Prediction Model for Severe Thrombocytopenia Induced by Gemcitabine Plus Cisplatin Combination Therapy in Patients with Urothelial Cancer.

BACKGROUND: Chemotherapy-induced thrombocytopenia is often a use-limiting adverse reaction to gemcitabine and cisplatin (GC) combination chemotherapy, reducing therapeutic intensity, and, in some cases, requiring platelet transfusion. OBJECTIVE: A retrospective cohort study was conducted on patients with urothelial cancer at the initiation of GC combination therapy and the objective was to develop a prediction model for the incidence of severe thrombocytopenia using machine learning. METHODS: We performed receiver operating characteristic analysis to determine the cut-off values of the associated factors. Multivariate analyses were conducted to identify risk factors associated with the occurrence of severe thrombocytopenia. The prediction model was constructed from an ensemble model and gradient-boosted decision trees to estimate the risk of an outcome using the risk factors associated with the occurrence of severe thrombocytopenia. RESULTS: Of 186 patients included in this study, 46 (25%) experienced severe thrombocytopenia induced by GC therapy. Multivariate analyses revealed that platelet count ≤ 21.4 (×104/µL) [odds ratio 7.19, p < 0.01], hemoglobin ≤ 12.1 (g/dL) [odds ratio 2.41, p = 0.03], lymphocyte count ≤ 1.458 (×103/µL) [odds ratio 2.47, p = 0.02], and dose of gemcitabine ≥ 775.245 (mg/m2) [odds ratio 4.00, p < 0.01] were risk factors of severe thrombocytopenia. The performance of the prediction model using these associated factors was high (area under the curve 0.76, accuracy 0.82, precision 0.68, recall 0.50, and F-measure 0.58). CONCLUSIONS: Platelet count, hemoglobin level, lymphocyte count, and gemcitabine dose contributed to the development of a novel prediction model to identify the incidence of GC-induced severe thrombocytopenia.

Macrophage-1 antigen exacerbates histone-induced acute lung injury and promotes neutrophil extracellular trap formation.

Acute lung injury (ALI), which occurs in association with sepsis, trauma, and coronavirus disease 2019 (COVID-19), is a serious clinical condition with high mortality. Excessive platelet-leukocyte aggregate (PLA) formation promotes neutrophil extracellular trap (NET) release and thrombosis, which are involved in various diseases, including ALI. Macrophage-1 antigen (Mac-1, CD11b/CD18), which is expressed on the surface of leukocytes, is known to promote NET formation. This study aimed to elucidate the role of Mac-1 in extracellular histone-induced ALI. Exogenous histones were administered to Mac-1-deficient mice and wild-type (WT) mice with or without neutrophil or platelet depletion, and several parameters were investigated 1 h after histone injection. Depletion of neutrophils or platelets improved survival time and macroscopic and microscopic properties of lung tissues, and decreased platelet-leukocyte formation and plasma myeloperoxidase levels. These improvements were also observed in Mac-1-/- mice. NET formation in Mac-1-/- bone marrow neutrophils (BMNs) was significantly lower than that in WT BMNs. In conclusion, our findings suggest that Mac-1 is associated with exacerbation of histone-induced ALI and the promotion of NET formation in the presence of activated platelets.

[Factors Related to Submission of Tracing Reports Regarding Cancer Chemotherapy by Pharmacy Pharmacists].

In Japan, use of a report for providing information from pharmacies to medical institutions called as "tracing report (TR)" is not widespread especially in the field of cancer chemotherapy. Identification of the factors related to submission of TRs could enhance the necessity of TRs. The purpose of this study is to clarify the factors related to submission of TRs regarding cancer chemotherapy through a questionnaire survey. A questionnaire survey was conducted at the live web-based seminar regarding cancer chemotherapy held for pharmacists in January 2023. After the questionnaire survey, the participants were divided into those who had submitted at least one TR regarding cancer chemotherapy within one month before the seminar (TR group) and those who had not (non-TR group). The multivariate analysis was conducted to identify factors related to submission of TRs regarding cancer chemotherapy. Of 118 participants, the responses from 93 pharmacy pharmacists involved in dispensing drugs who agreed to participate in this study and fulfilled all questionnaire were analyzed. TR group included 21 participants and non-TR group included 72. As a result of multivariate analysis, "Years of experience in counseling and following-up with patients undergoing cancer chemotherapy (odds ratio: 4.81, p=0.02)" and "Types of workplaces (odds ratio: 3.79, p=0.02)" significantly increased the incidence of submission of TRs regarding cancer chemotherapy. It was revealed that experience of intervention in cancer chemotherapy cases and an environment in which prescriptions for cancer chemotherapy can be handled on a daily basis are important for submission of TRs regarding cancer chemotherapy.

Remote follow-up by pharmacists for blood pressure control in patients with hypertension: a systematic review and a meta-analysis of randomized controlled trials.

Hypertension is a major cause of cardiovascular diseases. Several recent studies reported that pharmacists' remote follow-up reduced hypertension patients' blood pressure (BP). This meta-analysis aims to verify whether remote follow-up by pharmacists improves BP levels and reveal the factors that make the intervention effective. The search, conducted using PubMed/Medline, Embase, and Cochrane Library from June to July 2023, targeted articles published between October 1982 and June 2023, using terms including "pharmacist", "hypertension", and "randomized controlled trial (RCT)". The inclusion criteria were: (a) RCTs involving hypertension patients with or without comorbidities, (b) pharmacists using remote communication tools to conduct follow-up encounter during the intervention period, (c) reporting systolic blood pressure (SBP) at baseline and during intervention. SBP was the primary outcome for the meta-analysis. Thirteen studies (3969 participants) were included in this meta-analysis. The mean difference of SBP between intervention group and control group was - 7.35 mmHg (P < 0.0001). Subgroup analyses showed the greater reduction of SBP in the "regularly scheduled follow-up cohort" (- 8.89 mmHg) compared with the "as needed follow-up cohort" (- 3.23 mmHg, P < 0.0001). The results revealed that remote follow-up by pharmacists reduced SBP levels in hypertension patients and scheduled remote follow-up may contribute to the effectiveness.

Investigation of geriatric syndromes associated with medication in Japan using insurance claims data.

AIM: Multiple risk factors are involved in geriatric syndrome (GS) occurring in older adults. Although drug therapy often contributes to GS, the specific causes among older adults in Japan remain unclear. In this study, we examined the possible prescribing cascade rate among older outpatients eligible for Late-stage Elderly Health Insurance and elucidated the differences between GS and GS associated with medication (GSAM) trends. METHODS: This retrospective study enrolled patients from health insurance claims data in Japan between October 2018 and March 2019; hospitalized patients were excluded. Two groups were identified among the participants with GS: GS (no use of GS-causing medications) and possible-GSAM (p-GSAM; use of GS-causing medications). The collected data were analyzed using the Bell Curve for Excel, and statistical significance was set at P < 0.05. RESULTS: In total, 137 781 outpatients were enrolled. Of the 32 259 outpatients who did not use GS-causing medications, 7342 were classified into the GS group. Among 105 522 outpatients who used GS-causing medications, 8347 were classified as having p-GSAM. The mean number of prescriptions was significantly higher in the p-GSAM group than in the GS group (P < 0.01). Furthermore, all GS symptoms showed significant differences, with impaired appetite being the most prevalent in the p-GSAM group than in the GS group (P < 0.01). A possible prescribing cascade was suspected in 2826 (33.9%) of 8347 outpatients in the p-GSAM group. CONCLUSION: Impaired appetite in patients taking GS-causing medications might lead to prescribing cascades. Further studies are needed to prevent such prescribing cascades. Geriatr Gerontol Int 2024; 24: 61-67.

Sodium zirconium cyclosilicate reconciles management of hyperkalemia and continuity of renin-angiotensin-aldosterone system inhibitors: a retrospective observational study.

BACKGROUND: Sodium zirconium cyclosilicate, a non-absorbed non-polymer zirconium silicate, is a new potassium binder for hyperkalemia. A previous report showed that administering sodium zirconium cyclosilicate to patients with hyperkalemia allows a higher continuation rate of renin-angiotensin-aldosterone system inhibitors. However, no studies have compared sodium zirconium cyclosilicate with existing potassium binders for renin-angiotensin-aldosterone system inhibitor continuity. The purpose of this study was to evaluate the effect of sodium zirconium cyclosilicate on angiotensin-converting enzyme inhibitor /angiotensin receptor blocker continuation in patients with hyperkalemia compared to that of calcium polystyrene sulfonate. METHODS: Patients on angiotensin-converting enzyme inhibitors/angiotensin receptor blockers who were newly prescribed sodium zirconium cyclosilicate or calcium polystyrene sulfonate to treat hyperkalemia at a tertiary referral hospital between August 2020 and April 2022 were enrolled in this single-center, retrospective observational study. The primary outcome measure was angiotensin-converting enzyme inhibitor/angiotensin receptor blocker prescription three months after initiating potassium binders. RESULTS: In total, 174 patients on angiotensin-converting enzyme inhibitors/angiotensin receptor blockers who were newly administered sodium zirconium cyclosilicate (n = 62) or calcium polystyrene sulfonate (n = 112) were analyzed. The prescription rate of angiotensin-converting enzyme inhibitors /angiotensin receptor blockers at 3 months was significantly higher in the sodium zirconium cyclosilicate group than in the calcium polystyrene sulfonate group (89 vs. 72%). Multivariate logistic regression models showed that sodium zirconium cyclosilicate was independently associated with the primary outcome (odds ratio 2.66, 95% confidence interval 1.05-7.43). The propensity score-matched comparison also showed a significant association between sodium zirconium cyclosilicate and the primary outcome. CONCLUSIONS: Our study suggests that administering sodium zirconium cyclosilicate to patients with hyperkalemia allows for a higher continuation rate of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers than calcium polystyrene sulfonate. These findings suggest that sodium zirconium cyclosilicate has potential benefits for patients with chronic kidney disease receiving renin-angiotensin-aldosterone system inhibitors.

Effectiveness of Online Team-based Learning for Pharmacists on How to Conduct Clinical Medication Reviews for Old Patients in Japan: A Randomized Controlled Trial.

BACKGROUND/AIM: This study aimed to determine the effectiveness of online team-based learning (TBL) and the factors influencing dropouts from online TBL for pharmacists on how to conduct clinical medication reviews for older adults. PARTICIPANTS AND METHODS: All participants were randomly assigned to the TBL or non-TBL group by using a random number sequence table matched by their years of experience working as a pharmacist. The primary outcome was whether the score on the team readiness assurance test (TRAT) in the TBL group differed from that on the second individual readiness assurance test (IRAT) in the non-TBL group. The secondary outcome was to identify factors contributing to dropouts from the online TBL program. RESULTS: The TRAT score in the TBL group was significantly higher than the second IRAT score in the non-TBL group during the first session (p=0.010). There were no differences in TRAT and IRAT scores between groups in two subsequent sessions. Logistic regression analysis revealed that less than 10 years of pharmacy experience was a contributor to dropouts (p=0.039), whereas experience in home-based care prevented dropouts (p=0.026) in our online TBL program. CONCLUSION: This study revealed the short-term usefulness of online TBL on medication reviews for older adults and elucidated the factors related to dropouts. Although instructors should provide positive feedback to participants with insufficient experience in pharmacy practice and home-based care, online TBL has the potential to improve educational effectiveness for community pharmacists during the COVID-19 pandemic.

Influence of Brain Metastasis on Analgesia-Related Outcomes in Patients with Lung and Breast Cancers Treated with Naldemedine: A Propensity Score-Matched Analysis.

Naldemedine is structurally designed to prevent passage across the blood-brain barrier (BBB), resulting in the attenuation of opioid-induced constipation without interfering with the analgesic effects of opioids. However, the influence of brain metastasis (BM), as one indicator of BBB disruption, on the analgesic effects of opioids in patients treated with naldemedine remains unclear. To examine whether the analgesic effects of opioids following naldemedine treatment are lower in patients with BM than in those without BM, we surveyed inpatients with lung and breast cancers treated with naldemedine at Fujita Health University Hospital between April 2017 and March 2022. Changes in the numeric rating scale (NRS) scores, morphine milligram equivalents (MMEs), and the number of rescues were assessed as analgesia-related outcomes during the first 7 days of naldemedine treatment in patients with or without BM, matched by the propensity score. In total, 172 patients were enrolled. After propensity-score matching, 30 patients with BM and 60 patients without BM were included in the analysis. Changes in NRS scores, MMEs, and the number of rescues did not differ between patients with and without BM. In the linear mixed-effects model, the coefficient of interaction between patients with or without BM and the days for each outcome was not statistically significant. BM does not influence the analgesic effect of opioids in patients with lung and breast cancers treated with naldemedine. Naldemedine may be useful for treating BM.

[The Functional Roles and the Potential as Drug Targets of Glycoproteins Regulating Complement and Coagulation Pathways].

Complement (C) activation occurs via three pathways, namely the classical, lectin, and alternative pathways. Intercommunication occurs between the complement and coagulation systems, which can trigger tissue injury and inflammation. Disseminated intravascular coagulation (DIC) is a life-threatening disease characterized by disordered coagulation and systemic inflammation; here, the intercommunication between the complement and coagulation systems contributes to the development of DIC. Extracellular histones, which are contributors to the damage-associated molecular pattern, induce severe thrombosis. C5 is a key molecule in the intercommunication between the complement and coagulation systems and is associated with the development of lethal histone-induced thrombosis. Heparin and chondroitin sulfate (CS) are negatively charged, allowing them to bind to extracellular histones. As the coagulation system is less affected by CS than heparin, CS shows potential as an effective drug for the treatment of patients with DIC who have a high risk of bleeding. Complement receptor type-1-related gene Y (Crry) inhibits the complement pathway via binding to C3b and C4b. Hence, Crry is a potent inhibitor of the classical and alternative C pathways. The expression of Crry is decreased by the endothelial damage induced by extracellular histones. Crry dysfunction promotes the activation of C on the surface of endothelial cells. The prevention of C3 cleavage on endothelial cells might be a useful therapy targeting acute lung injury.

Novel function of transglutaminase 2 in extracellular histone-induced acute lung injury.

Extracellular histones induce endothelial damage, resulting in lung haemorrhage; however, the underlying mechanism remains unclear. Factor XIII, as a Ca2+-dependent cross-linking enzyme in blood, mediates fibrin deposition. As another isozyme, transglutaminase 2 (TG2) has a catalytic activity distributing in most tissues. Herein, we investigated whether TG2 promotes fibrin deposition and mediates the adhesion of platelets to ECs in histone-induced acute lung injury (ALI). We evaluated the lung histology and the adhesion of platelets to endothelial cells (ECs) after injecting histones to wild-type (WT) C57BL/6J and TG2 knockout (TG2-/-) mice, and administered a TG2 inhibitor (NC9) to WT mice. Pulmonary haemorrhage was more severe in TG2-/- mice than that in WT mice. The area of fibrin deposition and the proportion of CD41+CD31+ cells were lower in TG2-/- mice than in WT mice. Pre-treatment of NC9 decreased the area of fibrin deposition and the proportion of CD41+CD31+ cells in WT mice. These results suggest that TG2 prevents from pulmonary haemorrhage in ALI by promoting the adhesion of platelets to ECs and the fibrin deposition.

COVID-19 mRNA vaccination is associated with IgA nephropathy: an analysis of the Japanese adverse drug event report database.

Purpose: Coronavirus disease 2019 (COVID-19) mRNA vaccines are used worldwide to prevent severe symptoms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. IgA nephropathy (IgAN) is the most common form of glomerular injury after COVID-19 vaccination; however, because of the low frequency of such events, only a few reports have been published. A large pharmacovigilance database of real-world spontaneous adverse event (AE) reports is essential for evaluating the drug-associated safety signals regarding rare AEs. Herein, we aimed to investigate the frequency of IgAN after the COVID-19 vaccination, using the Japanese Adverse Drug Event Report (JADER) database. Methods: Data on drug-associated AEs reported between April 2004 and May 2022 were obtained from the JADER database on the Pharmaceuticals and Medical Devices Agency website. To evaluate the safety signals for the targeted AEs, reporting odds ratios (RORs), information components (ICs), and their 95% confidence intervals (CIs) were calculated using two-by-two contingency tables. Results: A total of 697,885 cases were included in the analysis. Safety signals were detected for IgAN (ROR: 6.49, 95% CI: 4.38-9.61; IC: 2.27, 95% CI: 1.70-2.83). Of 30 cases for IgAN associated with COVID-19 mRNA vaccines, 16 had information available on time to onset. Of the 16 cases, 11 occurred ≤2 days after vaccination, and two occurred >28 days after vaccination. Conclusion: These results suggest that, compared with other drugs, COVID-19 vaccination is associated with a higher frequency of IgAN. Monitoring of gross hematuria following COVID-19 vaccination should be needed.

Effect of fat emulsion administration on blood coagulation in terminal lung cancer patients.

Objectives: Patients with cancer, especially those with lung cancer, are at high risk of developing thrombosis. Intralipos® infusion 20% is contraindicated for thrombosis, and there is no consensus on whether it can be safely used in cases of advanced cancer. We conducted a retrospective observational study to elucidate the impact of fat emulsion administration on blood coagulation in patients with terminal lung cancer. Methods: The subjects were patients with terminal lung cancer in the Department of Surgery and Palliative Medicine, Fujita Health University Nanakuri Memorial Hospital between January 2016 and December 2019. We compared changes in their blood coagulation profile before hospitalization and one month later. Results: There were a total of 213 patients with lung cancer-139 who were administered fat emulsion and 74 who were not-with no significant differences in baseline characteristics. In the fat emulsion administration group (n=27), the prothrombin time-international normalized ratio (PT-INR) and activated partial thromboplastin time (APTT), respectively, were 1.17±0.26 (mean±standard deviation) and 30.5±5.0 s at hospitalization and 1.16±0.12 and 31.2±4.2 s one month later with no significant differences. In the non-administration group (n=6), the PT-INR and APTT, respectively, were 1.44±0.43 and 30.6±5.2 s before hospitalization and 1.28±0.18 and 33.0±7.5 s one month later with no significant differences. Conclusions: We did not identify any changes in PT-INR and APTT after fat emulsion administration in patients with terminal lung cancer. There were also no new cases of thrombosis, suggesting that fat emulsions were administered safely in patients with terminal lung cancer.

Efficacy of Ascorbic Acid, Thiamine, and Hydrocortisone Combination Therapy: Meta-analysis of Randomized Controlled Trials.

BACKGROUND/AIM: Sepsis is a life-threatening biological condition that induces systemic tissue and organ dysfunction and confers a high mortality risk. Although the use of hydrocortisone in combination with ascorbic acid and thiamine (HAT therapy) significantly reduced mortality from sepsis or septic shock in a previous study, it did not improve mortality in subsequent randomized controlled trials (RCTs). Therefore, no definitive conclusion has been established on the benefits of HAT therapy for sepsis or septic shock. We performed a meta-analysis to assess the treatment outcomes of HAT therapy in patients with sepsis or septic shock. PATIENTS AND METHODS: We searched databases (PubMed/MEDLINE, Embase, Scopus and Cochrane Library) for RCTs using the terms "ascorbic acid", "thiamine", "sepsis", "septic shock", and "RCT". The primary outcome of this meta-analysis was the mortality rate, and the secondary outcomes were the incidence of new-onset acute renal injury (AKI), intensive care unit (ICU) length of stay (ICU-LOS), change in the Sequential Organ Failure Assessment (SOFA) score within 72 hours, and duration of vasopressor use. RESULTS: Nine RCTs were identified and included in the outcome evaluation. HAT therapy did not improve the 28-day and ICU mortality, new-onset AKI, ICU-LOS, or SOFA scores. However, HAT therapy significantly shortened the duration of vasopressor use. CONCLUSION: HAT therapy did not improve mortality, the SOFA score, renal injury, or ICU-LOS. Further studies are needed to confirm whether it shortens the duration of vasopressor use.

A prospective randomized controlled study to assess the effectiveness of super FIXSORB WAVE® for sternal stabilization after sternotomy.

BACKGROUND: We developed a new sternal fixation device, Super FIXSORB WAVE®, a corrugated plate made of u-HA/PLLA, to improve sternal stability after sternotomy. This present study aimed to evaluate the new device clinically. METHODS: This prospective, single-blinded, multicenter trial randomized 69 patients to either wire cerclage only (group C, n = 30) or wire cerclage plus Super FIXSORB WAVE® (group W, n = 39). The primary endpoint was a degree of sternal displacement at six months. Displacement of the sternal halves in the anteroposterior and lateral directions was measured using computed tomography horizontal section images at the third costal and fourth intercostal levels. The secondary endpoints were sternal pain and quality-of-life over 6 months. RESULTS: Group W showed significantly reduced sternal anteroposterior displacement at both the third costal (0 [0-1.9] mm vs. 1.1 [0-2.1] mm; P = 0.014) and fourth intercostal (0 [0-1.0] mm) vs. 1.0 [0-1.8] mm; P = 0.015) levels than group C. In group W, lateral displacement was suppressed without a significant increase from 2 weeks to 6 months, while it increased in group C. There was no significant difference in postoperative sternal pain and quality-of-life between the two groups. No adverse events, such as infection, inflammation, or foreign body reaction, were observed with this device. CONCLUSIONS: Using Super FIXSORB WAVE®, sternal displacement was significantly suppressed in both the anteroposterior and lateral directions. The use of this device results in safe and easy sternal reinforcement without any adverse events, and sternal healing can be accelerated. CLINICAL TRIAL REGISTRY NUMBER: This study was registered in the Japan Registry of Clinical Trials (February 21, 2019; jRCTs032180146).

Ring annuloplasty, optionally combined with edge-to-edge leaflet plications, should be amended with subvalvular repair techniques to efficaciously treat tricuspid regurgitation with severe tethering.

OBJECTIVES: This study aimed to evaluate the outcomes of tricuspid annuloplasty with/without additional edge-to-edge plications in patients with functional tricuspid regurgitation (TR) and to clarify the impact of tethering on surgical outcomes. METHODS: This retrospective observational study included patients with moderate or greater functional TR who underwent initial tricuspid valve repair between January 2008 and December 2021. The patients were divided into 2 groups based on whether they had tethering (preoperative tethering area ≥0.75 cm2). All patients underwent annuloplasty, and edge-to-edge plications were added at the regurgitant leakage site identified by saline tests. The surgical outcomes of each group and the effect of tethering on recurrent moderate or greater TR were evaluated. RESULTS: One hundred and thirty-three patients were included in this study. During the follow-up period of 55.3 (standard deviation: 44.9) months, the 5-year survival rates were 78.4% in patients without tethering and 76.1% in patients with tethering (P = 0.78). The 5-year cumulative incidence rates of readmission for heart failure and recurrent TR were 10.8% and 1.3% in patients without tethering and 23.0% and 29.5% in patients with tethering, respectively (P = 0.12 and <0.001). Multivariable analyses revealed that the preoperative and predischarge tethering areas predicted recurrent TR. A large tethering area remained postoperatively in patients with tethering. CONCLUSIONS: In patients without tethering, annuloplasty and additional edge-to-edge plications are effective in avoiding recurrent TR with satisfactory midterm clinical outcomes. However, in patients with tethering, these procedures resulted in residual tethering, which could be leading to recurrent TR.

Surgical extraction of cardiac implantable electronic device leads based on a heart team approach.

BACKGROUND: As cardiac implantable electronic devices, such as pacemakers, cardioverter defibrillators, and cardiac resynchronization therapies, have become more popular, device extraction has become more frequent. At our institution, individual treatment strategies are discussed at a heart team meeting. Transvenous lead extraction (TVLE) is a first-line treatment; however, surgical lead extraction (SLE) is sometimes selected as a primary choice to provide optimal treatment and maintain the medical safety policy. This study aimed to investigate the validity of this heart team decision-making. METHODS: From 2013 to 2021, 384 consecutive patients underwent lead extraction at our institution. RESULTS: SLE was proposed as the primary intervention for 21 patients who had high risk of bleeding, difficult TVLE conditions, large vegetations, and other concomitant cardiac diseases. Of the 363 TVLE patients, 10 patients required surgical intervention; 5 had TVLE difficulty followed by SLE and 5 had excessive bleeding. SLE was performed in 26 patients, 19 of whom required valve surgery, and 8 required plication of the great veins. In 4 of the 17 hybrid procedures with SLE and TVLE, excessive bleeding occurred due to laceration of the superior vena cava and innominate vein. Operative mortality was not observed in SLE patients but was observed in 1 of the 4 TVLE patients who required emergent open-chest hemostasis. CONCLUSIONS: The heart team discussion was essential to provide optimal treatment and maintain medical safety policies for each patient. SLE should be selected for patients with high risk of TVLE or other cardiac complications such as tricuspid valve incompetence.

Innovative experimental animal models for real-time comparison of antithrombogenicity between two oxygenators using dual extracorporeal circulation circuits and indocyanine green fluorescence imaging.

BACKGROUND: Antithrombogenicity of extracorporeal membrane oxygenation (ECMO) devices, particularly oxygenators, is a current problem, with numerous studies and developments underway. However, there has been limited progress in developing methods to accurately compare the antithrombogenicity of oxygenators. Animal experiments are commonly conducted to evaluate the antithrombogenicity of devices; however, it is challenging to maintain a steady experimental environment. We propose an innovative experimental animal model to evaluate different devices in a constant experimental environment in real-time. METHODS: This model uses two venous-arterial ECMO circuits attached to one animal (one by jugular vein and carotid artery, one by femoral vein and artery) and real-time assessment of thrombus formation in the oxygenator by indocyanine green (ICG) fluorescence imaging. Comparison studies were conducted using three pigs: one to compare different oxygenators (MERA vs. CAPIOX) (Case 1), and two to compare antithrombotic properties of the oxygenator (QUADROX) when used under different hydrodynamic conditions (continuous flow vs. pulsatile flow) (Cases 2 and 3). RESULTS: Thrombi, visualized using ICG imaging, appeared as black dots on a white background in each oxygenator. In Case 1, differences in the site of thrombus formation and rate of thrombus growth were observed in real-time in two oxygenators. In Case 2 and 3, the thrombus region was smaller in pulsatile than in continuous conditions. CONCLUSIONS: We devised an innovative experimental animal model for comparison of antithrombogenicity in ECMO circuits. This model enabled simultaneous evaluation of two different ECMO circuits under the same biological conditions and reduced the number of sacrificed experimental animals.

The Effect and Tolerability of Second-line Chemotherapy Are Associated With Disease Control by Nivolumab Chemotherapy in Patients With Gastric Cancer.

BACKGROUND/AIM: Immune-related adverse events (irAEs) are associated with the efficacy of nivolumab. However, whether the tolerability of second-line chemotherapy is associated with the efficacy of nivolumab monotherapy (third-line chemotherapy) remains unclear. Our study aimed to investigate whether the results of second-line treatment were associated with the efficacy of nivolumab in patients with gastric cancer. PATIENTS AND METHODS: We enrolled Japanese patients aged ≥20 years with gastric cancer who were treated with nivolumab as a third-line chemotherapy at Fujita Health University Hospital from October 2017 to September 2021. Patients with the evaluations of complete response, partial response, and stable disease after third-line chemotherapy were included in the disease control (DC) group, while others were included in the progressive disease (PD) group. RESULTS: A total of 126 patients were enrolled. The population of patients aged over 65 years in the DC group was significantly higher than that in the PD group. The number of patients continuing second-line chemotherapy for >7 months was significantly higher in the DC than in the PD group. Age over 65 years [odds ratio (OR)=2.67], duration of second-line chemotherapy over 7 months (OR=3.10), and the occurrence of irAEs (OR=3.60) were detected as the factors associated with disease control after nivolumab chemotherapy. CONCLUSION: The effect and tolerability of second-line chemotherapy, and age over 65 years are the factors associated with DC after nivolumab chemotherapy. The control of tumour inflammatory status might be important for improving treatment outcomes.

Bovine pericardial patch repair for abdominal aortic pseudoaneurysm to preserve lumbar arteries.

We describe a case of aortic repair using bovine pericardium for a pseudoaneurysm of a dissecting abdominal aorta. A 71-year-old man had undergone several aortic replacement surgeries for type B aortic dissection. He developed paraparesis after thoraco-abdominal aortic surgery and recovered. After 3 years, the scheduled computed tomography scan showed a pseudoaneurysm of the dissecting abdominal aorta. Because he was at high risk of spinal cord ischaemia, aortic repair using bovine pericardium was performed, and all lumbar arteries were preserved. During the 12-month follow-up, he was asymptomatic, and computed tomography scans showed no dilation of the aorta.