[Colitis Suggested to be Related to Nivolumab in a Gastric Cancer Patient with a History of Ulcerative Colitis: A Case Report].

We experienced a case in which long-term use of nivolumab in a patient with a history of ulcerative colitis led to disease control of gastric cancer. The case is a 77-year-old man. The patient had a history of ulcerative colitis and remained in remission on mesalazine 1500 mg/d. With continuous monitoring, nivolumab could be continued up to 16 courses, but was withdrawn due to the appearance of diarrhea (grade 1) and bloody stools, which was relieved with prednisolone (PSL) 40 mg/d. After two more courses, diarrhea (grade 3) appeared again, which improved with PSL 60 mg/d and increased dose of mesalazine. It is difficult to distinguish whether colitis that occurs after nivolumab administration is due to relapse exacerbation or irAE. The onset of irAE colitis is often reported within 3 months, and the fact that this patient developed irAE colitis after 8 months, despite having ulcerative colitis, is considered novel. In the future, we hope to accumulate cases so that immune checkpoint inhibitors can be used safely in patients with ulcerative colitis, and to establish appropriate methods for their use.

The role of clinical engineers in the coronavirus disease 2019 pandemic.

The duties of a clinical engineer (CE) during the coronavirus infection 2019 (COVID-19) pandemic were diverse. The original duties of a CE included operation and maintenance of life support equipment used for respiratory therapy, hemodialysis, and extracorporeal membrane oxygenation. The management of life support equipment is critical. The PB-840 ventilator is equipped with a heat sink system that dissipates internal heat through thermal conduction. Therefore, internal contamination is less likely to occur. The exhalation filter used in the PB- 840 can be used for up to 15 days. It can be used for long periods of time without maintenance, reducing the risk of infection. The PB-840 is a suitable device for patients with COVID-19. Its use in critically ill patients was determined to be a priority. Thus, use of an appropriate device for infection control requires a proper understanding of and familiarity with the device in question.

Extracorporeal membrane oxygenation may decrease the plasma concentration of remdesivir in a patient with severe coronavirus disease 2019.

Remdesivir is an antiviral drug that results in clinical improvement after five days of treatment and accelerates recovery by 31%. No studies have discussed the pharmacokinetic analysis of remdesivir in patients with severe COVID-19 requiring extracorporeal membrane oxygenation (ECMO). A 63-year-old American man who underwent mechanical ventilation and ECMO for severe COVID-19 was administered remdesivir for ten days. The loading dosage was 200 mg at 7 PM on day 12 and 100 mg daily at 0:00 PM from day 13-21, administered within 1 h. The pharmacokinetic analysis was performed. The serum creatinine concentration was within the normal range of 0.5-0.7 mg/dL during treatment. According to the pharmacokinetic analysis, the plasma concentrations of remdesivir and GS-441524 4 h after administration (C4) were 662 ng/mL and 58 ng/mL, respectively, and the concentrations 18 h after administration (C18) were 32 ng/mL and 44 ng/mL, respectively. Therefore, the half-life of remdesivir and GS-441524 was 3.2 and 35.1 h, respectively. Monitoring the plasma concentrations of remdesivir and GS-441524 in patients undergoing ECMO may be necessary.

[Side Effect Management in the Early Stages of Cabozantinib Administration].

In 2 patients with postoperative lung metastases from renal cell carcinoma, we administered cabozantinib at a starting dose of 40 mg. The side effects were proteinuria(Grade 2), hand-foot syndrome(Grade 2), and hypertension(Grade 3), which subsided following dose reduction and drug suspension. We believe that a low starting dose of cabozantinib might be a suitable regimen for advanced renal cell carcinoma.

SARS-CoV-2 Leakage From the Gas Outlet Port During Extracorporeal Membrane Oxygenation for COVID-19.

Patients with the coronavirus disease 2019 (COVID-19) sometimes develop refractory respiratory failure and may require venovenous extracorporeal membrane oxygenation (VV-ECMO). It is known that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is sometimes present in the blood of COVID-19 patients. VV-ECMO is often used for several weeks, and plasma leaks can occur, albeit rarely. Hence, in terms of infection control, a concern is that SARS-CoV-2 may leak from the gas outlet port of the oxygenator during ECMO support of critically ill COVID-19 patients. The aim of this study was to clarify whether SARS-CoV-2 leaks from the oxygenator during ECMO support. Five patients with critical COVID-19 pneumonia were placed on VV-ECMO. Silicone-coated polypropylene membrane oxygenators were used in the ECMO circuits for these patients. SARS-CoV-2 ribonucleic acid (RNA) was measured by quantitative reverse transcription polymerase chain reaction in serum and at the gas outlet port of the ECMO circuit at the time of circuit replacement or liberation from ECMO. SARS-CoV-2 RNA was detected in the gas outlet port of the ECMO circuit for three of the five patients. None of the medical staff involved in the care of these five patients has been infected with COVID-19. In conclusion, SARS-CoV-2 could leak to the gas outlet port of the ECMO circuit through silicone-coated polypropylene membranes during ECMO support of critically ill COVID-19 patients.

[Evaluation of Risk Factors for Immune-Related Adverse Events Associated with Treatment with Immune Checkpoint Inhibitors].

OBJECTIVE: Risk factors for immune-related adverse events(irAEs)associated with immune checkpoint inhibitors(ICIs) remain to be obscure. Therefore, we evaluated the patient background and clinical findings to identify risk factors for the development of irAEs. METHODS: The subjects consisted of 86 patients treated with ICIs between August 2018 and March 2020. They were classified into 2 groups who developed irAEs(irAE group)and did not develop irAEs(non-irAE group). RESULTS: The median age of the subjects was 70 years(39-84 years), and there were 65 males. The underlying disease was non-small cell lung cancer in 51 patients, gastric cancer in 14, renal cell cancer in 9, urothelial cancer in 11, and MSI-high small bowel cancer in 1. The irAE group, in whom treatment with ICIs was discontinued, included 16 patients(18.6%), and the non-irAE group included 70 patients(81.4%). The median number of treatment cycles was 8(1-91), and the median treatment period was 4 months(1-45 months). Evaluation in our hospital revealed no significant background factors, such as gender, age, or the treatment period, as risk factors for the development of eras. Lung disorders were frequently observed after the third-line treatment and in patients with non-small cell lung cancer. CONCLUSION: At present, the prediction of the development of irAEs is difficult. Careful follow-up observation and early irAEs management are important. In addition, further studies are necessary to identify risk factors for the development of irAEs.

Direct hemoperfusion using a polymyxin B-immobilized polystyrene column for COVID-19.

OBJECTIVE: To evaluate the efficacy and safety of direct hemoperfusion using a polymyxin B-immobilized polystyrene column (PMX-DHP) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive pneumonia patients. METHODS: This study was a case series conducted at a designated infectious diseases hospital. Twelve SARS-CoV-2-positive patients with partial pressure of arterial oxygen/percentage of inspired oxygen (P/F) ratio < 300 were treated with PMX-DHP on two consecutive days each during hospitalization. We defined day 1 as the first day when PMX-DHP was performed. PMX-DHP efficacy was assessed on days 7 and 14 after the first treatment based on eight categories. Subsequently, improvement in P/F ratio and urinary biomarkers on days 4 and 8, malfunctions, and ventilator and extracorporeal membrane oxygenation avoidance rates were also evaluated. RESULTS: On day 14 after the first treatment, disease severity decreased in 58.3% of the patients. P/F ratio increased while urine ß2-microglobulin decreased on days 4 and 8. Cytokine measurement pre- and post-PMX-DHP revealed decreased levels of interleukin-6 and the factors involved in vascular endothelial injury, including vascular endothelial growth factor. Twenty-two PMX-DHPs were performed, of which seven and five PMX-DHPs led to increased inlet pressure and membrane coagulation, respectively. When the membranes coagulated, the circuitry needed to be reconfigured. Circuit problems were usually observed when D-dimer and fibrin degradation product levels were high before PMX-DHP. CONCLUSIONS: Future studies are expected to determine the therapeutic effect of PMX-DHP on COVID-19. Because of the relatively high risk of circuit coagulation, coagulation capacity should be assessed beforehand.

Continuous Renal Replacement Therapy for a Patient with Severe COVID-19.

The outbreak of coronavirus disease 2019 (COVID-19) is a global health threat. It is a respiratory disease, and acute kidney injury (AKI) is rare; however, if a patient develops severe AKI, renal replacement therapy (RRT) should be considered. Recently, we had a critically ill COVID-19 patient who developed severe AKI and needed continuous RRT (CRRT). To avoid the potential risk of infection from CRRT effluents, we measured severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genetic material in the effluents by qRT-PCR, and low copy numbers of the viral genome were detected. Due to unstable hemodynamic status in critically ill patients, CRRT should be the first choice for severe AKI in COVID-19 patients. We suggest prevention of clinical infection and control during administration of RRT in the acute phase of COVID-19 patients with AKI or multiple organ failure.

[Impact of Physician Order Support Duties on de novo Hepatitis Prevention].

"Immunosuppression and hepatitis B measures and guidelines for chemotherapy" were announced in 2009. However, a fulminant case that appeared when the guidelines were not observed was reported, and de novo hepatitis prevention is an urgent problem. The rate of compliance with these guidelines as of January 2014 was 20.4%, but this rose to 34.3%after the alert indication for de novo hepatitis prevention was set on an electronic chart system from June 2014. The rate of compliance increased to 63.9% at a hospital where de novo hepatitis alerts were put on clinical cards in April 2015, but it gradually decreased thereafter. HBV-DNA measurement was 100% in compliance with the guidelines from August 2016 when HB antigen, HB antibody, and anti-hepatitis B core antigen measurements were all performed in March 2016 because the pharmacists practiced physician order support duties at that time. This helped to reduce the burden on physicians, and the physician order support duties by the pharmacist were educational. Thus, de novo hepatitis prevention may contribute to safe cancer chemotherapy.

[A Case of Rectal Cancer and Multiple Liver Metastases Treated Using mFOLFOX and Bevacizumab under Maintenance Dialysis].

A 50s man receiving dialysis for chronic kidney disease due to IgA nephropathy underwent laparoscopic reversal via Hartmann 's procedure for rectal cancer and multiple liver metastases, followed by chemotherapy for the liver metastases. Following a single course of mFOLFOX therapy, bevacizumab was administered for 8 courses, resulting in tumor shrinkage and a decrease in tumor marker levels. The initial doses were 60mg/m2 oxaliplatin and 280(bolus injection)and 1,680mg/m2 (continuous infusion)of 5-FU. Subsequently, these doses were adjusted to be administered every 3 weeks. No serious adverse events other than neutropenia(Grade3 ), anorexia(Grade1 ), and hiccups(Grade1)were noted.