Prolonged paradoxical reaction requiring over 5 years of corticosteroid administration in a patient with severe tuberculous meningitis.

Tuberculous meningitis (TBM) is a rare disease in low-incidence countries like Japan, where general physicians have fewer experience with TBM. Despite its proper treatment and early improvement of the condition, TBM often causes paradoxical reactions (PRs), which can lead to severe complications such as stroke. As PRs in the brain are difficult to detect without regular neuroimaging surveillance and have a later onset than in other organs, delayed treatment can be fatal. We report a case of a 54-year-old, human immunodeficiency virus (HIV)-negative man who presented with TBM and miliary tuberculosis (TB) in an unconscious state. Standard anti-tuberculous therapy with adjunctive systemic high-dose dexamethasone brought rapid clinical and microbiological improvement, which allowed the dexamethasone to be tapered. However, he developed cerebral infarction with left hemiplegia due to a TBM-related PR five months after admission. Therefore, the initial high-dose dexamethasone was again added to the anti-tuberculous drugs, achieving the significant effects on the PR-related lesions. Anti-tuberculous drugs had been administered for 3 years and the dexamethasone was carefully tapered. Nevertheless, enlargement of PR-related lesions in the brain recurred 5 years later. Accordingly, the dose of corticosteroid was again increased, resulting in resolving the lesions. It is important to note that severe TBM may cause prolonged PRs, which require a long-term neuroimaging follow-up and anti-inflammatory drugs for the successful management of the TBM-related PR.

The challenge of differentiating tuberculous meningitis from bacterial meningitis.

Tuberculous meningitis (TBM) is a rare but important differential diagnosis in patients with impaired consciousness. Here, we describe a case of TBM in an 83-year-old Japanese woman who presented to a local hospital with fever and decreased consciousness of 20 days' duration (from day -40). She was started on treatment for bacterial meningitis due to an increased cerebrospinal fluid cell count, but her condition did not improve. She was transferred to a second hospital on suspicion for cholecystitis, then to a university hospital when consciousness did not improve and finally to us at a fourth hospital. On day -2, diffuse granulation was seen in both lung fields on chest computed tomography, sputum Mycobacterium test was positive and adenosine deaminase was elevated in spinal fluid. We diagnosed TBM secondary to miliary tuberculosis and started treatment with steroids and anti-tuberculous drugs (day 0). However, her level of consciousness did not improve and she died at a sanatorium on day 178. Delayed treatment of TBM has a prognostic impact and should be kept in mind as a differential diagnosis for impaired consciousness.

Systemic Adverse Effects Induced by the BNT162b2 Vaccine Are Associated with Higher Antibody Titers from 3 to 6 Months after Vaccination.

OBJECTIVE: We aimed to determine the relationship between vaccine-related adverse effects and antibody (Ab) titers from 3 to 6 months after the second dose of the BNT162b2 coronavirus disease 2019 (COVID-19) mRNA vaccine (Pfizer/BioNTech) in Japan. METHODS: We enrolled 378 healthcare workers (255 women and 123 men) whose Ab titers were analyzed 3 and 6 months after the second dose in our previous study and whose characteristics and adverse effects were collected previously by using a structured self-report questionnaire. RESULTS: The workers' median age was 44 years. Although injection-site symptoms occurred with almost equal frequency between the first and second doses, systemic adverse effects, such as general fatigue and fever, were significantly more frequent after the second dose than after the first dose. Multivariate analysis showed that fever was significantly correlated with female participants for the second dose (odds ratio (OR), 2.139; 95% confidence interval (95% CI), 1.185-3.859), older age for the first dose (OR, 0.962; 95% CI, 0.931-0.994) and second dose (OR, 0.957; 95% CI, 0.936-0.979), and dyslipidemia for the first dose (OR, 8.750; 95% CI, 1.814-42.20). Age-adjusted Ab titers at 3 months after vaccination were 23.7% and 23.4% higher in patients with a fever than in those without a fever after the first and second dose, respectively. In addition, age-adjusted Ab titers at 3 and 6 months after the second dose were, respectively, 21.7% and 19.3% higher in the group in which an anti-inflammatory agent was used than in the group without the use of an anti-inflammatory agent. CONCLUSION: Participants with systemic adverse effects tend to have higher Ab titers from 3 to 6 months after the second dose of the BNT162b2 vaccine. Our results may encourage vaccination, even among people with vaccine hesitancy related to relatively common systemic adverse effects.

Attenuation of Antibody Titers from 3 to 6 Months after the Second Dose of the BNT162b2 Vaccine Depends on Sex, with Age and Smoking Risk Factors for Lower Antibody Titers at 6 Months.

OBJECTIVE: We aimed to determine antibody titers at six months and their percentage change from three to six months after the second dose of the BNT162b2 coronavirus disease 2019 (COVID-19) mRNA vaccine (Pfizer/BioNTech) and to explore clinical variables associated with titers in Japan. METHODS: We enrolled 365 healthcare workers (250 women, 115 men) whose three-month antibody titers were analyzed in our previous study and whose blood samples were collected 183 ± 15 days after the second dose. Participant characteristics, collected previously, were used. The relationships of these factors with antibody titers at six months and percentage changes in antibody titers from three to six months were analyzed. RESULTS: Median age was 44 years. Median antibody titer at six months was 539 U/mL. Older participants had significantly lower antibody titers (20s, 752 U/mL; 60s-70s, 365 U/mL). In age-adjusted analysis, smoking was the only factor associated with lower antibody titers. Median percentage change in antibody titers from three to six months was -29.4%. The only factor significantly associated with the percentage change in Ab titers was not age or smoking, but sex (women, -31.6%; men, -25.1%). CONCLUSION: The most important factors associated with lower antibody titers at six months were age and smoking, as at three months, probably reflecting their effect on peak antibody titers. However, the only factor significantly associated with the attenuation in Ab titers from three to six months was sex, which reduced the sex difference seen during the first three months. Antibody titers may be affected by different factors at different time points.

Age and Smoking Predict Antibody Titres at 3 Months after the Second Dose of the BNT162b2 COVID-19 Vaccine.

OBJECTIVE: We aimed to determine antibody (Ab) titres 3 months after the second dose of the BNT162b2 coronavirus disease-2019 (COVID-19) vaccine and to explore clinical variables predicting these titres in Japan. METHODS: We enrolled 378 healthcare workers (255 women, 123 men) whose blood samples were collected 91 ± 15 days after the second of two inoculations of the BNT162b2 COVID-19 mRNA vaccine (Pfizer/BioNTech) given 3 weeks apart. Medical histories and demographic characteristics were recorded using a structured self-reported questionnaire. The relationships between Ab titres and these factors were analysed. RESULTS: Median age (interquartile range (IQR)) of the participants was 44 (32-54) years. Median Ab titre (IQR) against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike antigen was 764 (423-1140) U/mL. Older participants had significantly lower Ab titres; median (IQR) Ab titres were 942 (675-1390) and 1095 (741-1613) U/mL in men and women in their 20s, respectively, but 490 (297-571) and 519 (285-761) U/mL in men and women in their 60-70s, respectively. In the age-adjusted analysis, the only risk factors for lower Ab titres were male sex and smoking. However, the sex difference may have arisen from the sex difference in smoking rate. Moreover, Ab titres were significantly lower in current smokers than in ex-smokers. CONCLUSIONS: The most important factors associated with low Ab titres were age and smoking habit. In particular, current smoking status caused lower Ab titres, and smoking cessation before vaccination may improve the individual efficacy of the BNT162b2 vaccine.

[IMPACT OF COEXISTING NONTUBERCULOUS MYCOBACTERIA DURING THE TREATMENT OF PULMONARY TUBERCULOSIS].

BACKGROUND: Nontuberculous mycobacteria (NTM) are often detected in patients undergoing treatment for pulmonary tuberculosis. This clinical status is thought to represent NTM disease, contamination, or colonization, but discriminating between these three conditions is difficult. PURPOSE: We examined the clinical characteristics and pathogenicity of coexisting NTM among patients with pulmonary tuberculosis, as well as its impact on clinical practice. PATIENTS AND METHODS: The subjects comprised 59 patients with pulmonary tuberculosis treated at the National Hospital Organization Utsunomiya National Hospital between January and December 2013. Patients in whom NTM was detected in one or more cultures were defined as the NTM group (19 patients), and they were compared to the non-NTM group (40 patients). Antiglycopeptidolipid (anti-GPL) core antibody titers were investigated in 18 patients from the NTM group. RESULT: We observed no significant difference in patient characteristics (age, sex, complications, history of pulmonary tuberculosis, lung disease, chest imaging findings, degree of smear positivity on admission) between the two groups. Mean duration of hospitalization was markedly longer for the NTM group, excluding those with coexisting NTM after discharge (98.8 ± 7.9 days), than for the non-NTM group (58.3 ± 3.5 days; p < 0.001). No anti-GPL core antibodies were detected in any of the 18 patients from the NTM group, including 13 patients who fulfilled the ATS/IDSA criteria. CONCLUSION: Coexisting NTM observed during treatment for tuberculosis likely results from colonization or contamination and usually has low pathogenicity. However, this finding is related to prolonged hospitalization.

Successful Plasma Exchange for Acute Pancreatitis Complicated With Hypertriglyceridemia: A Case Report.

A 33-year-old male with acute pancreatitis induced by hypertriglyceridemia had problems during treatment with plasma exchange. The hypercoagulable state was prevented by introducing innovative methods for cleaning and warming of the circuit and dialyzer. This enabled successful therapy, and the patient fully recovered from life-threatening acute pancreatitis.

[A case of drug-induced hypersensitivity syndrome caused by levofloxacin used for treating pulmonary tuberculosis].

The patient was a 27-year-old man with pulmonary tuberculosis, who was initially treated with isoniazid, rifampicin, ethambutol, and pyrazinamide. However, because of hepatic dysfunction and visual impairment, the four-drug therapy was switched to a three-drug regimen with isoniazid, rifampicin, and levofloxacin. At 9 weeks after the initiation of levofloxacin, the patient developed cervical lymphadenopathy, fever, systemic erythema, and hepatic dysfunction. He was diagnosed with drug-induced hypersensitivity syndrome (DIHS) based on positive results in the human herpesvirus (HHV)-6 DNA test, an indicator of HHV-6 reactivation. The symptoms improved after withdrawal of the antituberculosis drugs and initiation of steroid administration. However, considering the risk of relapse of DIHS, the tuberculosis treatment, which was initially planned for 9 months, was stopped at 7 months. Neither DIHS nor tuberculosis recurred.