Single-centre observational study of the safety and efficacy of thoracoscopy under local anaesthesia for the management of thoracic infections.

OBJECTIVES: Thoracoscopy under local anaesthesia is widely performed to diagnose malignancies and infectious diseases. However, few reports have described the use of this procedure for diagnosing and treating intrathoracic infections. This study aimed to evaluate the safety and efficacy of thoracoscopy under local anaesthesia for the management of intrathoracic infections. RESULTS: Data from patients who underwent thoracoscopy procedures performed by chest physicians under local anaesthesia at our hospital between January 2018 and December 2023 were retrospectively reviewed. We analysed their demographic factors, reasons for the examinations, diseases targeted, examination lengths, anaesthetic methods used, diagnostic and treatment success rates, as well as any adverse events. Thirty patients were included. Of these, 12 (40%) had thoracoscopies to diagnose infections, and 18 (60%) had them to treat pyothorax. In terms of diagnosing pleurisy, the causative microorganism of origin was identified via thoracoscopy in only three of 12 (25.0%) patients. For diagnosing pyothorax, the causative microorganism was identified in 7 of 18 (38.9%) patients. Methicillin-resistant Staphylococcus aureus was the most common causative microorganism identified. The treatment success rates were very high, ranging between 94.4 and 100%, whereas the identification rate of the causative microorganisms behind infections was low, ranging between 25.0 and 38.9%. The most frequent adverse events included perioperative hypoxaemia and pain. There were two (6.7%) serious adverse events of grade ≥ 3, but none resulted in death. CONCLUSIONS: The efficacy of managing intrathoracic infections through thoracoscopy under local anaesthesia is commendable. Nonetheless, the diagnostic accuracy of the procedure, regarding the precise identification of the causative microorganisms responsible for intrathoracic infections, persists at a notably low level, presenting a substantial clinical hurdle.

Clinical features of pneumothorax associated with COVID-19: A retrospective analysis of two centres.

BACKGROUND: Pneumothorax is a known sequela of coronavirus disease 2019 (COVID-19). However, the clinical features of pneumothorax associated with COVID-19 have not been fully elucidated. METHODS: Patients who developed pneumothorax within 6 months of being diagnosed with COVID-19 were retrospectively analysed at two institutions. We investigated the background factors, COVID-19 severity and treatment, timing of pneumothorax onset, treatment modalities, treatment duration, and prognosis of these patients. RESULTS: A total of 21 patients were diagnosed with pneumothorax within 6 months of COVID-19 diagnosis. The combined incidence rate of pneumothorax at two institutions was 0.89 %. The mean age of these patients was 72.5 years, and they were predominantly male (90.5 %), with a history of smoking (76.1 %). The most frequent comorbidity was hypertension, followed by type 2 diabetes mellitus, COPD, and malignancy. Approximately 76 % of the patients had moderate or severe disease requiring oxygenation. Moreover, 90.5 % of these patients were taking antiviral drugs; 52.4 %, immunosuppressant agents (baricitinib/tocilizumab); and 66.7 % were on dexamethasone. The median time to the onset of pneumothorax was 15.0 days, and 86 % of cases occurred within 1 month of COVID-19 diagnosis. Bilateral pneumothorax and pneumomediastinum were noted in one patient each. Chest drainage was performed in 71.4 % of the patients. The mean treatment duration for pneumothorax was 14.1 days, and the 30-day mortality rate was 28.6 %. CONCLUSION: Pneumothorax associated with COVID-19 was more common in patients with moderate or severe disease requiring oxygenation, and occurred within 1 month of COVID-19 diagnosis. Pneumothorax associated with COVID-19 is a serious complication with a high mortality rate and clinicians should pay attention to it.

[Sleeve Resection for Right Upper Lobe Non-small Cell Lung Cancer After Systemic Chemotherapy and Immune Checkpoint Inhibitor Administration].

A man in his 50s was diagnosed with right upper lobe non-small-cell lung cancer (cT3N1M0, stage ⅢA) on bronchoscopy. The tumor was located at the right hilum and was bordered extensively on the pulmonary artery. We observed significant tumor shrinkage (ycT1bN1M0, stage ⅡB), following three cycles of systemic chemotherapy combined with an immune checkpoint inhibitor and performed right upper sleeve lobectomy + ND2a-2 via thoracotomy for radical resection. Postoperative histopathological examination showed no residual tumor cells, and the patient was deemed to have a histopathologic complete response. Currently, the patient is being followed up without adjuvant chemotherapy. Several recent studies have reported the usefulness of systemic chemotherapy combined with immune checkpoint inhibitor administration as preoperative induction chemotherapy. However, the role of adjuvant immunotherapy in patients with a histopathologic complete response remains unclear, and careful treatment decision-making is important.

Re-immunotherapy with nivolumab plus ipilimumab in advanced non-small cell lung cancer patients previously treated with anti-programmed death-1 and/or anti-programmed death ligand-1 antibodies.

BACKGROUND: The role of re-immunotherapy in advanced non-small cell lung cancer (NSCLC) remains unclear. No studies have evaluated the re-immunotherapy regimen including anti-cytotoxic T-lymphocyte antigen-4 antibody for lung cancer treatment. This study aimed to investigate the efficacy and safety of re-immunotherapy with nivolumab plus ipilimumab in patients with advanced NSCLC previously treated with anti-programmed death-1 (PD-1) and/or anti-programmed death ligand-1 (PD-L1) antibodies. METHODS: We retrospectively reviewed patients with advanced or recurrent NSCLC who received immunotherapy with nivolumab plus ipilimumab (without concomitant cytotoxic chemotherapy) between November 2020 and November 2022 at the National Hospital Organization Kyoto Medical Center, Kyoto, Japan. Data were extracted from patients who had previously received immunotherapies with anti-PD-1 and/or anti-PD-L1 antibodies. Treatment responses and adverse events were evaluated. RESULTS: Of the 67 patients who received immunotherapy with nivolumab plus ipilimumab, 23 were included in final analysis. The objective response rate was 17%, and the disease control rate was 48% for nivolumab plus ipilimumab therapy. The highest grade of immune-related adverse events was grade 3, occurring in 11% of cases. CONCLUSION: Re-immunotherapy with nivolumab plus ipilimumab after anti-PD-1 and/or anti-PD-L1 immunotherapy may be feasible and provide clinical benefit in selected patients. Further prospective studies are warranted to identify the patient population that may benefit from re-immunotherapy.

Impact of the COVID-19 pandemic on the trajectory of the number of bronchoscopies performed in a tertiary hospital in Kyoto city.

The coronavirus disease 2019 (COVID-19) pandemic has restricted many medical practices. We aimed to investigate the impact of the COVID-19 pandemic on the number of bronchoscopies, outpatients, and hospital admissions. We retrospectively analyzed the number of outpatients, admissions, and bronchoscopies performed between March 2020 and May 2022. We defined "Peak month of the pandemic," "Wave of the pandemic," "Month in the wave," and "Period of a state of emergency" for each analysis. In the first year of the COVID-19 pandemic, analysis of variance (ANOVA) in linear mixed models indicated significant effects of "month in each wave" on the number of bronchoscopies (P = .003), outpatients (P = .041), and admissions (P = .017). The number of outpatients, admissions, and bronchoscopies was significantly influenced by the first wave of the COVID-19 pandemic. In contrast, in the second year of the COVID-19 pandemic, a mixed-ANOVA indicated significant effects of "month in each wave" only on the number of outpatients (P = .020) but no significant effects on the number of bronchoscopies (P = .407) and admissions (P = .219). During the second year of the pandemic, the number of bronchoscopies and admissions was not significantly affected by the waves of the pandemic. There were no significant differences in the number of admissions and bronchoscopies between the fourth and sixth waves. Although the number of bronchoscopies was found to be significantly affected in the early stages of the COVID-19 pandemic, the impact of the pandemic was much more limited thereafter.

Natural course of pulmonary hyalinizing granuloma over a decade.

Background: Pulmonary hyalinizing granuloma (PHG) is a very rare pulmonary disease characterized by multiple fibrosclerotic inflammatory lung nodules. The disease is supposedly caused by an unusual immune response. Case presentation: We present a case involving a 53-year-old female with a history of lumpectomy surgery due to invasive ductal carcinoma who was admitted for slowly progressive pulmonary nodules. The patient's elevated serum IgG4 level and the pathological findings obtained in surgical biopsy indicated IgG4-related lung disease. The nodules continued to enlarge despite administration of corticosteroid therapy, and we performed a second surgical biopsy to obtain a correct diagnosis. The pathological findings obtained in the second biopsy were different and consistent with the features of PHG. Conclusions: In this report, the radiological follow-up data obtained after lumpectomy surgery demonstrate the very early stage of PHG and the following radiological changes over a decade, and the two surgical biopsies support us to realize the pathological change from previous diagnosed disease before PHG.

The risk of footswitch misstep during robot-assisted thoracoscopic surgery: a case report.

The Da Vinci Surgical System is an ergonomically devised and excellent surgical support device. However, surgeon skill is of paramount importance since human error cannot be completely eliminated. We report a case of bleeding from the pulmonary artery due to a footswitch misstep. A 72-year-old male with suspected right upper lobe lung cancer underwent robot-assisted thoracoscopic surgery (RATS). While avoiding the pulmonary artery with the right arm spatula and trying to cauterize V2t with the left arm bipolar-forceps, the footswitch was accidently activated and the spatula was energized, resulting in pulmonary artery trauma and blood loss. After this case, we changed the surgical procedure from a monopolar-bipolar combination use to a bipolar-only use and noted no significant difference in the console duration, and less intraoperative blood loss. Human errors can occur anytime. Especially for surgeons new to RATS, simplified foot management should be considered until RATS mastery is achieved.

[Experience of Treatment for Pneumothorax with Coronavirus Disease 2019( COVID-19) Pneumonia].

A 73 years old male patient with the past history of kidney transplantation was admitted to our hospital for treatment of coronavirus disease 2019 (COVID-19) pneumonia. On the 25th day after the onset of symptoms when his condition was improving, he suddenly developed pneumothorax. Chest tube drainage was performed and connected the tube to the drainage device using a high efficiency particulate air (HEPA) filter. Because of the improvement of infection, the HEPA filter was removed from the drainage device on day 28. Chest tube drainage was continued by day 35, and he was discharged and introduced home oxygen therapy on day 51.

Small cell transformation of non-small cell lung cancer under immunotherapy: Case series and literature review.

In advanced lung cancer treatment, immunotherapy provides durable responses in some patients. However, other patients experience progressive disease and the resistance mechanisms to immunotherapy have yet been fully elucidated. Small cell transformation of non-small cell lung cancer (NSCLC) is commonly recognized as one of the resistance mechanisms to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors in EGFR-mutant NSCLC treatment. As a resistant mechanism for immunotherapy, we report the first case of small cell transformation in 2017. Since then, eight similar cases have been reported and the concept of small cell transformation is now becoming more prevalent as a mechanism of immunotherapy resistance. In our facility, we have experienced four cases of small cell transformation after immunotherapy (including the reported case in 2017). The histology of each primary tumor was squamous cell carcinoma, large cell type neuroendocrine carcinoma, or poorly differentiated NSCLC. None had driver gene mutations. Nivolumab was administered in all four cases and atezolizumab was administered as a next line to nivolumab treatment in one case. The best response to immunotherapy was partial response or stable disease. There was a wide range of periods from the start of immunotherapy to confirmation of small cell transformation (from 2 weeks to almost 3 years). In conclusion, small cell transformation is an important resistance mechanism in cancer immunotherapy. When NSCLC progresses after immunotherapy, the possibility of small cell transformation and rebiopsy should always be encouraged, as it leads to clarification of the resistance mechanisms and frequency.

Efficacy and safety of immune checkpoint inhibitors in patients with non-small cell lung cancer aged 80 years or older.

BACKGROUND: In Japan, over 25% of the population is elderly. As the risk of lung cancer increases with age, the number of elderly patients with lung cancer also increases. Given the challenges of an aging society, it is critical that elderly patients receive safe therapies. AIM: We assessed the safety and efficacy of immune checkpoint inhibitors (ICIs) in patients with non-small cell lung cancer (NSCLC) aged ≥80 years. METHODS: We retrospectively reviewed NSCLC patients aged ≥80 years old who received ICIs in the National Hospital Organization Kyoto Medical Center. We collected data on patient characteristics, prior treatments, number of cycles, response, and immune-related adverse events (irAEs) during ICI monotherapy. RESULTS: A total of 45 patients were reviewed. The patients' median age was 85 years. Twenty-one, 17, and 7 patients received nivolumab, pembrolizumab, and atezolizumab, respectively. The disease control rate (partial response [PR] + stable disease [SD]) was 60.0%, and the progression-free survival was 3.4 months. In patients with nivolumab, seven patients (33.3%) achieved SD, and three patients (14.2%) achieved PR. In patients treated with pembrolizumab, seven patients (41.2%) achieved SD, and six patients (35.3%) achieved PR. In patients with atezolizumab, three patients (42.9%) achieved SD, and one patient (14.2%) achieved PR. Sixteen (36%) patients presented with a poor performance status. Three patients treated with pembrolizumab experienced grade 3 pneumonia, while one patient treated with nivolumab experienced grade 5 pneumonia. CONCLUSION: This study suggested that ICIs are an acceptable treatment option for NSCLC patients aged ≥80 years. Oncologists should pay attention to severe irAEs.

Effect of cyclooxygenase inhibitor use on immunotherapy efficacy in non-small cell lung cancer.

BACKGROUND: A synergistic effect of cyclooxygenase inhibitors (COX-I) and immune checkpoint inhibitors (ICIs) has been suggested. However, the impact of COX-I on the efficacy of ICIs is unclear. Here, we aimed to evaluate the relationship between COX-I use and the efficacy of ICI in patients with non-small cell lung cancer (NSCLC). METHODS: We retrospectively reviewed NSCLC patients who received ICI monotherapy. We defined COX-I use as regular use of COX-I other than low-dose aspirin during the initiation of ICIs to the first evaluation of efficacy. The efficacy of ICIs was evaluated with response rate (RR), disease control rate (DCR), progression free survival (PFS), and overall survival (OS). Differences in baseline characteristics by COX-I use were controlled by using an inverse probability of treatment weighting (IPW) adjusted analysis. RESULTS: A total of 198 patients with NSCLC received ICIs; 128, 50, and 20 patients received nivolumab, pembrolizumab, and atezolizumab, respectively; there were 65 (32.8%) COX-I users. While there was no significant difference in RR (15.4% vs. 13.5%; p = 0.828), DCR (41.5% vs. 49.6%; p = 0.294), PFS (median, 2.69 vs. 3.68 months; 95% confidence intervals [CI], 1.77-5.19 vs. 2.20-4.60 months; p = 0.630), COX-I users had significantly shorter OS than non-COX-I users (median, 6.08 vs. 16.10 months; 95% CI: 3.78-11.66 vs. 9.49-19.68 months; p = 0.003). On IPW adjusted analysis, there was no significant difference in OS (median, 7.85 vs. 15.11 months; 95% CI: 5.03-14.92 vs. 9.49-19.32 months; p = 0.081). CONCLUSIONS: There was no additional or negative impact of COX-I use on the efficacy of ICIs in NSCLC.

Allylic Hydroxylation Activity Is a Source of Saponin Chemodiversity in the Genus Glycyrrhiza.

Licorice (Glycyrrhiza) produces glycyrrhizin, a valuable triterpenoid saponin, which exhibits persistent sweetness and broad pharmacological activities. In the genus Glycyrrhiza, three species, Glycyrrhiza uralensis, Glycyrrhiza glabra and Glycyrrhiza inflata, produce glycyrrhizin as their main triterpenoid saponin, which has a ketone group at C-11. Other Glycyrrhiza species produce mainly oleanane-type saponins, which harbor homoannular or heteroannular diene structures that lack the C-11 ketone. Although the glycyrrhizin biosynthetic pathway has been fully elucidated, the pathway involving saponins with diene structures remains unclear. CYP88D6 from G. uralensis is a key enzyme in glycyrrhizin biosynthesis, catalyzing the sequential two-step oxidation of ß-amyrin at position C-11 to produce 11-oxo-ß-amyrin. In this study, we evaluated the functions of CYP88D6 homologs from the glycyrrhizin-producing species G. glabra and G. inflata and from the non-glycyrrhizin-producing species Glycyrrhiza pallidiflora and Glycyrrhiza macedonica, using yeast engineered to supply ß-amyrin as a substrate. Yeast expressing CYP88D6 homologs from glycyrrhizin-producing species produced 11-oxo-ß-amyrin. However, yeast expressing CYP88D6 homologs (such as CYP88D15) from the non-glycyrrhizin-producing Glycyrrhiza species accumulated oleana-9(11),12-dien-3ß-ol and oleana-11,13(18)-dien-3ß-ol; these diene compounds are non-enzymatic or yeast endogenous enzymatic dehydration derivatives of 11α-hydroxy-ß-amyrin, a direct reaction product of CYP88D15. These results suggest that the activities of CYP88D6 homologs, particularly their ability to catalyze the second oxidation, could influence glycyrrhizin productivity and diversify the chemical structures of saponins in Glycyrrhiza plants. A synthetic biological approach to engineer CYP88D15 could enable the production of pharmacologically active saponins with diene structures, such as saikosaponins, whose biosynthetic pathways have yet to be fully characterized.

[The Early Removal of the Implant after Nuss Procedure Due to the Infection in Case of Pectus Excavatum with Atopic Dermatitis].

Nuss procedure for pediatric patients with pectus excavatum has been practiced worldwide, including in Japan, due to the simple procedure and has a high therapeutic effect. Because it is usually performed under thoracoscopy to secure the safety, it is performed not only by pediatric or plastic surgeons but also by general thoracic surgeons. On the other hand, a risk of infection must always be considered in this method in which a foreign metal bar is used. In particular, when the skin barrier mechanism is declining due to skin diseases such as atopic dermatitis, the risk of infection of the implant may increase. The present case was an 8-year-old male with a history of atopic dermatitis. He underwent thoracoscopic Nuss procedure. Although there was no problem during his hospitalization, the bar was exposed from the skin on the 58th postoperative day with the infection triggered, and the unexpected early bar removal was performed on the 66th postoperative day. We report this case with some literature review.

Single-center analysis of antiresorptive agent-related osteonecrosis of the jaw in lung cancer patients.

BACKGROUND: Over the past two decades, antiresorptive agent-related osteonecrosis of the jaw (ARONJ) has become a growing concern. We examined the incidence of ARONJ and identified its risk factors in lung cancer patients in the real-world clinical setting. To our knowledge, we are the first to do so. PATIENTS AND METHODS: We retrospectively analyzed lung cancer patients with bone metastases who had received anti-resorptive agents (zoledronate or denosumab) at the National Hospital Organization Kyoto Medical Center from October 2012 to September 2018. All ARONJ cases were diagnosed by the dentists according to the established diagnostic criteria. RESULTS: A total of 171 patients were reviewed, 13 (7.6%) of whom experienced ARONJ. Among the 13 patients, six (46.2%), four (30.8%) and three (23.1%) had adenocarcinoma, squamous carcinoma and not otherwise specified, respectively. ARONJ was stage 2 in three (23.1%) patients and stage 3 in 10 (76.9%). More cycles of antiresorptive agents (odds ratio [OR] = 11.54; 95% confidence interval [CI], 2.47-53.99; P < 0.01), use of immune checkpoint inhibitors (ICIs; OR = 5.05; 95% CI, 1.56-16.37; P < 0.01) and longer survival duration (≥2 years; OR = 12.16; 95% CI, 3.17-46.65; P < 0.01) were independently associated with ARONJ in a multivariate analysis. CONCLUSIONS: The incidence of ARONJ was relatively high in lung cancer patients with bone metastases. When using antiresorptive agents, oncologists should closely monitor patients for ARONJ during the course of treatment and regularly consult with dentists, especially in patients receiving ICIs.

Targeted genome editing in tetraploid potato through transient TALEN expression by Agrobacterium infection.

Genome editing using site-specific nucleases, such as transcription activator-like effector nucleases (TALENs) and clustered regularly interspaced short palindromic repeat-CRISPR-associated protein 9 (CRISPR-Cas9), is a powerful technology for crop breeding. For plant genome editing, the genome-editing reagents are usually expressed in plant cells from stably integrated transgenes within the genome. This requires crossing processes to remove foreign nucleotides from the genome to generate null segregants. However, in highly heterozygous plants such as potato, the progeny lines have different agronomic traits from the parent cultivar and do not necessarily become elite lines. Agrobacteria can transfer exogenous genes on T-DNA into plant cells. This has been used both to transform plants stably and to express the genes transiently in plant cells. Here, we infected potato, with Agrobacterium tumefaciens harboring TALEN-expression vector targeting sterol side chain reductase 2 (SSR2) gene and regenerated shoots without selection. We obtained regenerated lines with disrupted-SSR2 gene and without transgene of the TALEN gene, revealing that their disruption should be caused by transient gene expression. The strategy using transient gene expression by Agrobacterium that we call Agrobacterial mutagenesis, developed here should accelerate the use of genome-editing technology to modify heterozygous plant genomes.

Incidence of Active Tuberculosis in Lung Cancer Patients Receiving Immune Checkpoint Inhibitors.

Although it ameliorates lung cancer, immunotherapy with immune checkpoint inhibitors (ICIs) presents complications of infectious diseases, including tuberculosis. Incidence of tuberculosis during immunotherapy remains unclear. We found that 1.7% of patients developed active tuberculosis during immunotherapy at our institution. In patients with a positive interferon-gamma release assay status before ICI therapy, physicians should pay close attention to developing tuberculosis.

Retreatment with anti-PD-1 antibody in non-small cell lung cancer patients previously treated with anti-PD-L1 antibody.

BACKGROUND: This study evaluated the efficacy and safety of retreatment with anti-programmed death 1 (anti-PD-1) antibodies in patients with advanced non-small cell lung cancer (NSCLC) after prior treatment with anti-programmed death-ligand 1 (anti-PD-L1) antibodies. METHODS: Data (N = 15) on patients' characteristics, number of cycles, regimens, their best response and immune-related adverse events (irAEs) were recorded retrospectively. RESULTS: NSCLC was initially treated with anti-PD-L1 antibody atezolizumab (N = 14) or durvalumab (N = 1). No patients had a high (≥50%) tumor expression of PD-L1. The median cycles for atezolizumab were five (range 1-15), and median progression-free survival was 2.8 and 6.0 months for atezolizumab and durvalumab, respectively. Five (33.3%) and nine (60.0%) patients showed stable and progressive disease as their best response, respectively. No differences in irAEs between anti-PD-L1 and anti-PD-1 antibodies occurred. CONCLUSION: Patients treated with anti-PD-L1 antibodies for NSCLC received limited benefits from retreatment with anti-PD-1 antibodies.

Molecular Basis of C-30 Product Regioselectivity of Legume Oxidases Involved in High-Value Triterpenoid Biosynthesis.

The triterpenes are structurally diverse group of specialized metabolites with important roles in plant defense and human health. Glycyrrhizin, with a carboxyl group at C-30 of its aglycone moiety, is a valuable triterpene glycoside, the production of which is restricted to legume medicinal plants belonging to the Glycyrrhiza species. Cytochrome P450 monooxygenases (P450s) are important for generating triterpene chemodiversity by catalyzing site-specific oxidation of the triterpene scaffold. CYP72A154 was previously identified from the glycyrrhizin-producing plant Glycyrrhiza uralensis as a C-30 oxidase in glycyrrhizin biosynthesis, but its regioselectivity is rather low. In contrast, CYP72A63 from Medicago truncatula showed superior regioselectivity in C-30 oxidation, improving the production of glycyrrhizin aglycone in engineered yeast. The underlying molecular basis of C-30 product regioselectivity is not well understood. Here, we identified two amino acid residues that control C-30 product regioselectivity and contribute to the chemodiversity of triterpenes accumulated in legumes. Amino acid sequence comparison combined with structural analysis of the protein model identified Leu149 and Leu398 as important amino acid residues for C-30 product regioselectivity. These results were further confirmed by mutagenesis of CYP72A154 homologs from glycyrrhizin-producing species, functional phylogenomics analyses, and comparison of corresponding residues of C-30 oxidase homologs in other legumes. These findings could be combined with metabolic engineering to further enhance the production of high-value triterpene compounds.

Postoperative delirium after lung resection for primary lung cancer: Risk factors, risk scoring system, and prognosis.

Delirium is a common post-surgical complication, but few studies have examined postoperative delirium following lung cancer surgery. The purpose of this study was to clarify the risk factors of postoperative delirium, to construct a useful scoring system, and to clarify the relationship between delirium and prognosis after lung cancer surgery. We retrospectively analyzed data from 570 patients who underwent surgery for primary lung cancer. Logistic regression analysis was used to determine the effects of various factors on the onset of delirium. Kaplan-Meier analysis was performed to determine the relationship between delirium and prognosis. Postoperative delirium occurred in 6.7% of the patients. Three risk factors were identified, and the risk scores were determined as follows: 2×(cerebrovascular disease history) + 1×(squamous cell carcinoma) + 1×(age older than 75 years). Scores 0-1 denoted low risk, 2 denoted intermediate risk, and 3-4 denoted high risk. Additionally, we found that patients who developed delirium had significantly shorter overall survival. However, there was no difference in the frequency between cancer-related death and non-cancer related death when comparing the delirium and non-delirium groups. We identified the risk factors, i.e., cerebrovascular disease history, squamous cell carcinoma, and age older than 75 years, that determine the onset of delirium after lung cancer surgery and constructed a useful scoring system. In addition, although the prognosis of the delirium group was poor, the factor that determines prognosis may not be cancer per se but vulnerability in the patient background.

Efficient genome engineering using Platinum TALEN in potato.

Potato (Solanum tuberosum) is one of the most important crops in the world. However, it is generally difficult to breed a new variety of potato crops because they are highly heterozygous tetraploid. Steroidal glycoalkaloids (SGAs) such as α-solanine and α-chaconine found in potato are antinutritional specialized metabolites. Because of their toxicity following intake, controlling the SGA levels in potato varieties is critical in breeding programs. Recently, genome-editing technologies using artificial site-specific nucleases such as TALEN and CRISPR-Cas9 have been developed and used in plant sciences. In the present study, we developed a highly active Platinum TALEN expression vector construction system, and applied to reduce the SGA contents in potato. Using Agrobacterium-mediated transformation, we obtained three independent transgenic potatoes harboring the TALEN expression cassette targeting SSR2 gene, which encodes a key enzyme for SGA biosynthesis. Sequencing analysis of the target sequence indicated that all the transformants could be SSR2-knockout mutants. Reduced SGA phenotype in the mutants was confirmed by metabolic analysis using LC-MS. In vitro grown SSR2-knockout mutants exhibited no differences in morphological phenotype or yields when compared with control plants, indicating that the genome editing of SGA biosynthetic genes such as SSR2 could be a suitable strategy for controlling the levels of toxic metabolites in potato. Our simple and powerful plant genome-editing system, developed in the present study, provides an important step for future study in plant science.