Impact of Anemia on Clinical Outcomes of Patients With Cancer-Associated Isolated Distal Deep Vein Thrombosis Receiving Edoxaban　- Insights From the ONCO DVT Study.

BACKGROUND: The ONCO DVT study demonstrated potential benefits of extended edoxaban treatment in patients with isolated distal deep vein thrombosis in terms of thrombotic risk. However, the risk-benefit balance in patients with anemia remains unclear. METHODS AND RESULTS: This prespecified subgroup analysis included 601 patients, divided into anemia (n=402) and no-anemia (n=199) groups. The primary endpoint was symptomatic recurrent venous thromboembolism (VTE) or VTE-related death. Anemia was defined as hemoglobin <12 g/dL for women and <13 g/dL for men. In the anemia subgroup, the primary endpoint occurred in 3 (1.5%) and 17 (8.4%) patients in the 12- and 3-month edoxaban treatment groups, respectively (odds ratio [OR] 0.17; 95% confidence interval [CI] 0.05-0.58), compared with 0 and 5 (4.9%) patients, respectively, in the no-anemia subgroup (P interaction=0.997). Major bleeding occurred in 26 (13.1%) and 17 (8.4%) patients with anemia in the 12- and 3-month edoxaban treatment groups, respectively (OR 1.64; 95% CI 0.86-3.14), compared with 2 (2.1%) and 5 (4.9%) patients without anemia (OR 0.67; 95% CI 0.26-1.73; P interaction=0.13). CONCLUSIONS: Regardless of the presence of anemia, edoxaban treatment for 12 months was superior to treatment for 3 months in reducing thrombotic events, whereas the risk of major bleeding did not differ significantly between the 2 treatment groups.

Utility of the modified Ottawa score for identification of more preferable candidates of extended anticoagulation therapy in cancer-associated isolated distal deep vein thrombosis: insight from the ONCO DVT Study.

BACKGROUND: The ONCO DVT study (Edoxaban for 12 Months Versus 3 Months in Patients With Cancer With Isolated Distal Deep Vein Thrombosis) revealed superiority of 12-month relative to 3-month edoxaban treatment for the thrombotic risk in cancer-associated isolated distal deep vein thrombosis. However, it is unknown whether the superiority could be common in different modified Ottawa score subgroups. OBJECTIVES: To identify more preferable candidates for extended anticoagulation in patients with cancer-associated isolated distal deep vein thrombosis using the modified Ottawa score. METHODS: In this post-hoc subgroup analysis of the ONCO DVT study, we stratified 601 patients into the low (≤-1, N = 126), intermediate (0, N = 323), and high (≥1, N = 152) modified Ottawa score subgroups and compared clinical outcomes between the 12-month and 3-month edoxaban treatment groups. RESULTS: The cumulative incidence of symptomatic recurrent venous thromboembolism or venous thromboembolism-related death was not different between the 12-month and 3-month edoxaban treatment groups in the low score subgroup (0.0% vs 2.2%), whereas it was lower in the 12-month than in the 3-month edoxaban treatment group in the intermediate (0.8% vs 7.6%) and high (3.1% vs 15.6%) score subgroups. There were no significant differences in the cumulative incidences of the major bleeding between the 12-month and 3-month edoxaban treatment groups in the low (10.1% vs 7.6%), intermediate (8.8% vs 5.0%), and high (13.9% vs 12.6%) score subgroups. CONCLUSION: A 12-month compared with 3-month edoxaban treatment showed a lower risk of thrombotic events in patients with cancer-associated isolated distal deep vein thrombosis in the intermediate and high modified Ottawa score subgroups but not in the low score subgroup, suggesting a limited benefit of extended anticoagulation therapy beyond 3 months in patients with low modified Ottawa score.

Edoxaban for 12 vs. 3 months in cancer-associated isolated distal deep vein thrombosis according to different doses: insights from the ONCO DVT study.

BACKGROUND: The ONCO DVT study revealed the superiority of 12-month relative to 3-month edoxaban treatment for cancer-associated isolated distal deep vein thrombosis (DVT) regarding the thrombotic risk. METHODS AND RESULTS: In this pre-specified subgroup analysis of the ONCO DVT study, we stratified the patients into those with a standard edoxaban dose (60 mg/day; N = 151) and those with a reduced edoxaban dose (30 mg/day; N = 450) and evaluated the clinical outcomes for the 12- and 3-month treatments. The cumulative 12-month incidence of symptomatic recurrent venous thromboembolism was lower in the 12-month than 3-month group for both the 60 mg (1.3% vs. 11.6%, P = 0.02; odds ratio [OR], 0.12; 95% confidence interval [CI], 0.01-0.97) and 30 mg (1.1% vs. 7.6%, P = 0.002; OR, 0.14; 95% CI, 0.03-0.60) edoxaban subgroups, which was consistent across the edoxaban doses without a significant interaction (P = 0.90). The 12-month cumulative incidence of major bleeding was higher in the 12-month group than in the 3-month group for the 60 mg edoxaban subgroup (14.3% vs. 4.4%, P = 0.046; OR, 3.61; 95% CI, 0.97-13.52), whereas it did not significantly differ between the two groups for the 30 mg edoxaban subgroup (8.7% vs. 8.6%, P = 0.89; OR, 0.97; 95% CI, 0.49-1.91), signalling there was a potential interaction (P = 0.07). CONCLUSIONS: A 12-month edoxaban regimen for cancer-associated isolated distal DVT was consistently superior to a 3-month regimen, across the edoxaban doses for the thrombotic risk. However, caution was suggested for the standard dose of edoxaban due to the potential for an increased risk of bleeding with prolonged anticoagulation therapy. TRIAL REGISTRATION NUMBER: NCT03895502 (ONCO DVT Trial): https://classic.clinicaltrials.gov/ct2/show/NCT03895502.

Rhabdomyosarcoma of the tongue in a neonatal calf.

A newborn male Holstein calf developed a nodular enlargement at the tip of the tongue. Histopathological examination of the mass revealed predominant proliferating small, round, spindloid or polygonal neoplastic cells with scattered myoblast- and myotube-like cells and multinuclear giant cells. Phosphotungstic acid haematoxylin staining revealed cytoplasmic cross-striations in a few neoplastic cells. Neoplastic cells were immunopositive for vimentin, desmin, myoD1, myogenin, myoglobin and α-smooth muscle actin. The mass was diagnosed as embryonal rhabdomyosarcoma. To the best of our knowledge, this is the first reported case of bovine congenital lingual rhabdomyosarcoma, which is rare in animals.

The impact of renal function on clinical outcomes of patients with cancer-associated isolated distal deep vein thrombosis: Insights from the ONCO DVT study.

BACKGROUND: The multicenter, open-label, randomized clinical trial ONCO DVT compared 3-month and 12-month edoxaban treatment regimens for isolated distal deep vein thrombosis (DVT) and suggested potential benefits of prolonged edoxaban treatment in terms of thrombotic risk. However, the risk-benefit balance of prolonged edoxaban treatment in patients with renal function remains unclear. OBJECTIVES: To compare the safety and efficacy of 3-month and 12-month edoxaban treatment regimens in patients with cancer-associated isolated distal DVT and different renal functions. METHODS: This pre-specified subgroup analysis of the ONCO DVT study included 601 patients divided into subgroups according to renal function using a 50 mL/min creatinine clearance (Ccr) cutoff. The primary endpoint was symptomatic recurrent venous thromboembolism (VTE) and VTE-related death at 12 months and the major secondary endpoint was major bleeding at 12 months. RESULTS: Among the 601 patients, 131 (21.8 %) comprised the renal dysfunction subgroup. The primary endpoint occurred in 6 (9.7 %) and 1 (1.4 %) patients in the 3-month and 12-month edoxaban groups in the renal dysfunction subgroup, respectively, and in 16 (6.6 %) and 2 (0.9 %) patients in the no renal dysfunction subgroup, respectively. The major secondary endpoint occurred in 9 (14.5 %) and 7 (10.1 %) patients in the 12-month and 3-month edoxaban groups in the renal dysfunction subgroup, and in 13 (5.3 %) and 21 (9.3 %) patients in the no renal dysfunction subgroup, respectively. CONCLUSIONS: A 12-month edoxaban regiment was superior to a 3-month treatment in terms of thrombotic risk irrespective of renal function. A higher bleeding risk was not identified in patients with renal dysfunction who received prolonged edoxaban treatment.

Relapsing cytokine release syndrome in a patient with metastatic renal cell carcinoma treated with pembrolizumab and axitinib therapy.

As immune checkpoint inhibitors become more widely available, the optimal management of immune-related adverse events (irAEs) is becoming increasingly important. Although irAEs are diverse, reports on cytokine release syndrome are rare. Here, we report a case of a 48-year-old man with relapsing cytokine release syndrome after receiving pembrolizumab and axitinib combination therapy for metastatic renal cell carcinoma. During dose reduction of prednisolone for immune-related hepatitis on day 33 after starting pembrolizumab plus axitinib, the patient suddenly developed abdominal pain, and a few hours later became hypotensive and poorly oxygenated. Despite the use of a ventilator and high doses of catecholamines, blood pressure and oxygenation could not be maintained. Extracorporeal membrane oxygenation and intra-aortic balloon pumping were also administered. The cytokine release syndrome (CRS) was treated with tocilizumab, and his general condition improved. Lower-grade CRS relapsed four times despite a moderate dose of oral prednisolone with mycophenolate mofetil or tacrolimus. After gradual reduction in prednisolone over 5 months, the patient was discharged from the hospital. Partial remission of renal cell carcinoma continued for 21 months, and salvage radical nephrectomy was performed. The patient remained disease-free without the need for further treatment 9 months after surgery.

Tenascin-C as a potential marker for immunohistopathology of doxorubicin-induced cardiomyopathy.

Aims: Doxorubicin is used in classical chemotherapy for several cancer types. Doxorubicin-induced cardiomyopathy (DOX-CM) is a critical issue among cancer patients. However, differentiating the diagnosis of DOX-CM from that of other cardiomyopathies is difficult. Therefore, in this study, we aimed to determine novel histopathological characteristics to diagnose DOX-CM. Methods and results: Twelve consecutive patients with DOX-CM who underwent cardiac histopathological examination in two medical centres were included. Twelve patients with dilated cardiomyopathy, who were matched with DOX-CM patients in terms of age, sex, and left ventricular ejection fraction, formed the control group. Another control group comprised five consecutive patients with cancer therapy-related cardiac dysfunction induced by tyrosine kinase inhibitors or vascular endothelial growth factor inhibitors were the controls. The positive area of tenascin-C, number of infiltrating macrophages, and presence of p62- and ubiquitin-positive cardiomyocytes were evaluated. Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were used for in vitro investigation. The myocardium exhibited significantly greater tenascin-C-positive area and macrophage number in the DOX-CM group than in the control groups (P < 0.01). The tenascin-C-positive area correlated with the number of both CD68- and CD163-positive cells (r = 0.748 and r = 0.656, respectively). Immunostaining for p62 was positive in 10 (83%) patients with DOX-CM. Furthermore, western blotting analysis revealed significant increase in tenascin-C levels in hiPSC-CMs upon doxorubicin treatment (P < 0.05). Conclusion: The combined histopathological assessment for tenascin-C, macrophages, and p62/ubiquitin may serve as a novel tool for the diagnosis of DOX-CM. Doxorubicin may directly affect the expression of tenascin-C in the myocardium.

Edoxaban for 12 Months Versus 3 Months in Patients With Cancer With Isolated Distal Deep Vein Thrombosis (ONCO DVT Study): An Open-Label, Multicenter, Randomized Clinical Trial.

BACKGROUND: The optimal duration of anticoagulation therapy for isolated distal deep vein thrombosis in patients with cancer is clinically relevant, but the evidence is lacking. The prolonged anticoagulation therapy could have a potential benefit for prevention of thrombotic events; however, it could also increase the risk of bleeding. METHODS: In a multicenter, open-label, adjudicator-blinded, randomized clinical trial at 60 institutions in Japan, we randomly assigned patients with cancer with isolated distal deep vein thrombosis, in a 1-to-1 ratio, to receive either a 12-month or 3-month edoxaban treatment. The primary end point was a composite of a symptomatic recurrent venous thromboembolism (VTE) or VTE-related death at 12 months. The major secondary end point was major bleeding at 12 months, according to the criteria of the International Society on Thrombosis and Haemostasis. The primary hypothesis was that a 12-month edoxaban treatment was superior to a 3-month edoxaban treatment with respect to the primary end point. RESULTS: From April 2019 through June 2022, 604 patients were randomized, and after excluding 3 patients who withdrew consent, 601 patients were included in the intention-to-treat population: 296 patients in the 12-month edoxaban group and 305 patients in the 3-month edoxaban group. The mean age was 70.8 years, 28% of the patients were men, and 20% of the patients had symptoms of deep vein thrombosis at baseline. The primary end point of a symptomatic recurrent VTE event or VTE-related death occurred in 3 of the 296 patients (1.0%) in the 12-month edoxaban group and in 22 of the 305 patients (7.2%) in the 3-month edoxaban group (odds ratio, 0.13; 95% CI, 0.03-0.44). The major secondary end point of major bleeding occurred in 28 of the 296 patients (9.5%) in the 12-month edoxaban group and in 22 of the 305 patients (7.2%) in the 3-month edoxaban group (odds ratio, 1.34; 95% CI, 0.75-2.41). The prespecified subgroups did not affect the estimates on the primary end point. CONCLUSIONS: In patients with cancer with isolated distal deep vein thrombosis, 12 months was superior to 3 months for an edoxaban treatment with respect to the composite outcome of a symptomatic recurrent VTE or VTE-related death. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03895502.

Prevalence and characteristics of immune checkpoint inhibitor-related myocardial damage: A prospective observational study.

An increasing number of patients with cancer are being treated with immune checkpoint inhibitors. Consequently, the incidence of immune checkpoint inhibitor-related myocarditis has been increasing. Nonetheless, the diagnostic criteria for the immune checkpoint inhibitor-related myocarditis have not been sufficiently established. Therefore, the real-world incidence or prevalence of immune checkpoint inhibitor-related myocardial damage remains unknown. This was a single-center cohort study that included 100 patients admitted for immune checkpoint inhibitor therapy for any type of cancer. The patients underwent monthly measurement of cardiac troponin I and N-terminal pro-brain natriuretic peptide levels with electrocardiography. Additionally, echocardiography was performed every 3 months. Our protocol was continued until 6 months after the initiation of immune checkpoint inhibitors. We defined immune checkpoint inhibitor-related myocardial damage as an increase in cardiac troponin I levels by >0.026 ng/mL and/or a decrease in the left ventricular ejection fraction by >10% to <53% on echocardiography. The mean patient age was 64 years; 71% were men. The most commonly used immune checkpoint inhibitor was nivolumab (47%), followed by pembrolizumab (29%). Overall, 5% of patients received combination therapy. Among 100 patients, 10 (10%) were diagnosed with immune checkpoint inhibitor-related myocardial damage. Among them, five patients underwent endomyocardial biopsy. Of these patients, four were histopathologically observed to have lymphocyte infiltration in their myocardium. In conclusion, serial cardiac troponin I measurement during immune checkpoint inhibitor treatment could help detect early-phase myocardial damage. The prevalence of myocardial damage was much higher than previously expected.

A Case of Lung Cancer with Very-Late-Onset Immune Checkpoint Inhibitor-Related Myocarditis.

Immune checkpoint inhibitor (ICI)-related myocarditis has been reported to appear in the early phase after ICI initiation. Herein, we report the case of a 78-year-old man with non-small cell lung cancer. Pembrolizumab was introduced as first-line therapy. After 9 months, second-line therapy, including bevacizumab, was initiated. After another 7 months, echocardiography showed diffuse left ventricular dysfunction. Based on the histopathologic examination of the myocardium, the patient was diagnosed with ICI-related myocarditis. Initiation of prednisolone therapy improved cardiac function. This case of late-onset ICI-related myocarditis illustrates that endomyocardial biopsy can be useful in the differential diagnosis of cancer-related left ventricular dysfunction.

Il a été rapporté qu'une myocardite pouvait survenir peu après l'instauration d'un traitement par des inhibiteurs des points de contrôle immunitaire (ICI). Nous présentons le cas d'un homme de 78 ans atteint d'un cancer du poumon non à petites cellules. Le pembrolizumab a été administré comme traitement de première intention. Neuf mois plus tard, un traitement de deuxième intention par le bévacizumab a été instauré. Après sept autres mois, l'échocardiographie a montré une dysfonction ventriculaire gauche diffuse. À la suite des résultats de l'examen histopathologique du myocarde, une myocardite liée aux ICI a été diagnostiquée. L'instauration d'un traitement par la prednisolone a amélioré la fonction cardiaque du patient. Ce cas de myocardite tardive liée aux ICI montre l'utilité éventuelle de la biopsie de l'endomyocarde dans le diagnostic différentiel d'une dysfonction ventriculaire gauche liée au cancer.

Sinus Node Dysfunction Co-occurring with Immune Checkpoint Inhibitor-associated Myocarditis.

Immune checkpoint inhibitor (ICI)-induced myocarditis is a potentially life-threatening adverse event. We herein report a rare case of sick sinus syndrome (SSS) co-occurring with ICI-associated myocarditis. A 71-year-old woman with lung cancer undergoing pembrolizumab monotherapy was admitted owing to a fever, worsening kidney function, and sinus bradycardia. She was diagnosed with multi-organ immune-related adverse events, including myocarditis. Pulse steroid therapy was initiated immediately under the support of a temporary pacemaker, which resulted in the resolution of SSS in a few days. Biopsy specimens of the endomyocardium showed active myocarditis. Thus, we should be aware that SSS can co-occur with ICI-induced myocarditis.

Clinical trajectory of a patient with filaminopathy who developed arrhythmogenic cardiomyopathy, myofibrillar myopathy, and multiorgan tumors.

We report a case of a patient presenting with arrhythmogenic cardiomyopathy, myofibrillar myopathy, and multiorgan tumors. A 41-year-old woman with a history of hypertrophic cardiomyopathy, diagnosed at 6 years of age, developed scoliosis after puberty. Following spinal surgery to address the scoliosis, she developed recurrent severe arrhythmia and heart failure. She developed hypoventilation at age 29 years. Proximal dominant weakness and mild elevation of serum creatine kinase indicated possible myopathy. Myofibrillar myopathy was diagnosed by muscle biopsy at age 30 year. Acute abdomen was repeatedly reported from age 33 years, eventually leading to a diagnosis of gastric polyp and erosive ulcer. A urinary bladder tumor was found at age 35 years, and breast cancer was diagnosed at age 40 years. Whole exome sequencing detected a heterozygous missense mutation in Filamin C. Recent evidences suggest that filamins are associated with tumors, and this case further highlights the clinical spectrum of filaminopathy.

Multiple G-quadruplexes in the LMNA promoter regulate LMNA variant 6 transcription and promote colon cancer cell growth.

Lamin A/C proteins, major components of the nuclear lamina, are encoded by the LMNA gene. These proteins have multiple cellular functions, including DNA transcription and replication, chromatin organization, regulation of the cell cycle, and apoptosis. Mutations in LMNA are associated with a variety of diseases called laminopathies. LMNA has implications in cancer; however, its mechanisms of dysregulation in cancer cells are not yet fully understood. In this study, among the LMNA transcript variants, we focused on a transcriptional variant 6 (termed LMNA-V6), which contains unique 3 exons upstream of exon 1 of LMNA. The promoter region of LMNA-V6 formed multiple G-quadruplexes and increased its transcriptional activity. Moreover, LMNA-V6 negatively regulated other LMNA mRNA variants, lamin A and lamin C, via direct interaction with their promoter. Knockdown of LMNA-V6 decreased the proliferation of colon cancer cells, whereas overexpression of the unique 3 exons of LMNA-V6 increased cell growth. Furthermore, microarray gene expression profiling showed that alteration of LMNA-V6 levels influenced the expression of p53 in colon cancer cells. Taken together, the results suggest that LMNA-V6 may be a novel functional RNA whose expression is regulated through multiple G-quadruplexes in colon cancer cells.

Prognostic Impact of Cancer Activity on Clinically Relevant Bleeding Events After Percutaneous Coronary Intervention.

Purpose : Limited data exist about clinically relevant bleeding events related to antiplatelet therapy after percutaneous coronary intervention (PCI) in cancer patients. We investigated the risk factors for clinically relevant bleeding events in patients with cancer after PCI with stent implantation. Patients and Methods : Patients with solid cancer subjected to first PCI were divided into active (n = 45) and non-active cancer groups (n = 44). The active group included non-operable patients on treatment or with metastasis ; the non-active included those already subjected to or for whom radical surgery was planned within 3 months after the index PCI. Results : During a median follow-up of 2.2 years, 11 bleeding events occurred, with only one occurring in the non-active cancer group. Half of them occurred during the dual-antiplatelet therapy (DAPT) period, and the rest occurred during single-antiplatelet therapy (SAPT) period. Kaplan-Meier analysis showed significantly more bleeding events in the active cancer group (p = 0.010). Multivariate Cox regression hazard analysis revealed cancer activity as a significant independent risk factor for bleeding (p = 0.023) ; but not for three-point major adverse cardiovascular events. Conclusion : Clinically relevant bleeding risk after PCI was significantly lower in non-active cancer. Active cancer group had clinically relevant bleeding during both DAPT and SAPT periods. J. Med. Invest. 68 : 29-37, February, 2021.

Serial Changes in Cardiac Strain and Contractility After Hematopoietic Stem Cell Transplantation in Patients with Hematologic Malignancies.

Hematopoietic stem cell transplantation (HSCT) is occasionally associated with cardiac dysfunction during long-term follow-up. Global longitudinal strain (GLS) has emerged as an early predictor of cardiotoxicity associated with cancer therapy; however, the serial changes in GLS before and after HSCT have not been elucidated. To clarify the association between HSCT and GLS, we investigated serial changes in GLS before and after HSCT. We evaluated cardiac function before and 1, 3, and 6 months after HSCT in 38 consecutive HSCT patients enrolled in this study. Overall, GLS and left ventricular (LV) ejection fraction (EF) temporally decreased 1 month post-HSCT. LVEF completely recovered to baseline at 3 months after HSCT, whereas GLS partially recovered 6 months after HSCT. Except for five patients who died within 6 months, GLS values in the low EF group (LVEF ≤ 55% at 6 months post-HSCT, n = 6) were significantly and consistently lower than those in the normal EF group (LVEF > 55% at 6 months post-HSCT, n = 27) at any time during follow-up. These findings suggest that GLS before HSCT might be associated with a decrease in LVEF after HSCT in patients with hematologic malignancies. Further prospective and long-term data will be important for understanding the management of HSCT-associated cardiac dysfunction.

Multicentre cohort study of the impact of percutaneous coronary intervention on patients with concurrent cancer and ischaemic heart disease.

BACKGROUND: The incidence of concurrent cancer and ischaemic heart disease (IHD) is increasing; however, the long-term patient prognoses remain unclear. METHODS: Five-year all-cause mortality data pertaining to patients in the Osaka Cancer Registry, who were diagnosed with colorectal, lung, prostate, and gastric cancers between 2010 and 2015, were retrieved and analysed together with linked patient administrative data. Patient characteristics (cancer type, stage, and treatment; coronary risk factors; medications; and time from cancer diagnosis to index admission for percutaneous coronary intervention [PCI] or IHD diagnosis) were adjusted for propensity score matching. Three groups were identified: patients who underwent PCI within 3 years of cancer diagnosis (n = 564, PCI + group), patients diagnosed with IHD within 3 years of cancer diagnosis who did not undergo PCI (n = 3058, PCI-/IHD + group), and patients without IHD (n = 27,392, PCI-/IHD- group). Kaplan-Meier analysis was used for comparisons. RESULTS: After propensity score matching, the PCI + group had better prognosis (n = 489 in both groups, hazard ratio 0.64, 95% confidence interval 0.51-0.81, P < 0.001) than the PCI-/IHD + group. PCI + patients (n = 282) had significantly higher mortality than those without IHD (n = 280 in each group, hazard ratio 2.88, 95% confidence interval 1.90-4.38, P < 0.001). CONCLUSIONS: PCI might improve the long-term prognosis in cancer patients with IHD. However, these patients could have significantly worse long-term prognosis than cancer patients without IHD. Since the present study has some limitations, further research will be needed on this important topic in cardio-oncology.

Symptomatic Sinus Bradycardia in a Patient with Solitary Fibrous Tumor/Hemangiopericytoma Treated with Pazopanib.

Pazopanib, a multi-targeted tyrosine kinase inhibitor, is associated with cardiovascular adverse events, such as hypertension, cardiac dysfunction, and thromboembolism. However, symptomatic pazopanib-related bradycardia is uncommon. We herein report a case of symptomatic bradycardia of 35 beats per minute in a patient with solitary fibrous tumor/hemangiopericytoma (SFT/HPC) treated with pazopanib for 1 month. His heart rate recovered to a normal range soon after pazopanib cessation. He restarted pazopanib at a reduced dose, which was continued without SFT/HPC progression or bradycardia recurrence. This case highlights the possibility of bradycardia induced by pazopanib and the importance of monitoring the patient's heart rate.

Prognostic Effect of Incidental Pulmonary Embolism on Long-Term Mortality in Cancer Patients.

BACKGROUND: The effect of incidental pulmonary embolism (PE) on long-term prognosis in cancer patients is unclear. This study assessed the characteristics of cancer and venous thromboembolism (VTE) and the effect of incidental PE identified by oncologists on long-term survival of patients with cancer.Methods and Results:This single-center, retrospective, cohort study used hospital-based cancer registry data from the Osaka International Cancer Institute linked with electronic medical records and administrative data from Japan's Diagnosis Procedure Combination Per-diem Payment System. Overall, 15,689 cancer patients underwent contrast-enhanced thoracic computed tomography during 2010-2018. After excluding patients with missing data, symptomatic patients, or patients with suspected PE, 174 with incidental PE (PE+ group) and 13,197 with no PE (PE- group) were identified. The total incidence of incidental PE was 1.3%. No deaths from thrombotic events were identified in the PE+ group. Both groups were adjusted for cancer- and VTE-related characteristics using inverse probability weighting. After adjusting for immortal time bias in the PE+ group, Kaplan-Meier analysis revealed that all-cause mortality was higher in the PE+ group (hazard ratio, 2.26; 95% confidence interval, 1.53-3.33). A Cox proportional hazard model revealed that metastatic cancer and a history of curative treatment were significant prognostic factors, whereas central PE and residual proximal deep vein thrombosis were not. CONCLUSIONS: Incidental PE in cancer patients indicates poorer prognosis. Cancer-related but not thrombosis-related factors determine prognosis.

Unusual Overlapping Cardiac Sarcoidosis and Long-QT Type 3 Induced Ventricular Fibrillation.

A 54-year-old woman had been resuscitated after ventricular fibrillation and her electrocardiogram showed a QT prolongation (QTc=510 ms), and genetic screening revealed a missense variant, R1644C, in the SCN5A gene. She was therefore diagnosed with congenital long-QT syndrome (LQTS) type 3. However, the patient had left ventricular dysfunction, and based on the findings of cardiac magnetic resonance imaging, positron emission tomography and pathological examinations, she was diagnosed with cardiac sarcoidosis. Although both are rare diseases, their overlapping presence in this case may have led to an increased cardiovascular risk compared with either alone. Thus, not only genetic but comprehensive clinical examinations are important for making a correct diagnosis.

Nutritional condition in the dry period is related to the incidence of postpartum subclinical endometritis in dairy cattle.

OBJECTIVE: Endometritis is a major disease, that causes infertility in cattle, and is usually categorized as clinical or subclinical endometritis (SCE). The nutritional condition during the dry period is important for recovery after the last stage of the lactation period, and for postpartum production and reproduction. This study aimed to clarify the relationship between nutritional and metabolic characteristics in the dry period, and the risk of postpartum SCE. METHODS: Multiparous Holstein dairy cows (n = 25, raised in a tied stall) were used. Endometrial cytological analysis was performed around 30 days post-partum, with 5% to 14% polymorphonuclear (PMN) as a cut-off point to define SCE. Serum levels of glucose, non-esterified fatty acids, ß-hydroxybutyric acid (BHBA), blood urea nitrogen, total cholesterol, aspartate aminotransferase, γ-glutamyl transpeptidase, calcium, phosphorus, and magnesium were measured in the cows at the dry period to evaluate energy status, protein metabolism, and mineral metabolism. RESULTS: The incidence of SCE in the cows was 60.0% (n = 15/25) and the mean PMN% in postpartum cows diagnosed as SCE was 8.05%±2.6%. Overall, 17 and 8 samples were collected from the cows in the far-off and close-up periods, respectively. The serum concentration of BHBA in the far-off period and serum glucose concentration in the closeup period were correlated with postpartum PMN% (r = 0.62, p<0.01; r = -0.74, p<0.05, respectively). Serum levels of calcium and magnesium in the dry period were associated with the incidence of postpartum SCE (healthy vs SCE cows, p<0.05). CONCLUSION: Blood levels of glucose, BHBA, calcium, and magnesium in dry periods could be useful parameters for predicting the risk of postpartum SCE. The present study also suggests that management in the close-up period is essential for promoting recovery from calving fatigue.