A Case of an Increase in Prothrombin Time-International Normalized Ratio by Interaction Between Warfarin and Baloxavir Marboxil in a Patient on Implantable Ventricular Assist Device.

BACKGROUND: Baloxavir marboxil (BM) is a novel drug with a cap-dependent endonuclease inhibitory action for influenza A or B; it is highly safe and requires just a single oral dose. Patients with severe heart failure use implantable ventricular assist device (iVAD) until transplantation, but they have an increased risk of thrombosis development. Their warfarin is administered based on point-of-care testing (POCT) with a strict control of prothrombin time-international normalized ratio (PT-INR). CASE REPORT: Here, we report a case of a patient with iVAD whose PT-INR was significantly increased from the target range after BM administration. The patient was a 45-year-old man and transplanted with iVAD; warfarin treatment was started when his PT-INR target range was 3.0-3.5. At home, he frequently self-measured PT-INR by POCT and precisely controlled the warfarin dose. He had a fever, was diagnosed with influenza A and was administered BM 40 mg. Thereafter, his PT-INR continued to increase, reaching 4.8 on day 12 of BM administration, exceeding his target range; warfarin was skipped for 1 day. In this case, based on the history of BM administration and clinical course, the increase in PT-INR could be due to BM. Considering the interaction between warfarin and BM, we suspected a possibility of competition for protein-binding sites. Increased PT-INR in the patient was detected early by POCT and thus severe bleeding was avoided. CONCLUSION: Strict monitoring of PT-INR when using BM in patients taking warfarin is of clinical importance.

Successful treatment of left subclavian artery penetration due to ingestion of a safety pin by an elderly person.

BACKGROUND: Ingestion cases are increasing in elderly persons. Herein, we report a rare case of ingestion of a safety pin by an elderly person. CASE PRESENTATION: The patient was an 87-year-old bedridden woman who had fever with left pleural effusion. Chest X-ray revealed a foreign body, confirmed to be a safety pin, in the cervical esophagus. A contrast multidetector row computed tomography scan revealed that the opened safety pin penetrated the left subclavian artery, leading to the diagnosis of an esophageal foreign body penetrating the left subclavian artery. The safety pin was removed, and the subclavian artery aneurysm caused by the penetration was embolized by interventional radiology. After treatment, she was returned to the nursing home on postoperative day 8. CONCLUSION: Penetration by ingestion of a safety pin is rare; in this case, safe treatment was possible due to a team of certified specialist physicians and surgeons.

Cutaneous histopathology of the tick-bite region in severe fever with thrombocytopenia syndrome.

A case of severe fever with thrombocytopenia syndrome (SFTS) in which a skin biopsy from the tick-bite region was analyzed is reported. The patient was a 72-year-old woman who developed fever and thrombocytopenia after a tick bite. SFTS was diagnosed from polymerase chain reaction (PCR) analysis of a blood sample. Histopathological analysis of a skin biopsy specimen from the tick-bite region showed CD20-positive perivascular and interstitial immunoblastic cells, which were positive to anti-SFTS virus (SFTSV) nucleoprotein antibody. In addition, SFTSV RNA was detected by real-time PCR from this biopsy specimen. Moreover, hemophagocytosis was also found in the tick-bite region. To the best of our knowledge, this is the first report to analyze the details of the tick-bite region of skin in SFTS, and the first to detect virus-infected cells in the skin. The present findings may help elucidate the mechanisms of entry of SFTSV.

Naturally absorbed polyunsaturated fatty acids, lithium, and suicide-related behaviors: A case-controlled study.

OBJECTIVE: Previous studies have investigated the effects of omega-3, omega-6 and lithium on suicide-related behaviors separately. This study was performed to comprehensively investigate the effects of naturally absorbed EPA, DHA, arachidonic acid and lithium in relation to suicide attempt and deliberate self-harm, with adjustment for each other. METHODS: We analyzed plasma EPA, DHA, arachidonic acid levels and serum lithium levels of 197 patients including 33 patients with suicide attempts, 18 patients with deliberate self-harm, and 146 control patients. RESULTS: Multivariate logistic regression analysis with adjustment for age, gender, EPA, DHA, arachidonic acid and log-transformed lithium levels revealed that the negative associations with EPA levels (adjusted OR 0.972, 95% CI 0.947-0.997, p = 0.031) and log-transformed lithium levels (adjusted OR 0.156, 95% CI 0.038-0.644, p = 0.01) and the positive association with DHA levels (adjusted OR 1.026, 95% CI 1.010-1.043, p = 0.002) were significant in patients with suicide attempts than in control patients. The analysis also demonstrated that the positive association with arachidonic acid levels (adjusted OR 1.015, 95% CI 1.005-1.025, p = 0.004) was significant in patients with deliberate self-harm than in control patients. LIMITATIONS: The limitations are relatively small number of patients and the effects of demographics of individual patients could not be adjusted for the analyses. CONCLUSIONS: The present findings suggest that, as naturally absorbed nutrients, higher EPA and lithium levels may be associated with less suicide attempt, and that higher arachidonic acid levels may be associated with more deliberate self-harm.

Serum lithium levels and suicide attempts: a case-controlled comparison in lithium therapy-naive individuals.

BACKGROUND: Several epidemiological studies have shown the inverse association of lithium levels in drinking water and suicide rates; however, it is necessary to perform a clinical study dealing with individual patients. METHODS: We analyzed 199 patients including 31 patients with suicide attempts, 21 patients with self-harm, and 147 control patients. All were transferred to a university emergency department suffering from intoxication or injury, were aged 20 or more years, and were alive at the start of the study. The exclusion criteria consisted of suffering from schizophrenia and a past or present history of lithium therapy. These exclusions were applied because it is difficult to determine whether their suicide attempt was induced by the intent to end their life or by psychotic symptoms such as auditory hallucinations, and if the patient had received lithium therapy, the association between the small amount of lithium taken from drinking water and food and serum lithium levels cannot be detected. RESULTS: There was a significant difference (p = 0.043) between the three groups whereby patients with suicide attempts had significantly lower lithium levels than control patients (p = 0.012) in males but not females. Multivariate logistic regression analysis with adjustment for age and gender revealed that patients with suicide attempts had significantly lower lithium levels than control patients (p = 0.032, odds ratio 0.228, 95% CI 0.059-0.883). LIMITATIONS: The limitations of the present study are the nature of observational research which cannot reveal a causal relationship and the relatively small number of subjects. CONCLUSIONS: The present findings suggest that higher serum lithium levels may be protective against suicide attempts in lithium therapy-naive individuals.

Severe hypothermia secondary to spinal cord injury without radiographic abnormality.

Case: A 64-year-old female was found lying by a river. She was unconscious and her lower body was under water. The patient was transported to the emergency room of our hospital. On arrival, her rectal temperature was 24.6°C. We immediately started rewarming and artificial respiration. Five days after admission, rewarming was completed and she became conscious and could communicate. Initially, she had been injured and examination showed paraplegia. Magnetic resonance imaging of her cervical spine showed no findings indicating bony or ligament injury, but there was a T2 high intensity area at C5/6 and C6/7 levels. The patient was diagnosed with spinal cord injury without radiological abnormality. Outcome: At 5 months post-injury, the patient was able to walk without crutches. Conclusion: Spinal cord injury might be missed if there are no radiographic abnormalities. Spinal cord injury without radiological abnormality should be considered as a differential diagnosis of accidental hypothermia.

Characterization of a novel oncogenic K-ras mutation in colon cancer.

Activating mutations of RAS are frequently observed in subsets of human cancers, indicating that RAS activation is involved in tumorigenesis. Here, we identified and characterized a novel G to T transversion mutation of the K-ras gene at the third position of codon 19 (TTG) which substituted phenylalanine for leucine in 3 primary colon carcinomas. Biological and biochemical activity was examined using transformed NIH3T3 cells expressing mutant or wild-type K-ras. Transformants harboring the K-ras mutation at codon 19 showed proliferative capacity under serum-starved conditions, less contact inhibition, anchorage-independent growth, tumorigenicity in nude mice and elevation of active Ras-GTP levels. These results indicated that this novel mutation possesses high oncogenic activity.

Identification of phosphoproteins associated with maintenance of transformed state in temperature-sensitive Rous sarcoma-virus infected cells by proteomic analysis.

To identify phosphotyrosine-containing proteins essential for maintaining the transformed state, we studied the tyrosine phosphorylation profile of temperature-sensitive mutant of Rous sarcoma virus, tsNY68, infected cells (68N7). Shifting the temperature from 39 degrees C (nonpermissive) to 32 degrees C (permissive) markedly increased the expression of phosphotyrosine-containing cell membrane proteins of approximately 40kDa, as assessed by SDS-PAGE. Membrane and nuclear proteins were separated by two-dimensional gel electrophoresis and immunoblotted with anti-phosphotyrosine antibody. Proteins showing temperature-dependent changes in phosphorylation profile were subjected to in-gel digestion with trypsin and analyzed by mass spectrometry. Five proteins were identified: heterogeneous nuclear ribonucleoprotein (hnRNP) A3, hnRNP A2, annexin II, phosphoglycerate mutase 1, and triosephosphate isomerase 1. hnRNP A3 was phosphorylated at serine residues and had both serine and tyrosine phosphorylated sites. These results suggest an important complementary role for proteomics in identifying molecular abnormalities associated with tumor progression that may be attractive candidates for tumor diagnosis.