Incidence and location of perioperative deep vein thrombosis in patients with bladder cancer undergoing radical cystectomy.

OBJECTIVES: To determine the incidence and location of lower extremity deep vein thrombosis in patients undergoing radical cystectomy. METHODS: We performed radical cystectomy in 137 patients with bladder cancer between August 2014 and February 2020. Since 2014, we have had a policy to screen for deep vein thrombosis using lower extremity ultrasonography both before and after radical cystectomy. We determined the incidence and location of deep vein thrombosis and classified it as either proximal or distal type. Furthermore, we explored the incidence of pulmonary embolism within 3 months after radical cystectomy. RESULTS: After excluding six patients with a lack of ultrasonographic data, we evaluated 131 patients. Preoperative deep vein thrombosis (one proximal and 17 distal) was diagnosed in 18 patients (14%) with no symptoms. Postoperative deep vein thrombosis was diagnosed in 41 patients (31%; three proximal and 38 distal), of whom 26 (63%) had new-onset deep vein thrombosis after cystectomy. Three patients, two with proximal and one with distal type deep vein thrombosis, developed nonfatal pulmonary embolism postoperatively. Multivariate analysis showed that preoperative D-dimer levels (odds ratio 5.35, 95% confidence interval 1.74-16.50; P < 0.003), type of urinary diversion (ileal neobladder; odds ratio 11.15, 95% confidence interval 2.16-57.55; P = 0.004), and preoperative deep vein thrombosis (odds ratio 15.93, 95% confidence interval 3.82-66.30; P < 0.001) were significant risk factors for postoperative deep vein thrombosis. CONCLUSIONS: Pre- and post-radical cystectomy whole-leg ultrasonography can lead to an early perioperative diagnosis and immediate treatment of proximal deep vein thrombosis, thereby potentially preventing fatal pulmonary embolism.

Increased hydrostatic pressure induces nuclear translocation of DAF-16/FOXO in C. elegans.

Mechanical stimulation is well known to be important for maintaining tissue and organ homeostasis. Here, we found that hydrostatic pressure induced nuclear translocation of a forkhead box O (FOXO) transcription factor DAF-16, in C. elegans within minutes, whereas the removal of this pressure resulted in immediate export of DAF-16 to the cytoplasm. We also monitored DAF-16-dependent transcriptional changes by exposure to 1 MPa pressure for 5 min, and found significant changes in collagen and other genes in a DAF-16 dependent manner. Lifespan was markedly prolonged with exposure to cyclic pressure treatment (1 MPa once a day for 5 min from L1 larvae until death). Furthermore, age-dependent decline in locomotor activity was suppressed by the treatment. In contrast, the nuclear translocation of the yes-associated protein YAP-1 was not induced under the same pressure conditions. Thus, moderate hydrostatic pressure improves ageing progression through activation of DAF-16/FOXO in C. elegans.

Exanthem subitum-associated encephalitis: nationwide survey in Japan.

We sought to clarify clinical features of exanthem subitum associated-encephalitis/encephalopathy, generally caused by primary human herpesvirus-6 infection in Japan. A two-part questionnaire was sent to hospitals between January 2003-December 2004. Of 3357 questionnaires, 2357 (70.2%) were returned, and 2293 (68.3%) were eligible for analysis. Eighty-six cases of exanthem subitum-associated encephalitis/encephalopathy were reported. Seventy-seven (89.5%) of 86 patients were diagnosed with human herpesvirus-6 infection by virologic examination. Although 41 (50.6%) of 81 patients had no sequelae, 38 (46.9%) had neurologic sequelae. Moreover, two fatal cases (2.5%) were reported. Pleocytosis was evident in only 4 (7.5%) of 53 patients, and cerebrospinal fluid protein levels were within normal range (23.4 +/- 14.6 mg/dL S.D.) in all patients. Human herpesvirus-6 DNA was detected in 21 (53.8%) of 39 patients. Abnormal computed tomography findings were a predictor of neurologic sequelae (P = 0.0097). As a consequence of this survey, we estimate that 61.9 cases of exanthem subitum-associated encephalitis occur every year. The disease prognosis was unexpectedly poor.

Recombinant human monoclonal antibodies to human cytomegalovirus glycoprotein B neutralize virus in a complement-dependent manner.

Human antibodies specific for HCMV are currently considered as potential anti-HCMV therapeutic agents. In this study, we used a combinatorial human antibody library to isolate and characterize complete human monoclonal antibodies that effectively neutralize HCMV in a complement-dependent manner. One hundred and six clones were isolated in two independent screens using HCMV virions and recombinant glycoprotein B, gB654, as antigens. All of the clones recognized the same molecule gB and were classified into 14 groups based on the amino acid sequence of the V(H) region. Seven representative clones from these 14 groups had a strong gB654 binding affinity by surface plasmon resonance (SPR). A pairwise binding competition analysis suggested that there were three groups based on differences in the gB recognition sites. Although Fab fragments of the seven groups showed strong affinity for gB, none of the Fab fragments neutralized HCMV infectivity in vitro. In contrast, complete human IgG(1) antibodies of at least three groups neutralized HCMV in a complement-dependent manner. These data suggest that potent therapeutic antibodies can be obtained from a human antibody library, including most of the functional antibodies that mediate humoral immunity to the selected pathogen.

Elevated serum cytokine levels are associated with human herpesvirus 6 reactivation in hematopoietic stem cell transplantation recipients.

Although it has been demonstrated that human herpesvirus 6 (HHV-6) reactivation generally occurs approximately 2-3 weeks after transplantation in the hematopoietic stem cell transplantation (HSCT) recipients, the mechanism of viral reactivation remains unclear. To explore the relationship between HHV-6 reactivation and plasma cytokine levels, 24 HSCT recipients underwent measurements of plasma proinflammatory cytokine levels (IL-6, TNF-alpha, IL-1 beta, and IFN-gamma), viral isolation, and serological assays. Of these patients, 14 developed an HHV-6 reactivation, and 9 developed HHV-6 viremia approximately 2-3 weeks after transplantation. IL-6 levels were significantly higher in the recipients with an HHV-6 reactivation than in the subjects without an HHV-6 reactivation at 1 week, 2 weeks, and 4 weeks after transplantation. In addition, the level of TNF-alpha was significantly higher in recipients with an HHV-6 reactivation than in those without an HHV-6 reactivation at 2 weeks post-transplantation. Low levels of IL-1 beta and IFN-gamma were detected in a small number of the plasma samples, although there were no significant differences between the two groups in the levels of these cytokines. These results imply that proinflammatory cytokines, in particular IL-6 and TNF-alpha, play a role in the pathogenesis of HHV-6 reactivation after HSCT.

Direct detection of human herpesvirus 6 DNA in serum by the loop-mediated isothermal amplification method.

BACKGROUND: A more rapid and easier method is needed for monitoring human herpesvirus 6 (HHV-6) infections. The loop-mediated isothermal amplification method (LAMP) can detect viral DNA with high specificity, efficiency, and speed under isothermal conditions. LAMP requires only simple equipment that is available in hospital laboratories. OBJECTIVES: We evaluated LAMP as a means of detecting HHV-6 DNA directly from patients' sera. RESULTS: The sensitivity of the HHV-6 LAMP protocol without heat denaturation was 1000 copies/tube; with heat denaturation 10 copies/tube were detected. Three hundred serum samples from children with fever were analyzed. Using HHV-6 isolation as a definition of HHV-6 infection, the sensitivity, specificity, positive predictive value, and negative predictive value of the HHV-6 LAMP method without DNA extraction were 95.5%, 95.2%, 94.0%, and 96.4%, respectively. CONCLUSION: Direct detection of HHV-6 DNA in serum with a modified HHV-6 LAMP could be used for rapid diagnosis of exanthem subitum (ES).

Pneumonia with marked pleural effusion caused by Aspergillus infection.

We present a case of pneumonia with marked pleural effusion caused by Aspergillus infection in a 2-year-old Japanese girl with Down's syndrome. The patient was previously diagnosed with acute myeloid leukemia, developing the pneumonia during induction treatment. Although no pathogens could be isolated from any clinical specimens, 135,000 copies/mL of Aspergillus DNA were detected in the pleural fluid using real time polymerase chain reaction. The copy numbers of DNA decreased rapidly after appropriate antifungal treatment.

Human herpesvirus 6 reactivation and inflammatory cytokine production in patients with drug-induced hypersensitivity syndrome.

BACKGROUND: Human herpesvirus 6 (HHV-6) reactivation has been suggested to modify the clinical features of drug induced hypersensitivity syndrome (DIHS). However, mechanisms for viral reactivation and modification of the clinical features remain unclear. OBJECTIVE: To determine whether cytokines play an important role in viral reactivation and modification of the clinical features. STUDY DESIGN: We examined the kinetics of serum cytokines and viral load in HHV-6 infections of six patients with DIHS. RESULTS: HHV-6 infection occurred three to four weeks after the onset of disease. Elevated TNF-alpha and IL-6 levels were observed to precede HHV-6 infection in four of the six patients. Although high levels of IL-6 were observed in samples collected prior to HHV-6 infection, the amounts of this cytokine significantly decreased to undetectable levels during viral infection in five of the six patients. Subsequently, serum IL-6 levels were increased after viral infection in five patients. IL-1beta levels were also increased at the time of viral infection in three of the six patients. Neither IL-4 nor IFN-gamma could be detected in any of the samples. CONCLUSION: These results demonstrate that cytokines play an important role in HHV-6 reactivation in patients with DIHS.

Severe acute tonsillitis caused by Rothia dentocariosa in a healthy child.

A 4-year-old Japanese girl developed a sore throat and high fever. Her tonsils were enlarged, red and covered with a thick white membrane. There was marked leukocytosis (26,600 leukocytes per mm) and elevated C-reactive protein levels (23.3 mg/dL). Rothia dentocariosa was recovered from the throat swab; many Gram-positive cocci were observed in the smear from the pseudomembrane covering the tonsil.

Atypical clinical features of a human herpesvirus-6 infection in a neonate.

A case of neonatal human herpesvirus 6 (HHV-6) B infection is presented. Although HHV-6 B was isolated from peripheral blood at the onset of the illness, a significant increase in viral antibody titers was not observed. The patient had a slight fever with generalized maculopapular skin rash and an increased number of atypical lymphocytes, which is quite different from the typical clinical features of exanthem subitum.