-type ligands as precursors for GeO2 through atomic layer deposition (ALD). A series of Ge(ß-diketonate)Cl complexes such as Ge(acac)Cl (1) and Ge(tmhd)Cl (2) were synthesized by using acetylacetone (acacH) and 2,2,6,6-tetramethyl-3,5-heptanedione (tmhdH). N-Alkoxy carboxamidate-type ligands such as N-methoxypropanamide (mpaH), N-methoxy-2,2-dimethylpropanamide (mdpaH), N-ethoxy-2-methylpropanamide (empaH), N-ethoxy-2,2-dimethylpropanamide (edpaH), and N-methoxybenzamide (mbaH) were used to afford further substituted complexes Ge(acac)(mpa) (3), Ge(acac)(mdpa) (4), Ge(acac)(empa) (5), Ge(acac)(edpa) (6), Ge(acac)(mba) (7), Ge(tmhd)(mpa) (8), Ge(tmhd)(mdpa) (9), Ge(tmhd)(empa) (10), Ge(tmhd)(edpa) (11), and Ge(tmhd)(mba) (12), respectively. Thermogravimetric analysis curves, which mostly exhibited single-step weight losses, were used to determine the evaporation properties of complexes 1-12. Interestingly, liquid complex 2 has no residue at 198 °C and therefore exhibits excellent vaporization properties and high volatility. Single-crystal X-ray diffraction studies of 1 and 7 demonstrated that the complexes had monomeric molecular structures with germanium chelated by the oxygen atoms of one or two bidentate ligands, respectively. An ALD process was developed for the growth of GeO2 using Ge(tmhd)Cl (2) as a new precursor and H2O2 as an oxidant. This study demonstrates the achievement of self-limiting growth of GeO2 films by varying the duration of injection/purge, with an observed ALD window at deposition temperatures ranging from 300 to 350 °C. The saturated growth per cycle of the GeO2 film was determined as 0.27 Å/cycle at a deposition temperature of 300 °C. The deposited films were observed to be amorphous consisting of GeO2.

A Case of Spontaneous Hemothorax with a Ruptured Variceal Phrenic Vein.

Spontaneous hemothorax is rare, with limited data available on its etiology and treatment. We report a case of massive spontaneous hemothorax with a ruptured variceal phrenic vein during pregnancy, likely a complication of the Kasai procedure. Despite closed thoracostomy, the patient's symptoms and imaging findings did not improve. Emergent open thoracotomy and bleeding control were performed.

Multivariate Analysis of Risk Factor for Mortality and Feasibility of Extracorporeal Membrane Oxygenation in High-Risk Thoracic Surgery.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) as intraoperative cardiorespiratory support during lung transplantation is well known, but use for other types of surgery are limited. To assess risk factor for mortality after high-risk thoracic surgery and feasibility of ECMO, we reviewed. METHODS: This study was an observational study. Between January 2011 and October 2018, 63 patients underwent thoracic surgery with ECMO for severe airway disease, pulmonary insufficiency requiring lung surgery, and other conditions. RESULTS: In all, 46 patients remained alive at 30 days after surgery. The mean patient age was 50.38 ± 16.16 years. ECMO was most commonly used to prevent a lethal event (34 [73.9%]) in the Survival (S) group and rescue intervention (13 [76.5%]) in the Non-survival (N) group. In all, 11 patients experienced arrest during surgery (S vs N: 2 [4.3%] vs 9 [52.9%], p ≤0.001). The multivariate analysis revealed that arrest during surgery (odds ratio [OR], 24.44; 95% confidence interval [CI], 1.82-327.60; p = 0.016) and age (OR, 7.47; 95% CI, 1.17-47.85; p = 0.034) were independently associated with mortality. CONCLUSIONS: ECMO provides a safe environment during thoracic surgery, and its complication rate is acceptable except for extracorporeal cardiopulmonary resuscitation (ECPR).

Surgical Treatment Outcomes of Acquired Benign Tracheoesophageal Fistula: A Literature Review.

BACKGROUND: Tracheoesophageal fistula (TEFs) is a rare condition that requires complex surgical treatment. We analyzed the surgical outcomes of TEF reported in the literature and at Pusan National University Yangsan Hospital using standardized techniques. METHODS: This retrospective study included 8 patients diagnosed with acquired benign TEF between March 2010 and December 2019. The surgical method was determined based on the size of the fistula observed within the endoscope. RESULTS: TEF occurred in 7 patients (87.5%) after intubation or tracheostomy and in 1 patient (12.5%) after esophageal surgery due to conduit necrosis. For tracheal management, 5 and 2 patients underwent tracheal resection and end-to-end anastomosis and primary repair, respectively. The median length of resection was 2.5 cm (range, 1.3-3.4 cm). For esophageal management, 6 patients underwent primary repair and 1 patient underwent esophageal diversion. One patient underwent TEF division with a stapler. Interposition of a muscle flap was performed in 2 patients. TEF recurrence, esophageal stenosis, and dehiscence or granulation occurred in 1, 1, and 2 patients, respectively. A long-term tracheostomy tube or T-tube was used in 2 patients for >2 months. CONCLUSION: Although TEF surgery is complex and challenging, good results can be achieved if surgical standards are established and experience is accumulated.

Oxy-right Ventricular Assist Device for Bridging of Right Heart Failure to Lung Transplantation.

BACKGROUND: Right heart failure develops in lung transplantation candidates on extracorporeal membrane oxygenation (ECMO) support and increases mortality. The safety and feasibility of the oxy-right ventricular assist device (oxyRVAD) as a bridge to lung transplantation in severe right heart failure caused by terminal lung disease have not been evaluated. METHODS: We retrospectively reviewed 14 patients who used oxyRVAD for bridging of right heart failure to lung transplantation. RESULTS: The major cause of lung transplantation was acute exacerbation of interstitial lung disease (78.6%), and the median venovenous ECMO duration was 7 d. Before oxyRVAD, median mean pulmonary artery pressure was 60.5 mm Hg (interquartile range [IQR], 54-68), and the median peak tricuspid regurgitation velocity was 3.9 m/s (IQR, 3.7-4.1). After oxyRVAD conversion, median mean pulmonary artery pressure was 60.5 mm Hg (IQR, 57.3-65), and the median peak tricuspid regurgitation velocity was 2.9 (IQR, 2.6-3.2). All patients were hemodynamically stable (median arterial blood pressure, 83 mm Hg; median heart rate, 79 bpm). Three patients developed pulmonary congestion (21.4%), and all patients stabilized within 24 h. Active rehabilitation during ECMO was possible in all patients, and the median duration of awake state during ECMO was 14 d. A total of 10 patients were bridged successfully to lung transplantation, and hospital survival rates were 90%. CONCLUSIONS: OxyRVAD stabilized hemodynamic parameters without fatal complications, permitted the discontinuation of sedation, and allowed active rehabilitation in patients with severe right heart failure. OxyRVAD may be a feasible option for bridging of right heart failure to lung transplantation.

Catastrophic Mechanical Complications of Extracorporeal Membrane Oxygenation.

Technical advances in extracorporeal membrane oxygenation (ECMO) have increased the number of cases that maintain longer duration. Long-term use of ECMO results in ECMO-related complications. Anticipation of the life-threatening mechanical complications and their management are critical for safe ECMO. In this study, we analyzed the incidence, nature, and risk factors of life-threatening mechanical complications during ECMO support. Furthermore, we presented our bedside algorithms to manage catastrophic ECMO complications. Data from 549 patients who underwent ECMO between December 2008 and December 2018 were retrospectively analyzed. The incidence of all life-threatening mechanical complications was 4.0%. Accidental decannulation (1.3%) was most common, followed by abrupt falling circuit flows (1.1%), pump failure (1.1%), circuit rupture (0.4%), and air in circuit (0.2%). Most (90.9%) of life-threatening events required circuit and cannula change, while 9.1% required vein collapse relief procedure. There was no death related to the event; however, six (27.3%) died during ECMO due to the underlying disease for which ECMO was required, and three (13.6%) died after weaning from ECMO. Multivariate regression analysis showed that awake ECMO and long-term ECMO support were significantly associated with life-threatening mechanical complications (p < 0.01). Our algorithm safely managed catastrophic ECMO problems without event-related deaths.

Successful treatment of catamenial hemoptysis by single-incision thoracoscopic left S9 + 10 segmentectomy using indocyanine green injection-assisted targeting.

Catamenial hemoptysis is a rare condition. A 28-year-old woman presented with a 1-year history of repetitive hemoptysis occurring on the first day of her menstrual period. Chest computed tomography revealed catamenial hemoptysis during her menstrual period. The patient underwent single-incision thoracoscopic left S9 + 10 segmentectomy using indocyanine green injection-assisted targeting. The endometriosis lesions would not be enhanced by perfusion defects during ICG injection due to the lung contusion. Surgical resection with accurate localization of catamenial hemoptysis was a fundamental treatment method. The localization of lesions using indocyanine green effectively enabled a minimally invasive surgery.

Is the pleating technique superior to the invaginating technique for plication of diaphragmatic eventration in infants?

BACKGROUNDS: The pleating technique is widely used in plication but is difficult to perform with thoracoscopy because of its complex procedure and the limited surgical space. Thus, the invaginating technique was introduced to facilitate thoracoscopic surgery and is now widely used in video-assisted thoracoscopic surgery (VATS) plication. However, the usefulness of the invaginating technique in children has not been established because of the lack of data on long-term outcomes after surgery using the technique. METHODS: From March 2007 to December 2017, 21 patients who were surgically treated for congenital diaphragmatic eventration and phrenic nerve palsy after congenital cardiac surgery were divided into 2 groups according to the surgical method used (pleating technique: 10 patients, invaginating technique: 11 patients). We evaluated the patients for postoperative outcomes and recurrence of diaphragmatic eventration over 5 years. Postoperative recurrence of diaphragmatic eventration was confirmed by calculating the ratio of the eventration level between the eventrated and normal diaphragms. RESULTS: In the 21 patients who underwent diaphragmatic plication, the pleating and invaginating techniques were used in 10 and 11 patients, respectively. The mean follow-up duration was 63.4 ±â€¯48.4 months (pleating group [P] vs invaginating group [I]: 89.1 ±â€¯52.4 vs 40.1 ±â€¯30.8 months, p = 0.022). The mean eventration rates in the 21 patients was 26.7% ±â€¯9.1% (P vs I: 26.6% ±â€¯6.1% vs 26.9% ±â€¯11.3%, p = 0.945) before operation and -2.1% ±â€¯7.3% (-2.8% ±â€¯7.5% vs -1.5% ±â€¯7.4%, p = 0.695) in the immediate postoperative period. From the first to the fifth postoperative year, no recurrence of diaphragmatic eventration was found in any of the groups during the follow-up. CONCLUSIONS: The invaginating technique was easier to perform but showed a similar long-term result as compared with the pleating technique in terms of the growth and development of the chest cavity in the pediatric patients in this study. Thus, we recommend that the invaginating technique be applied in VATS plication for children as an alternative to the pleating technique. LEVEL OF EVIDENCE: Level III.

New Volatile Tantalum Imido Precursors with Carboxamide Ligands.

A series of Ta(V) t Bu-imido/N-alkoxy carboxamide complexes, TaCl2(N t Bu)(pyridine)(edpa) (1), TaCl(N t Bu)(edpa)2 (2), Ta(N t Bu)(edpa)3 (3), TaCl2(N t Bu)(pyridine)(mdpa) (4), and Ta(N t Bu)(mdpa)3 (5), were successfully synthesized by metathesis reactions between Ta(N t Bu)Cl3(py)2 and several equivalents of Na(edpa) (edpaH = N-ethoxy-2,2-dimethylpropanamide) and Na(mdpa) (mdpaH = N-methoxy-2,2-dimethylpropanamide). Furthermore, complexes 3 and 5 were simply transformed to new dimeric structures [Ta(µ2-O)(edpa)3]2 (6) and [Ta(µ2-O)(mdpa)3]2 (7) with the elimination of the N t Bu imido group by air exposure. Compounds 1-7 were characterized by 1H and 13C nuclear magnetic resonance spectroscopy, Fourier transform infrared spectroscopy, elemental analysis, thermogravimetric analysis (TGA), and single-crystal X-ray diffraction. Single-crystal X-ray diffraction analysis revealed that complexes 3 and 5 have a distorted pentagonal bipyramidal geometry around the central Ta atom, with three monoanionic bidentate N-alkoxy carboxamide ligands and one t Bu imido ligand saturating the coordination of tantalum ions. TGA revealed that complexes 3 and 5 had superior thermal characteristics and stability. These complexes could potentially be applied as precursors for tantalum oxide thin films.

Effect of dietary supplementation of a phytogenic blend containing Schisandra chinensis, Pinus densiflora, and Allium tuberosum on productivity, egg quality, and health parameters in laying hens.

OBJECTIVE: This study was conducted to investigate the supplementary effect of a phytogenic blend (SPA: a mixture containing fermented Schisandra chinensis pomace, fermented Pinus densiflora needle extract, and Allium tuberosum powder in the ratio of 2:2:1) on egg production, egg quality, blood constituents, and visceral organs in laying hens. METHODS: A total of 135 Hy-line brown laying hens (48-wk-old) were randomly allocated to three dietary treatments with 5 replicates of 9 hens. The control group (CON) was fed a basal diet (no exogenous SPA addition) and the experimental groups were fed the basal diet containing SPA at the level of 0.1% and 0.3% for 6 weeks. RESULTS: The feed intake was significantly improved in SPA supplemented groups as compared with the control (p<0.05). However, egg production, daily egg mass, and feed conversion ratio were not different among the dietary treatments (p>0.05). For egg quality traits, only Haugh unit (HU) was significantly improved in SPA (0.3%) (p<0.05) as compared with other groups. However, HU was not affected during 4-wk of storage at 18°C among the dietary treatments (p>0.05). Furthermore, SPA supplementation did not affect the blood biochemical constituents except for the phosphate content, which was significantly higher in SPA groups than the CON group (p<0.05). There were no significant differences in visceral organ characteristics and immune indicators (immunoglobulin A [IgA], IgG, and IgM) in SPA or CON groups. CONCLUSION: This study suggested that the supplementation of SPA may have beneficial effects on feed intake and egg quality in laying hens.

Study on elution behavior of poly(amidoamine) dendrimers and their interaction with bovine serum albumin in asymmetrical flow field-flow fractionation.

Polyamidoamine (PAMAM) dendrimers have an amine surface and an ethylenediamine core and are of great interest in various applications such as in drug delivery. Physiochemical properties of PAMAM dendrimers vary with pH. At neutral to basic pH, PAMAM dendrimers are either weakly charged or uncharged and tend to adsorb on to the neutral packing material, making chromatographic separation of the dendrimers difficult. Asymmetrical flow field-flow fractionation (AsFlFFF) was tested as an alternative to the chromatographic techniques for separation of the PAMAM dendrimers. AsFlFFF provided generation-based separation of the dendrimers even at neutral and basic pH. The elution time increased gradually as the generation number (and thus the size) increased. Separation of impurities such as generational or missing-arm impurities and aggregates from the main population was also achieved. Electrostatic and hydrophobic interactions (e.g., repulsive elecrostatic interaction among the dendrimer molecules or attractive hydrophobic interaction between the dendrimer molecules and the membrane) may result in an inaccurate size measurement. Careful optimization of experimental conditions such as the flow rate, pH, and the salt concentration may be required to minimize the interactions with the membrane. AsFlFFF was also tested for a study on the interaction between the PAMAM dendrimers and proteins. AsFlFFF was able to show the growth in the size of bovine serum albumin (BSA) when BSA is mixed with increasing amounts of PAMAM dendrimers. Results suggest that, with proper optimization, AsFlFFF could become a useful tool for separation and characterization of large charged molecules such as PAMAM dendrimers.

Lung transplantation using argatroban in severe heparin-induced thrombocytopenia during extracorporeal membrane oxygenation: a case series.

Lung transplantation during heparin-induced thrombocytopenia (HIT) is controversial and often considered a contraindication because of the risk of increased bleeding and thrombosis in the recipient. Although lung transplantation offers the best chance for cure in end-stage lung disease, the outcome after transplantation is still controversial in patients with HIT. In our center, two patients developed HIT type II during venovenous extracorporeal membrane oxygenation (ECMO) support for acute respiratory failure. They underwent successful lung transplantation using argatroban. The subsequent clinical course was uneventful except evacuation of post-operative hematoma in 1 patient, and they were discharged. Argatroban was successfully used during lung transplant surgery in patients who developed HIT type II during ECMO support. Further studies on the feasibility and safety of lung transplantation using a direct thrombin inhibitor in patients with HIT during ECMO are required.

Hybrid surgical resection of a tumor invading the superior vena cava.

Recently, hybrid operations featuring vascular interventions have become more common, but applications in the thoracic surgery are few. Superior vena cava (SVC) resection and reconstruction is a typical complex thoracic surgery. Traditional SVC resection/reconstruction requires advanced vascular surgical skills. We developed a simple and safe procedure; we insert a stent during malignant tumor surgery involving the SVC. This approach renders such surgery easier, increasing the probability of success.

Successful use of an EZ-blocker for lung isolation and management in a hemoptysis patient.

When massive hemoptysis develops suddenly, patients typically die due to hypovolemia or airway obstruction. Intubation, endobronchial blocking, and elimination of blood clots are urgently required. However, existing double-lumen tubes and single endobronchial balloon systems are inadequate. We herein report successful EZ-blocker-mediated one-lung ventilation of a patient with a massive hemoptysis who required emergency life-saving surgery.