Outcomes in children with first-relapsed acute lymphoblastic leukemia in Japan: Results from JCCG Study JPLSG-ALL-R08.

BACKGROUND/OBJECTIVES: The Berlin-Frankfurt-Münster (BFM)-S classification is a crucial prognostic indicator in children experiencing first-relapsed acute lymphoblastic leukemia (ALL). Early molecular response to therapy, evaluated by measurable/minimal residual disease (MRD), has a significant impact on the survival of patients with childhood ALL. Applying risk stratification based on the BFM-S classification and MRD response after induction, the first nationwide prospective multicenter study, ALL-R08, was conducted in children with first-relapsed ALL in Japan. METHODS: The ALL-R08 study comprised two parts: ALL-R08-I, an observational study aimed at obtaining an overall picture of outcomes in first-relapsed childhood ALL, and ALL-R08-II, a clinical trial for the non-T-ALL S2 risk group. In ALL-R08-II, patients with an MRD level of ≥10-3 at the end of induction therapy were assigned to undergo allogeneic hematopoietic stem cell transplantation (allo-HCT), whereas those with an MRD level less than 10-3 and isolated extramedullary relapse continued to receive chemotherapy. RESULTS: In total, 163 patients were enrolled in the ALL-R08 study, and 82 and 81 patients were enrolled in the ALL-R08-I and the ALL-R08-II, respectively. In ALL-R08-I, the probability of 3-year event-free survival (EFS) for patients with S1, S2, S3, S4, and post-HCT groups was 83% ± 15%, 37% ± 11%, 28% ± 8%, 14% ± 7%, and 0%, respectively. In the ALL-R08-II trial, 3-year EFS in patients with post-induction MRD less than 10-3 and ≥10-3 was 70% ± 9% (n = 27) and 68% ± 8% (n = 31) (p = .591), respectively. CONCLUSIONS: ALL-REZ BFM-type treatment is equally effective for children with first-relapsed ALL treated according to the Japanese frontline protocols and for children with first-relapsed ALL treated according to the BFM-type frontline protocols.

Correlates of Nucleocapsid Antibodies and a Combination of Spike and Nucleocapsid Antibodies Against Protection of SARS-CoV-2 Infection During the Omicron XBB.1.16/EG.5-Predominant Wave.

Background: We aimed to examine the association among nucleocapsid (N) antibodies, a combination of N and spike (S) antibodies, and protection against SARS-CoV-2 reinfection. Methods: We conducted a prospective cohort study among staff at a national medical research center in Tokyo and followed them for the incidence of SARS-CoV-2 infection between June and September 2023 (Omicron XBB.1.16/EG.5 wave). At baseline, participants donated blood samples to measure N- and S-specific antibodies. Cox regression was used to estimate the hazard ratio and protection ([1 - hazard ratio] × 100) against subsequent SARS-CoV-2 infection across these antibody levels. Results: Among participants with previous infection, higher pre-reinfection N antibodies were associated with a lower risk of reinfection, even after adjusting S antibody levels (P < .01 for trend). Estimation of the protection matrix for N and S antibodies revealed that high levels in N and S antibodies conferred robust protection (>90%) against subsequent infection. In addition, a pattern of low pre-reinfection N antibodies but high vaccine-enhanced S antibodies showed high protection (>80%). Conclusions: Pre-reinfection N antibody levels correlated with protection against reinfection, independent of S antibodies. If the N antibodies were low, vaccine-boosted S antibodies might enhance the reinfection protection.

Characteristics of CYP3A4-related potential drug-drug interactions in outpatients receiving prescriptions from multiple clinical departments.

BACKGROUND: Drug-drug interactions (DDIs) increase the incidence of adverse drug reactions (ADRs). In a previous report, we revealed that the incidence of potential DDIs due to the same CYP molecular species in one prescription exceeds 90% among patients taking six or more drugs and that CYP3A4 markedly influences the increase in the number of potential DDIs in clinical practice. However, the factors contributing to an increased number of potential DDIs in prescriptions from multiple clinical departments remain poorly clarified. METHODS: This observational study was performed at five pharmacies in Okayama Prefecture, Japan. Patients who visited these pharmacies from 11 April 2022 to 24 April 2022 were included, except those who had prescriptions only from a single clinical department. A stratified analysis was performed to determine the incidence of CYP3A4-related potential DDIs according to the number of drugs taken. Additionally, factors associated with an increase in the number of drugs involved in CYP3A4-related potential DDIs were identified using multiple linear regression analysis. In this study, potential DDIs for the prescription data subdivided by clinical department, containing two or more drugs, were used as control data. RESULTS: Overall, 372 outpatients who received prescriptions from multiple clinical departments were included in the current study. The number of drugs contributing to CYP3A4-related potential DDIs increased with an increase in the number of clinical departments. Notably, in cases taking fewer than six drugs, prescriptions from multiple clinical departments had a higher frequency of CYP3A4-related potential DDIs than those in prescriptions subdivided by clinical department. Multiple regression analysis identified "Cardiovascular agents", "Agents affecting central nervous system", and "Urogenital and anal organ agents" as the top three drug classes that increase CYP3A4-related potential DDIs. CONCLUSION: Collectively, these results highlight the importance of a unified management strategy for prescribed drugs and continuous monitoring of ADRs in outpatients receiving prescriptions from multiple clinical departments even if the number of drugs taken is less than six.

Allogeneic stem cell transplantation for inherited metabolic disorders: 35 years' experience at a single institution.

Hematopoietic stem cell transplants for inherited metabolic disorders performed at Tokai University Hospital between June 5, 1986, and May 28, 2021, were analyzed and compared between the period before 2007 and the period from 2007 onward based on availability of medical resources. Transplants were performed for 38 patients with mucopolysaccharidosis, 33 with adrenoleukodystrophy, and 16 with another disorder. Before 2007, oral busulfan-based regimens were mainly used. From 2007 onward, intravenous busulfan-based regimens or 4 Gy of thoracoabdominal irradiation (TAI), fludarabine, and melphalan (Mel)/treosulfan were adopted. Between 2002 and 2010, adrenoleukodystrophy was treated with 12 Gy of TAI and Mel. HLA-identical sibling bone marrow was used in 43% of cases before 2007 and 15% from 2007 onward, while alternative donors were selected for other transplants. Overall survival and event-free survival (EFS) before 2007 and from 2007 onward were 76% and 62%, and 97% and 85%, respectively (P = 0.006 and 0.017). Transplant era predicted superior overall survival and EFS, while myeloablative conditioning also predicted EFS. The incidence of primary graft failure decreased from 2007 onward, especially in cord blood transplant when 4 Gy of TAI with 150 mg/m2 fludarabine and 180 mg/m2 Mel or 42 g/m2 treosulfan were used as conditioning.

Subcutaneous Panniculitis-like T Cell Lymphoma Diagnosed with a Slowly Progressive Course: A Case Report.

Panniculitis is an inflammation that occurs in subcutaneous adipose tissue. Panniculitis includes physical panniculitis (e.g., traumatic) and infectious panniculitis (e.g., bacterial, fungal, subcutaneous panniculitis-like T cell lymphoma [SPCTL], etc.). Accurate diagnosis is crucial due to similar clinical presentation of all types of panniculitis. Here, we report a case of SPCTL which was initially diagnosed with traumatic panniculitis. A 15-year-old male patient was admitted to a previous hospital due to a progressively enlarged right flank and inguinal mass after an abdominal bruise. He was initially diagnosed with traumatic panniculitis, but the mass expanded throughout the chest and abdomen accompanied by a fever of over 11 months. Computed tomography (CT) revealed a subcutaneous mass in the anterior chest and abdominal wall. Fludeoxyglucose F18 (FDG) uptake was observed at those lesions using FDG-positron emission tomography (PET). A biopsy of the mass lesion was performed, during which SPCTL was diagnosed based on pathological examination. He was initially treated with prednisolone and cyclosporine A for two weeks. His fever went down, but subcutaneous mass in the chest and abdominal wall persisted. Therefore, he received a cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) regimen. After 6 courses of CHOP, CT revealed no disease evidence. He remained in complete remission at 30 months of therapy.

Association of conventional cigarette smoking, heated tobacco product use, and dual use with hearing loss: A working population-based study.

INTRODUCTION: Although conventional cigarette smoking has been linked to an increased risk of hearing loss, the association between heated tobacco products (HTPs) and hearing loss is unknown. The objective of this study was to investigate the association between cigarette and HTP use and hearing loss. METHODS: This cross-sectional study examined the data of 7769 employees from five companies (Study I) and 34404 employees from a large company (Study II), all participants in the Japan Epidemiology Collaboration on Occupational Health Study. The participants were categorized into five groups based on their self-reported tobacco use: never smokers, former smokers, exclusive cigarette smokers, exclusive users of HTPs, and those who used both cigarettes and HTPs. Hearing levels were measured using pure-tone audiometry at 1 and 4 kHz frequencies. Separate analyses were carried out for each study, and the results were then combined using fixed-effect models to pool the estimates. RESULTS: The analysis included 42173 participants, with a prevalence of 12.9% for exclusive cigarette smoking, 9.8% for exclusive HTP use, and 5.5% for dual use. The pooled adjusted odds ratios with 95% confidence intervals for unilateral hearing loss at 4 kHz were 1.21 (95% CI: 1.10-1.33) for former smokers, 1.83 (95% CI: 1.64-2.05) for exclusive cigarette smokers,1.46 (95% CI: 1.28-1.67) for exclusive HTP users, and 1.66 (95% CI: 1.41-1.96) for dual users, compared to never smokers. Additionally, the adjusted odds ratios for hearing loss at 4 kHz among exclusive cigarette smokers, exclusive HTP users, and dual users increased with the intensity of cigarette/HTP consumption (all p for trend <0.001). No significant associations were found between exclusive HTP use, dual use, and hearing loss at 1 kHz, apart from exclusive cigarette smoking. CONCLUSIONS: In this cross-sectional study, associations were found between exclusive cigarette smoking, exclusive HTP use, dual use, and hearing loss, particularly at 4 kHz. Further research is needed to confirm these findings.

Prevalence and relevance of cachexia as diagnosed by two different definitions in patients undergoing hemodialysis: A retrospective and exploratory study.

OBJECTIVE: Cachexia is present in various chronic diseases and is associated with decreased quality of life and increased risk of morbidity and mortality. However, evidence regarding the association of cachexia with prognosis in patients undergoing hemodialysis is limited. We assessed cachexia using two definitions and compared prevalence, functional impairment, and prognostic impact in patients undergoing hemodialysis. METHODS: We enrolled outpatients undergoing hemodialysis at two centers retrospectively. We assessed cachexia using the conventional cachexia (Evans' criteria) and the Asian Working Group for Cachexia (AWGC) criteria. The study examined all-cause mortality and functional status (Clinical Frailty Scale and short physical performance battery). We used Cox proportional hazards model to examine the association with prognosis, and logistic regression analysis to examine the association with functional impairment. RESULTS: Among 367 patients (mean age, 67 years; 63 % male), cachexia prevalence, as defined by Evans' criteria and AWGC, was 21.3 % and 35.2 %, respectively. Cachexia as defined by Evans' criteria was associated with an increased risk of all-cause mortality (hazard ratio [HR], 95 % confidence interval [CI]: 1.81, 1.02-3.23). Also, cachexia as defined by AWGC criteria showed suggestive association with increasing mortality (HR, 95 % CI: 1.56, 0.90-2.70). Similar results were seen between cachexia and functional impairment. CONCLUSIONS: Among patients on hemodialysis, cachexia was highly prevalent and was associated with poor prognosis and functional impairment. Detecting cachexia in earlier stages may be useful for risk stratification in this population.

Association between Fish Intake and Serum Testosterone Levels in Older Males: The Hitachi Health Study II.

Background: Fish are rich in omega-3 polyunsaturated fatty acids and vitamin D, which can promote testosterone synthesis and secretion. However, some contaminants present in fish may disrupt testosterone production. Objective: This study aimed to investigate the association between fish intake (total, fatty, and lean fish) and serum testosterone levels in older males. Methods: This cross-sectional study included 1545 Japanese males aged 60-69 y who participated in the baseline survey of the Hitachi Health Study II. Fish intake was estimated using a validated brief-type self-administered diet history questionnaire. Total testosterone levels were measured by chemiluminescence immunoassay. Multivariable linear regression analysis was used to analyze the association between fish intake and serum testosterone levels. Results: Higher total fish intake was associated with higher levels of serum testosterone, with an adjusted mean [95% confidence interval (CI) of 5.63 (5.43, 5.83) and 5.99 (5.78, 6.20)] ng/mL for the 1st and 4th quartiles of total fish intake, respectively (P for trend = 0.06). When analyzing fatty and lean fish separately, higher intake of lean fish, but not fatty fish, was associated with higher levels of serum testosterone: adjusted mean (95% CI): 5.63 (5.43, 5.82) and 6.00 (5.79, 6.20) ng/mL for the 1st and 4th quartiles of lean fish intake, respectively (P for trend = 0.01). Conclusions: Among older males, higher intake of total fish, particularly lean fish, was associated with higher serum testosterone levels. Curr Dev Nutr 20xx;x:xx.

Vitamin D deficiency during the coronavirus disease 2019 (COVID-19) pandemic among healthcare workers.

BACKGROUND & AIMS: Vitamin D deficiency is a common nutritional problem worldwide that may have worsened during the coronavirus disease 2019 (COVID-19) pandemic. The present study sought to examine the prevalence and correlates of vitamin D deficiency among healthcare workers three years after the start of the COVID-19 pandemic. METHODS: Participants comprised 2543 staff members from a medical research institute, who completed a questionnaire and donated blood samples in June 2023. 25-hydroxyvitamin D (25[OH]D) levels were measured using an electrochemiluminescence immunoassay. Logistic regression was used to calculate the odds ratio and its 95% confidence interval while adjusting for covariates. RESULTS: The proportions of participants with vitamin D insufficiency (25[OH]D 20-29 ng/mL) and deficiency (25[OH]D < 20 ng/mL) were 44.9% and 45.9%, respectively. In a multivariable-adjusted model, factors associated with a higher prevalence of vitamin D deficiency included younger age, female sex, fewer hours of daytime outdoor physical activity during leisure time (without regular use of sunscreen), lower intake of fatty fish, no use of vitamin D supplements, smoking, and no alcohol consumption. Occupational factors, including shift work, were not independently associated with vitamin D deficiency. CONCLUSIONS: Our results suggest that vitamin D insufficiency and deficiency are highly prevalent among healthcare workers. Health education regarding lifestyle modifications for this occupational group are warranted to improve their vitamin D status in the COVID-19 era.

Molecular basis promoting centriole triplet microtubule assembly.

The triplet microtubule, a core structure of centrioles crucial for the organization of centrosomes, cilia, and flagella, consists of unclosed incomplete microtubules. The mechanisms of its assembly represent a fundamental open question in biology. Here, we discover that the ciliopathy protein HYLS1 and the ß-tubulin isotype TUBB promote centriole triplet microtubule assembly. HYLS1 or a C-terminal tail truncated version of TUBB generates tubulin-based superstructures composed of centriole-like incomplete microtubule chains when overexpressed in human cells. AlphaFold-based structural models and mutagenesis analyses further suggest that the ciliopathy-related residue D211 of HYLS1 physically traps the wobbling C-terminal tail of TUBB, thereby suppressing its inhibitory role in the initiation of the incomplete microtubule assembly. Overall, our findings provide molecular insights into the biogenesis of atypical microtubule architectures conserved for over a billion years.

Comparison of waist circumference and waist-to-height ratio as predictors of clustering of cardiovascular risk factors among middle-aged people in rural Khanh Hoa, Vietnam.

OBJECTIVE: Given the population-level variation in stature, a universal cut-off for waist circumference (WC) may not be appropriate for some populations. We compared the performance of WC and waist-to-height ratio (WHtR) to detect the clustering of cardiovascular disease (CVD) risk factors in rural Vietnam. METHODS: We obtained data from a baseline survey of the Khanh Hoa Cardiovascular Study comprising 2942 middle-aged residents (40-60 years). We used areas under the receiver operating characteristics curve (AUROC), net reclassification index (NRI), and integrated discrimination improvement (IDI) to compare the performance of WC and WHtR in predicting CVD risk clustering (≥2 of the following risk factors: hypertension, diabetes, dyslipidemia, and elevated C-reactive protein). RESULTS: The optimal cut-off values for WC were 81.8 and 80.7 cm for men and women, respectively. Regarding the clustering of CVD risk factors, the AUROC (95% CI) of WC and WHtR were 0.707 (0.676 to 0.739) and 0.719 (0.689 to 0.749) in men, and 0.682 (0.654 to 0.709) and 0.690 (0.663 to 0.717) in women, respectively. Compared with WC, WHtR had a better NRI (0.229; 0.102-0.344) and IDI (0.012; 0.004-0.020) in men and a better NRI (0.154; 0.050-0.257) in women. CONCLUSIONS: The optimal WC cut-off for Vietnamese men was approximately 10 cm below the recommended Asian cut-off. WHtR might perform slightly better in predicting the clustering of CVD risk factors among the rural population in Vietnam.

Prevalence of osteosarcopenia and its association with mortality and fractures among patients undergoing hemodialysis.

INTRODUCTION: Osteosarcopenia is an age-related syndrome characterized by the coexistence of osteoporosis and sarcopenia. Little is known about the clinical implications of osteosarcopenia among patients undergoing hemodialysis. This study investigated the prevalence of osteosarcopenia and its association with all-cause mortality and fractures in this population. MATERIALS AND METHODS: This retrospective cohort study included outpatients undergoing hemodialysis in Japan. Sarcopenia was defined according to the recommendations of the Asian Working Group for Sarcopenia 2019. Osteoporosis was defined as a T-score of the calcaneus bone < - 2.5. We divided patients into three groups: robust (no osteoporosis or sarcopenia), osteoporosis or sarcopenia alone (osteoporosis without sarcopenia or sarcopenia without osteoporosis), and osteosarcopenia (osteoporosis and sarcopenia). Cox proportional-hazard and negative binomial regression models were used to estimate the associations between osteosarcopenia and all-cause mortality and fractures. RESULTS: Among the 328 patients (mean age, 65.5 ± 11.3 years; men, 59.1%), the prevalence of osteosarcopenia was 22.9%. During the follow-up period (1972 person-years), 131 deaths and 113 fractures occurred. Patients with osteoporosis or sarcopenia alone (hazard ratio 1.36; 95% confidence interval 0.85-2.18) and osteosarcopenia (hazard ratio 2.13; 95% confidence interval, 1.23-3.68) showed a higher risk of all-cause mortality than the robust group. Similar results were observed for the risk of fractures in patients with osteosarcopenia. CONCLUSIONS: Patients undergoing hemodialysis showed a high prevalence of osteosarcopenia, and osteosarcopenia was associated with a poor prognosis in this patient population. Assessing osteosarcopenia may be useful for accurate prognostic stratification of patients undergoing hemodialysis.

Coffee and Green Tea Consumption With the Risk of COVID-19 Among the Vaccine Recipients in Japan: A Prospective Study.

BACKGROUND: While coffee and green tea have been suggested to have immunoprotective effects, it remains elusive whether they can decrease the risk of coronavirus disease 2019 (COVID-19). OBJECTIVE: We prospectively examined the associations of coffee and green tea consumption with the risk of COVID-19 among mRNA vaccine recipients during the epidemic of the Omicron variant. METHODS: Participants were 2,110 staff (aged 18 to 76 years) of a large medical facility in Tokyo, who attended a serosurvey in June 2022, predominantly received ≥3 doses of vaccine, and were followed for COVID-19 until December 2022. Coffee and green tea consumption was ascertained via a questionnaire. COVID-19 was identified through the in-house registry. Cox proportional hazards model was used to estimate the hazard ratios (HRs) of COVID-19 across the categories of beverage consumption. RESULTS: During 6 months of follow-up, 225 (10.6%) cases of COVID-19 were identified. Contrary to the expectation, higher consumption of coffee was associated with a significant increase in the risk of COVID-19; multivariable-adjusted HRs were 1.00 (reference), 0.92 (95% confidence interval [CI], 0.62-1.35), 1.48 (95% CI, 0.99-2.22), and 1.82 (95% CI, 1.20-2.76) for <1 cup/day, 1 cup/day, 2 cups/day, and ≥3 cups/day, respectively (P trend = 0.003). Green tea consumption was not significantly associated with the risk of COVID-19. The association with coffee was attenuated if serologically detected infection was added to the cases. CONCLUSION: In a cohort of Japanese hospital staff who received COVID-19 vaccine, higher consumption of coffee was associated with an increased risk of COVID-19 during the epidemic of the Omicron variant. There was no evidence of a significant association between green tea consumption and COVID-19 risk.

TBI, etoposide, and cyclophosphamide conditioning for intermediate-risk relapsed childhood acute lymphoblastic leukemia.

BACKGROUND: In children with intermediate-risk relapsed acute lymphoblastic leukemia (ALL), allogeneic hematopoietic stem cell transplantation (allo-HSCT) has markedly improved the outcome of patients with an unsatisfactory minimal residual disease (MRD) response. Total body irradiation (TBI), etoposide (ETP), and cyclophosphamide (CY) have been shown to be equivalent to or better than TBI + ETP for conditioning, so we hypothesized that even greater survival could be achieved due to recent advances in HSCT and supportive care. PROCEDURE: We prospectively analyzed the efficacy and safety of allo-HSCT with a unified conditioning regimen of TBI + ETP + CY in children with intermediate-risk relapsed ALL, based on MRD in the bone marrow after induction, from the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) ALL-R08-II nationwide cohort (UMIN000002025). RESULTS: Twenty patients with post-induction MRD ≥ 10-3 and two not evaluated for MRD underwent allo-HSCT. Engraftment was confirmed in all patients, and no transplantation-related mortality was observed. The 3-year event-free survival and overall survival rates after transplantation were 86.4% ± 7.3% and 95.5% ± 4.4%, respectively. CONCLUSION: Allo-HSCT based on post-induction MRD with TBI + ETP + CY conditioning was feasible in Japanese children with intermediate-risk relapsed ALL.

Association between Physical Frailty and Sleep Disturbances among Patients on Hemodialysis: A Cross-Sectional Study.

INTRODUCTION: Among patients on hemodialysis (HD), physical frailty and sleep disturbances are not only common but also associated with adverse outcomes. The aim of this study was to evaluate the association between physical frailty and sleep disturbances in patients on HD. METHODS: This cross-sectional study was conducted from June 2017 to March 2021, with outpatients receiving HD 3 times a week at two dialysis facilities in Japan. Sleep disturbances were identified with the Athens Insomnia Scale (AIS). Physical frailty was defined using the Fried Frailty Phenotype. Patients were classified as "non-frailty (number of frailty components: 0-2)" or "frailty (3-5)." We examined the association of sleep disturbances with physical frailty and its components by performing a logistic regression analysis. RESULTS: We analyzed 360 patients (mean age 65.6 years; 62% men). Eighty-one patients (23%) were classified into the group with frailty, and the mean AIS score was 5.2 ± 4.2 points. After adjusting for clinical characteristics, increasing the AIS score per 1 point was associated with higher odds of physical frailty (odds ratio, 1.12; 95% confidence interval, 1.05-1.20; p < 0.01). As for the frailty components, exhaustion, low physical activity, and weak grip strength showed an association with sleep disturbances (all p < 0.05). CONCLUSIONS: Sleep disturbances were independently associated with physical frailty in patients on HD. Future studies are warranted to investigate the causality between physical frailty and sleep disturbances in this population.

Isoflavone intake and depressive symptoms among workers.

BACKGROUND & AIM: High intake of isoflavones has been reported to be associated with decreased prevalence of depressive symptoms. However, no prospective study has examined this association. We prospectively investigated the association between isoflavone intake and depressive symptoms in a Japanese working population. METHODS: Participants were 1162 workers (1033 men and 129 women aged 18-68 years) without depressive symptoms at baseline. Dietary intake was assessed using a validated self-administered diet history questionnaire. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) scale. Cox proportional hazards regression for interval-censored data was used to estimate the hazard ratio of depressive symptoms (CES-D ≥16) according to the tertile of isoflavone intake with adjustment for covariates. RESULTS: During 5065 person-years of follow-up, 276 (23.8 %) workers were newly identified as having depressive symptoms. Isoflavone intake was not associated with risk of depressive symptoms. After adjustment for lifestyle and dietary factors and baseline CES-D score, the multivariable-adjusted hazard ratios (95 % confidence interval) for the lowest through highest tertile of isoflavone intake were 1.00 (reference), 0.93 (0.66-1.31), and 0.93 (0.62-1.38) (P for trend = 0.70). CONCLUSIONS: Our findings suggest that higher isoflavone intake is not associated with decreased risk of depressive symptoms among Japanese.

The association between antipyretic analgesics use and SARS-CoV-2 antibody titers following the second dose of the BNT162b2 mRNA vaccine: An observational study.

Antipyretic analgesics are used to manage and control symptoms occurring after vaccination, but may hamper immunogenicity or vaccine efficacy. We examined the association between prophylactic or therapeutic use of antipyretic analgesics and SARS-CoV-2 antibody titers for vaccine recipients. Data were obtained from 1,498 staff members of a medical and research institution in Tokyo, Japan, who had received the second dose of the BNT162b2 vaccine. We quantitatively measured anti-SARS-CoV-2 spike protein IgG titers in the participants three months after vaccination. The prophylactic and therapeutic use of antipyretic analgesics was ascertained via a questionnaire. A linear regression model was used to examine the association between antipyretic analgesic use and log-transformed anti-SARS-CoV-2 spike protein IgG titers. Based on model parameters, we estimated geometric mean titers (GMT) and the corresponding 95 % confidence intervals (CI). The results showed that IgG titers in vaccine recipients who used antipyretic analgesics therapeutically was higher than the titers in those who did not (geometric mean ratio [GMR] = 1.26, 95 % CI = 1.17-1.34) with GMTs being 6,147 (95 % CI = 5,833-6,460) and 4,895 (95 % CI = 4,676-5,115) for those who used antipyretic analgesics therapeutically and those who did not, respectively. The association was attenuated, but remained statistically significant after adjusting for symptoms (GMR = 1.14, 95 % CI = 1.06-1.23). We did not find any evidence of significant association in relation to the prophylactic use of antipyretic analgesics (GMR = 0.96, 95 % CI = 0.84-1.10), with GMTs being 5,245 (95 % CI = 4,577-5,913) and 5,452 (95 % CI = 5,258-5,645) for those who used antipyretic analgesics prophylactically and those who did not, respectively. In conclusion, we did not find any evidence of suppression of the humoral response after the second dose of SARS-CoV-2 vaccination by prophylactic or therapeutic use of antipyretic analgesics.