Sequential Treatment by Antiviral Drugs Followed by Immunosuppressive Agents for COVID-19 Patients with Hematological Malignancy.

Background: The detailed treatment regimen of COVID-19 patients with hematological malignancies has been unclear, and some fatalities have occurred, although combination therapy with antiviral agents and corticosteroids has been established for moderate to severe COVID-19 patients. Case Series: Case 1 was a 57-year-old woman who had malignant lymphoma and received CHOP therapy with obinutuzumab, and case 2 was a 70-year-old-man who had myeloma and received molecular targeted therapy with weekly corticosteroid. In both cases, SARS-CoV-2 genes and antigens were detected from their nasal swabs, and treatment was started for moderate to severe COVID-19. Case 1 received antiviral agents with high doses of corticosteroids for a long term simultaneously, but the high titer of viral antigens in her nasal swabs persisted. Ground-glass opacities and interstitial shadows also worsened in both lungs, and she finally died on day 60. In contrast, in case 2, antiviral agents were started first, and restarted the immunosuppressive agents, such as gamma globulin and corticosteroids after no titer of SARS-CoV-2 antigens was confirmed. The patient survived, and his abnormal chest shadows showed gradual improvement. Both of the patients received two vaccinations, but showed the low antibody titers for SARS-CoV-2. Conclusion: Administration of both antiviral agents and corticosteroids has been recommended for moderate to severe COVID-19 patients, but in patients with hematological malignancies, it might be better to use antiviral agents first to reduce the viral titers, and then add steroid and related immunosuppressive agents later appropriately to inhibit the excessive inflammatory state. The dose, timing, and order of the antivirals and immunosuppressive agents for COVID-19 should be considered carefully in the patients with hematological malignancies who showed low vaccine effectiveness.

Cancer disclosure to friends: Survey on psychological distress and perceived social support provision.

OBJECTIVE: To determine the factors associated with the degree of distress experienced by patients with cancer before disclosing their cancer diagnosis to a friend and their perceptions of social support upon disclosure. METHODS: Adult patients with cancer participated in a cross-sectional Internet-based survey on their behaviour when disclosing their diagnosis to a selected friend, degree of distress before this disclosure and perceived social support upon disclosure. RESULTS: Of 473 eligible respondents, around half were middle-aged (40-59 years) and around half were men. Having a younger age (20-39 years), being a woman and delaying disclosure were factors associated with greater pre-disclosure distress. Most participants perceived receiving emotional support upon disclosure. Telling a close friend or a female friend and early disclosure timing were associated with perceived social support, although this varied by social support type. CONCLUSION: Younger patients and women may need more support in deciding to disclose their cancer diagnosis to friends. Selection of to whom to disclose this information and disclosure timing should be considered to achieve more desirable outcomes. In addition to selective disclosure-including planning and scheduling-communication skills may be required for effectively disclosing a cancer diagnosis and achieving favourable results following this disclosure.

Development and validation of the Cancer Knowledge Scale for the general population: An item response theory approach.

OBJECTIVE: To develop and validate a new measure of cancer knowledge for members of the general population who have never been diagnosed with cancer. METHODS: Initially, 20 items were generated to measure cancer knowledge. After expert refinement and cognitive interviews, 11 items remained and were completed by 1,076 adults with no history of cancer. Responses were assessed using an item response theory (IRT) approach and differential item functioning. RESULTS: Items were analyzed using a two-parameter logistic IRT model. Two items with tetrachoric correlation coefficients>0.8 and one item with a discrimination parameter>2.0 were excluded. The final eight items demonstrated a good range of discrimination (1.13 to 1.86) and difficulty (-1.11 to 0.85). No meaningful differential item functioning by participant attributes was detected for these eight items. CONCLUSION: The Cancer Knowledge Scale appears to be a reliable and valid measure for the general population. PRACTICE IMPLICATIONS: The eight-item scale could be used to assess the effects of psychoeducational programs, including those on cancer knowledge, for members of the general population with no cancer history.

Remifentanil for sedation and analgesia during awake division of tongue flap in children: a report of two cases.

BACKGROUND: The tongue flap is an accepted treatment method for cleft palate repair. Orotracheal or nasotracheal intubation using a fiberoptic scope is preferred for the division of the tongue flap. We report two cases of tongue flap division in which the patients received adequate sedation and analgesia without tracheal intubation. CASE PRESENTATION: Twelve- and 13-year-old male patients were treated at our hospital for tongue flap division, performed as part of a cleft palate repair. We planned to divide the tongue flap under sedation with remifentanil (1 µg/kg/min continuous infusion) and local anesthesia, followed by induction of general anesthesia, and orotracheal intubation after the tongue flap was divided. During the procedure, patients were breathing spontaneously and were cooperative. Patients were able to follow the surgeons' verbal cues to thrust out the tongue during the procedure, so that the surgeons could easily insert the sutures. CONCLUSIONS: During the division of the tongue flap in two children, excellent sedative and analgesic effects were achieved using continuous remifentanil infusion.

A cross-sectional observation of effect of exposure to N-methyl-2-pyrrolidone (NMP) on workers' health.

This study was aimed at clarifying the effect of exposure to N-methyl-2-pyrrolidone (NMP) on workers' health. Fifteen male NMP-exposed workers and 15 referent male workers were recruited for this study. Exposure concentrations were assessed by determining NMP in the breathing zones and urinary NMP. Clinical examinations, motor and sensory nerve conduction velocities in the dominant arm, and neurobehavioral tests were carried out. The subjects were asked to complete self-administered questionnaires for subjective symptoms and psychological assessment. The mean NMP exposure concentrations ranged from 0.14 to 0.26 ppm, and urinary NMP levels at the end of each workday ranged from 0.17 to 0.22 mg/l, throughout the work week. In terms of clinical data, motor and sensory nerve conduction velocities, neurobehavioral tests, and subjective symptom assessments, there were no differences and no dose-dependent changes in either the means or the prevalence of abnormal findings between NMP-exposed and referent workers.

A secreted type of beta1,6 N-acetylglucosaminyltransferase V (GnT-V), a novel angiogenesis inducer, is regulated by gamma-secretase.

Glycosyltransferases are present in the Golgi apparatus in a membrane-bound form and are released from cells after cleavage by certain proteases. Beta1,6-N-acetylglucosaminyltransferase V (GnT-V), which is cleaved and secreted from the cells, is involved in the biosynthesis of beta1-6GlcNAc branching on N-glycans and has been implicated in tumor progression and metastasis. We recently reported that a secreted type of GnT-V (soluble GnT-V) itself could promote angiogenesis, which is completely different from its original function as a glycosyltransferase, and this might play a role in tumor invasion. In this study, to explore the molecular basis for this functional glycosyltransferase secretion, its cleavage site was examined and the protease(s) involved in that cleavage were identified. The NH2-terminal protein sequence of purified soluble GnT-V (approximately 100 kDa) from GnT-V-overexpressed cells revealed that its terminus started at His31, located at the boundary position between the transmembrane and stem regions. This secretion was not inhibited by a single amino acid mutation at the cleavage site (Leu29, Leu30 to Asp, His31 to Ala), but specifically inhibited by addition of DFK-167, a gamma-secretase inhibitor, suggesting that gamma-secretase is a plausible protease for secretion processing. In addition, transfection of the gene of familial Alzheimer's disease (FAD)[corrected]-linked presenilin-1, a component of gamma-secretase, increased the secretion rate of endogenous GnT-V; the secretion of soluble GnT-V (approximately 100 kDa) was completely inhibited in presenilin-1/2 double-deficient cells, which have no gamma-secretase activity. Collectively, these results demonstrate that Golgi-resident GnT-V is cleaved at the transmembrane region by gamma-secretase, and this might control tumor angiogenesis through a novel pathway.

Structure and function of lipid rafts in human activated T cells.

Lipid rafts, specialized membrane microdomains enriched in sphingolipids and cholesterol, have been shown to function as signaling platforms in T cells. Surface raft expression is known to be increased in human T cells upon activation, and this increased raft expression may account for efficient signaling capability and decreased dependency for co-stimulation in effector and/or activated T cells. However, raft-mediated signaling ability in activated T cells remains to be clarified. In this study, we analyzed the structure and function of lipid rafts in human activated T cells. We demonstrated that raft protein constituents are dramatically changed after activation along with an increase in lipid contents. T cells stimulated with anti-CD3 plus anti-CD28 antibodies showed an increase not only in surface monosialoganglioside GM1 expression but also in total amounts of raft-associated lipids such as sphingomyelin, cholesterol and glycosphingolipids. Raft proteins increased after activation include Csk, Csk-binding protein and Fyn, the molecules known to be involved in negative regulation of T cell activation. Consistent with the increase in expression of these proteins, TCR-mediated Ca(2+) response, a response dependent on raft integrity, was clearly inhibited in activated T cells. Thus, the structure and function of lipid rafts in human activated T cells seem to be quite distinct from those in naive T cells. Further, human activated T cells are relatively resistant to signaling, at least transiently, by TCR re-stimulation even though their raft expression is increased.