A case of coagulation factor V inhibitor induced by immune checkpoint inhibitor therapy.

A 73-year-old woman with lung adenocarcinoma (cT4N3M1a: Stage IVA) was treated with atezolizumab as the eighth line of therapy. Four weeks after the fourth dose of atezolizumab, the prothrombin time (PT) and activated thromboplastin time (APTT) were prolonged. Coagulation factor V (FV) activity was decreased, and FV inhibitors were observed. There was no history of PT or APTT prolongation or bleeding before the use of atezolizumab. Atezolizumab-induced coagulation FV inhibitor was diagnosed. After 2 weeks, the PT and APTT spontaneously normalized. FV activity improved and the FV inhibitors disappeared after 6 and 9 weeks, respectively.

Bacillus subtilis TO-A extends the lifespan of Caenorhabditis elegans.

Clostridium butyricum TO-A, Enterococcus faecium T-110, and Bacillus subtilis TO-A are sold as oral probiotic preparations and reportedly exhibit many beneficial effects on the health of hosts, including humans and livestock. In this study, we compared the ability of these clinically applied probiotic bacteria with Escherichia coli OP50 in extending the lifespan of Caenorhabditis elegans. To compare the C. elegans lifespan-extending effects of the three bacteria, experiments were performed using a nematode growth medium containing a small amount of trypticase soy agar. The maximum lifespans of worms fed C. butyricum TO-A, E. faecium T-110, or B. subtilis TO-A increased by 11, 12, and 26%, respectively, compared with worms fed E. coli OP50. In addition, we conducted a metabolomic analysis of methanol extracts of B. subtilis TO-A cells, which exhibited the strongest lifespan-extending effect on C. elegans among the probiotic bacteria tested in this study. As a result, 59 candidate substances involved in extending the lifespan of C. elegans were identified in B. subtilis TO-A cells.

Estimating time-series changes in social sentiment @Twitter in U.S. metropolises during the COVID-19 pandemic.

Since early 2020, the global coronavirus pandemic has strained economic activities and traditional lifestyles. For such emergencies, our paper proposes a social sentiment estimation model that changes in response to infection conditions and state government orders. By designing mediation keywords that do not directly evoke coronavirus, it is possible to observe sentiment waveforms that vary as confirmed cases increase or decrease and as behavioral restrictions are ordered or lifted over a long period. The model demonstrates guaranteed performance with transformer-based neural network models and has been validated in New York City, Los Angeles, and Chicago, given that coronavirus infections explode in overcrowded cities. The time-series of the extracted social sentiment reflected the infection conditions of each city during the 2-year period from pre-pandemic to the new normal and shows a concurrency of waveforms common to the three cities. The methods of this paper could be applied not only to analysis of the COVID-19 pandemic but also to analyses of a wide range of emergencies and they could be a policy support tool that complements traditional surveys in the future.

Immune Profile Analysis in Peripheral Blood and Tumor in Patients with Malignant Melanoma.

Melanoma is a severe and life-threatening malignancy derived from melanocytes. The traditional treatment for melanoma could not sustain satisfactory outcomes long term; however, the recent immune checkpoint treatment has made a breakthrough in these problems. Nivolumab is a representative immune checkpoint treatment, and this PD-1-targeted therapy has evolutionally developed and improved the clinical outcome in a recent decade. On the other hand, the clinical application of immune checkpoint treatment presents clinicians with novel questions, especially how to obtain additional efficacy and overcome the disadvantage by using this treatment. To answer these problems, we first investigated the distribution of PD-L1 in various organs to clarify the organs most affected by anti-PD-1 antibody treatment. Among various organs, lung, placenta, spleen, heart, and thyroid highly expressed PD-L1, while skin, thalamus, hippocampus, ovary, stomach, testis, and prostate showed lower expressions of PD-L1. Furthermore, the immune profiles were also examined in tumors and peripheral blood in patients with melanoma. PD-1 was highly expressed in CD8 and CD4 cells, and B cells also highly expressed PD-1 compared with NK cells. However, there was no significant difference in Th1/Th2/Th17 cytokines and inhibitory cytokine IL-10. Although nevus showed a low expression of PD-L1 compared with healthy skin, PD-L1 expression was increased in growth-phase melanoma. Finally, we analyzed the peripheral blood profiles in patients treated with nivolumab. PD-1-bearing dendritic cells (DCs) were increased during nivolumab treatment and Lin-CD11c+HLA-DR+ cells were highly increased during nivolumab treatment. These findings indicate a clue to answering the problems during nivolumab treatment and suggest to us the importance of multiple aspect observation during immune checkpoint treatment.

Intestinal F-box protein regulates quick avoidance behavior of Caenorhabditis elegans to the pathogenic bacterium Pseudomonas aeruginosa.

In most animals, avoiding pathogenic bacteria is crucial for better health and a long life span. For this purpose, animals should be able to quickly sense the presence or uptake of pathogens. The intestine could be a candidate organ to induce escape behaviors; however, the intestinal signaling mechanism for acute regulation of neuronal activity is not well understood. Here, we show that adult Caenorhabditis elegans can respond to the pathogenic bacterium Pseudomonas aeruginosa within 30 min of exposure. This behavior was much faster than previously observed avoidance behaviors in response to P. aeruginosa. By genetic screening, we isolated a mutant defective in this quick avoidance behavior and found that the novel F-box protein FBXC-58 is involved. FBXC-58 is expressed in several tissues, but defective avoidance was rescued by expression of the protein in the intestine. Interestingly, we also found that some but not all mutants in the p38-MAPK and insulin-like signaling pathways, which function in the immune response to pathogens in the intestine, were defective in the quick avoidance behavior to P. aeruginosa. These results suggest that a novel signaling pathway in the intestine exists to regulate neuronal activity for a quick behavioral response.

Profile fluctuation of peripheral blood in advanced melanoma patients treated with nivolumab.

Melanoma is a malignant tumor of the melanocytes with an unfavorable clinical behavior. Nivolumab, a representative anti-programmed death 1 (PD-1) antibody, has recently been used for the treatment of metastatic malignant melanoma. However, there have been few appropriate biomarkers predicting the effect of nivolumab before the administration. Furthermore, the detailed characteristics of peripheral blood mononuclear cell (PBMC) profiles during nivolumab treatment remains unclear. In this study, we investigated fluctuations of PBMC profile during nivolumab treatment. PBMC analysis showed T-helper (Th)2-dominant conditions after a first course of nivolumab treatment. In a favorable case treated with nivolumab, a Th1/T-cytotoxic 1 shift was observed after nivolumab was administrated. These results suggest that flow cytometric analysis of PBMC may be helpful for the treatment of nivolumab.

Epidemiological and pathological study of feline morbillivirus infection in domestic cats in Japan.

BACKGROUND: Feline morbillivirus (FmoPV) is a novel paramyxovirus found to infect domestic cats. FmoPV has been isolated in several countries in Asia and Europe and is considered to have genetic diversity. Also, it is suspected to be associated with feline renal diseases including tubulointerstitial nephritis (TIN), which affects domestic cats with a high incidence rate. RESULTS: To clarify the state of FmoPV infection among domestic cats in Japan, an epidemiological survey was conducted. Twenty-one out of 100 cats were found to have serum antibodies (Ab) against FmoPV-N protein by indirect immunofluorescence assay (IF) using FmoPV-N protein-expressing HeLa cells. Twenty-two of the cats were positive for FmoPV RNA in the urine and/or renal tissues. In total, 29 cats were positive for Ab and/or viral RNA. These FmoPV-infected cats were classified into three different phases of infection: RNA+/Ab + (14 cats), RNA+/Ab- (8 cats) and RNA-/Ab + (7 cats). In immunohistochemistry (IHC), 19 out of 29 cats were positive for FmoPV-N protein in kidney tissues; however, the FmoPV-N protein was located in the inflammatory lesions with severe grade in only four out of the 19 cats. Since 15 out of 29 infected cats were positive for viral RNA and Ab, approximately half of the infected cats were persistently infected with FmoPV. CONCLUSIONS: A statistically significant difference was observed between infection of FmoPV and the presence of inflammatory changes in renal lesions, indicating a relationship between FmoPV infection and feline renal diseases. However, we could not obtain histopathological evidence of a relationship between FmoPV infection and TIN.

Identification of a natural recombination in the F and H genes of feline morbillivirus.

Feline morbillivirus (FmoPV) has recently been identified in Hong Kong and Japan. FmoPV is considered to belong to the genus Morbillivirus, in the family Paramyxoviridae. In this study, the complete nucleotide sequences of three strains of FmoPV detected in cats in Japan were determined. Among the six genes in FmoPV; N, P/V/C, M, F, H and L, the P gene showed the highest polymorphism in the nucleotide and putative amino acid sequences among the FmoPV strains. There was no geographical association in terms of the FmoPV phylogeny; however, from extensive phylogenetic and recombination analyses, we found that one Japanese FmoPV strain, MiJP003, was a probable recombinant between two virus strains in the independent lineages found in Japan and Hong Kong, respectively. The recombination was considered to have occurred within the F and H genes. Such recombination is thought to be involved in the evolution of FmoPV.

[Propiverine hydrochloride improved correlatively subjective QOL and objective findings in Japanese patients with urinary frequency and/or incontinence].

To investigate how urinary frequency and incontinence affect the patient's subjective quality of life (QOL) and whether an improvement in objective findings by medical treatment affects his/her subjective QOL, a voiding diary using the King's Health Questionnaire (KHQ) and International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) was delivered to patients with urinary frequency and/or incontinence before and after treatment with propiverine hydrochloride for 8 weeks. Sixty-eight patients completed the diary and the questionnaires. Objective symptoms decreased significantly with respect to the mean frequency of urination and to the mean incidence of urinary incontinence. The KHQ and ICIQ-SF scores improved significantly with respect to all domains except personal relationships in the KHQ. In the KHQ, furthermore, a significant correlation was found between decreased incidence of urinary incontinence and improvement in role limitations and between decreased incidence of urinary incontinence and improvement in emotional problems. In the ICIQ-SF, a significant correlation was found between decreased incidence of urinary frequency and subjective improvement in quantity of leakage, between decreased incidence of urinary frequency and improvement in subjective QOL scores, between decreased incidence of urinary frequency and improvement in the total ICIQ-SF score, and between decreased incidence of urinary incontinence and improvement in subjective QOL scores. Thirty-two episodes of adverse reactions were observed. None of them were serious. These results suggest that an improvement in objective symptoms with propiverine hydrochloride favorably improves subjective QOL of the patient, and provide further evidence about the safety and efficacy of propiverine hydrochloride.

[Clinical evaluation of transcatheter arterial embolization for the management of retroperitoneal bleeding in cases of pelvic fracture].

PURPOSE: We evaluated the clinical efficacy of TAE for the management of retroperitoneal bleeding in a case of pelvic fracture. MATERIALS AND METHODS: A retrospective review of 206 patients with pelvic fractures was performed. Thirty-four patients who were hemodynamically unstable or had evidence of ongoing hemorrhage required TAE. Rescue rate, effective rate, and mortality rate among the patients with multiple organ injuries were calculated. Charts were reviewed for age, Japanese coma scale (JCS), hemoglobin, blood pressures, extent of retroperitoneal hemorrhage, pelvic fracture pattern/extent of embolization, and time from judging indication of TAE to angiography. Data of patients who died of pelvic fracture hemorrhage was compared with that of others. Statistical analysis was done with analysis of variance, and the two groups were compared using Student's t-test. RESULTS: Rescue rate, success rate, and mortality rate were 76% (26/34), 91% (31/34), and 33% (8/24), respectively. Only JCS reached statistical significance. The complications of gluteal skin and muscle necrosis were experienced in one patient. Two patients with lung contusion and one patient who had suffered from idiopathic interstitial pneumonia died from disseminated intravascular coagulation associated with pneumonia. Viscorectal dysfunctions, which were observed in ten patients, were considered to be independent of TAE. CONCLUSION: TAE for pelvic fracture hemorrhage was considered effective. Complications of gluteal skin and muscle necrosis should be kept in mind.

[Clinical evaluation of esophageal cancer complicated with head and neck cancer].

We prospectively investigated endoscopic findings of the upper digestive tract in patients with head and neck (H & N) cancer, from 1992 to 2001. Of 687 patients with H & N cancer, esophageal cancers were found to affect 74 patients (10.8%). The 74 patients consisted of 49 (66.2%) with the superficial type and 25 (33.8%) with the advanced type. Other additional cancers were detected in 32 cases (4.7%), including 21 gastric cancers. The incidence was highest in patients with hypopharyngeal cancer (32.4%), whereas the incidences in those with oral floor cancer and mesopharyngeal cancer were 14.3% and 13.1%, respectively. The incidence of stage I cancers was lower than that of stage II, III, or IV cancers. Therapy for superficial esophageal cancers consisted of trisection for endoscopic mucosal resection (EMR), surgery, and no treatment. Surgery, radiation therapy, or no treatment was selected in advanced type. For double cancers of H & N and esophagus, treatment should be selected in consideration of the prognosis of the disease. These findings suggest that endoscopy with the Lugol-spraying method should be performed in H & N cancers for early detection of esophageal cancers.

[Clinical evaluation of gastric diverticulum on indirect radiograph for gastric mass survey].

The aim of this study was to evaluate the clinical conditions of gastric diverticulum. Fifty-four patients with gastric diverticulum (20 men and 34 women among 34,314 patients who underwent medical check-ups) were evaluated on indirect radiographs, for an incidence of 0.16% among the total number of examined cases, a rate lower than that of previous reports. Almost all cases were asymptomatic, had a single diverticulum, and showed a saccular shape. The age distribution indicated higher frequencies in the 5th and 6th decades, and the posterior wall of the fornix was the most common location. Size ranged from 0.6 cm to 12 cm, and 41 cases (75.9%) were between 1.0 cm and 4.0 cm in size. This entity should be kept in mind when reading radiographs of upper gastrointestinal series as well as recognition of pseudodiverticulum and aberrant pancreas as noted for the stomach in several past report. Diverticulum on the cardia, which was previously classified as gastric diverticulum, should be excluded because of the possibility of normal variation.