Refractory Depression With Persistent Sore Throat and Hypochondriacal Delusion of SARS-CoV-2 Infection: A Case Study.

ABSTRACT: Herein, we present a case of a female patient with a persistent sore throat, which preceded a hypochondriacal delusion of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Both the sore throat and hypochondriacal delusion persisted together, despite the repeatedly negative results of reverse transcription polymerase chain reaction (RT-PCR) for SARS-CoV-2 and a moderate improvement in her depression. Four possibilities for the patient's sore throat were discussed: pain symptoms of somatic symptom disorder, pain symptoms of depression, delusion of pain in her throat, and somatic hallucination as a sore throat. Consequently, somatic hallucinations were considered the most likely. In any case, the present findings suggest that sore throat can precede hypochondriacal delusion of SARS-CoV-2 infection in some noninfected patients. When patients continue to complain of a sore throat despite the negative results of SARS-CoV-2 by the RT-PCR test, we should consider that it might be a somatic hallucination and soon hypochondriacal delusions may occur, leading to the manifestation of other symptoms of psychiatric disorders, such as depression, which may be refractory and/or suicidal.

Lithium in drinking water and Alzheimer's dementia: Epidemiological Findings from National Data Base of Japan.

OBJECTIVES: The aim of this study was to investigate the association between lithium levels in drinking water and prevalence of Alzheimer's dementia (AD). METHODS: Lithium levels in the drinking water of 808 cities and wards (i.e., 785 Japanese cities of 46 prefectures and 23 wards of Tokyo) in Japan were examined in relation to the prevalence of AD during the 5 years from 2010 to 2014, which was calculated on the basis of the national data base of Ministry of Health, Labor, and Welfare of Japan. Multiple regression analyses were used to investigate the association of lithium levels with the prevalence of AD with adjustment for relevant factors (proportions of one-person households as a family factor and people in primary industry employment as a job factor, annual total sunshine hours as a meteorological factor, and total number of beds of psychiatric hospitals as a medical factor) in total, male, and female elderly populations. RESULTS: The adjusted model showed a significant inverse association of lithium levels with female, but not with male, or total prevalence of AD. CONCLUSIONS: These findings suggest that higher lithium levels in drinking water may be associated with lower prevalence of AD in female, but not male, populations.

Outcomes of methotrexate-associated lymphoproliferative disorders in rheumatoid arthritis patients treated with disease-modifying anti-rheumatic drugs.

Recently, the use of targeted synthetic or biological disease-modifying anti-rheumatic drugs (ts/bDMARDs) in addition to conventional synthetic (cs)DMARDs including methotrexate (MTX) for rheumatoid arthritis (RA) has increased. However, whether ts/bDMARDs are associated with the development and clinicopathological features of MTX-associated lymphoproliferative disorder (MTX-LPD) in patients with RA remains unknown. Therefore, we evaluated the clinical outcomes of 121 patients with MTX-LPD. Results showed that prior use of ts/bDMARDs was not associated with the different histopathological subtypes of MTX-LPD. Patients with polymorphic-type LPD had a better event-free survival than those with diffuse large B-cell lymphoma (DLBCL), classical Hodgkin lymphoma and peripheral T-cell lymphoma. The pathological subtype of lymphoma could predict the clinical outcome of MTX-LPD. In patients with DLBCL, the use of tumour necrosis factor-alpha (TNF-α) inhibitors prior to MTX-LPD onset was associated with a higher non-relapse mortality. Further, patients with RA previously treated with Janus kinase (JAK) inhibitors more commonly required chemotherapy than those treated with csDMARDs alone, indicating disease aggressiveness. Hence, special caution should be observed when managing patients with MTX-LPD previously treated with JAK or TNF-α inhibitors for RA.

Lithium in drinking water and suicide prevention: The largest nationwide epidemiological study from Japan.

OBJECTIVES: The aims of the present study thus were (a) to further investigate the association between lithium levels in drinking water and suicide rates by adjusting relevant factors using the so far largest available dataset in Japan, (b) to confirm sex differences, (c) to estimate the effects of long-term exposure to trace lithium, (d) to investigate the effects of drinking bottled instead of tap water, and (e) to exploratorily investigate which lithium levels may be associated with lower suicide rates. METHODS: Mean lithium levels in drinking water of all 808 cities and wards (ie, 785 cities of 46 prefectures and 23 wards of Tokyo) in Japan were examined in relation to mean suicide standardized mortality ratios (SMRs) during the 7 years from 2010 to 2016. Multiple regression analyses adjusted for the size of each population were used to investigate the association of lithium levels with suicide SMRs with adjustments for relevant factors. RESULTS: The adjusted model showed significant inverse associations of lithium levels with total and male SMRs, but not with female SMRs. Neither the proportion of residents who continued to live in the same city nor the consumption of bottled water changed the association between lithium levels and suicide SMRs. Finally, it was 30 µg/L or more that was associated with lower suicide SMRs. CONCLUSIONS: The present findings reconfirm the inverse association between lithium levels in drinking water and suicide rates particularly in the male population.

Addition of plerixafor for mobilization of stem cells with bortezomib is feasible in dialysis-dependent multiple myeloma.

Plerixafor and bortezomib have recently been used in autologous stem cell collection to increase the amount of stem cells collected. However, no reports have described the combined use of plerixafor and bortezomib in cases of dialysis-dependent multiple myeloma. The dialysis-dependent multiple myeloma patient in the present study had a small amount of CD34-positive cells with plerixafor and filgrastim, and also with bortezomib and cyclophosphamide. However, by adding plerixafor to bortezomib and cyclophosphamide, collected CD34-positive cells were increased six-fold compared to the previous day. These findings suggest that the combination of plerixafor and bortezomib may be effective in those patients.

Tyrosine kinase inhibitors induce alternative spliced BCR-ABLIns35bp variant via inhibition of RNA polymerase II on genomic BCR-ABL.

To elucidate dynamic changes in native BCR-ABL and alternatively spliced tyrosine kinase inhibitor (TKI)-resistant but function-dead BCR-ABLIns35bp variant, following commencement or discontinuation of TKI therapy, each transcript was serially quantified in patients with chronic myeloid leukemia (CML) by deep sequencing. Because both transcripts were amplified together using conventional PCR system for measuring International Scale (IS), deep sequencing method was used for quantifying such BCR-ABL variants. At the initial diagnosis, 7 of 9 patients presented a small fraction of cells possessing BCR-ABLIns35bp , accounting for 0.8% of the total IS BCR-ABL, corresponding to actual BCR-ABLIns35bp value of 1.1539% IS. TKI rapidly decreased native BCR-ABL but not BCR-ABLIns35bp , leading to the initial increase in the proportion of BCR-ABLIns35bp . Thereafter, both native BCR-ABL and BCR-ABLIns35bp gradually decreased in the course of TKI treatment, whereas small populations positive for TKI-resistant BCR-ABLIns35bp continued fluctuating at low levels, possibly underestimating the molecular response (MR). Following TKI discontinuation, sequencing analysis of 54 patients revealed a rapid relapse, apparently derived from native BCR-ABL+ clones. However, IS fluctuating at low levels around MR4.0 marked a predominant persistence of cells expressing function-dead BCR-ABLIns35bp , suggesting that TKI resumption was unnecessary. We clarified the possible mechanism underlying mis-splicing BCR-ABLIns35bp , occurring at the particular pseudo-splice site within intron8, which can be augmented by TKI treatment through inhibition of RNA polymerase II phosphorylation. No mutations were found in spliceosomal genes. Therefore, monitoring IS functional BCR-ABL extracting BCR-ABLIns35bp would lead us to a correct evaluation of MR status, thus determining the adequate therapeutic intervention.

Safety and Seropositivity after Live Attenuated Vaccine in Adult Patients Receiving Hematopoietic Stem Cell Transplantation.

Vaccination against vaccine-preventable diseases (VPDs) is highly recommended for hematopoietic stem cell transplantation (HSCT) recipients by several guidelines; however, the safety and seropositivity after live attenuated vaccines remain unclear in adult HSCT recipients. We analyzed titers of antibodies against measles, rubella, mumps, and varicella zoster virus (VZV) from Japanese adult patients who underwent allogeneic HSCT (allo-HSCT) (n = 74), autologous HSCT (auto-HSCT) (n = 39), or chemotherapy (n = 93). The seropositive rates for measles, rubella, mumps, and VZV in allo-HSCT recipients were 20.2%, 36.4%, 5.4%, and 55.4%, respectively. These rates were equivalent to those in auto-HSCT recipients but were significantly lower than those in patients receiving chemotherapy. Antibody titers tended to gradually decrease with time. Twenty-nine allo-HSCT recipients and 8 auto-HSCT recipients received live attenuated vaccines against VPDs for which they tested seronegative. The titers of antibodies against measles, rubella, and mumps significantly increased after 2 shots of vaccine, and the seropositive rate increased up to 19%, 30%, and 27%, respectively. Three patients (8.1%) experienced mild adverse events, which resolved promptly, indicating safe administration of the live attenuated vaccines. In multivariate analysis, history of chronic graft-versus-host disease was significantly associated with high seropositivity for measles as well as high seroconversion rate for measles after vaccination. Live attenuated vaccines against VPDs were safely administered in seronegative adult HSCT recipients. A further observational study is crucial to evaluate the efficacy of vaccination in seronegative HSCT patients.

Relationship between hyperthymic temperament, self-directedness, and self-transcendence in medical students and staff members.

AIM: We aimed to investigate the hypotheses that hyperthymic temperament may be positively associated with self-directedness and self-transcendence with adjustment for relevant factors. METHODS: Using the database of our previous studies, the data from 111 healthy subjects with scores for both the Temperament and Character Inventory and the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego Autoquestionnaire were secondarily used for the present study. RESULTS: Hyperthymic Temperament scores were significantly and positively associated with Self-Transcendence scores, but not with Self-Directedness scores, following adjustment for relevant factors. Despite the lack of association between self-transcendence and self-directedness, cooperativeness was significantly and positively associated with self-transcendence and self-directedness, but not with hyperthymic temperament. Moreover, despite the lack of association between hyperthymic temperament and self-directedness, harm avoidance was significantly and negatively associated with hyperthymic temperament and self-directedness, but not with self-transcendence. CONCLUSION: The present findings suggest that hyperthymic temperament may be positively associated with self-transcendence, but not with self-directedness. Moreover, hyperthymic temperament may be, a selfish and reckless trait, self-transcendence may be altruistic and not reckless, and self-directedness may be altruistic but reckless.

Relationship between ambient light and glucose metabolism in healthy subjects.

BACKGROUND: Given the reported inverse association between light and depressive mood, ambient light may also be associated with some of the brain regions in healthy subjects. The present study aims to investigate the effects of ambient light on glucose metabolism in the brain. We used the data of 28 healthy participants of the no intervention group from our previous randomized controlled trial and analyzed the association between ambient light and [18F]-FDG uptake in the brain. RESULTS: A whole brain analysis revealed a cluster of [18F]-FDG uptake that was significantly and inversely associated with log-transformed ambient light in the left culmen of the left cerebellum vermis. After adjustment for age, gender and serum melatonin levels, there remained a significant cluster of [18F]-FDG uptake with log-transformed ambient light in the left cerebellar vermis. CONCLUSIONS: The present findings suggest that the uptake of [18F]-FDG is significantly and inversely associated with ambient light in the left cerebellar vermis in healthy subjects. The cerebellar vermis may be involved in mood suppression which may be alleviated by light exposure where glucose uptake and metabolism in this area are decreased. Trial Registration This study is a secondary analysis of the previous randomized study which was registered as UMIN000007537. Retrospectively registered (March 20th, 2012).