Reduction of adverse reactions and correlation between post-vaccination fever and specific antibody response across successive SARS-CoV-2 mRNA vaccinations.

Background: SARS-CoV-2 mRNA vaccination, recognized for high immunogenicity, frequently induces adverse reactions, especially fever. We previously reported a correlation between post-vaccination fever and specific antibody responses to the primary series and first booster. We herein report changes in adverse reactions and the correlation between post-vaccination fever and antibody responses across successive vaccinations, from monovalent to bivalent mRNA vaccines. Methods: This cohort study was conducted at a Japanese hospital to investigate adverse reactions to the monovalent primary, first booster, and BA.4/5 bivalent BNT162b2 vaccinations. Local and systemic reactions were reported through a self-reporting diary after each dose. The spike-specific IgG titers were measured following each vaccination. Results: Across 727 vaccinations in the vaccine series, the bivalent booster induced fewer adverse reactions than earlier doses. Fever ≥ 38.0 °C was significantly less frequent in the bivalent booster (12.3 %) compared to the primary series and monovalent booster (22.0 %, 26.2 %, p < 0.001). Reaction severity was also reduced in the bivalent booster. In the analysis of 70 participants with complete data for all doses, post-vaccination fever ≥ 38.0 °C exhibited the highest relative risk (RR) among all solicited reactions throughout the vaccine series (RR: 5.24 [95 % CI: 2.40-11.42] for monovalent and 6.24 [95 % CI: 2.14-18.15] for bivalent). The frequency of fever ≥ 38.0 °C after all doses was 8.6 % (6/70), with no fever ≥ 39.0 °C across all vaccinations. A high-grade post-vaccination fever was correlated with higher IgG titers, with multivariate analyses confirming this correlation as independent for each dose and unaffected by previous post-vaccination fever. Conclusions: The bivalent mRNA vaccine booster showed fewer and milder adverse reactions than the monovalent doses. Although vaccinees with a history of post-vaccination fever were more likely to experience fever after a subsequent dose, such recurrences were infrequent. A correlation between post-vaccination fever and increased IgG titers was identified for each vaccination, irrespective of post-vaccination fever history.

Comparison of pathological findings and accumulation of fluorin-18 fluorodeoxyglucose on positron emission tomography/computed tomography: A case of relapsing polychondritis.

A 70-year-old woman with a hoarse voice and dry cough was referred to our hospital. Positron emission tomography/computed tomography showed abnormal accumulation of fluorine-18 fluorodeoxyglucose (FDG) at the nasal septum, larynx, trachea, bronchus, and costal cartilages. The maximum standard uptake values of FDG accumulation in the nasal septum and costal cartilage were similar. Biopsies of the nasal septum and costal cartilage were performed. The patient was diagnosed with relapsing polychondritis (RP) based on the clinical features and pathological findings. Histopathological examination revealed progressive initial RP findings. The disease progression was different, even with the same FDG accumulation.

Comparison of the slow-pull and aspiration methods of endobronchial ultrasound-guided transbronchial needle aspiration for next-generation sequencing-compatible tissue collection in non-small cell lung cancer.

BACKGROUND: Personalized treatment for non-small cell lung cancer (NSCLC) has advanced rapidly, and elucidating the genetic changes that trigger this disease is crucial for appropriate treatment selection. Both slow-pull and aspiration methods of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) are accepted methods for collecting samples suitable for next-generation sequencing (NGS) to examine driver gene mutations and translocations in NSCLC. Here, we aimed to determine which of these two methods is superior for obtaining higher-quality samples from patients with NSCLC. METHODS: Seventy-one patients diagnosed with NSCLC via EBUS-TBNA using the slow-pull or aspiration (20-mL negative pressure) methods between July 2019 and September 2022 were included. A total of 203 tissue samples from the 71 patients were fixed in formalin, embedded in paraffin, and mounted on slides. The presence of tissue cores, degree of blood contamination, and number of tumor cells were compared between the groups. The success rate of NGS, using Oncomine Dx Target Test Multi-CDx, was also compared between the groups. RESULTS: The slow-pull method was associated with a higher yield of tissue cores, lower degree of blood contamination, and higher number of tumor cells than the aspiration method. The success rate of the NGS was also significantly higher for the slow-pull group (95%) than for the aspiration group (68%). CONCLUSION: Overall, these findings suggest that the slow-pull method is a superior technique for EBUS-TBNA to obtain high-quality tissue samples for NGS. The slow-pull method may contribute to the identification of driver gene mutations and translocations and facilitate personalized treatment of NSCLC.

Achievement of sufficient antibody response after a fourth dose of wild-type SARS-CoV-2 mRNA vaccine in nursing home residents.

BACKGROUND: Infection control during COVID-19 outbreaks in nursing facilities is a critical public health issue. Antibody responses before and after the fourth (second booster) dose of wild-type severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in nursing home residents have not been fully characterized. METHODS: This study included 112 individuals: 54 nursing home residents (mean age: 84.4 years; 35 SARS-CoV-2-naive and 19 previously infected) and 58 healthcare workers (mean age: 47.7 years; 25 SARS-CoV-2-naive and 33 previously infected). Antispike and antinucleocapsid antibody responses to messenger RNA vaccination were evaluated using serum samples collected shortly and 5 months after the third dose, and shortly after the fourth dose. RESULTS: The median immunoglobulin G (IgG) level in SARS-CoV-2-naive residents was similar to that in SARS-CoV-2-naive healthcare workers after the fourth dose (24,026.3 vs. 30,328.6 AU/mL, p = .79), whereas after the third dose the IgG level of SARS-CoV-2-naive residents was approximately twofold lower than that in SARS-CoV-2-naive healthcare workers. In residents with previous SARS-CoV-2 infection, timing of infection in relation to vaccination affected the kinetics of antibody responses. Residents infected after the third dose showed the highest IgG levels after the fourth dose among all groups (median: 64,328.8 AU/mL), in contrast to residents infected before initiating vaccination with antibody levels similar to those of SARS-CoV-2-naive residents. CONCLUSIONS: Advanced aged nursing home residents, poor responders in the initial SARS-CoV-2 vaccine series, could achieve sufficient antibody responses after the fourth (second booster) vaccination, comparable to those of younger adults.

SARS-CoV-2 Testing of the Maxillary Sinus Immediately after COVID-19 Recovery.

We report the case of a 19-year-old woman with left orbital floor fracture after a motorcycle accident. She presented with headache and diplopia; computed tomography showed herniation of the inferior rectus muscle into the maxillary sinus with orbital floor fracture. She was admitted for observation of her concussion and tested positive for coronavirus disease 2019 (COVID-19) half a day after admission. Her COVID-19 symptoms were mild; the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) antigen quantification test was below the standard value on the 10th day of hospitalization, and her isolation was lifted. She had diplopia with vertical eye motion disorder and underwent reconstruction of her orbital floor fracture on the 11th day. Although the orbital floor was connected to the maxillary sinus due to the orbital floor fracture, the presence and the viral load of SARS-CoV-2 in the maxillary sinus were unknown. The surgeons performed the operation while wearing N95 masks. A SARS-CoV-2 antigen quantification test and PCR test were performed on a sample from the maxillary sinus mucosa obtained through the orbital floor fracture before reconstruction of orbital floor with a titanium mesh implant; both were negative. To our knowledge, this is the first report of SARS-CoV-2 testing from the maxillary sinus immediately after COVID-19 recovery. We believe that the risk of SARS-CoV-2 infection from the maxillary sinus is small if the antigen test from the nasopharynx is negative.

Coproduction of lipids and carotenoids by the novel green alga Coelastrella sp. depending on cultivation conditions.

A novel green alga Coelastrella sp. D3-1 was isolated, and its unique and significant lipid and carotenoid coproduction capability was characterised depending on cultivation conditions. The main component of produced lipids was triacylglycerol under nutrient depletion conditions, in which fatty-methyl-esters made up 20-44% of the dry cell weight (DCW) and consisted of abundant C16:0 and C18:1 fatty acids. The red (orange)-stage cells also produced a large portion of carotenoids (38.5% of the DCW) involving echinenone, canthaxanthin, and astaxanthin as major components accumulated over only 5-6 days under optimal conditions. Stress tests revealed resistance of the cells to pH 2-11, high temperatures (40-60 °C), ultraviolet irradiation, drought, and H2O2 treatment, thereby showing a robust nature. Both green- and red (orange)-stage cell extracts also showed antioxidant and anti-inflammatory abilities, implying that they have significant functions as useful biorefinery materials.

[Progressive multifocal leukoencephalopathy during the treatment for mycosis fungoides].

A 58-year-old man was diagnosed with mycosis fungoides (MF) confirmed by skin biopsy for systemic erythema that appeared in 2006 and had been on psoralen plus ultraviolet A (PUVA) therapy and topical steroids. In September 2017, he had diffuse large B-cell lymphoma and received chemotherapy. Since March 2019, tumor stage MF with large cell transformation was observed, and chemotherapy containing brentuximab vedotin (BV) was performed, which yielded a remarkable response. During the preparation for allogeneic hematopoietic stem cell transplantation, bradykinesia, delayed response, and cognitive decline were observed. Head magnetic resonance imaging fluid-attenuated inversion recovery images showed hyperintensity in the deep white matter below the bilateral frontal cortex. The general cerebrospinal fluid test revealed no abnormalities and was below the sensitivity of JC virus (JCV) quantitative PCR. As progressive multifocal leukoencephalopathy (PML) was strongly suspected from clinical symptoms and radiographic signs, ultrasensitive JCV testing was performed. The test result was positive; hence, the patient was diagnosed with PML. Chemotherapy was discontinued, but his central nervous system symptoms worsened, and he died on the 135th day of illness. We considered that PML developed based on the underlying disease and immunodeficiency caused by chemotherapy such as BV.

Scrotal Abscess in a Japanese Patient Caused by Prevotella bivia and Streptococcus agalactiae, Successfully Treated with Cefazolin and Amoxicillin: A Case Report.

BACKGROUND: Infections caused by Prevotella bivia, a gram-negative anaerobic bacillus, are rare, with no reported cases in Japan. We present a novel case of scrotal abscess in a Japanese patient co-infected with Prevotella bivia and Streptococcus agalactiae. CASE PRESENTATION: A 41-year-old uncontrolled diabetic man complained of swelling and pain in the scrotum. On examination, computed tomography revealed an abscess of 5-cm diameter in the scrotum. Then, the abscess was incised and drained. He was treated with cefazolin empirically. Prevotella bivia and Streptococcus agalactiae were identified in the pus cultures obtained from the abscess. However, the susceptibility tests for Prevotella bivia could not be submitted. Seven days following admission, the pain reduced, and the drainage slowed. The patient was discharged on day 14 when cefazolin was discontinued and oral amoxicillin (750 mg/day) was started. Amoxicillin was continued until day 42; improvement was confirmed. CONCLUSION: To the best of our knowledge, this case is the first report of Prevotella bivia in Japan. We suggest that cephem antibiotics such as cefazolin may be effective against Prevotella bivia in Japan.

One-Pot Preparation of (E)-α,ß-Unsaturated Aldehydes by a Julia-Kocienski Reaction of 2,2-Dimethoxyethyl PT Sulfone Followed by Acid Hydrolysis.

(E)-α,ß-Unsaturated aldehydes were synthesized by the Julia-Kocienski reaction of 2,2-dimethoxyethyl 1-phenyl-1H-tetrazol-5-yl (PT) sulfone 3 with various aldehydes, followed by acid hydrolysis. The reaction could be carried out in one pot, and various (E)-α,ß-unsaturated aldehydes were obtained in a short time and with high yields.

Outcomes in Patients with Classic Hodgkin Lymphoma Treated with ABVD: A Single-center Retrospective Study.

Objective Classic Hodgkin lymphoma (CHL) has been regarded as a curable disease when treated appropriately, especially in younger patients, and ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) has been regarded as the standard regimen. However, a relatively poor prognosis has been reported in older patients with CHL, and the efficacy and tolerability of the ABVD regimen has not been fully elucidated. We retrospectively investigated the outcomes in patients with CHL treated with ABVD at our institute. Methods Twenty-five patients were evaluated; 14 were ≤60 years of age, and 11 were >60 years of age (older group). Results The ABVD doses were reduced in all patients in the older group; the median average relative dose intensity was 0.58. In the older group, the 5-year overall survival (OS) and median OS were 100% and not reached, respectively, for patients with early-stage CHL and 66.7% and not reached, respectively, for those with advanced-stage CHL. No patients died of CHL, and only one treatment-related death was observed in the older group. Conclusion ABVD with dose attenuation may represent a feasible and effective strategy for the treatment of older patients with CHL in clinical practice, particularly in those with early-stage disease, although the optimal degree of attenuation remains unclear.

Clinical significance of SARS-CoV-2-specific IgG detection with a rapid antibody kit for COVID-19 patients.

BACKGROUND: The longitudinal observation of the detection of antibody responses to SARS-CoV-2 using antibody kits during the clinical course of COVID-19 is not yet fully investigated. OBJECTIVES: To understand the significance of the detection of anti-SARS-CoV-2 antibodies, particularly IgG, using a rapid antibody kit, during the clinical course of COVID-19 patients with different severities. METHODS: Sixty-three serum samples from 18 patients (5 asymptomatic and 13 symptomatic patients) were retrospectively examined using a commercial SARS-CoV-2 IgM/IgG antibody kit. PCR positivity of patient samples was also examined as a marker of current SARS-CoV-2 infection. RESULTS: IgG antibodies were detected in all cases in this study. The IgG detection rates reached 100.0% in samples collected on day 13 or later. IgG seropositivity after an initial negative status was observed in 13 patients (3/5 asymptomatic and 10/13 symptomatic cases). Interestingly, the persistence of both PCR and IgG positivity was detected in seven cases, of which three were asymptomatic. The longest overlap duration of the PCR and IgG positivity was 17 days in asymptomatic status. CONCLUSIONS: SARS-CoV-2-specific IgG production can be detected in all infected individuals, using a rapid antibody kit, irrespective of clinical status. However, these findings suggest that, in some infected individuals, particularly those with asymptomatic status, the presence of virus-specific IgG antibodies does not imply prompt viral clearance.

A case report of psychiatric symptoms following direct-acting antiviral and ribavirin combination therapy for chronic hepatitis C in a patient with innate anxiety.

BACKGROUND: Direct-acting antivirals (DAAs) result in a highly sustained virological response rate and better patient tolerance. However, this therapeutic approach may, on rare occasions, give rise to psychiatric symptoms. We describe a case requiring discontinuation of DAA and ribavirin combination therapy due to psychiatric symptoms in a patient with congenital anxious personality traits. The information summarized here will be helpful to physicians treating chronic hepatitis C virus (HCV) infection in patients with underlying psychiatric problems. CASE PRESENTATION: A 57-year-old Japanese woman diagnosed with chronic HCV infection was prescribed DAA and ribavirin combination therapy. She had a history of mild innate anxiety and development of psychiatric symptoms due to interferon (IFN) therapy 8 years prior, which subsided with discontinuation of the therapy. Similar psychiatric symptoms such as enervation, palpitations, an episode of hyperventilation, and consciousness disturbances with myotonia were observed after the administration of the antiviral agents. No abnormal findings related to her symptoms were observed on laboratory or imaging results. Psychiatrists diagnosed the patient as having a somatization disorder induced by the antiviral agents on the basis of innate anxiety. After the discontinuation of therapy, her symptoms gradually improved. CONCLUSIONS: Although DAAs were not causative factors for psychiatric symptoms in phase 3 studies, a post-marketing study reported psychiatric symptoms such as depression in patients with underlying psychiatric problems. Our case suggests psychiatric symptoms might worsen after DAA and ribavirin administration in patients with underlying psychiatric disorders, and therefore, close monitoring is necessary for these patients, especially if they have a history of psychiatric symptoms after IFN.

A year-round evidence-based medicine-learning course organized by medical students at Ehime University.

To resolve the problem that evidence-based medicine (EBM) courses are not sufficiently taught in Japanese medical schools, we organized a year-round EBM-learning course. This study was an observational study and was designed to evaluate the participants' understanding of EBM using an original survey. The survey was given three times. In total, 18 students responded to our survey. Of those 18 students, six students answered both the first and the last surveys, and their mean score increased 1.17 of 4.00 (95% CI: 0.72-1.65). These results suggest our course improved students' ability to read clinical articles.

Exposure to ozone enhances antigen-presenting activity concentration dependently in rats.

The effect of ozone (O(3)) on the symptoms of allergic asthma and the mechanisms underlying have not yet been fully elucidated. Antigen presentation is one of the factors contributing to the allergic reaction. Therefore, we investigated the effects of repeated exposure to O(3) on antigen-presenting (AP) activity, on the expression of cell-surface molecules associated with antigen presentation (Ia, B7.1, B7.2 and CD11b/c) in bronchoalveolar lavage cells (BAL cells), and on allergic asthma-like symptoms. Rats were exposed to 0.3, 0.56, 1ppm O(3) or filtered air for a 3-day period every 2 weeks, this was replicated three times. AP activity was assessed by measuring antigen-specific T-cell proliferation; and the expression of cell-surface molecules, by flow cytometry. Rats were also made to inhale aerosolized 1% ovalbumin (OVA) or saline for 10min post-exposure to O(3), and allergic asthma-like symptoms were measured by determining the increase in enhanced pause (Penh), which correlates well with lung resistance. O(3) increased both AP activity and expression of Ia and costimulatory molecules in BAL cells concentration dependently. It also increased lung resistance, and the increase in lung resistance after O(3) exposure was significantly higher in the OVA-inhaled group than in the saline-inhaled group. The present results show that O(3) increased AP activity concentration dependently and suggest that O(3) might aggravate allergy symptoms by enhancing AP activity.