KRASG12C Inhibitor as a Treatment Option for Non-Small-Cell Lung Cancer with Comorbid Interstitial Pneumonia.

Non-small-cell lung cancer (NSCLC) with comorbid interstitial pneumonia (IP) is a population with limited treatment options and a poor prognosis. Patients with comorbid IP are at high risk of developing fatal drug-induced pneumonitis, and data on the safety and efficacy of molecularly targeted therapies are lacking. KRAS mutations have been frequently detected in patients with NSCLC with comorbid IP. However, the low detection rate of common driver gene mutations, such as epidermal growth factor receptor and anaplastic lymphoma kinase, in patients with comorbid IP frequently results in inadequate screening for driver mutations, and KRAS mutations may be overlooked. Recently, sotorasib and adagrasib were approved as treatment options for advanced NSCLC with KRASG12C mutations. Although patients with comorbid IP were not excluded from clinical trials of these KRASG12C inhibitors, the incidence of drug-induced pneumonitis was low. Therefore, KRASG12C inhibitors may be a safe and effective treatment option for NSCLC with comorbid IP. This review article discusses the promise and prospects of molecular-targeted therapies, especially KRASG12C inhibitors, for NSCLC with comorbid IP, along with our own clinical experience.

Tunnel-Structured Phosphate Exhibiting High Proton Conductivity and Thermal Stability over a Wide Intermediate Temperature Range.

For the practical application of fuel cells in vehicles, it is a challenge to develop a proton solid electrolyte that coexhibits thermal stability and high proton conductivity at wide intermediate temperatures. Here, we report on the tunnel structured phosphate KNi1-xH2x(PO3)3·yH2O, which exhibits high proton conductivity at room temperature up to 500 °C, with the conductivity value reaching 1.7 × 10-2 S cm-1 at 275 °C for x = 0.18. This material, composed of the smallest cations that form the tunnel framework with face-shared (KO6) and (NiO6) chains and PO4 tetrahedral chains, retained the rigid framework up to 600 °C. Two oxygen sites of water molecules located adjacent to each other along the PO4 tetrahedral chains in the tunnel provided the proton conduction pathway. The sample maintained a conductivity of 5.0 × 10-3 S cm-1 for 10 h at 150 °C while changing the measurement atmosphere to a N2 gas flow, a 4% H2-96% Ar gas flow, and an O2 gas flow. The conductivity value at x = 0.18 obtained from the DC measurement was in the order of 10-6 S cm-1, close to the instrument's measurement limit. These results demonstrate that tunnel phosphate has potential as a proton solid electrolyte for next-generation fuel cells.

A nationwide phase II study of delayed local treatment for children with high-risk neuroblastoma: The Japan Children's Cancer Group Neuroblastoma Committee Trial JN-H-11.

PURPOSE: Survival rates of patients with high-risk neuroblastoma are unacceptable. A time-intensified treatment strategy with delayed local treatment to control systemic diseases has been developed in Japan. We conducted a nationwide, prospective, single-arm clinical trial with delayed local treatment. This study evaluated the safety and efficacy of delayed surgery to increase treatment intensity. PATIENTS AND METHODS: Seventy-five patients with high-risk neuroblastoma were enrolled in this study between May 2011 and September 2015. Delayed local treatment consisted of five courses of induction chemotherapy (cisplatin, pirarubicin, vincristine, and cyclophosphamide) and myeloablative high-dose chemotherapy (melphalan, etoposide, and carboplatin), followed by local tumor extirpation with surgery and irradiation. The primary endpoint was progression-free survival (PFS). The secondary endpoints were overall survival (OS), response rate, adverse events, and surgical complications. RESULTS: Seventy-five patients were enrolled, and 64 were evaluable (stage 3, n = 8; stage 4, n = 56). The estimated 3-year PFS and OS rates (95% confidence interval [CI]) were 44.4% [31.8%-56.3%] and 80.7% [68.5%-88.5%], resspectively. The response rate of INRC after completion of the treatment protocol was 66% (42/64; 95% CI: 53%-77%; 23 CR [complete response], 10 VGPR [very good partial response], and nine PR [partial response]). None of the patients died during the protocol treatment or within 30 days of completion. Grade 4 adverse effects, excluding hematological adverse effects, occurred in 48% of patients [31/64; 95% CI: 36%-61%]. Major Surgical complications were observed in 25% of patients [13/51; 95% CI: 14%-40%]. CONCLUSION: This study indicates that delayed local treatment is feasible and shows promising efficacy, suggesting that this treatment should be considered further in a comparative study of high-risk neuroblastoma.

Impact of a Cancer History on Cardiovascular Events Among Patients With Myocardial Infarction Who Received Revascularization.

BACKGROUND: It remains controversial whether a cancer history increases the risk of cardiovascular (CV) events among patients with myocardial infarction (MI) who undergo revascularization.Methods and Results: Patients who were confirmed as type 1 acute MI (AMI) by coronary angiography were retrospectively analyzed. Patients who died in hospital or those not undergoing revascularization were excluded. Patients with a cancer history were compared with those without it. A cancer history was examined in the in-hospital cancer registry. The primary outcome was a composite of cardiac death, recurrent type 1 MI, post-discharge coronary revascularization, heart failure hospitalization, and stroke. Among 551 AMI patients, 55 had a cancer history (cancer group) and 496 did not (non-cancer group). Cox proportional hazards model revealed that the risk of composite endpoint was significantly higher in the cancer group than in the non-cancer group (adjusted hazard ratio [HR]: 1.78; 95% confidence interval [CI]: 1.13-2.82). Among the cancer group, patients who were diagnosed as AMI within 6 months after the cancer diagnosis had a higher risk of the composite endpoint than those who were diagnosed as AMI 6 months or later after the cancer diagnosis (adjusted HR: 5.43; 95% CI: 1.55-19.07). CONCLUSIONS: A cancer history increased the risk of CV events after discharge among AMI patients after revascularization.

Development of adolescent childhood cancer survivors' psychosocial issues scale.

BACKGROUND: Follow-up care for adolescent childhood cancer survivors (ACCS) after they return to school requires an understanding of their psychosocial issues. Therefore, this study developed the adolescent childhood cancer survivors' psychosocial issues scale (ACCSPIS) and evaluated its reliability and validity. METHODS: In the development phase, pediatric oncology clinical professionals created the 24 item questionnaire of ACCS's psychosocial issues. In the feasibility phase, a survey was administered to 165 ACCS aged 12-18 years after discharge from hospital in Japan, and 57 completed questionnaires were analyzed. The survey items were psychosocial issues, attributes, K6 scale, and impact of event scale-revised (IES-R) scale. Factor analysis was conducted for psychosocial issues. Regarding reliability, Cronbach's α coefficients and item-total correlation coefficients were calculated. Regarding validity, Spearman's rank correlation coefficients between ACCSPIS and K6 and IES-R were calculated, and confirmatory factor analysis was conducted. RESULTS: Four factors comprising 15 items were extracted: "appearance changes due to treatment effects," "anxiety about marriage and the future," "change in appearance due to treatment", and "psychological distress due to interpersonal relationships and information about the disease." The model fit was good, with a total ACCSPIS α coefficient of 0.901 and α coefficients for the subscales ranging from 0.651 to 0.914. The K6 and IES-R were significantly associated with the total ACCSPIS, and item-total correlations were satisfactory. CONCLUSIONS: The reliability and validity of ACCSPIS were generally confirmed. This scale could be useful to measure psychosocial issues in ACCS aged 12-18 years after their return to school.

TiO2-Photocatalyst-Induced Degradation of Dog and Cat Allergens under Wet and Dry Conditions Causes a Loss in Their Allergenicity.

Allergies to dogs and cats can cause enormous damage to human health and the economy. Dog and cat allergens are mainly found in dog and cat dander and are present in small particles in the air and in carpets in homes with dogs and cats. Cleaning houses and washing pets are the main methods for reducing allergens in homes; however, it is difficult to eliminate them completely. Therefore, we aimed to investigate whether a TiO2 photocatalyst could degrade dog and cat allergens. Under wet conditions, exposure to the TiO2 photocatalyst for 24 h degraded Can f1, which is a major dog allergen extracted from dog dander, by 98.3%, and Fel d1, which is a major cat allergen extracted from cat dander, by 93.6-94.4%. Furthermore, under dry conditions, the TiO2 photocatalyst degraded Can f1 and Fel d1 by 92.8% and 59.2-68.4%, respectively. The TiO2 photocatalyst abolished the binding of dog and cat allergens to human IgE by 104.6% and 108.6%, respectively. The results indicated that the TiO2 photocatalyst degraded dog and cat allergens, causing a loss in their allergenicity. Our results suggest that TiO2 photocatalysis can be useful for removing indoor pet allergens and improving the partnership between humans and pets.

Nelarabine, intensive L-asparaginase, and protracted intrathecal therapy for newly diagnosed T-cell acute lymphoblastic leukaemia in children and young adults (ALL-T11): a nationwide, multicenter, phase 2 trial including randomisation in the very high-risk group.

BACKGROUND: T-cell acute lymphoblastic leukaemia has distinct biological characteristics and a poorer prognosis than B-cell precursor acute lymphoblastic leukaemia. This trial aimed to reduce the rate of radiation and haematopoietic stem-cell transplantation (HSCT) while improving outcomes by adding nelarabine, intensified L-asparaginase, and protracted intrathecal therapy in the Berlin-Frankfurt-Münster (BFM)-type treatment. METHODS: In this nationwide, multicenter, phase 2 trial, we enrolled patients with newly diagnosed T-cell acute lymphoblastic leukaemia (age <25 years at diagnosis) conducted by Japan Children's Cancer Group and Japan Adult Leukemia Study Group. Patients were stratified into standard-risk, high-risk, and very-high-risk groups according to prednisolone response, CNS status, and end-of-consolidation minimal residual disease. We used the Associazione Italiana di Ematologia Oncologia Pediatrica (AIEOP)-BFM-ALL 2000-backbone chemotherapy. Nelarabine (650 mg/m2 per day for 5 days) was given to high-risk and very high-risk patients. All patients received, until the measurement of end-of-consolidation minimal residual disease, an identical therapy schedule, which included the prednisolone pre-phase remission induction therapy with dexamethasone (10 mg/m2 per day, for 3 weeks [for patients <10 years] or for 2 weeks including a 7-day off interval [for patients ≥10 years]) instead of prednisolone, and consolidation therapy added with Escherichia coli-derived L-asparaginase. On the basis of the stratification, patients received different intensities of treatment; L-asparaginase-intensified standard BFM-type therapy for standard risk and nelarabine-added high risk BFM-type therapy for high risk. In the very high-risk group, patients were randomly assigned (1:1) to group A (BFM-based block therapy) and group B (another block therapy, including high-dose dexamethasone) stratified by hospital, age (≥18 years or <18 years), and end-of-induction bone marrow blast percentage of M1 (<5%) or M2 (≥5%, <25%)+M3 (≥25%). Cranial radiotherapy was limited to patients with overt CNS disease at diagnosis (CNS3; >5 white blood cells per µL with blasts) and patients with no evidence of CNS disease received protracted triple intrathecal therapy. Only very high-risk patients were scheduled to receive HSCT. The primary endpoint was 3-year event-free survival for the entire cohort and the proportion of patients with disappearance of minimal residual disease between randomly assigned groups A and B in the very high-risk group. Secondary endpoints were overall survival, remission induction rate, and occurrence of adverse events. 3 years after the completion of patient accrual, a primary efficacy analysis was performed in the full analysis set and the per-protocol set. This study is registered with the Japan Registry of Clinical Trials, jRCTs041180145. FINDINGS: Between Dec 1, 2011, and Nov 30, 2017, of 349 eligible patients (median age 9 years [IQR 6-13]), 238 (68%) were male, and 28 (8%) patients had CNS3 status. 168 (48%) patients were stratified as standard risk, 103 (30%) as high risk, 39 (11%) as very high risk, and 39 (11%) as no risk (patients who had off protocol treatment before risk assessment. The composite complete remission (complete remission plus complete remission in suppression) rate after remission induction therapy was 89% (298 of 335 patients). HSCT was performed in 35 (10%) of 333 patients. With a median follow-up of 5·2 years (IQR 3·6-6·7), 3-year event-free survival was 86·4% (95% CI 82·3-89·7%) and 3-year overall survival was 91·3% (87·7-93·8%). The proportion of minimal residual disease disappearance was 0·86 (12 of 14 patients; 95% CI 0·57-0·98) in group A and 0·50 (6 of 12 patients, 0·21-0·79) in group B. Grade 3 peripheral motor neuropathy was seen in 11 (3%) of 349 patients and sensory neuropathy was seen in 6 (2%) patients. The most common grade 3 or worse adverse event was febrile neutropenia (294 [84%] of 349 patients). Treatment-related death occurred in three patients due to sepsis, gastric perforation, or intracranial haemorrhage during remission induction. INTERPRETATION: The ALL-T11 protocol produced encouraging outcomes with acceptable toxicities despite limited cranial radiotherapy and HSCT use. FUNDING: Ministry of Health, Labor and Welfare of Japan, and Japan Agency for Medical Research and Development. TRANSLATION: For the Japanese translation of the abstract see Supplementary Materials section.

Rare Case of BCOR::CCNB3 Sarcoma of Bone.

BACKGROUND BCOR: CCNB3 sarcoma is a rare mesenchymal tumor that was formerly included in the undifferentiated/unclassified sarcoma group and was recently reclassified as one of undifferentiated small round cell sarcomas with a genetically distinct subtype in the WHO 2020 classification. Because of its rarity, still not much is known, especially about its clinical features. CASE REPORT A 15-year-old boy presented with almost 1-year intermittent thigh pain. On the first visit, a pathologic fracture of the femur and a big mass expanding through the femoral cortex with lobular shape and homogenous appearance were recognized on radiography and magnetic resonance imaging. Plain radiography, which was taken 6 months before at a local clinic, showed an expansion and thickening of the right proximal femoral shaft. Biopsy specimen of the lesion revealed a proliferation of round to spindle tumor cells with diffuse and strong immunohistochemical nuclear positivity for BCOR and CCNB3. Under the diagnosis of BCOR::CCNB3 sarcoma of the femur, a chemotherapy based on a protocol of Ewing sarcoma, followed by a wide resection and total femoral replacement surgery, were conducted. The effect of chemotherapy was favorable, showing no microscopic residual tumor. Although postoperative chemotherapy was not completed because of a minor infection detected on the surgical site, the patient was doing well, without any recurrence, for 26 months. CONCLUSIONS BCOR: CCNB3 sarcoma of the bone is a quite rare tumor with much lower incidence than Ewing sarcoma. Notable clinical characteristics of the current case were a 1-year-long symptomatic period and homogenous appearance on MRI.

Intra-articular injection of culture-expanded adipose tissue-derived stem cells for knee osteoarthritis: Assessments with clinical symptoms and quantitative measurements of articular cartilage volume.

BACKGROUND: Intra-articular administration of adipose tissue-derived stem cells (ADSC) is an alternative treatment option for knee osteoarthritis (OA) after conventional treatment fails; however, the clinical results related to the severity of OA grade and changes of cartilage volumes after the administration of ADSC is unknown. This study aimed to determine 1) clinical outcomes after the ADSC administration in knee OA with consideration of radiographic OA grades and 2) changes in cartilage volumes after ADSC administration. METHODS: This observational study included 86 knees from 51 patients who underwent intra-articular administration of cultured ADSC; 47 patients (80 knees) completed follow-up for 6 months (follow-up rate: 93%). The Knee injury and Osteoarthritis Outcome Scores (KOOS) were reported at baseline and 1, 3, and 6 months after the administration. The efficacy rate in the Outcome Measures in Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) was evaluated using the KOOS. Cartilage volume of the knee joint was measured using quantitative 3-dimensional magnetic resonance imaging (3D-MRI) software at baseline and 6 months in 52 knees in 31 patients (follow-up rate: 61%). RESULTS: All items on the KOOS except "sports/recreation" improved significantly at 6 months with more significance in knees with a Kellgren-Lawrence (KL) grade 2 or 3 compared with KL grade 4 knees. The OMERACT-OARSI responder at 6 months was significantly greater in knees with KL grade 2 or 3 (64%) than in knees with KL grade 4 (42%, p = 0.045). Cartilage volume changes varied among patients and were not related to the changes in KOOS after ADSC administration. CONCLUSIONS: Intra-articular administration of ADSC in knee OA improved KOOS at 6 months. The effects were more significant in knees with KL grade 2 or 3 than with KL grade 4. Changes in KOOS were not related to change in cartilage volumes after ADSC administration.

Effects of potassium on hydrothermal carbonization of sorghum bagasse.

Hydrothermal carbonization (HTC) reacts with biomass in water at a high temperature and pressure to produce hydrochar with a higher heating value (HHV) and lower ash content than dry torrefaction. The high potassium content in biomass can promote thermochemical conversion; however, it lowers the melting temperature of the ash, causing slugging and fouling. Therefore, this study, investigated the effect of potassium on the HTC of sorghum bagasse by comparing the removal of potassium by washing with the addition of K2CO3. Consequently, the ash content was the highest in the potassium-added hydrochar and was 3.81% at a reaction time of 2 h. Elemental analysis showed that the lower the potassium content, the higher the carbon content, and the hydrochar with potassium removed by water washing at a reaction time of 3 h had the highest carbon content at 68.3%. Fourier transform infrared spectrometer showed dehydration and decarboxylation reactions due to HTC, but no significant differences were observed between the potassium concentrations. The mass yield decreased with increasing potassium content, and was 27.2% for the potassium-added hydrochar after 3 h. This trend was more pronounced with increasing reaction temperature. On the other hand, HHV was not affected by the potassium content. Therefore, the energy yield was similar to the weight yield. Thermal gravimetry and derivative thermal gravimetry (TG-DTG) analysis showed that higher potassium tended to accelerate the decomposition of lignin and decrease the oxidation temperature.

Feasibility and safety of platinum-doublet therapy in patients with small-cell lung cancer in the third-line setting: A multi-institutional retrospective study.

Small-cell lung cancer (SCLC) is a highly malignant tumor, and no standard third-line therapy has been established. The present study retrospectively analyzed the efficacy and safety of platinum-based regimens in patients with third-line SCLC who received third-line chemotherapy. The association of regimen type with overall survival (OS) or time to treatment failure (TTF) was evaluated using the Cox hazard proportional method, including well-known covariates affecting the prognosis of SCLC. TTF and OS analyses were conducted using the Kaplan-Meier method. The data cutoff date was June 30, 2020. As a result, from January 2015 to August 2019, 111 patients were diagnosed with SCLC, and 37 received third-line chemotherapy. Subsequently, 15 patients received a platinum-doublet regimen, and 22 patients received a single-agent regimen. Only the type of regimen was significantly associated with TTF in univariate analysis (odds ratio, 0.44; 95% confidence interval, 0.20-0.95; P=0.03). There were no significant factors associated with OS. The median TTF of patients receiving a platinum-doublet regimen and those receiving a single-agent regimen were 3.9 and 2.3 months, respectively (P=0.03). The overall response rates of the platinum-doublet and single-agent regimens were 20.0 and 4.5%, respectively. Similarly, the disease control rates were 73.3 and 36.4% for platinum-doublet and single-agent regimens, respectively. There was a tendency for adverse events (AEs) with any grade to occur more often in platinum-based regimens compared with in single-agent regimens. Severe AEs of grade 3 or higher were observed more often in the platinum-based regimen, especially in myelosuppression. In conclusion, the present study demonstrated the feasibility and safety of platinum-doublet regimens in patients with SCLC in a third-line setting (Registration no. 2020-048. Date of registration, June 5, 2020).

Effect of Germline MEFV Polymorphisms on the Prognosis of Japanese Children with Cancer: A Regional Analysis.

INTRODUCTION: MEFV is the gene responsible for familial Mediterranean fever. It encodes pyrin, which controls inflammation. Besides, previous studies have reported that some germline MEFV variants were associated with tumour susceptibility. MATERIALS AND METHODS: The loci of 12 germline MEFV variants were genotyped in 153 Japanese children with cancer, and the frequencies of these variants among the patient groups were compared with those in the general Japanese population. Additionally, the relationship between these variants and clinical data, including relapse and death, was investigated. RESULTS: Minor allele frequencies did not differ between patients and the general population, or between sex, age at diagnosis, and diagnosis among patients. P369S/R408Q associated with significantly lower relapse-free survival in all patient analyses and in patients with solid tumours. Additionally, although the results were not significant, E148Q/L110P was likely to associate with worse relapse-free survival in patients with solid tumours. DISCUSSION/CONCLUSION: Despite several limitations, this study provided the novel insight that the germline MEFV variants are associated with the clinical outcome of paediatric cancer.

Diabetic ketoacidosis shortly after COVID-19 vaccination in a non-small-cell lung cancer patient receiving combination of PD-1 and CTLA-4 inhibitors: A case report.

We describe a case of diabetic ketoacidosis (DKA) shortly after the SARS-CoV-2 (COVID-19) vaccination in a 65-year-old woman with non-small-cell lung cancer under a combination treatment of programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors. She had no history of diabetic mellitus. A few days after the second shot of COVID-19 vaccination, she developed DKA. We speculate that the immune-related adverse event and immunogenicity of vaccination synergistically induced DKA.

Temporary Rise in Blood Thrombogenicity in Patients with Acute Myocardial Infarction.

Objective Although blood thrombogenicity seems to be one of the determinant factors for the development of acute myocardial infarction (MI), it has not been dealt with in-depth. This study aimed to investigate blood thrombogenicity and its change in acute MI patients. Methods and Results We designed a prospective, observational study that included 51 acute MI patients and 83 stable coronary artery disease (CAD) patients who underwent cardiac catheterization, comparing thrombogenicity of the whole blood between: (1) acute MI patients and stable CAD patients; and (2) acute and chronic phase in MI patients. Blood thrombogenicity was evaluated by the Total Thrombus-Formation Analysis System (T-TAS) using the area under the flow pressure curve (AUC 30 ) for the AR-chip. Acute MI patients had significantly higher AUC 30 than stable CAD patients (median [interquartile range], 1,771 [1,585-1,884] vs. 1,677 [1,527-1,756], p = 0.010). Multivariate regression analysis identified acute MI with initial TIMI flow grade 0/1 as an independent determinant of high AUC 30 ( ß = 0.211, p = 0.013). In acute MI patients, AUC 30 decreased significantly from acute to chronic phase (1,859 [1,550-2,008] to 1,521 [1,328-1,745], p = 0.001). Conclusion Blood thrombogenicity was significantly higher in acute MI patients than in stable CAD patients. Acute MI with initial TIMI flow grade 0/1 was significantly associated with high blood thrombogenicity by multivariate analysis. In acute MI patients, blood thrombogenicity was temporarily higher in acute phase than in chronic phase.

Out-of-hospital cardiac arrest due to acute myocardial infarction possibly caused by coronary vasospasm.

A 60-year-old man with out-of-hospital cardiac arrest was transported to our hospital by an emergency medical service. Ventricular fibrillation was finally terminated after the initiation of circulation support by percutaneous cardiopulmonary support device. Although acute myocardial infarction was suspected, emergency coronary angiography could not identify the culprit lesion of myocardial infarction while there were multiple intermediate stenotic lesions. Since re-elevation of troponin I was recorded on the 4th day after admission, coronary angiography was performed again, and diffuse severe stenosis in the right coronary artery and total occlusion in the left circumflex coronary artery that disappeared by the injection of isosorbide dinitrate was detected. Therefore, we reached the diagnosis of acute myocardial infarction due to coronary vasospasm. It is very rare that emergency coronary angiogram reveals coronary vasospasm at the culprit lesion of myocardial infarction. The guideline recommends calcium channel antagonist and long-acting nitrates for vasospastic angina; however, it would be really difficult to make correct diagnosis of coronary vasospasm among the patients with acute myocardial infarction or out-of-hospital cardiac arrest. Repeated measurements of troponin and coronary angiography identified the cause of acute myocardial infarction as coronary vasospasm in the present case. .

Investigation into the combustion kinetics and spontaneous ignition of sweet sorghum as energy resource.

This study investigated the combustion kinetics and spontaneous ignition of sweet sorghum using thermogravimetric analysis and the Frank-Kamenetskii theory. The aim was to determine the proper operating conditions for a direct combustion reactor and predict the safe ambient temperature limits for given silo designs. Oxidative heating rates of 2, 5, and 10 °C/min were set up. Graphical observation shows that combustion was composed of two different stages representing the overlapping processes of pyrolysis and char oxidation, at 131-336 °C and 336-475 °C, respectively. Samples were found to ignite at 215 °C and were extinguished at 433 °C. Different heating rates shifted combustion characteristics to higher temperatures and increased reactivity for ignition and combustion indices up to 12 and 10 times higher. The Friedman method determined the apparent activation energies representing the combustion reaction by 132.91 kJ/mol. Regarding spontaneous ignition, the temperature safe limits were predicted to be 83-84 °C and 84-87 °C for cylindrical and box silos with diameter and height of 15 and 10 m, respectively. Calculations of silos were designed within the limits of certain dimension ratios.

Long-term outcomes following surgical repair of coronary artery fistula in adults.

BACKGROUND AND AIM OF THE STUDY: Coronary artery fistula (CAF) is a relatively rare cardiac anomaly. We investigated long-term outcomes following surgical repair of CAF in adults. METHODS: We retrospectively investigated 13 consecutive patients undergoing surgical repair of CAF in our institution between 2008 and 2019 (67.3 ± 10.4 years old, 38% male). CAF types were coronary artery-pulmonary artery fistula (77%), coronary artery-coronary sinus fistula (15%), and both (8%). CAFs originated from the left coronary artery (38%), right coronary artery (8%), and bilateral coronary arteries (38%). Pulmonary and systemic flow (Qp/Qs) was measured in seven patients (54%), with a mean value of 1.52. Seven patients underwent surgery for CAFs alone, and others simultaneously underwent surgery for comorbid cardiac diseases. RESULTS: All procedures were conducted under cardiopulmonary bypass. Surgical procedures were direct epicardial ligation of fistula (92%), direct closure of CAF through pulmonary artery incision (38%), direct closure of CAF through coronary sinus incision (8%), or patch closure of CAF through coronary artery incision (8%). Myocardial perfusion scintigraphy showed asymptomatic myocardial ischemia in the right coronary area after surgery in one patient. There were no deaths perioperatively or during follow-up (mean: 66.6 months). There were no coronary or other CAF-related events. CONCLUSIONS: Several anatomical variations in CAF were observed which coexist with cardiac disease. Long-term outcomes following surgical repair were satisfactory, and the concurrent intervention of CAFs during surgery for comorbid cardiac disease is useful to prevent future complications related CAFs in adults.

Proton beam therapy with concurrent chemotherapy is feasible in children with newly diagnosed rhabdomyosarcoma.

BACKGROUND: The optimal treatment for rhabdomyosarcoma (RMS) requires multidisciplinary treatment with chemotherapy, surgery, and radiotherapy. Surgery and radiotherapy are integral to the local control (LC) of RMS. However, postsurgical and radiotherapy-related complications could develop according to the local therapy and tumor location. In this study, we conducted a single-center analysis of the outcomes and toxicity of multidisciplinary treatment using proton beam therapy (PBT) for pediatric RMS. MATERIALS AND METHODS: RMS patients aged younger than 20 years whose RMS was newly diagnosed and who underwent PBT at University of Tsukuba Hospital (UTH) during the period from 2009 to 2019 were enrolled in this study. The patients' clinical information was collected by retrospective medical record review. RESULTS: Forty-eight patients were included. The 3-year progression-free survival (PFS) and overall survival (OS) rates of all the patients were 68.8% and 94.2%, respectively. The 3-year PFS rates achieved with radical resection, conservative resection, and biopsy only were 65.3%, 83.3%, and 67.6%, respectively (p = 0.721). The 3-year LC rates achieved with radical resection, conservative resection, and biopsy only were 90.9%, 83.3%, and 72.9%, respectively (p = 0.548). Grade 3 or higher mucositis/dermatitis occurred in 14 patients. Although the days of opioid use due to mucositis/dermatitis during the chemotherapy with PBT were longer than those during the chemotherapy without PBT [6.1 and 1.6 (mean), respectively, p = 0.001], the frequencies of fever and elevation of C-reactive protein were equivalent. CONCLUSIONS: Multidisciplinary therapy containing PBT was feasible and provided a relatively fair 3-year PFS, even in children with newly diagnosed RMS without severe toxicity.